Full text data of AQP1
AQP1
(CHIP28)
[Confidence: high (a blood group or CD marker)]
Aquaporin-1; AQP-1 (Aquaporin-CHIP; Urine water channel; Water channel protein for red blood cells and kidney proximal tubule)
Aquaporin-1; AQP-1 (Aquaporin-CHIP; Urine water channel; Water channel protein for red blood cells and kidney proximal tubule)
hRBCD
IPI00024689
IPI00024689 aquaporin 1 (Aquaporin-CHIP) aquaporin 1 (Aquaporin-CHIP) membrane n/a 2 1 n/a 1 n/a n/a 1 1 n/a 2 1 n/a 2 1 n/a n/a 2 n/a n/a integral membrane protein n/a found at its expected molecular weight found at molecular weight
IPI00024689 aquaporin 1 (Aquaporin-CHIP) aquaporin 1 (Aquaporin-CHIP) membrane n/a 2 1 n/a 1 n/a n/a 1 1 n/a 2 1 n/a 2 1 n/a n/a 2 n/a n/a integral membrane protein n/a found at its expected molecular weight found at molecular weight
BGMUT
colton
1173 colton AQP1 AQP1 112T 112C>T P38S exons 1 to 4 in gDNA Co (a-,b weak) rare AM992149 Karpasitou et al. Vox Sang 2010 99 158-162 the allele, on the CO1 allele background, is silenced;thus, there is no expression of Coa antigen; expression of Cob is decreased. Blumenfeld OO., curator 2010-08-09 14:07:29.907 NA
1173 colton AQP1 AQP1 112T 112C>T P38S exons 1 to 4 in gDNA Co (a-,b weak) rare AM992149 Karpasitou et al. Vox Sang 2010 99 158-162 the allele, on the CO1 allele background, is silenced;thus, there is no expression of Coa antigen; expression of Cob is decreased. Blumenfeld OO., curator 2010-08-09 14:07:29.907 NA
UniProt
P29972
ID AQP1_HUMAN Reviewed; 269 AA.
AC P29972; B5BU39; E7EM69; E9PC21; F5GY19; Q8TBI5; Q8TDC1;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 159.
DE RecName: Full=Aquaporin-1;
DE Short=AQP-1;
DE AltName: Full=Aquaporin-CHIP;
DE AltName: Full=Urine water channel;
DE AltName: Full=Water channel protein for red blood cells and kidney proximal tubule;
GN Name=AQP1; Synonyms=CHIP28;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=1722319; DOI=10.1073/pnas.88.24.11110;
RA Preston G.M., Agre P.;
RT "Isolation of the cDNA for erythrocyte integral membrane protein of 28
RT kilodaltons: member of an ancient channel family.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:11110-11114(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8340403;
RA Moon C., Preston G.M., Griffin C.A., Jabs E.W., Agre P.;
RT "The human aquaporin-CHIP gene. Structure, organization, and
RT chromosomal localization.";
RL J. Biol. Chem. 268:15772-15778(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Retinal pigment epithelium;
RX PubMed=8703970; DOI=10.1016/0005-2736(96)00076-4;
RA Ruiz A.C., Bok D.;
RT "Characterization of the 3' UTR sequence encoded by the AQP-1 gene in
RT human retinal pigment epithelium.";
RL Biochim. Biophys. Acta 1282:174-178(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
RX PubMed=7517253;
RA Li X., Yu H., Koide S.S.;
RT "The water channel gene in human uterus.";
RL Biochem. Mol. Biol. Int. 32:371-377(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Mesangial cell;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-45 AND ASP-165.
RG SeattleSNPs variation discovery resource;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H.,
RA Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M.,
RA Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T.,
RA Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A.,
RA Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K.,
RA Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S.,
RA Isogai T., Imai J., Watanabe S., Nomura N.;
RT "Human protein factory for converting the transcriptome into an in
RT vitro-expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 5-269.
RC TISSUE=Articular cartilage;
RA Trujillo E., Gonzalez T., Martin-Vasallo P., Marples D., Mobasheri A.;
RT "Human chondrocytes in situ express aquaporin water channels: changes
RT in AQP1 abundance in pathologies of articular cartilage.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP PROTEIN SEQUENCE OF 2-36.
RX PubMed=2007592;
RA Smith B.L., Agre P.;
RT "Erythrocyte Mr 28,000 transmembrane protein exists as a multisubunit
RT oligomer similar to channel proteins.";
RL J. Biol. Chem. 266:6407-6415(1991).
RN [13]
RP FUNCTION.
RX PubMed=1373524; DOI=10.1126/science.256.5055.385;
RA Preston G.M., Carroll T.P., Guggino W.B., Agre P.;
RT "Appearance of water channels in Xenopus oocytes expressing red cell
RT CHIP28 protein.";
RL Science 256:385-387(1992).
RN [14]
RP TARGET OF MERCURY INHIBITION.
RX PubMed=7677994;
RA Preston G.M., Jung J.S., Guggino W.B., Agre P.;
RT "The mercury-sensitive residue at cysteine 189 in the CHIP28 water
RT channel.";
RL J. Biol. Chem. 268:17-20(1993).
RN [15]
RP TOPOLOGY.
RX PubMed=7507481;
RA Preston G.M., Jung J.S., Guggino W.B., Agre P.;
RT "Membrane topology of aquaporin CHIP. Analysis of functional epitope-
RT scanning mutants by vectorial proteolysis.";
RL J. Biol. Chem. 269:1668-1673(1994).
RN [16]
RP STRUCTURE BY ELECTRON MICROSCOPY (1.6 ANGSTROMS).
RX PubMed=7518771;
RA Walz T., Smith B.L., Agre P., Engel A.;
RT "The three-dimensional structure of human erythrocyte aquaporin
RT CHIP.";
RL EMBO J. 13:2985-2993(1994).
RN [17]
RP STRUCTURE BY ELECTRON MICROSCOPY (6 ANGSTROMS).
RX PubMed=9177353; DOI=10.1038/42512;
RA Walz T., Hirai T., Murata K., Heymann J.B., Mitsuoka K., Fujiyoshi Y.,
RA Smith B.L., Agre P., Engel A.;
RT "The three-dimensional structure of aquaporin-1.";
RL Nature 387:624-627(1997).
RN [18]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.8 ANGSTROMS).
RX PubMed=11034202; DOI=10.1038/35036519;
RA Murata K., Mitsuoka K., Hirai T., Walz T., Agre P., Heymann J.B.,
RA Engel A., Fujiyoshi Y.;
RT "Structural determinants of water permeation through aquaporin-1.";
RL Nature 407:599-605(2000).
RN [19]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.54 ANGSTROMS).
RX PubMed=11532455; DOI=10.1016/S0014-5793(01)02743-0;
RA de Groot B.L., Engel A., Grubmueller H.;
RT "A refined structure of human aquaporin-1.";
RL FEBS Lett. 504:206-211(2001).
RN [20]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.7 ANGSTROMS).
RX PubMed=11171962; DOI=10.1073/pnas.041489198;
RA Ren G., Reddy V.S., Cheng A., Melnyk P., Mitra A.K.;
RT "Visualization of a water-selective pore by electron crystallography
RT in vitreous ice.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:1398-1403(2001).
RN [21]
RP VARIANT BLOOD GROUP COLTON VAL-45.
RX PubMed=7521882; DOI=10.1172/JCI117418;
RA Smith B.L., Preston G.M., Spring F., Anstee D.J., Agre P.;
RT "Human red cell aquaporin CHIP. I. Molecular characterization of ABH
RT and Colton blood group antigens.";
RL J. Clin. Invest. 94:1043-1049(1994).
RN [22]
RP VARIANT LEU-38.
RX PubMed=7521540; DOI=10.1126/science.7521540;
RA Preston G.M., Smith B.L., Zeidel M.L., Moulds J.J., Agre P.;
RT "Mutations in aquaporin-1 in phenotypically normal humans without
RT functional CHIP water channels.";
RL Science 265:1585-1587(1994).
CC -!- FUNCTION: Forms a water-specific channel that provides the plasma
CC membranes of red cells and kidney proximal tubules with high
CC permeability to water, thereby permitting water to move in the
CC direction of an osmotic gradient.
CC -!- SUBUNIT: Homotetramer. Interacts with EPHB2; involved in endolymph
CC production in the inner ear (By similarity).
CC -!- INTERACTION:
CC Q99750:MDFI; NbExp=4; IntAct=EBI-745213, EBI-724076;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P29972-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P29972-2; Sequence=VSP_046109, VSP_046110;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=P29972-3; Sequence=VSP_046679;
CC Note=Gene prediction based on EST data;
CC Name=4;
CC IsoId=P29972-4; Sequence=VSP_046680, VSP_046681;
CC Note=Gene prediction based on EST data;
CC -!- TISSUE SPECIFICITY: Expressed in a number of tissues including
CC erythrocytes, renal tubules, retinal pigment epithelium, heart,
CC lung, skeletal muscle, kidney and pancreas. Weakly expressed in
CC brain, placenta and liver.
CC -!- DOMAIN: Aquaporins contain two tandem repeats each containing
CC three membrane-spanning domains and a pore-forming loop with the
CC signature motif Asn-Pro-Ala (NPA).
CC -!- POLYMORPHISM: AQP1 is responsible for the Colton blood group
CC system. Approximately 92% of Caucasians are Co(A+B-) (Ala-46),
CC approximately 8% are Co(A+B+), and only 0.2% are Co(A-B+) (Val-
CC 46). Co(A-B-) which is very rare, is due to a complete absence of
CC AQP1.
CC -!- MISCELLANEOUS: Pharmacologically inhibited by submillimolar
CC concentrations of mercury.
CC -!- SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family.
CC -!- WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene
CC mutation database;
CC URL="http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system;=colton";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/aqp1/";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Liquid states - Issue
CC 36 of July 2003;
CC URL="http://web.expasy.org/spotlight/back_issues/sptlt036.shtml";
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DR EMBL; M77829; AAA58425.1; -; mRNA.
DR EMBL; U41517; AAC50648.1; -; mRNA.
DR EMBL; U41518; AAC50649.1; -; mRNA.
DR EMBL; S73482; AAB31193.1; -; mRNA.
DR EMBL; AK309608; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY953319; AAX24129.1; -; Genomic_DNA.
DR EMBL; AC004691; AAC16481.1; -; Genomic_DNA.
DR EMBL; AC005155; AAC23788.1; -; Genomic_DNA.
DR EMBL; AB451275; BAG70089.1; -; mRNA.
DR EMBL; AB451402; BAG70216.1; -; mRNA.
DR EMBL; CH471073; EAW93971.1; -; Genomic_DNA.
DR EMBL; BC022486; AAH22486.1; -; mRNA.
DR EMBL; AF480415; AAL87136.1; -; Genomic_DNA.
DR PIR; A41616; A41616.
DR PIR; I52366; I52366.
DR RefSeq; NP_001171989.1; NM_001185060.1.
DR RefSeq; NP_001171990.1; NM_001185061.1.
DR RefSeq; NP_001171991.1; NM_001185062.1.
DR RefSeq; NP_932766.1; NM_198098.2.
DR UniGene; Hs.76152; -.
DR PDB; 1FQY; X-ray; 3.80 A; A=1-269.
DR PDB; 1H6I; X-ray; 3.54 A; A=1-269.
DR PDB; 1IH5; X-ray; 3.70 A; A=1-269.
DR PDBsum; 1FQY; -.
DR PDBsum; 1H6I; -.
DR PDBsum; 1IH5; -.
DR ProteinModelPortal; P29972; -.
DR SMR; P29972; 9-233.
DR DIP; DIP-29607N; -.
DR IntAct; P29972; 8.
DR MINT; MINT-1439356; -.
DR STRING; 9606.ENSP00000311165; -.
DR DrugBank; DB00819; Acetazolamide.
DR GuidetoPHARMACOLOGY; 688; -.
DR TCDB; 1.A.8.8.1; the major intrinsic protein (mip) family.
DR PhosphoSite; P29972; -.
DR DMDM; 267412; -.
DR PaxDb; P29972; -.
DR PRIDE; P29972; -.
DR DNASU; 358; -.
DR Ensembl; ENST00000311813; ENSP00000311165; ENSG00000240583.
DR Ensembl; ENST00000409611; ENSP00000387178; ENSG00000240583.
DR Ensembl; ENST00000409899; ENSP00000386712; ENSG00000240583.
DR Ensembl; ENST00000441328; ENSP00000405698; ENSG00000240583.
DR GeneID; 358; -.
DR KEGG; hsa:358; -.
DR UCSC; uc010kwh.1; human.
DR CTD; 358; -.
DR GeneCards; GC07P030894; -.
DR HGNC; HGNC:633; AQP1.
DR HPA; CAB001707; -.
DR HPA; HPA019206; -.
DR MIM; 107776; gene.
DR MIM; 110450; phenotype.
DR neXtProt; NX_P29972; -.
DR PharmGKB; PA24918; -.
DR eggNOG; COG0580; -.
DR HOGENOM; HOG000288286; -.
DR HOVERGEN; HBG000312; -.
DR InParanoid; P29972; -.
DR KO; K09864; -.
DR OMA; SALGFHY; -.
DR OrthoDB; EOG7N8ZWD; -.
DR PhylomeDB; P29972; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR EvolutionaryTrace; P29972; -.
DR GeneWiki; Aquaporin_1; -.
DR GenomeRNAi; 358; -.
DR NextBio; 1497; -.
DR PRO; PR:P29972; -.
DR ArrayExpress; P29972; -.
DR Bgee; P29972; -.
DR CleanEx; HS_AQP1; -.
DR Genevestigator; P29972; -.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0009925; C:basal plasma membrane; IDA:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; IDA:UniProtKB.
DR GO; GO:0020003; C:symbiont-containing vacuole; ISS:UniProtKB.
DR GO; GO:0051739; F:ammonia transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0035379; F:carbon dioxide transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015168; F:glycerol transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0005223; F:intracellular cGMP activated cation channel activity; IDA:UniProtKB.
DR GO; GO:0030184; F:nitric oxide transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0005267; F:potassium channel activity; IMP:UniProtKB.
DR GO; GO:0015250; F:water channel activity; IDA:UniProtKB.
DR GO; GO:0015696; P:ammonium transport; IDA:UniProtKB.
DR GO; GO:0015701; P:bicarbonate transport; TAS:Reactome.
DR GO; GO:0006884; P:cell volume homeostasis; IMP:UniProtKB.
DR GO; GO:0071474; P:cellular hyperosmotic response; IMP:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; IDA:UniProtKB.
DR GO; GO:0071280; P:cellular response to copper ion; IDA:UniProtKB.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IDA:UniProtKB.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IDA:UniProtKB.
DR GO; GO:0071288; P:cellular response to mercury ion; IDA:UniProtKB.
DR GO; GO:0071732; P:cellular response to nitric oxide; IDA:UniProtKB.
DR GO; GO:0071300; P:cellular response to retinoic acid; IDA:UniProtKB.
DR GO; GO:0071472; P:cellular response to salt stress; IDA:UniProtKB.
DR GO; GO:0034644; P:cellular response to UV; IDA:UniProtKB.
DR GO; GO:0033326; P:cerebrospinal fluid secretion; IEP:UniProtKB.
DR GO; GO:0006182; P:cGMP biosynthetic process; IDA:UniProtKB.
DR GO; GO:0030950; P:establishment or maintenance of actin cytoskeleton polarity; IMP:UniProtKB.
DR GO; GO:0021670; P:lateral ventricle development; IEP:UniProtKB.
DR GO; GO:0085018; P:maintenance of symbiont-containing vacuole by host; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:0042476; P:odontogenesis; IEP:UniProtKB.
DR GO; GO:0030157; P:pancreatic juice secretion; IEP:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IDA:UniProtKB.
DR GO; GO:0046878; P:positive regulation of saliva secretion; IMP:UniProtKB.
DR GO; GO:0003097; P:renal water transport; IDA:UniProtKB.
DR GO; GO:0042493; P:response to drug; IDA:UniProtKB.
DR GO; GO:0035377; P:transepithelial water transport; IDA:UniProtKB.
DR Gene3D; 1.20.1080.10; -; 1.
DR InterPro; IPR023271; Aquaporin-like.
DR InterPro; IPR023274; Aquaporin_1.
DR InterPro; IPR000425; MIP.
DR InterPro; IPR022357; MIP_CS.
DR PANTHER; PTHR19139; PTHR19139; 1.
DR Pfam; PF00230; MIP; 1.
DR PRINTS; PR02013; AQUAPORIN1.
DR PRINTS; PR00783; MINTRINSICP.
DR SUPFAM; SSF81338; SSF81338; 1.
DR TIGRFAMs; TIGR00861; MIP; 1.
DR PROSITE; PS00221; MIP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Blood group antigen;
KW Complete proteome; Direct protein sequencing; Glycoprotein; Membrane;
KW Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 269 Aquaporin-1.
FT /FTId=PRO_0000063920.
FT TOPO_DOM 2 7 Cytoplasmic.
FT TRANSMEM 8 36 Helical; Name=Helix 1.
FT TOPO_DOM 37 48 Extracellular.
FT TRANSMEM 49 66 Helical; Name=Helix 2.
FT TOPO_DOM 67 70 Cytoplasmic.
FT INTRAMEM 71 76
FT INTRAMEM 77 84 Helical; Name=Helix B.
FT TOPO_DOM 85 94 Cytoplasmic.
FT TRANSMEM 95 115 Helical; Name=Helix 3.
FT TOPO_DOM 116 136 Extracellular.
FT TRANSMEM 137 155 Helical; Name=Helix 4.
FT TOPO_DOM 156 166 Cytoplasmic.
FT TRANSMEM 167 183 Helical; Name=Helix 5.
FT TOPO_DOM 184 186 Extracellular.
FT INTRAMEM 187 192
FT INTRAMEM 193 200 Helical; Name=Helix E.
FT TOPO_DOM 201 207 Extracellular.
FT TRANSMEM 208 228 Helical; Name=Helix 6.
FT TOPO_DOM 229 269 Cytoplasmic.
FT MOTIF 76 78 NPA 1.
FT MOTIF 192 194 NPA 2.
FT COMPBIAS 159 162 Poly-Arg.
FT SITE 56 56 Substrate discrimination.
FT SITE 180 180 Substrate discrimination.
FT SITE 189 189 Hg(2+)-sensitive residue.
FT SITE 195 195 Substrate discrimination.
FT MOD_RES 262 262 Phosphoserine (By similarity).
FT CARBOHYD 42 42 N-linked (GlcNAc...).
FT CARBOHYD 205 205 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 1 128 MASEFKKKLFWRAVVAEFLATTLFVFISIGSALGFKYPVGN
FT NQTAVQDNVKVSLAFGLSIATLAQSVGHISGAHLNPAVTLG
FT LLLSCQISIFRALMYIIAQCVGAIVATAILSGITSSLTGNS
FT LGRND -> MFWTFGYEAVSPAGPSHLFASLLLGVLLTITF
FT MPGARPLPLVLVPQNTLAWMQLDAKAPAHPRPLQLLGRVGP
FT GSRQ (in isoform 3).
FT /FTId=VSP_046679.
FT VAR_SEQ 1 45 MASEFKKKLFWRAVVAEFLATTLFVFISIGSALGFKYPVGN
FT NQTA -> MPGARPLPLVLVPQNTLAWMQLDAKAPAHPRPL
FT QLLGRVGPGSRQ (in isoform 2).
FT /FTId=VSP_046109.
FT VAR_SEQ 1 13 MASEFKKKLFWRA -> MQSGMGWNVLDFW (in
FT isoform 4).
FT /FTId=VSP_046680.
FT VAR_SEQ 14 128 Missing (in isoform 4).
FT /FTId=VSP_046681.
FT VAR_SEQ 46 128 Missing (in isoform 2).
FT /FTId=VSP_046110.
FT VARIANT 38 38 P -> L (in Co(A-B-) antigen; non
FT functional AQP1; red cells show low
FT osmotic water permeability).
FT /FTId=VAR_013279.
FT VARIANT 45 45 A -> V (in Co(A-B+) antigen;
FT dbSNP:rs28362692).
FT /FTId=VAR_004400.
FT VARIANT 165 165 G -> D (in dbSNP:rs28362731).
FT /FTId=VAR_022318.
FT CONFLICT 45 45 A -> T (in Ref. 10; AAH22486).
FT HELIX 8 35
FT STRAND 37 42
FT HELIX 48 65
FT STRAND 68 71
FT HELIX 76 83
FT HELIX 94 114
FT TURN 119 122
FT STRAND 132 135
FT HELIX 136 154
FT HELIX 166 182
FT TURN 183 185
FT HELIX 192 199
FT HELIX 207 227
SQ SEQUENCE 269 AA; 28526 MW; BA204D82FB26352E CRC64;
MASEFKKKLF WRAVVAEFLA TTLFVFISIG SALGFKYPVG NNQTAVQDNV KVSLAFGLSI
ATLAQSVGHI SGAHLNPAVT LGLLLSCQIS IFRALMYIIA QCVGAIVATA ILSGITSSLT
GNSLGRNDLA DGVNSGQGLG IEIIGTLQLV LCVLATTDRR RRDLGGSAPL AIGLSVALGH
LLAIDYTGCG INPARSFGSA VITHNFSNHW IFWVGPFIGG ALAVLIYDFI LAPRSSDLTD
RVKVWTSGQV EEYDLDADDI NSRVEMKPK
//
ID AQP1_HUMAN Reviewed; 269 AA.
AC P29972; B5BU39; E7EM69; E9PC21; F5GY19; Q8TBI5; Q8TDC1;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 159.
DE RecName: Full=Aquaporin-1;
DE Short=AQP-1;
DE AltName: Full=Aquaporin-CHIP;
DE AltName: Full=Urine water channel;
DE AltName: Full=Water channel protein for red blood cells and kidney proximal tubule;
GN Name=AQP1; Synonyms=CHIP28;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=1722319; DOI=10.1073/pnas.88.24.11110;
RA Preston G.M., Agre P.;
RT "Isolation of the cDNA for erythrocyte integral membrane protein of 28
RT kilodaltons: member of an ancient channel family.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:11110-11114(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8340403;
RA Moon C., Preston G.M., Griffin C.A., Jabs E.W., Agre P.;
RT "The human aquaporin-CHIP gene. Structure, organization, and
RT chromosomal localization.";
RL J. Biol. Chem. 268:15772-15778(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Retinal pigment epithelium;
RX PubMed=8703970; DOI=10.1016/0005-2736(96)00076-4;
RA Ruiz A.C., Bok D.;
RT "Characterization of the 3' UTR sequence encoded by the AQP-1 gene in
RT human retinal pigment epithelium.";
RL Biochim. Biophys. Acta 1282:174-178(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
RX PubMed=7517253;
RA Li X., Yu H., Koide S.S.;
RT "The water channel gene in human uterus.";
RL Biochem. Mol. Biol. Int. 32:371-377(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Mesangial cell;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-45 AND ASP-165.
RG SeattleSNPs variation discovery resource;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H.,
RA Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M.,
RA Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T.,
RA Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A.,
RA Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K.,
RA Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S.,
RA Isogai T., Imai J., Watanabe S., Nomura N.;
RT "Human protein factory for converting the transcriptome into an in
RT vitro-expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 5-269.
RC TISSUE=Articular cartilage;
RA Trujillo E., Gonzalez T., Martin-Vasallo P., Marples D., Mobasheri A.;
RT "Human chondrocytes in situ express aquaporin water channels: changes
RT in AQP1 abundance in pathologies of articular cartilage.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP PROTEIN SEQUENCE OF 2-36.
RX PubMed=2007592;
RA Smith B.L., Agre P.;
RT "Erythrocyte Mr 28,000 transmembrane protein exists as a multisubunit
RT oligomer similar to channel proteins.";
RL J. Biol. Chem. 266:6407-6415(1991).
RN [13]
RP FUNCTION.
RX PubMed=1373524; DOI=10.1126/science.256.5055.385;
RA Preston G.M., Carroll T.P., Guggino W.B., Agre P.;
RT "Appearance of water channels in Xenopus oocytes expressing red cell
RT CHIP28 protein.";
RL Science 256:385-387(1992).
RN [14]
RP TARGET OF MERCURY INHIBITION.
RX PubMed=7677994;
RA Preston G.M., Jung J.S., Guggino W.B., Agre P.;
RT "The mercury-sensitive residue at cysteine 189 in the CHIP28 water
RT channel.";
RL J. Biol. Chem. 268:17-20(1993).
RN [15]
RP TOPOLOGY.
RX PubMed=7507481;
RA Preston G.M., Jung J.S., Guggino W.B., Agre P.;
RT "Membrane topology of aquaporin CHIP. Analysis of functional epitope-
RT scanning mutants by vectorial proteolysis.";
RL J. Biol. Chem. 269:1668-1673(1994).
RN [16]
RP STRUCTURE BY ELECTRON MICROSCOPY (1.6 ANGSTROMS).
RX PubMed=7518771;
RA Walz T., Smith B.L., Agre P., Engel A.;
RT "The three-dimensional structure of human erythrocyte aquaporin
RT CHIP.";
RL EMBO J. 13:2985-2993(1994).
RN [17]
RP STRUCTURE BY ELECTRON MICROSCOPY (6 ANGSTROMS).
RX PubMed=9177353; DOI=10.1038/42512;
RA Walz T., Hirai T., Murata K., Heymann J.B., Mitsuoka K., Fujiyoshi Y.,
RA Smith B.L., Agre P., Engel A.;
RT "The three-dimensional structure of aquaporin-1.";
RL Nature 387:624-627(1997).
RN [18]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.8 ANGSTROMS).
RX PubMed=11034202; DOI=10.1038/35036519;
RA Murata K., Mitsuoka K., Hirai T., Walz T., Agre P., Heymann J.B.,
RA Engel A., Fujiyoshi Y.;
RT "Structural determinants of water permeation through aquaporin-1.";
RL Nature 407:599-605(2000).
RN [19]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.54 ANGSTROMS).
RX PubMed=11532455; DOI=10.1016/S0014-5793(01)02743-0;
RA de Groot B.L., Engel A., Grubmueller H.;
RT "A refined structure of human aquaporin-1.";
RL FEBS Lett. 504:206-211(2001).
RN [20]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.7 ANGSTROMS).
RX PubMed=11171962; DOI=10.1073/pnas.041489198;
RA Ren G., Reddy V.S., Cheng A., Melnyk P., Mitra A.K.;
RT "Visualization of a water-selective pore by electron crystallography
RT in vitreous ice.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:1398-1403(2001).
RN [21]
RP VARIANT BLOOD GROUP COLTON VAL-45.
RX PubMed=7521882; DOI=10.1172/JCI117418;
RA Smith B.L., Preston G.M., Spring F., Anstee D.J., Agre P.;
RT "Human red cell aquaporin CHIP. I. Molecular characterization of ABH
RT and Colton blood group antigens.";
RL J. Clin. Invest. 94:1043-1049(1994).
RN [22]
RP VARIANT LEU-38.
RX PubMed=7521540; DOI=10.1126/science.7521540;
RA Preston G.M., Smith B.L., Zeidel M.L., Moulds J.J., Agre P.;
RT "Mutations in aquaporin-1 in phenotypically normal humans without
RT functional CHIP water channels.";
RL Science 265:1585-1587(1994).
CC -!- FUNCTION: Forms a water-specific channel that provides the plasma
CC membranes of red cells and kidney proximal tubules with high
CC permeability to water, thereby permitting water to move in the
CC direction of an osmotic gradient.
CC -!- SUBUNIT: Homotetramer. Interacts with EPHB2; involved in endolymph
CC production in the inner ear (By similarity).
CC -!- INTERACTION:
CC Q99750:MDFI; NbExp=4; IntAct=EBI-745213, EBI-724076;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P29972-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P29972-2; Sequence=VSP_046109, VSP_046110;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=P29972-3; Sequence=VSP_046679;
CC Note=Gene prediction based on EST data;
CC Name=4;
CC IsoId=P29972-4; Sequence=VSP_046680, VSP_046681;
CC Note=Gene prediction based on EST data;
CC -!- TISSUE SPECIFICITY: Expressed in a number of tissues including
CC erythrocytes, renal tubules, retinal pigment epithelium, heart,
CC lung, skeletal muscle, kidney and pancreas. Weakly expressed in
CC brain, placenta and liver.
CC -!- DOMAIN: Aquaporins contain two tandem repeats each containing
CC three membrane-spanning domains and a pore-forming loop with the
CC signature motif Asn-Pro-Ala (NPA).
CC -!- POLYMORPHISM: AQP1 is responsible for the Colton blood group
CC system. Approximately 92% of Caucasians are Co(A+B-) (Ala-46),
CC approximately 8% are Co(A+B+), and only 0.2% are Co(A-B+) (Val-
CC 46). Co(A-B-) which is very rare, is due to a complete absence of
CC AQP1.
CC -!- MISCELLANEOUS: Pharmacologically inhibited by submillimolar
CC concentrations of mercury.
CC -!- SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family.
CC -!- WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene
CC mutation database;
CC URL="http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system;=colton";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/aqp1/";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Liquid states - Issue
CC 36 of July 2003;
CC URL="http://web.expasy.org/spotlight/back_issues/sptlt036.shtml";
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DR EMBL; M77829; AAA58425.1; -; mRNA.
DR EMBL; U41517; AAC50648.1; -; mRNA.
DR EMBL; U41518; AAC50649.1; -; mRNA.
DR EMBL; S73482; AAB31193.1; -; mRNA.
DR EMBL; AK309608; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY953319; AAX24129.1; -; Genomic_DNA.
DR EMBL; AC004691; AAC16481.1; -; Genomic_DNA.
DR EMBL; AC005155; AAC23788.1; -; Genomic_DNA.
DR EMBL; AB451275; BAG70089.1; -; mRNA.
DR EMBL; AB451402; BAG70216.1; -; mRNA.
DR EMBL; CH471073; EAW93971.1; -; Genomic_DNA.
DR EMBL; BC022486; AAH22486.1; -; mRNA.
DR EMBL; AF480415; AAL87136.1; -; Genomic_DNA.
DR PIR; A41616; A41616.
DR PIR; I52366; I52366.
DR RefSeq; NP_001171989.1; NM_001185060.1.
DR RefSeq; NP_001171990.1; NM_001185061.1.
DR RefSeq; NP_001171991.1; NM_001185062.1.
DR RefSeq; NP_932766.1; NM_198098.2.
DR UniGene; Hs.76152; -.
DR PDB; 1FQY; X-ray; 3.80 A; A=1-269.
DR PDB; 1H6I; X-ray; 3.54 A; A=1-269.
DR PDB; 1IH5; X-ray; 3.70 A; A=1-269.
DR PDBsum; 1FQY; -.
DR PDBsum; 1H6I; -.
DR PDBsum; 1IH5; -.
DR ProteinModelPortal; P29972; -.
DR SMR; P29972; 9-233.
DR DIP; DIP-29607N; -.
DR IntAct; P29972; 8.
DR MINT; MINT-1439356; -.
DR STRING; 9606.ENSP00000311165; -.
DR DrugBank; DB00819; Acetazolamide.
DR GuidetoPHARMACOLOGY; 688; -.
DR TCDB; 1.A.8.8.1; the major intrinsic protein (mip) family.
DR PhosphoSite; P29972; -.
DR DMDM; 267412; -.
DR PaxDb; P29972; -.
DR PRIDE; P29972; -.
DR DNASU; 358; -.
DR Ensembl; ENST00000311813; ENSP00000311165; ENSG00000240583.
DR Ensembl; ENST00000409611; ENSP00000387178; ENSG00000240583.
DR Ensembl; ENST00000409899; ENSP00000386712; ENSG00000240583.
DR Ensembl; ENST00000441328; ENSP00000405698; ENSG00000240583.
DR GeneID; 358; -.
DR KEGG; hsa:358; -.
DR UCSC; uc010kwh.1; human.
DR CTD; 358; -.
DR GeneCards; GC07P030894; -.
DR HGNC; HGNC:633; AQP1.
DR HPA; CAB001707; -.
DR HPA; HPA019206; -.
DR MIM; 107776; gene.
DR MIM; 110450; phenotype.
DR neXtProt; NX_P29972; -.
DR PharmGKB; PA24918; -.
DR eggNOG; COG0580; -.
DR HOGENOM; HOG000288286; -.
DR HOVERGEN; HBG000312; -.
DR InParanoid; P29972; -.
DR KO; K09864; -.
DR OMA; SALGFHY; -.
DR OrthoDB; EOG7N8ZWD; -.
DR PhylomeDB; P29972; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR EvolutionaryTrace; P29972; -.
DR GeneWiki; Aquaporin_1; -.
DR GenomeRNAi; 358; -.
DR NextBio; 1497; -.
DR PRO; PR:P29972; -.
DR ArrayExpress; P29972; -.
DR Bgee; P29972; -.
DR CleanEx; HS_AQP1; -.
DR Genevestigator; P29972; -.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0009925; C:basal plasma membrane; IDA:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; IDA:UniProtKB.
DR GO; GO:0020003; C:symbiont-containing vacuole; ISS:UniProtKB.
DR GO; GO:0051739; F:ammonia transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0035379; F:carbon dioxide transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015168; F:glycerol transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0005223; F:intracellular cGMP activated cation channel activity; IDA:UniProtKB.
DR GO; GO:0030184; F:nitric oxide transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0005267; F:potassium channel activity; IMP:UniProtKB.
DR GO; GO:0015250; F:water channel activity; IDA:UniProtKB.
DR GO; GO:0015696; P:ammonium transport; IDA:UniProtKB.
DR GO; GO:0015701; P:bicarbonate transport; TAS:Reactome.
DR GO; GO:0006884; P:cell volume homeostasis; IMP:UniProtKB.
DR GO; GO:0071474; P:cellular hyperosmotic response; IMP:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; IDA:UniProtKB.
DR GO; GO:0071280; P:cellular response to copper ion; IDA:UniProtKB.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IDA:UniProtKB.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IDA:UniProtKB.
DR GO; GO:0071288; P:cellular response to mercury ion; IDA:UniProtKB.
DR GO; GO:0071732; P:cellular response to nitric oxide; IDA:UniProtKB.
DR GO; GO:0071300; P:cellular response to retinoic acid; IDA:UniProtKB.
DR GO; GO:0071472; P:cellular response to salt stress; IDA:UniProtKB.
DR GO; GO:0034644; P:cellular response to UV; IDA:UniProtKB.
DR GO; GO:0033326; P:cerebrospinal fluid secretion; IEP:UniProtKB.
DR GO; GO:0006182; P:cGMP biosynthetic process; IDA:UniProtKB.
DR GO; GO:0030950; P:establishment or maintenance of actin cytoskeleton polarity; IMP:UniProtKB.
DR GO; GO:0021670; P:lateral ventricle development; IEP:UniProtKB.
DR GO; GO:0085018; P:maintenance of symbiont-containing vacuole by host; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:0042476; P:odontogenesis; IEP:UniProtKB.
DR GO; GO:0030157; P:pancreatic juice secretion; IEP:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IDA:UniProtKB.
DR GO; GO:0046878; P:positive regulation of saliva secretion; IMP:UniProtKB.
DR GO; GO:0003097; P:renal water transport; IDA:UniProtKB.
DR GO; GO:0042493; P:response to drug; IDA:UniProtKB.
DR GO; GO:0035377; P:transepithelial water transport; IDA:UniProtKB.
DR Gene3D; 1.20.1080.10; -; 1.
DR InterPro; IPR023271; Aquaporin-like.
DR InterPro; IPR023274; Aquaporin_1.
DR InterPro; IPR000425; MIP.
DR InterPro; IPR022357; MIP_CS.
DR PANTHER; PTHR19139; PTHR19139; 1.
DR Pfam; PF00230; MIP; 1.
DR PRINTS; PR02013; AQUAPORIN1.
DR PRINTS; PR00783; MINTRINSICP.
DR SUPFAM; SSF81338; SSF81338; 1.
DR TIGRFAMs; TIGR00861; MIP; 1.
DR PROSITE; PS00221; MIP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Blood group antigen;
KW Complete proteome; Direct protein sequencing; Glycoprotein; Membrane;
KW Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 269 Aquaporin-1.
FT /FTId=PRO_0000063920.
FT TOPO_DOM 2 7 Cytoplasmic.
FT TRANSMEM 8 36 Helical; Name=Helix 1.
FT TOPO_DOM 37 48 Extracellular.
FT TRANSMEM 49 66 Helical; Name=Helix 2.
FT TOPO_DOM 67 70 Cytoplasmic.
FT INTRAMEM 71 76
FT INTRAMEM 77 84 Helical; Name=Helix B.
FT TOPO_DOM 85 94 Cytoplasmic.
FT TRANSMEM 95 115 Helical; Name=Helix 3.
FT TOPO_DOM 116 136 Extracellular.
FT TRANSMEM 137 155 Helical; Name=Helix 4.
FT TOPO_DOM 156 166 Cytoplasmic.
FT TRANSMEM 167 183 Helical; Name=Helix 5.
FT TOPO_DOM 184 186 Extracellular.
FT INTRAMEM 187 192
FT INTRAMEM 193 200 Helical; Name=Helix E.
FT TOPO_DOM 201 207 Extracellular.
FT TRANSMEM 208 228 Helical; Name=Helix 6.
FT TOPO_DOM 229 269 Cytoplasmic.
FT MOTIF 76 78 NPA 1.
FT MOTIF 192 194 NPA 2.
FT COMPBIAS 159 162 Poly-Arg.
FT SITE 56 56 Substrate discrimination.
FT SITE 180 180 Substrate discrimination.
FT SITE 189 189 Hg(2+)-sensitive residue.
FT SITE 195 195 Substrate discrimination.
FT MOD_RES 262 262 Phosphoserine (By similarity).
FT CARBOHYD 42 42 N-linked (GlcNAc...).
FT CARBOHYD 205 205 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 1 128 MASEFKKKLFWRAVVAEFLATTLFVFISIGSALGFKYPVGN
FT NQTAVQDNVKVSLAFGLSIATLAQSVGHISGAHLNPAVTLG
FT LLLSCQISIFRALMYIIAQCVGAIVATAILSGITSSLTGNS
FT LGRND -> MFWTFGYEAVSPAGPSHLFASLLLGVLLTITF
FT MPGARPLPLVLVPQNTLAWMQLDAKAPAHPRPLQLLGRVGP
FT GSRQ (in isoform 3).
FT /FTId=VSP_046679.
FT VAR_SEQ 1 45 MASEFKKKLFWRAVVAEFLATTLFVFISIGSALGFKYPVGN
FT NQTA -> MPGARPLPLVLVPQNTLAWMQLDAKAPAHPRPL
FT QLLGRVGPGSRQ (in isoform 2).
FT /FTId=VSP_046109.
FT VAR_SEQ 1 13 MASEFKKKLFWRA -> MQSGMGWNVLDFW (in
FT isoform 4).
FT /FTId=VSP_046680.
FT VAR_SEQ 14 128 Missing (in isoform 4).
FT /FTId=VSP_046681.
FT VAR_SEQ 46 128 Missing (in isoform 2).
FT /FTId=VSP_046110.
FT VARIANT 38 38 P -> L (in Co(A-B-) antigen; non
FT functional AQP1; red cells show low
FT osmotic water permeability).
FT /FTId=VAR_013279.
FT VARIANT 45 45 A -> V (in Co(A-B+) antigen;
FT dbSNP:rs28362692).
FT /FTId=VAR_004400.
FT VARIANT 165 165 G -> D (in dbSNP:rs28362731).
FT /FTId=VAR_022318.
FT CONFLICT 45 45 A -> T (in Ref. 10; AAH22486).
FT HELIX 8 35
FT STRAND 37 42
FT HELIX 48 65
FT STRAND 68 71
FT HELIX 76 83
FT HELIX 94 114
FT TURN 119 122
FT STRAND 132 135
FT HELIX 136 154
FT HELIX 166 182
FT TURN 183 185
FT HELIX 192 199
FT HELIX 207 227
SQ SEQUENCE 269 AA; 28526 MW; BA204D82FB26352E CRC64;
MASEFKKKLF WRAVVAEFLA TTLFVFISIG SALGFKYPVG NNQTAVQDNV KVSLAFGLSI
ATLAQSVGHI SGAHLNPAVT LGLLLSCQIS IFRALMYIIA QCVGAIVATA ILSGITSSLT
GNSLGRNDLA DGVNSGQGLG IEIIGTLQLV LCVLATTDRR RRDLGGSAPL AIGLSVALGH
LLAIDYTGCG INPARSFGSA VITHNFSNHW IFWVGPFIGG ALAVLIYDFI LAPRSSDLTD
RVKVWTSGQV EEYDLDADDI NSRVEMKPK
//
MIM
107776
*RECORD*
*FIELD* NO
107776
*FIELD* TI
*107776 AQUAPORIN 1; AQP1
;;AQUAPORIN-CHIP;;
AQP-CHIP;;
CHANNEL-LIKE INTEGRAL MEMBRANE PROTEIN, 28-KD; CHIP28
read more*FIELD* TX
CLONING
Aquaporin-CHIP is a 28-kD integral protein purified from the plasma
membranes of red cells and renal tubules by Denker et al. (1988). The
protein was thought at first to be a breakdown product of the Rh
polypeptide but was later shown to be a unique molecule that is abundant
in erythrocytes and renal tubules. A subpopulation is N-glycosylated.
Preston and Agre (1991) isolated a cDNA for this protein, called CHIP28
(channel forming integral protein of 28 kD), from human fetal liver.
Analysis of the deduced amino acid sequence suggested that CHIP28
protein contains 6 bilayer-spanning domains, 2 exofacial potential
N-glycosylation sites, and intracellular N and C termini. The sequence
showed strong homology with the major intrinsic protein of bovine lens
(MIP26; 154050), which is the prototype of an ancient family of membrane
channels. These proteins are believed to form channels permeable to
water and possibly other small molecules.
GENE STRUCTURE
Moon et al. (1995) showed that the 13-kb Aqp1 gene in the mouse contains
4 exons with intronic boundaries corresponding to other known aquaporin
genes.
MAPPING
Moon et al. (1993) isolated the AQP1 structural gene and partially
sequenced it. Genomic Southern analysis indicated the existence of a
single AQP1 gene, which was localized to 7p14 by in situ hybridization.
Sequence comparisons with similar proteins from diverse species
suggested a common evolutionary origin. Deen et al. (1994) showed that
the gene is on chromosome 7 by Southern blot hybridization to
human/rodent hybrid cell lines and regionalized it to 7p15-p14 by in
situ hybridization. By interspecific backcross mapping, Moon et al.
(1995) showed that the mouse Aqp1 gene is located on chromosome 6 in a
region with homology of synteny with human 7p14.
Keen et al. (1995) localized the AQP1 gene on chromosome 7 within a YAC
contig containing 2 polymorphic markers, D7S632 and D7S526. Since
aquaporin is known to be expressed in a diverse range of secretory and
absorptive epithelia, including many in the eye, it had been proposed as
a possible candidate for disorders involving an imbalance in ocular
fluid movement. Keen et al. (1995) raised a question of possible
involvement in 2 eye diseases that map to that region, retinitis
pigmentosa-9 (180104) and dominant cystoid macular dystrophy (153880).
BIOCHEMICAL FEATURES
Murata et al. (2000) described an atomic model of AQP1 at 3.8-angstrom
resolution from electron crystallographic data. Multiple highly
conserved amino acid residues stabilize the novel fold of AQP1. The
aqueous pathway is lined with conserved hydrophobic residues that permit
rapid water transport, whereas the water selectivity is due to a
constriction of the pore diameter to about 3 angstroms over a span of 1
residue. The atomic model provided a possible molecular explanation to a
longstanding puzzle in physiology--how membranes can be freely permeable
to water but impermeable to protons.
Sui et al. (2001) reported the structure of the dumbbell-shaped AQP1
water channel at 2.2-angstrom resolution. The channel consists of 3
topologic elements, an extracellular and a cytoplasmic vestibule
connected by an extended narrow pore or selectivity filter, averaging 4
angstroms in diameter. Within the selectivity filter, 4 bound waters are
localized along 3 hydrophilic nodes, which punctuate an otherwise
extremely hydrophobic pore segment, facilitating water transport. The
highly conserved histidine-182 residue is critical in establishing water
specificity. AQP1 lacks a suitable chain of hydrogen-bonded water
molecules in the selectivity filter that could act as a proton wire,
indicating that proton transport through the channel is highly
energetically unfavorable.
GENE FUNCTION
The AQP-CHIP protein exists as a homotetramer which physically resembles
channel proteins and was the first molecular water channel identified.
The AQP-CHIP cDNA isolated from a human bone marrow cDNA library was
found to be related to the major intrinsic protein of lens (154050). Two
other related proteins were found to be water transporters (Fushimi et
al., 1993; Maurel et al., 1993) and these 3 proteins were referred to as
the aquaporins. AQP-CHIP is also expressed in diverse epithelia with
distinct developmental patterns. By immunochemical and functional means,
Smith et al. (1993) showed that AQP-CHIP is essentially absent in
neonatal red cells of the rat. After birth, AQP-CHIP appears in the red
cells and increases within several weeks to the adult level of
expression. The neonatal kidney, while displaying low levels of AQP-CHIP
expression, has a parallel increase in the amount and distribution of
AQP-CHIP in the proximal tubules and the descending thin limbs of the
loops of Henle, commensurate with the kidney's ability to form
concentrated urine. Smith et al. (1993) suggested that the water
channels act to promote the rehydration of red cells after their
shrinkage in the hypertonic environment of the renal medulla. Rapid
rehydration would return the cells to their normal volume, optimizing
their deformability for transit in the microcirculation. See Hoffman
(1993).
Using colocalization studies and biochemical analysis, Cowan et al.
(2000) demonstrated that a protein complex containing mouse Ephb2
(600997) and aquaporin-1 is formed in vivo.
The location of the human AQP1 gene is the same as that of the Colton
blood group (110450) on 7p. Smith et al. (1994) demonstrated that the
CHIP-glycan is the molecular site of the Colton polymorphism. They also
showed that Colton blood group antigen differences result from an
ala-val polymorphism at residue 45, located on the first extracellular
loop of CHIP. CHIP was selectively immunoprecipitated with anti-Co(a) or
anti-Co(b). Approximately 92% of Caucasians are Co(a+b-), approximately
8% are Co(a+b+), and only 0.2% are Co+(a-b+).
Colton antigens cause clinical difficulties infrequently, although
maternal-fetal incompatibility and transfusion reactions are known. The
power of worldwide blood group referencing makes the rarest of
phenotypes accessible, and the single Co+(a-b-) red cell membrane sample
in the reference collection was found to lack CHIP by immunoblot. Lack
of Colton antigens in association with monosomy 7 has been reported in
some cases of leukemia (de la Chapelle et al., 1975; Pasquali et al.,
1982).
King et al. (2001) examined the finding that aquaporin-1 deficiency had
no obvious clinical consequences in the 6 kindreds identified worldwide
who lacked the Colton blood group. Since aquaporin-1 is abundant in
renal proximal tubular epithelium, the thin descending limb of the loop
of Henle, and the descending vasa recta of the kidney, the authors
hypothesized that persons with a deficiency of aquaporin-1 have defects
in water homeostasis in the kidneys that can be identified only under
conditions of stress. They studied 2 unrelated subjects with aquaporin-1
deficiency and found that they had impaired urinary concentrating
ability, suggesting that aquaporin-1 has a physiologic role in renal
function. Both were patients in whom homozygous mutations in the AQP1
gene had been identified by Preston et al. (1994). Both were women who
had developed antibodies against the Colton blood group in association
with pregnancy. One subject had occasional edema of the lower legs, for
which she infrequently took a diuretic. She drank 2 to 4 liters of fluid
per day. The second drank 2 liters of fluid per day and urinated 2 to 3
times daily, without nocturia.
King et al. (2002) studied the effect of absence of aquaporin-1 on water
permeability in the human lung, with a rationale parallel to that used
in the study of ability to concentrate urine maximally (King et al.,
2001). AQP1 is present in endothelial cells in the lung, including those
in the vascular plexus around the airways. They used high-resolution
computed tomography scans of the lung to evaluate the response to
intravenous fluid challenge in 2 unrelated AQP1-null individuals and 5
normal controls. The airways and pulmonary vessels were measured at
baseline and after intravenous administration of 3 liters of saline.
Increases in airway wall thickness after fluid administration reflected
peribronchiolar edema formation. Both control and AQP1-null subjects had
approximately a 20% increase in pulmonary vessel area in response to
saline infusion, suggesting similar degrees of loading. Control subjects
had a 44% increase in the thickness of the airway wall, consistent with
peribronchiolar edema formation. In marked contrast, airway wall
thickness did not change in AQP1-null subjects in response to saline
infusion. These studies indicated that AQP1 is a determinant of vascular
permeability in the lung, and demonstrate a role for aquaporins in human
pulmonary physiology.
Worldwide blood group referencing had led to the identification of 5
kindreds in which red cells expressed no Colton antigens; these
individuals were said to be Co(a-b-). Preston et al. (1994) obtained
blood samples and urine sediment from 3 of these individuals, 1 member
from each of 3 kindreds. They were unrelated women of northern European
ancestry, and none had hematologic, renal, ocular, respiratory,
gastrointestinal, reproductive, or neurologic dysfunction. Cells in
these Co(a-b-) individuals appeared morphologically normal, but their
red cells exhibited low osmotic water permeability. Genomic DNA analyses
demonstrated that 2 individuals were homozygous for different nonsense
mutations (exon deletion or frameshift), and the third had a missense
mutation encoding a nonfunctioning CHIP molecule. Surprisingly, none of
the 3 suffered any apparent clinical consequence, which raised questions
about the physiologic importance of CHIP and implied that other
mechanisms may compensate for its absence.
Agre et al. (1994) found that, compared with the adult, second and third
trimester human fetal red cells had lower CHIP/spectrin ratios and
reduced osmotic water permeability; CHIP was already present in human
renal tubules by the second trimester.
Using molecular dynamics simulations of water permeation through AQP1,
de Groot and Grubmuller (2001) showed that AQP1 acts as a 2-stage
filter. The conserved NPA (asp-pro-ala) motifs form a
selectivity-determining, or size-exclusion, region. The authors proposed
that a second aromatic/arginine (ar/R) region functions as a proton
filter.
Agre and Kozono (2003) reviewed the topic of aquaporin water channels.
The atomic structure of mammalian AQP1 illustrates how this family of
proteins is freely permeated by water but not protons (hydronium ions,
H(3)O+). The mercury sensitivity of AQP1 is well explained by
localization of the specific residue (C189) at the narrowest segment of
the channel at the same level as H180 and R195. Cysteines are present at
the corresponding position in several other members of the aquaporin
family (AQP2, 107777; AQP5, 600442; AQP6, 601383; and AQP9, 602914).
Prior to the introduction of modern loop diuretics, patients with
refractory fluid overload were treated with mercurial diuretics, which
deliver profound renal diuresis.
AQP1 and AQP4 (600308) regulate the movement of water in ischemic brain,
and they appear to play a role in cerebral edema. By searching a
microRNA (miRNA) database for miRNAs that could target the 3-prime UTRs
of AQP1 and AQP4, Sepramaniam et al. (2010) identified MIR320A (614112).
Knockdown of MIR320A via anti-MIR320A in a human astrocytoma cell line
upregulated expression of AQP1 and AQP4 mRNA and protein. Conversely,
overexpression of pre-MIR320A reduced expression of AQP1 and AQP4 mRNA
and protein. Reporter gene assays confirmed direct targeting of the
3-prime UTRs of AQP1 and AQP4 by MIR320A. Astrocytes subjected to oxygen
and glucose deprivation, which mimics the ischemic environment,
downregulated expression of MIR320A, concomitant with upregulated
expression of AQP1 and AQP4. Administration of anti-MIR320A to rats
following occlusion of the middle cerebral artery reduced the infarct
volume, whereas pre-MIR320A caused a further increase in infarct volume.
Sepramaniam et al. (2010) concluded that MIR320 modulates AQP1 and AQP2
and may have a role in cerebral ischemia.
GENE FAMILY
Knepper (1994) provided a review of the aquaporin family of molecular
water channels.
Sorani et al. (2008) reviewed genetic variation in human aquaporins and
the effect on phenotypes of water homeostasis, focusing on naturally
occurring nonsynonymous coding variants. They noted that there is a
significant amount of uncharacterized variation in the
aquaglyceroporins.
ANIMAL MODEL
Ma et al. (1998) generated transgenic mice lacking detectable AQP1 by
targeted gene disruption. In kidney proximal tubule membrane vesicles
from knockout mice, osmotic water permeability was reduced 8-fold
compared with vesicles from wildtype mice. Although the knockout mice
were grossly normal in terms of survival, physical appearance, and organ
morphology, they became severely dehydrated and lethargic after water
deprivation for 36 hours. Body weight decreased by 35 +/- 2%, serum
osmolality increased to greater than 500 mOsm, and urinary osmolality
(657 +/- 59 mOsm) did not change from that before water deprivation. In
contrast, wildtype and heterozygous mice remained active after water
deprivation, body weight decreased by 20 to 22%, serum osmolality
remained normal, and urine osmolality rose to greater than 2,500 mOsm.
Urine sodium concentration in water-deprived knockout mice was less than
10 mM and urine osmolality was not increased by the V2 agonist DDAVP.
The results suggested that AQP1 knockout mice are unable to create a
hypertonic medullary interstitium by countercurrent multiplication. Ma
et al. (1998) concluded that AQP1 is thus required for the formation of
a concentrated urine by the kidney.
Yang et al. (2001) generated Aqp1/Aqp3 double-knockout mice by
intercross of Aqp1 -/- and Aqp3 -/- mice. The mice had reduced survival
and growth compared with single-knockout mice. Erythrocyte water
permeability was not further reduced by the elimination of Aqp3, nor did
the deletion affect glycerol permeability. The double-knockout mice
manifested tumor-like bilateral swelling of the flanks due to kidney
enlargement that was associated with serum azotemia and mortality by age
12 weeks. Most Aqp3- and Aqp3-/Aqp1-deficient mice showed medullary
atrophy and cortical thinning.
Two AQP water channels are expressed in mammalian cornea, AQP1 in
endothelial cells and AQP5 in epithelial cells. Thiagarajah and Verkman
(2002) examined the effect of Aqp1 or Aqp5 knockout in mice. Corneal
thickness in fixed sections was reduced in Aqp1-null mice and increased
in Aqp5-null mice. After exposure of the external corneal surface to
hypotonic saline, the rate of corneal swelling was reduced by Aqp5
deletion. After exposure of the endothelial surface to hypotonic saline
by anterior chamber perfusion, the rate of corneal swelling was reduced
by Aqp1 deletion. The recovery of corneal transparency and thickness
after hypotonic swelling was delayed in Aqp1-null mice. Thiagarajah and
Verkman (2002) concluded that AQP1 and AQP5 provide the principal routes
for corneal water transport across the endothelial and epithelial
barriers, respectively.
Saadoun et al. (2005) demonstrated remarkably impaired tumor growth in
aquaporin-null mice after subcutaneous or intracranial tumor cell
implantation, with reduced tumor vascularity and extensive necrosis. A
mechanism for the impaired angiogenesis was established from cell
culture studies. Although adhesion and proliferation were similar in
primary cultures of aortic endothelia from wildtype and from Aqp1-null
mice, cell migration was greatly impaired in Aqp1-deficient cells, with
abnormal vessel formation in vitro. Stable transfection of
nonendothelial cells with Aqp1 or with a structurally different
water-selective transporter (AQP4; 600308) accelerated cell migration
and wound healing in vitro. Motile Aqp1-expressing cells had prominent
membrane ruffles at the leading edge with polarization of Aqp1 protein
to lamellipodia, where rapid water fluxes occur. Saadoun et al. (2005)
concluded that their findings supported a fundamental role of water
channels in cell migration, which is central to diverse biologic
phenomena including angiogenesis, wound healing, tumor spread, and organ
regeneration.
*FIELD* AV
.0001
COLTON BLOOD GROUP POLYMORPHISM
AQP1, ALA45VAL
Smith et al. (1994) found that the DNA sequence of the AQP1 gene from
Colton-typed individuals (see 110450) predicted that residue 45 is
alanine in the Co(a+b-) phenotype and valine in the Co(a-b+) phenotype.
The nucleotide polymorphism corresponds to a PflMI endonuclease
digestion site in the DNA from Co(a-b+) individuals.
.0002
AQUAPORIN 1 DEFICIENCY
COLTON-NULL, INCLUDED
AQP1, PRO38LEU
One of the 3 Colton-null probands studied by Preston et al. (1994) had a
pro38-to-leu missense mutation in the aquaporin-1 gene, as a result of a
C-to-T transition at nucleotide 113. Like the other individuals with
Co(a-b-), the subject had experienced no hematologic, renal, ocular,
respiratory, gastrointestinal, reproductive, or neurologic dysfunction.
The red cells exhibited low osmotic water permeabilities.
*FIELD* RF
1. Agre, P.; Kozono, D.: Aquaporin water channels: molecular mechanisms
for human disease. FEBS Lett. 555: 72-78, 2003.
2. Agre, P.; Smith, B. L.; Baumgarten, R.; Preston, G. M.; Pressman,
E.; Wilson, P.; Illum, N.; Anstee, D. J.; Lande, M. B.; Zeidel, M.
L.: Human red cell aquaporin CHIP. II. Expression during normal fetal
development and in a novel form of congenital dyserythropoietic anemia. J.
Clin. Invest. 94: 1050-1058, 1994.
3. Cowan, C. A.; Yokoyama, N.; Bianchi, L. M.; Henkemeyer, M.; Fritzsch,
B.: EphB2 guides axons at the midline and is necessary for normal
vestibular function. Neuron 26: 417-430, 2000.
4. Deen, P. M. T.; Weghuis, D. O.; Geurts van Kessel, A.; Wieringa,
B.; van Os, C. H.: The human gene for water channel aquaporin 1 (AQP1)
is localized on chromosome 7p15-p14. Cytogenet. Cell Genet. 65:
243-246, 1994.
5. de Groot, B. L.; Grubmuller, H.: Water permeation across biological
membranes: mechanism and dynamics of aquaporin-1 and Glpf. Science 294:
2353-2357, 2001.
6. de la Chapelle, A.; Vuopio, P.; Sanger, R.; Teesdale, P.: Monosomy-7
and the Colton blood-groups. (Letter) Lancet 306: 817 only, 1975.
Note: Originally Volume II.
7. Denker, B. M.; Smith, B. L.; Kuhajda, F. P.; Agre, P.: Identification,
purification, and partial characterization of a novel M(r) 28,000
integral membrane protein from erythrocytes and renal tubules. J.
Biol. Chem. 263: 15634-15642, 1988.
8. Fushimi, K.; Uchida, S.; Hara, Y.; Hirata, Y.; Marumo, F.; Sasaki,
S.: Cloning and expression of apical membrane water channel of rat
kidney collecting tubule. Nature 361: 549-552, 1993.
9. Hoffman, J. F.: Aquaporin: a wee burn runs through it. (Editorial) J.
Clin. Invest. 92: 1604-1605, 1993.
10. Keen, T. J.; Inglehearn, C. F.; Patel, R. J.; Green, E. D.; Peluso,
D. C.; Bhattacharya, S. S.: Localization of the aquaporin 1 (AQP1)
gene within a YAC contig containing the polymorphic markers D7S632
and D7S526. Genomics 25: 599-600, 1995.
11. King, L. S.; Choi, M.; Fernandez, P. C.; Cartron, J.-P.; Agre,
P.: Defective urinary concentrating ability due to a complete deficiency
of aquaporin-1. New Eng. J. Med. 345: 175-179, 2001.
12. King, L. S.; Nielsen, S.; Agre, P.; Brown, R. H.: Decreased pulmonary
vascular permeability in aquaporin-1-null humans. Proc. Nat. Acad.
Sci. 99: 1059-1063, 2002.
13. Knepper, M. A.: The aquaporin family of molecular water channels. Proc.
Nat. Acad. Sci. 91: 6255-6258, 1994.
14. Ma, T.; Yang, B.; Gillespie, A.; Carlson, E. J.; Epstein, C. J.;
Verkman, A. S.: Severely impaired urinary concentrating ability in
transgenic mice lacking aquaporin-1 water channels. J. Biol. Chem. 273:
4296-4299, 1998.
15. Maurel, C.; Reizer, J.; Schroeder, J. I.; Chrispeels, M.: The
vacuolar membrane protein gamma-TIP creates water specific channels
in Xenopus oocytes. EMBO J. 12: 2241-2247, 1993.
16. Moon, C.; Preston, G. M.; Griffin, C. A.; Jabs, E. W.; Agre, P.
: The human aquaporin-CHIP gene: structure, organization, and chromosomal
localization. J. Biol. Chem. 268: 15772-15778, 1993.
17. Moon, C.; Williams, J. B.; Preston, G. M.; Copeland, N. G.; Gilbert,
D. J.; Nathans, D.; Jenkins, N. A.; Agre, P.: The mouse Aquaporin-1
gene. Genomics 30: 354-357, 1995.
18. Murata, K.; Mitsuoka, K.; Hirai, T.; Walz, T.; Agre, P.; Heymann,
J. B.; Engel, A.; Fujiyoshi, Y.: Structural determinants of water
permeation through aquaporin-1. Nature 407: 599-605, 2000.
19. Pasquali, F.; Bernasconi, P.; Casalone, R.; Fraccaro, M.; Bernasconi,
C.; Lazzarino, M.; Morra, E.; Alessandrino, E. P.; Marchi, M. A.;
Sanger, R.: Pathogenic significance of 'pure' monosomy 7 in myeloproliferative
disorders: analysis of 14 cases.. Hum. Genet. 62: 40-51, 1982.
20. Preston, G. M.; Agre, P.: Isolation of the cDNA for erythrocyte
integral membrane protein of 28 kilodaltons: member of an ancient
channel family. Proc. Nat. Acad. Sci. 88: 11110-11114, 1991.
21. Preston, G. M.; Smith, B. L.; Zeidel, M. L.; Moulds, J. J.; Agre,
P.: Mutations in aquaporin-1 in phenotypically normal humans without
functional CHIP water channels. Science 265: 1585-1587, 1994.
22. Saadoun, S.; Papadopoulos, M. C.; Hara-Chikuma, M.; Verkman, A.
S.: Impairment of angiogenesis and cell migration by targeted aquaporin-1
gene disruption. Nature 434: 786-792, 2005.
23. Sepramaniam, S.; Armugam, A.; Lim, K. Y.; Karolina, D. S.; Swaminathan,
P.; Tan, J. R.; Jeyaseelan, K.: MicroRNA 320a functions as a novel
endogenous modulator of aquaporins 1 and 4 as well as a potential
therapeutic target in cerebral ischemia. J. Biol. Chem. 285: 29223-29230,
2010.
24. Smith, B. L.; Baumgarten, R.; Nielsen, S.; Raben, D.; Zeidel,
M. L.; Agre, P.: Concurrent expression of erythroid and renal aquaporin
CHIP and appearance of water channel activity in perinatal rats. J.
Clin. Invest. 92: 2035-2041, 1993.
25. Smith, B. L.; Preston, G. M.; Spring, F.; Anstee, D. J.; Agre,
P.: Human red blood cell aquaporin CHIP: I. Molecular characterization
of ABH and Colton blood group antigens. J. Clin. Invest. 94: 1043-1049,
1994.
26. Sorani, M. D.; Manley, G. T.; Giacomini, K. M.: Genetic variation
in human aquaporins and effects on phenotypes of water homeostasis. Hum.
Mutat. 29: 1108-1117, 2008.
27. Sui, H.; Han, B.-G.; Lee, J. K.; Walian, P.; Jap, B. K.: Structural
basis of water-specific transport through the AQP1 water channel. Nature 414:
872-878, 2001.
28. Thiagarajah, J. R.; Verkman, A. S.: Aquaporin deletion in mice
reduces corneal water permeability and delays restoration of transparency
after swelling. J. Biol. Chem. 277: 19139-19144, 2002.
29. Yang, B.; Ma, T.; Verkman, A. S.: Erythrocyte water permeability
and renal function in double knockout mice lacking aquaporin-1 and
aquaporin-3. J. Biol. Chem. 276: 624-628, 2001.
*FIELD* CN
Patricia A. Hartz - updated: 07/22/2011
Marla J. F. O'Neill - updated: 10/20/2009
Ada Hamosh - updated: 6/2/2005
Patricia A. Hartz - updated: 5/4/2004
Victor A. McKusick - updated: 1/20/2004
Paul J. Converse - updated: 8/1/2002
Victor A. McKusick - updated: 6/10/2002
Paul J. Converse - updated: 1/2/2002
Dawn Watkins-Chow - updated: 12/7/2001
Victor A. McKusick - updated: 8/3/2001
Ada Hamosh - updated: 10/11/2000
Ada Hamosh - updated: 7/20/2000
Victor A. McKusick - updated: 10/25/1999
Alan F. Scott - edited: 12/27/1996
*FIELD* CD
Victor A. McKusick: 9/14/1993
*FIELD* ED
mgross: 07/22/2011
carol: 12/20/2010
ckniffin: 12/20/2010
wwang: 10/26/2009
terry: 10/20/2009
terry: 2/3/2009
tkritzer: 6/3/2005
terry: 6/2/2005
mgross: 5/4/2004
cwells: 1/22/2004
terry: 1/20/2004
mgross: 8/1/2002
cwells: 7/2/2002
terry: 6/10/2002
alopez: 1/2/2002
carol: 12/12/2001
terry: 12/7/2001
carol: 8/17/2001
cwells: 8/14/2001
cwells: 8/7/2001
terry: 8/3/2001
alopez: 10/11/2000
terry: 10/11/2000
mcapotos: 8/1/2000
mcapotos: 7/26/2000
terry: 7/20/2000
carol: 10/25/1999
carol: 6/10/1998
mark: 6/16/1997
terry: 5/6/1997
mark: 12/27/1996
mark: 1/15/1996
terry: 3/7/1995
carol: 10/5/1994
carol: 10/29/1993
carol: 9/14/1993
*RECORD*
*FIELD* NO
107776
*FIELD* TI
*107776 AQUAPORIN 1; AQP1
;;AQUAPORIN-CHIP;;
AQP-CHIP;;
CHANNEL-LIKE INTEGRAL MEMBRANE PROTEIN, 28-KD; CHIP28
read more*FIELD* TX
CLONING
Aquaporin-CHIP is a 28-kD integral protein purified from the plasma
membranes of red cells and renal tubules by Denker et al. (1988). The
protein was thought at first to be a breakdown product of the Rh
polypeptide but was later shown to be a unique molecule that is abundant
in erythrocytes and renal tubules. A subpopulation is N-glycosylated.
Preston and Agre (1991) isolated a cDNA for this protein, called CHIP28
(channel forming integral protein of 28 kD), from human fetal liver.
Analysis of the deduced amino acid sequence suggested that CHIP28
protein contains 6 bilayer-spanning domains, 2 exofacial potential
N-glycosylation sites, and intracellular N and C termini. The sequence
showed strong homology with the major intrinsic protein of bovine lens
(MIP26; 154050), which is the prototype of an ancient family of membrane
channels. These proteins are believed to form channels permeable to
water and possibly other small molecules.
GENE STRUCTURE
Moon et al. (1995) showed that the 13-kb Aqp1 gene in the mouse contains
4 exons with intronic boundaries corresponding to other known aquaporin
genes.
MAPPING
Moon et al. (1993) isolated the AQP1 structural gene and partially
sequenced it. Genomic Southern analysis indicated the existence of a
single AQP1 gene, which was localized to 7p14 by in situ hybridization.
Sequence comparisons with similar proteins from diverse species
suggested a common evolutionary origin. Deen et al. (1994) showed that
the gene is on chromosome 7 by Southern blot hybridization to
human/rodent hybrid cell lines and regionalized it to 7p15-p14 by in
situ hybridization. By interspecific backcross mapping, Moon et al.
(1995) showed that the mouse Aqp1 gene is located on chromosome 6 in a
region with homology of synteny with human 7p14.
Keen et al. (1995) localized the AQP1 gene on chromosome 7 within a YAC
contig containing 2 polymorphic markers, D7S632 and D7S526. Since
aquaporin is known to be expressed in a diverse range of secretory and
absorptive epithelia, including many in the eye, it had been proposed as
a possible candidate for disorders involving an imbalance in ocular
fluid movement. Keen et al. (1995) raised a question of possible
involvement in 2 eye diseases that map to that region, retinitis
pigmentosa-9 (180104) and dominant cystoid macular dystrophy (153880).
BIOCHEMICAL FEATURES
Murata et al. (2000) described an atomic model of AQP1 at 3.8-angstrom
resolution from electron crystallographic data. Multiple highly
conserved amino acid residues stabilize the novel fold of AQP1. The
aqueous pathway is lined with conserved hydrophobic residues that permit
rapid water transport, whereas the water selectivity is due to a
constriction of the pore diameter to about 3 angstroms over a span of 1
residue. The atomic model provided a possible molecular explanation to a
longstanding puzzle in physiology--how membranes can be freely permeable
to water but impermeable to protons.
Sui et al. (2001) reported the structure of the dumbbell-shaped AQP1
water channel at 2.2-angstrom resolution. The channel consists of 3
topologic elements, an extracellular and a cytoplasmic vestibule
connected by an extended narrow pore or selectivity filter, averaging 4
angstroms in diameter. Within the selectivity filter, 4 bound waters are
localized along 3 hydrophilic nodes, which punctuate an otherwise
extremely hydrophobic pore segment, facilitating water transport. The
highly conserved histidine-182 residue is critical in establishing water
specificity. AQP1 lacks a suitable chain of hydrogen-bonded water
molecules in the selectivity filter that could act as a proton wire,
indicating that proton transport through the channel is highly
energetically unfavorable.
GENE FUNCTION
The AQP-CHIP protein exists as a homotetramer which physically resembles
channel proteins and was the first molecular water channel identified.
The AQP-CHIP cDNA isolated from a human bone marrow cDNA library was
found to be related to the major intrinsic protein of lens (154050). Two
other related proteins were found to be water transporters (Fushimi et
al., 1993; Maurel et al., 1993) and these 3 proteins were referred to as
the aquaporins. AQP-CHIP is also expressed in diverse epithelia with
distinct developmental patterns. By immunochemical and functional means,
Smith et al. (1993) showed that AQP-CHIP is essentially absent in
neonatal red cells of the rat. After birth, AQP-CHIP appears in the red
cells and increases within several weeks to the adult level of
expression. The neonatal kidney, while displaying low levels of AQP-CHIP
expression, has a parallel increase in the amount and distribution of
AQP-CHIP in the proximal tubules and the descending thin limbs of the
loops of Henle, commensurate with the kidney's ability to form
concentrated urine. Smith et al. (1993) suggested that the water
channels act to promote the rehydration of red cells after their
shrinkage in the hypertonic environment of the renal medulla. Rapid
rehydration would return the cells to their normal volume, optimizing
their deformability for transit in the microcirculation. See Hoffman
(1993).
Using colocalization studies and biochemical analysis, Cowan et al.
(2000) demonstrated that a protein complex containing mouse Ephb2
(600997) and aquaporin-1 is formed in vivo.
The location of the human AQP1 gene is the same as that of the Colton
blood group (110450) on 7p. Smith et al. (1994) demonstrated that the
CHIP-glycan is the molecular site of the Colton polymorphism. They also
showed that Colton blood group antigen differences result from an
ala-val polymorphism at residue 45, located on the first extracellular
loop of CHIP. CHIP was selectively immunoprecipitated with anti-Co(a) or
anti-Co(b). Approximately 92% of Caucasians are Co(a+b-), approximately
8% are Co(a+b+), and only 0.2% are Co+(a-b+).
Colton antigens cause clinical difficulties infrequently, although
maternal-fetal incompatibility and transfusion reactions are known. The
power of worldwide blood group referencing makes the rarest of
phenotypes accessible, and the single Co+(a-b-) red cell membrane sample
in the reference collection was found to lack CHIP by immunoblot. Lack
of Colton antigens in association with monosomy 7 has been reported in
some cases of leukemia (de la Chapelle et al., 1975; Pasquali et al.,
1982).
King et al. (2001) examined the finding that aquaporin-1 deficiency had
no obvious clinical consequences in the 6 kindreds identified worldwide
who lacked the Colton blood group. Since aquaporin-1 is abundant in
renal proximal tubular epithelium, the thin descending limb of the loop
of Henle, and the descending vasa recta of the kidney, the authors
hypothesized that persons with a deficiency of aquaporin-1 have defects
in water homeostasis in the kidneys that can be identified only under
conditions of stress. They studied 2 unrelated subjects with aquaporin-1
deficiency and found that they had impaired urinary concentrating
ability, suggesting that aquaporin-1 has a physiologic role in renal
function. Both were patients in whom homozygous mutations in the AQP1
gene had been identified by Preston et al. (1994). Both were women who
had developed antibodies against the Colton blood group in association
with pregnancy. One subject had occasional edema of the lower legs, for
which she infrequently took a diuretic. She drank 2 to 4 liters of fluid
per day. The second drank 2 liters of fluid per day and urinated 2 to 3
times daily, without nocturia.
King et al. (2002) studied the effect of absence of aquaporin-1 on water
permeability in the human lung, with a rationale parallel to that used
in the study of ability to concentrate urine maximally (King et al.,
2001). AQP1 is present in endothelial cells in the lung, including those
in the vascular plexus around the airways. They used high-resolution
computed tomography scans of the lung to evaluate the response to
intravenous fluid challenge in 2 unrelated AQP1-null individuals and 5
normal controls. The airways and pulmonary vessels were measured at
baseline and after intravenous administration of 3 liters of saline.
Increases in airway wall thickness after fluid administration reflected
peribronchiolar edema formation. Both control and AQP1-null subjects had
approximately a 20% increase in pulmonary vessel area in response to
saline infusion, suggesting similar degrees of loading. Control subjects
had a 44% increase in the thickness of the airway wall, consistent with
peribronchiolar edema formation. In marked contrast, airway wall
thickness did not change in AQP1-null subjects in response to saline
infusion. These studies indicated that AQP1 is a determinant of vascular
permeability in the lung, and demonstrate a role for aquaporins in human
pulmonary physiology.
Worldwide blood group referencing had led to the identification of 5
kindreds in which red cells expressed no Colton antigens; these
individuals were said to be Co(a-b-). Preston et al. (1994) obtained
blood samples and urine sediment from 3 of these individuals, 1 member
from each of 3 kindreds. They were unrelated women of northern European
ancestry, and none had hematologic, renal, ocular, respiratory,
gastrointestinal, reproductive, or neurologic dysfunction. Cells in
these Co(a-b-) individuals appeared morphologically normal, but their
red cells exhibited low osmotic water permeability. Genomic DNA analyses
demonstrated that 2 individuals were homozygous for different nonsense
mutations (exon deletion or frameshift), and the third had a missense
mutation encoding a nonfunctioning CHIP molecule. Surprisingly, none of
the 3 suffered any apparent clinical consequence, which raised questions
about the physiologic importance of CHIP and implied that other
mechanisms may compensate for its absence.
Agre et al. (1994) found that, compared with the adult, second and third
trimester human fetal red cells had lower CHIP/spectrin ratios and
reduced osmotic water permeability; CHIP was already present in human
renal tubules by the second trimester.
Using molecular dynamics simulations of water permeation through AQP1,
de Groot and Grubmuller (2001) showed that AQP1 acts as a 2-stage
filter. The conserved NPA (asp-pro-ala) motifs form a
selectivity-determining, or size-exclusion, region. The authors proposed
that a second aromatic/arginine (ar/R) region functions as a proton
filter.
Agre and Kozono (2003) reviewed the topic of aquaporin water channels.
The atomic structure of mammalian AQP1 illustrates how this family of
proteins is freely permeated by water but not protons (hydronium ions,
H(3)O+). The mercury sensitivity of AQP1 is well explained by
localization of the specific residue (C189) at the narrowest segment of
the channel at the same level as H180 and R195. Cysteines are present at
the corresponding position in several other members of the aquaporin
family (AQP2, 107777; AQP5, 600442; AQP6, 601383; and AQP9, 602914).
Prior to the introduction of modern loop diuretics, patients with
refractory fluid overload were treated with mercurial diuretics, which
deliver profound renal diuresis.
AQP1 and AQP4 (600308) regulate the movement of water in ischemic brain,
and they appear to play a role in cerebral edema. By searching a
microRNA (miRNA) database for miRNAs that could target the 3-prime UTRs
of AQP1 and AQP4, Sepramaniam et al. (2010) identified MIR320A (614112).
Knockdown of MIR320A via anti-MIR320A in a human astrocytoma cell line
upregulated expression of AQP1 and AQP4 mRNA and protein. Conversely,
overexpression of pre-MIR320A reduced expression of AQP1 and AQP4 mRNA
and protein. Reporter gene assays confirmed direct targeting of the
3-prime UTRs of AQP1 and AQP4 by MIR320A. Astrocytes subjected to oxygen
and glucose deprivation, which mimics the ischemic environment,
downregulated expression of MIR320A, concomitant with upregulated
expression of AQP1 and AQP4. Administration of anti-MIR320A to rats
following occlusion of the middle cerebral artery reduced the infarct
volume, whereas pre-MIR320A caused a further increase in infarct volume.
Sepramaniam et al. (2010) concluded that MIR320 modulates AQP1 and AQP2
and may have a role in cerebral ischemia.
GENE FAMILY
Knepper (1994) provided a review of the aquaporin family of molecular
water channels.
Sorani et al. (2008) reviewed genetic variation in human aquaporins and
the effect on phenotypes of water homeostasis, focusing on naturally
occurring nonsynonymous coding variants. They noted that there is a
significant amount of uncharacterized variation in the
aquaglyceroporins.
ANIMAL MODEL
Ma et al. (1998) generated transgenic mice lacking detectable AQP1 by
targeted gene disruption. In kidney proximal tubule membrane vesicles
from knockout mice, osmotic water permeability was reduced 8-fold
compared with vesicles from wildtype mice. Although the knockout mice
were grossly normal in terms of survival, physical appearance, and organ
morphology, they became severely dehydrated and lethargic after water
deprivation for 36 hours. Body weight decreased by 35 +/- 2%, serum
osmolality increased to greater than 500 mOsm, and urinary osmolality
(657 +/- 59 mOsm) did not change from that before water deprivation. In
contrast, wildtype and heterozygous mice remained active after water
deprivation, body weight decreased by 20 to 22%, serum osmolality
remained normal, and urine osmolality rose to greater than 2,500 mOsm.
Urine sodium concentration in water-deprived knockout mice was less than
10 mM and urine osmolality was not increased by the V2 agonist DDAVP.
The results suggested that AQP1 knockout mice are unable to create a
hypertonic medullary interstitium by countercurrent multiplication. Ma
et al. (1998) concluded that AQP1 is thus required for the formation of
a concentrated urine by the kidney.
Yang et al. (2001) generated Aqp1/Aqp3 double-knockout mice by
intercross of Aqp1 -/- and Aqp3 -/- mice. The mice had reduced survival
and growth compared with single-knockout mice. Erythrocyte water
permeability was not further reduced by the elimination of Aqp3, nor did
the deletion affect glycerol permeability. The double-knockout mice
manifested tumor-like bilateral swelling of the flanks due to kidney
enlargement that was associated with serum azotemia and mortality by age
12 weeks. Most Aqp3- and Aqp3-/Aqp1-deficient mice showed medullary
atrophy and cortical thinning.
Two AQP water channels are expressed in mammalian cornea, AQP1 in
endothelial cells and AQP5 in epithelial cells. Thiagarajah and Verkman
(2002) examined the effect of Aqp1 or Aqp5 knockout in mice. Corneal
thickness in fixed sections was reduced in Aqp1-null mice and increased
in Aqp5-null mice. After exposure of the external corneal surface to
hypotonic saline, the rate of corneal swelling was reduced by Aqp5
deletion. After exposure of the endothelial surface to hypotonic saline
by anterior chamber perfusion, the rate of corneal swelling was reduced
by Aqp1 deletion. The recovery of corneal transparency and thickness
after hypotonic swelling was delayed in Aqp1-null mice. Thiagarajah and
Verkman (2002) concluded that AQP1 and AQP5 provide the principal routes
for corneal water transport across the endothelial and epithelial
barriers, respectively.
Saadoun et al. (2005) demonstrated remarkably impaired tumor growth in
aquaporin-null mice after subcutaneous or intracranial tumor cell
implantation, with reduced tumor vascularity and extensive necrosis. A
mechanism for the impaired angiogenesis was established from cell
culture studies. Although adhesion and proliferation were similar in
primary cultures of aortic endothelia from wildtype and from Aqp1-null
mice, cell migration was greatly impaired in Aqp1-deficient cells, with
abnormal vessel formation in vitro. Stable transfection of
nonendothelial cells with Aqp1 or with a structurally different
water-selective transporter (AQP4; 600308) accelerated cell migration
and wound healing in vitro. Motile Aqp1-expressing cells had prominent
membrane ruffles at the leading edge with polarization of Aqp1 protein
to lamellipodia, where rapid water fluxes occur. Saadoun et al. (2005)
concluded that their findings supported a fundamental role of water
channels in cell migration, which is central to diverse biologic
phenomena including angiogenesis, wound healing, tumor spread, and organ
regeneration.
*FIELD* AV
.0001
COLTON BLOOD GROUP POLYMORPHISM
AQP1, ALA45VAL
Smith et al. (1994) found that the DNA sequence of the AQP1 gene from
Colton-typed individuals (see 110450) predicted that residue 45 is
alanine in the Co(a+b-) phenotype and valine in the Co(a-b+) phenotype.
The nucleotide polymorphism corresponds to a PflMI endonuclease
digestion site in the DNA from Co(a-b+) individuals.
.0002
AQUAPORIN 1 DEFICIENCY
COLTON-NULL, INCLUDED
AQP1, PRO38LEU
One of the 3 Colton-null probands studied by Preston et al. (1994) had a
pro38-to-leu missense mutation in the aquaporin-1 gene, as a result of a
C-to-T transition at nucleotide 113. Like the other individuals with
Co(a-b-), the subject had experienced no hematologic, renal, ocular,
respiratory, gastrointestinal, reproductive, or neurologic dysfunction.
The red cells exhibited low osmotic water permeabilities.
*FIELD* RF
1. Agre, P.; Kozono, D.: Aquaporin water channels: molecular mechanisms
for human disease. FEBS Lett. 555: 72-78, 2003.
2. Agre, P.; Smith, B. L.; Baumgarten, R.; Preston, G. M.; Pressman,
E.; Wilson, P.; Illum, N.; Anstee, D. J.; Lande, M. B.; Zeidel, M.
L.: Human red cell aquaporin CHIP. II. Expression during normal fetal
development and in a novel form of congenital dyserythropoietic anemia. J.
Clin. Invest. 94: 1050-1058, 1994.
3. Cowan, C. A.; Yokoyama, N.; Bianchi, L. M.; Henkemeyer, M.; Fritzsch,
B.: EphB2 guides axons at the midline and is necessary for normal
vestibular function. Neuron 26: 417-430, 2000.
4. Deen, P. M. T.; Weghuis, D. O.; Geurts van Kessel, A.; Wieringa,
B.; van Os, C. H.: The human gene for water channel aquaporin 1 (AQP1)
is localized on chromosome 7p15-p14. Cytogenet. Cell Genet. 65:
243-246, 1994.
5. de Groot, B. L.; Grubmuller, H.: Water permeation across biological
membranes: mechanism and dynamics of aquaporin-1 and Glpf. Science 294:
2353-2357, 2001.
6. de la Chapelle, A.; Vuopio, P.; Sanger, R.; Teesdale, P.: Monosomy-7
and the Colton blood-groups. (Letter) Lancet 306: 817 only, 1975.
Note: Originally Volume II.
7. Denker, B. M.; Smith, B. L.; Kuhajda, F. P.; Agre, P.: Identification,
purification, and partial characterization of a novel M(r) 28,000
integral membrane protein from erythrocytes and renal tubules. J.
Biol. Chem. 263: 15634-15642, 1988.
8. Fushimi, K.; Uchida, S.; Hara, Y.; Hirata, Y.; Marumo, F.; Sasaki,
S.: Cloning and expression of apical membrane water channel of rat
kidney collecting tubule. Nature 361: 549-552, 1993.
9. Hoffman, J. F.: Aquaporin: a wee burn runs through it. (Editorial) J.
Clin. Invest. 92: 1604-1605, 1993.
10. Keen, T. J.; Inglehearn, C. F.; Patel, R. J.; Green, E. D.; Peluso,
D. C.; Bhattacharya, S. S.: Localization of the aquaporin 1 (AQP1)
gene within a YAC contig containing the polymorphic markers D7S632
and D7S526. Genomics 25: 599-600, 1995.
11. King, L. S.; Choi, M.; Fernandez, P. C.; Cartron, J.-P.; Agre,
P.: Defective urinary concentrating ability due to a complete deficiency
of aquaporin-1. New Eng. J. Med. 345: 175-179, 2001.
12. King, L. S.; Nielsen, S.; Agre, P.; Brown, R. H.: Decreased pulmonary
vascular permeability in aquaporin-1-null humans. Proc. Nat. Acad.
Sci. 99: 1059-1063, 2002.
13. Knepper, M. A.: The aquaporin family of molecular water channels. Proc.
Nat. Acad. Sci. 91: 6255-6258, 1994.
14. Ma, T.; Yang, B.; Gillespie, A.; Carlson, E. J.; Epstein, C. J.;
Verkman, A. S.: Severely impaired urinary concentrating ability in
transgenic mice lacking aquaporin-1 water channels. J. Biol. Chem. 273:
4296-4299, 1998.
15. Maurel, C.; Reizer, J.; Schroeder, J. I.; Chrispeels, M.: The
vacuolar membrane protein gamma-TIP creates water specific channels
in Xenopus oocytes. EMBO J. 12: 2241-2247, 1993.
16. Moon, C.; Preston, G. M.; Griffin, C. A.; Jabs, E. W.; Agre, P.
: The human aquaporin-CHIP gene: structure, organization, and chromosomal
localization. J. Biol. Chem. 268: 15772-15778, 1993.
17. Moon, C.; Williams, J. B.; Preston, G. M.; Copeland, N. G.; Gilbert,
D. J.; Nathans, D.; Jenkins, N. A.; Agre, P.: The mouse Aquaporin-1
gene. Genomics 30: 354-357, 1995.
18. Murata, K.; Mitsuoka, K.; Hirai, T.; Walz, T.; Agre, P.; Heymann,
J. B.; Engel, A.; Fujiyoshi, Y.: Structural determinants of water
permeation through aquaporin-1. Nature 407: 599-605, 2000.
19. Pasquali, F.; Bernasconi, P.; Casalone, R.; Fraccaro, M.; Bernasconi,
C.; Lazzarino, M.; Morra, E.; Alessandrino, E. P.; Marchi, M. A.;
Sanger, R.: Pathogenic significance of 'pure' monosomy 7 in myeloproliferative
disorders: analysis of 14 cases.. Hum. Genet. 62: 40-51, 1982.
20. Preston, G. M.; Agre, P.: Isolation of the cDNA for erythrocyte
integral membrane protein of 28 kilodaltons: member of an ancient
channel family. Proc. Nat. Acad. Sci. 88: 11110-11114, 1991.
21. Preston, G. M.; Smith, B. L.; Zeidel, M. L.; Moulds, J. J.; Agre,
P.: Mutations in aquaporin-1 in phenotypically normal humans without
functional CHIP water channels. Science 265: 1585-1587, 1994.
22. Saadoun, S.; Papadopoulos, M. C.; Hara-Chikuma, M.; Verkman, A.
S.: Impairment of angiogenesis and cell migration by targeted aquaporin-1
gene disruption. Nature 434: 786-792, 2005.
23. Sepramaniam, S.; Armugam, A.; Lim, K. Y.; Karolina, D. S.; Swaminathan,
P.; Tan, J. R.; Jeyaseelan, K.: MicroRNA 320a functions as a novel
endogenous modulator of aquaporins 1 and 4 as well as a potential
therapeutic target in cerebral ischemia. J. Biol. Chem. 285: 29223-29230,
2010.
24. Smith, B. L.; Baumgarten, R.; Nielsen, S.; Raben, D.; Zeidel,
M. L.; Agre, P.: Concurrent expression of erythroid and renal aquaporin
CHIP and appearance of water channel activity in perinatal rats. J.
Clin. Invest. 92: 2035-2041, 1993.
25. Smith, B. L.; Preston, G. M.; Spring, F.; Anstee, D. J.; Agre,
P.: Human red blood cell aquaporin CHIP: I. Molecular characterization
of ABH and Colton blood group antigens. J. Clin. Invest. 94: 1043-1049,
1994.
26. Sorani, M. D.; Manley, G. T.; Giacomini, K. M.: Genetic variation
in human aquaporins and effects on phenotypes of water homeostasis. Hum.
Mutat. 29: 1108-1117, 2008.
27. Sui, H.; Han, B.-G.; Lee, J. K.; Walian, P.; Jap, B. K.: Structural
basis of water-specific transport through the AQP1 water channel. Nature 414:
872-878, 2001.
28. Thiagarajah, J. R.; Verkman, A. S.: Aquaporin deletion in mice
reduces corneal water permeability and delays restoration of transparency
after swelling. J. Biol. Chem. 277: 19139-19144, 2002.
29. Yang, B.; Ma, T.; Verkman, A. S.: Erythrocyte water permeability
and renal function in double knockout mice lacking aquaporin-1 and
aquaporin-3. J. Biol. Chem. 276: 624-628, 2001.
*FIELD* CN
Patricia A. Hartz - updated: 07/22/2011
Marla J. F. O'Neill - updated: 10/20/2009
Ada Hamosh - updated: 6/2/2005
Patricia A. Hartz - updated: 5/4/2004
Victor A. McKusick - updated: 1/20/2004
Paul J. Converse - updated: 8/1/2002
Victor A. McKusick - updated: 6/10/2002
Paul J. Converse - updated: 1/2/2002
Dawn Watkins-Chow - updated: 12/7/2001
Victor A. McKusick - updated: 8/3/2001
Ada Hamosh - updated: 10/11/2000
Ada Hamosh - updated: 7/20/2000
Victor A. McKusick - updated: 10/25/1999
Alan F. Scott - edited: 12/27/1996
*FIELD* CD
Victor A. McKusick: 9/14/1993
*FIELD* ED
mgross: 07/22/2011
carol: 12/20/2010
ckniffin: 12/20/2010
wwang: 10/26/2009
terry: 10/20/2009
terry: 2/3/2009
tkritzer: 6/3/2005
terry: 6/2/2005
mgross: 5/4/2004
cwells: 1/22/2004
terry: 1/20/2004
mgross: 8/1/2002
cwells: 7/2/2002
terry: 6/10/2002
alopez: 1/2/2002
carol: 12/12/2001
terry: 12/7/2001
carol: 8/17/2001
cwells: 8/14/2001
cwells: 8/7/2001
terry: 8/3/2001
alopez: 10/11/2000
terry: 10/11/2000
mcapotos: 8/1/2000
mcapotos: 7/26/2000
terry: 7/20/2000
carol: 10/25/1999
carol: 6/10/1998
mark: 6/16/1997
terry: 5/6/1997
mark: 12/27/1996
mark: 1/15/1996
terry: 3/7/1995
carol: 10/5/1994
carol: 10/29/1993
carol: 9/14/1993
MIM
110450
*RECORD*
*FIELD* NO
110450
*FIELD* TI
#110450 BLOOD GROUP--COLTON; CO
*FIELD* TX
A number sign (#) is used with this entry because of evidence that the
read morepolymorphism is due to variation in the aquaporin-CHIP gene (AQP1;
107776).
Co(a) was described by Race and Sanger (1968) as 'well on the way to
establishment as a separate system.' Its independence of Lutheran, Kell,
Diego and Yt remained to be demonstrated. De la Chapelle et al. (1975)
reported the very rare Co(a-b-) phenotype in 2 of 5 cases of monosomy 7
in the bone marrow. Mohr and Eiberg (1977) found a lod score of 2.57 for
the linkage of Kidd (JK) and Colton. Each had been tentatively assigned
to chromosome 7. Lewis et al. (1984) presented further data that
weakened the previously proposed linkage of Colton with Kidd from
'probable' to 'possible.' Combined data gave a peak lod of 0.55 at theta
= 0.36. Sherman and Simpson (1985) assigned the Kidd blood group locus,
erroneously as it turned out, to 2p, and suggested that the CO locus
might be located there also. The observations of de la Chapelle et al.
(1975) prompted Zelinski et al. (1990) to revisit chromosome 7 in an
attempt to map CO. This was successfully achieved when they demonstrated
linkage to the argininosuccinate synthetase pseudogene (ASSP11) which is
located on 7p; maximum lod = 5.79 at theta = 0.07 for combined paternal
and maternal meiosis. In further linkage studies, Zelinski et al. (1991)
provided very strong evidence that the CO locus is on 7p.
Smith et al. (1994) described the structure of the aquaporin protein and
demonstrated that the Colton blood group antigens result from an ala-val
polymorphism at residue 45, located on the first extracellular loop of
the aquaporin-1 protein. In red cells from 3 individuals who lacked
Colton antigens, i.e., were Co(a-b-), Preston et al. (1994) found
mutations in the AQP1 gene that resulted in a nonfunctioning CHIP
molecule. Surprisingly, none of the 3 suffered any apparent clinical
consequences.
King et al. (2001) found that Colton-null individuals who lack
aquaporin-1 have, under stress, a demonstrable defect in urinary
concentration capacity. King et al. (2002), again studying Colton-null
individuals, showed that there is decreased pulmonary vascular
permeability in such individuals. Joshi et al. (2001) described a
seventh Colton-null individual.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
*FIELD* SA
Heisto et al. (1967); Lewis et al. (1977); Race and Sanger (1975)
*FIELD* RF
1. de la Chapelle, A.; Vuopio, P.; Sanger, R.; Teesdale, P.: Monosomy-7
and the Colton blood-groups. (Letter) Lancet 306: 817 only, 1975.
Note: Originally Volume II.
2. Heisto, H.; Van Der Hart, M.; Madsen, G.; Moes, M.; Noades, J.;
Pickles, M. M.; Race, R. R.; Sanger, R.; Swanson, J.: Three examples
of a new red cell antibody, anti-Co-(a). Vox Sang. 12: 18-24, 1967.
3. Joshi, S. R.; Wagner, F. F.; Vasantha, K.; Panjwani, S. R.; Flegel,
W. A.: An AQP1 null allele in an Indian woman with Co(a-b-) phenotype
and high-titer anti-Co3 associated with mild HDN. Transfusion 41:
1273-1278, 2001.
4. King, L. S.; Choi, M.; Fernandez, P. C.; Cartron, J.-P.; Agre,
P.: Defective urinary concentrating ability due to a complete deficiency
of aquaporin-1. New Eng. J. Med. 345: 175-179, 2001.
5. King, L. S.; Nielsen, S.; Agre, P.; Brown, R. H.: Decreased pulmonary
vascular permeability in aquaporin-1-null humans. Proc. Nat. Acad.
Sci. 99: 1059-1063, 2002.
6. Lewis, M.; Kaita, H.; Chown, B.; Giblett, E. R.; Anderson, J.:
Colton blood groups in Canadian Caucasians: frequencies, inheritance
and linkage analysis. Vox Sang. 32: 208-213, 1977.
7. Lewis, M.; Kaita, H.; Philipps, S.: Dwindling odds for Jk:Co linkage.
(Abstract) Cytogenet. Cell Genet. 37: 524 only, 1984.
8. Mohr, J.; Eiberg, H.: Colton blood groups: indication of linkage
with the Kidd (Jk) system as support for assignment to chromosome
7. Clin. Genet. 11: 372-374, 1977.
9. Preston, G. M.; Smith, B. L.; Zeidel, M. L.; Moulds, J. J.; Agre,
P.: Mutations in aquaporin-1 in phenotypically normal humans without
functional CHIP water channels. Science 265: 1585-1587, 1994.
10. Race, R. R.; Sanger, R.: Blood Groups in Man. Philadelphia:
F. A. Davis Co. (pub.) (5th ed.): 1968.
11. Race, R. R.; Sanger, R.: Blood Groups in Man. Oxford: Blackwell
Sci. Publ. (pub.) 1975.
12. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
13. Sherman, S. L.; Simpson, S. P.: Evidence for the location of
JK and CO on chromosome 2 based on family studies. (Abstract) Cytogenet.
Cell Genet. 40: 743 only, 1985.
14. Smith, B. L.; Preston, G. M.; Spring, F.; Anstee, D. J.; Agre,
P.: Human red blood cell aquaporin CHIP. I. Molecular characterization
of ABH and Colton blood group antigens. J. Clin. Invest. 94: 1043-1049,
1994.
15. Zelinski, T.; Kaita, H.; Gilson, T.; Coghlan, G.; Philipps, S.;
Lewis, M.: Linkage between the Colton blood group locus and ASSP11
on chromosome 7. Genomics 6: 623-625, 1990.
16. Zelinski, T. A.; White, L. J.; Coghlan, G. E.; Philipps, S. E.
: Linkage relationships between CO, D7S135 and ASSP11 on chromosome
7p. (Abstract) Cytogenet. Cell Genet. 58: 1927 only, 1991.
*FIELD* CN
Victor A. McKusick - updated: 11/6/2003
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
terry: 12/16/2009
terry: 2/3/2009
tkritzer: 11/11/2003
terry: 11/6/2003
terry: 11/1/1994
mimadm: 4/19/1994
warfield: 4/7/1994
carol: 10/14/1993
supermim: 3/16/1992
carol: 2/26/1992
*RECORD*
*FIELD* NO
110450
*FIELD* TI
#110450 BLOOD GROUP--COLTON; CO
*FIELD* TX
A number sign (#) is used with this entry because of evidence that the
read morepolymorphism is due to variation in the aquaporin-CHIP gene (AQP1;
107776).
Co(a) was described by Race and Sanger (1968) as 'well on the way to
establishment as a separate system.' Its independence of Lutheran, Kell,
Diego and Yt remained to be demonstrated. De la Chapelle et al. (1975)
reported the very rare Co(a-b-) phenotype in 2 of 5 cases of monosomy 7
in the bone marrow. Mohr and Eiberg (1977) found a lod score of 2.57 for
the linkage of Kidd (JK) and Colton. Each had been tentatively assigned
to chromosome 7. Lewis et al. (1984) presented further data that
weakened the previously proposed linkage of Colton with Kidd from
'probable' to 'possible.' Combined data gave a peak lod of 0.55 at theta
= 0.36. Sherman and Simpson (1985) assigned the Kidd blood group locus,
erroneously as it turned out, to 2p, and suggested that the CO locus
might be located there also. The observations of de la Chapelle et al.
(1975) prompted Zelinski et al. (1990) to revisit chromosome 7 in an
attempt to map CO. This was successfully achieved when they demonstrated
linkage to the argininosuccinate synthetase pseudogene (ASSP11) which is
located on 7p; maximum lod = 5.79 at theta = 0.07 for combined paternal
and maternal meiosis. In further linkage studies, Zelinski et al. (1991)
provided very strong evidence that the CO locus is on 7p.
Smith et al. (1994) described the structure of the aquaporin protein and
demonstrated that the Colton blood group antigens result from an ala-val
polymorphism at residue 45, located on the first extracellular loop of
the aquaporin-1 protein. In red cells from 3 individuals who lacked
Colton antigens, i.e., were Co(a-b-), Preston et al. (1994) found
mutations in the AQP1 gene that resulted in a nonfunctioning CHIP
molecule. Surprisingly, none of the 3 suffered any apparent clinical
consequences.
King et al. (2001) found that Colton-null individuals who lack
aquaporin-1 have, under stress, a demonstrable defect in urinary
concentration capacity. King et al. (2002), again studying Colton-null
individuals, showed that there is decreased pulmonary vascular
permeability in such individuals. Joshi et al. (2001) described a
seventh Colton-null individual.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
*FIELD* SA
Heisto et al. (1967); Lewis et al. (1977); Race and Sanger (1975)
*FIELD* RF
1. de la Chapelle, A.; Vuopio, P.; Sanger, R.; Teesdale, P.: Monosomy-7
and the Colton blood-groups. (Letter) Lancet 306: 817 only, 1975.
Note: Originally Volume II.
2. Heisto, H.; Van Der Hart, M.; Madsen, G.; Moes, M.; Noades, J.;
Pickles, M. M.; Race, R. R.; Sanger, R.; Swanson, J.: Three examples
of a new red cell antibody, anti-Co-(a). Vox Sang. 12: 18-24, 1967.
3. Joshi, S. R.; Wagner, F. F.; Vasantha, K.; Panjwani, S. R.; Flegel,
W. A.: An AQP1 null allele in an Indian woman with Co(a-b-) phenotype
and high-titer anti-Co3 associated with mild HDN. Transfusion 41:
1273-1278, 2001.
4. King, L. S.; Choi, M.; Fernandez, P. C.; Cartron, J.-P.; Agre,
P.: Defective urinary concentrating ability due to a complete deficiency
of aquaporin-1. New Eng. J. Med. 345: 175-179, 2001.
5. King, L. S.; Nielsen, S.; Agre, P.; Brown, R. H.: Decreased pulmonary
vascular permeability in aquaporin-1-null humans. Proc. Nat. Acad.
Sci. 99: 1059-1063, 2002.
6. Lewis, M.; Kaita, H.; Chown, B.; Giblett, E. R.; Anderson, J.:
Colton blood groups in Canadian Caucasians: frequencies, inheritance
and linkage analysis. Vox Sang. 32: 208-213, 1977.
7. Lewis, M.; Kaita, H.; Philipps, S.: Dwindling odds for Jk:Co linkage.
(Abstract) Cytogenet. Cell Genet. 37: 524 only, 1984.
8. Mohr, J.; Eiberg, H.: Colton blood groups: indication of linkage
with the Kidd (Jk) system as support for assignment to chromosome
7. Clin. Genet. 11: 372-374, 1977.
9. Preston, G. M.; Smith, B. L.; Zeidel, M. L.; Moulds, J. J.; Agre,
P.: Mutations in aquaporin-1 in phenotypically normal humans without
functional CHIP water channels. Science 265: 1585-1587, 1994.
10. Race, R. R.; Sanger, R.: Blood Groups in Man. Philadelphia:
F. A. Davis Co. (pub.) (5th ed.): 1968.
11. Race, R. R.; Sanger, R.: Blood Groups in Man. Oxford: Blackwell
Sci. Publ. (pub.) 1975.
12. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
13. Sherman, S. L.; Simpson, S. P.: Evidence for the location of
JK and CO on chromosome 2 based on family studies. (Abstract) Cytogenet.
Cell Genet. 40: 743 only, 1985.
14. Smith, B. L.; Preston, G. M.; Spring, F.; Anstee, D. J.; Agre,
P.: Human red blood cell aquaporin CHIP. I. Molecular characterization
of ABH and Colton blood group antigens. J. Clin. Invest. 94: 1043-1049,
1994.
15. Zelinski, T.; Kaita, H.; Gilson, T.; Coghlan, G.; Philipps, S.;
Lewis, M.: Linkage between the Colton blood group locus and ASSP11
on chromosome 7. Genomics 6: 623-625, 1990.
16. Zelinski, T. A.; White, L. J.; Coghlan, G. E.; Philipps, S. E.
: Linkage relationships between CO, D7S135 and ASSP11 on chromosome
7p. (Abstract) Cytogenet. Cell Genet. 58: 1927 only, 1991.
*FIELD* CN
Victor A. McKusick - updated: 11/6/2003
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
terry: 12/16/2009
terry: 2/3/2009
tkritzer: 11/11/2003
terry: 11/6/2003
terry: 11/1/1994
mimadm: 4/19/1994
warfield: 4/7/1994
carol: 10/14/1993
supermim: 3/16/1992
carol: 2/26/1992