RBCC

Full text data of AQP3

AQP3 [Confidence: high (a blood group or CD marker)]
Aquaporin-3; AQP-3 (Aquaglyceroporin-3)

BGMUT gil
271 gil AQP3 AQP3 reference reference common 7517548 AB001325 Ishibashi et al. 2005-07-17 NA

UniProt Q92482
ID AQP3_HUMAN Reviewed; 292 AA.
AC Q92482; A8K843; B2RE16; D3DRL3; O00108; Q6FGT2; Q6FGW6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1997, sequence version 2.
DT 22-JAN-2014, entry version 125.
DE RecName: Full=Aquaporin-3;
DE Short=AQP-3;
DE AltName: Full=Aquaglyceroporin-3;
GN Name=AQP3;
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).
RC TISSUE=Kidney;
RX PubMed=7558005; DOI=10.1006/geno.1995.1055;
RA Ishibashi K., Sasaki S., Saito F., Ikeuchi T., Marumo F.;
RT "Structure and chromosomal localization of a human water channel
RT (AQP3) gene.";
RL Genomics 27:352-354(1995).
RN [2]
RP SEQUENCE REVISION TO 91; 96 AND 186.
RA Ishibashi K.;
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND GIL BLOOD GROUP SYSTEM.
RC TISSUE=Blood;
RX PubMed=12239222; DOI=10.1074/jbc.M208999200;
RA Roudier N., Ripoche P., Gane P., Le Pennec P.Y., Daniels G.,
RA Cartron J.-P., Bailly P.;
RT "AQP3 deficiency in humans and the molecular basis of a novel blood
RT group system, GIL.";
RL J. Biol. Chem. 277:45854-45859(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Esophagus, and Trachea;
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT MET-43.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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 INDUCTION.
RX PubMed=18495115; DOI=10.1016/j.ejphar.2008.03.063;
RA Okahira M., Kubota M., Iguchi K., Usui S., Hirano K.;
RT "Regulation of aquaporin 3 expression by magnesium ion.";
RL Eur. J. Pharmacol. 588:26-32(2008).
CC -!- FUNCTION: Water channel required to promote glycerol permeability
CC and water transport across cell membranes. Acts as a glycerol
CC transporter in skin and plays an important role in regulating SC
CC (stratum corneum) and epidermal glycerol content. Involved in skin
CC hydration, wound healing, and tumorigenesis. Provides kidney
CC medullary collecting duct with high permeability to water, thereby
CC permitting water to move in the direction of an osmotic gradient.
CC Slightly permeable to urea and may function as a water and urea
CC exit mechanism in antidiuresis in collecting duct cells. It may
CC play an important role in gastrointestinal tract water transport
CC and in glycerol metabolism (By similarity).
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane; Multi-pass
CC membrane protein. Note=In collecting ducts of kidney.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q92482-1; Sequence=Displayed;
CC Name=2; Synonyms=delta5;
CC IsoId=Q92482-2; Sequence=VSP_003229, VSP_003230;
CC Note=Due to a polymorphism at the 5'-splice donor site of intron
CC 5, leading to exon 5 skipping and premature termination of
CC translation. This is the molecular basis of the GIL blood group;
CC -!- TISSUE SPECIFICITY: Widely expressed in epithelial cells of kidney
CC (collecting ducts) and airways, in keratinocytes, immature
CC dendritic cells and erythrocytes. Isoform 2 is not detectable in
CC erythrocytes at the protein level.
CC -!- INDUCTION: Up-regulated by magnesium.
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: AQP3 is responsible for the GIL blood group system.
CC Isoform 2 is detected in GIL-negative individuals that lack
CC functional AQP3.
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;=gil";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/aqp3/";
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DR EMBL; AB001325; BAA19237.1; -; mRNA.
DR EMBL; AJ493597; CAD38526.1; -; mRNA.
DR EMBL; CR541991; CAG46788.1; -; mRNA.
DR EMBL; CR542025; CAG46822.1; -; mRNA.
DR EMBL; BT007199; AAP35863.1; -; mRNA.
DR EMBL; AK292208; BAF84897.1; -; mRNA.
DR EMBL; AK315760; BAG38113.1; -; mRNA.
DR EMBL; DQ083949; AAY68214.1; -; Genomic_DNA.
DR EMBL; AL356218; CAI13311.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58500.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58504.1; -; Genomic_DNA.
DR EMBL; BC013566; AAH13566.1; -; mRNA.
DR PIR; A57119; A57119.
DR RefSeq; NP_004916.1; NM_004925.4.
DR UniGene; Hs.234642; -.
DR ProteinModelPortal; Q92482; -.
DR SMR; Q92482; 24-269.
DR IntAct; Q92482; 1.
DR STRING; 9606.ENSP00000297991; -.
DR GuidetoPHARMACOLOGY; 690; -.
DR DMDM; 2497938; -.
DR PaxDb; Q92482; -.
DR PRIDE; Q92482; -.
DR DNASU; 360; -.
DR Ensembl; ENST00000297991; ENSP00000297991; ENSG00000165272.
DR GeneID; 360; -.
DR KEGG; hsa:360; -.
DR UCSC; uc003zsx.3; human.
DR CTD; 360; -.
DR GeneCards; GC09M033431; -.
DR HGNC; HGNC:636; AQP3.
DR MIM; 600170; gene.
DR MIM; 607457; phenotype.
DR neXtProt; NX_Q92482; -.
DR PharmGKB; PA24921; -.
DR eggNOG; COG0580; -.
DR HOGENOM; HOG000288287; -.
DR HOVERGEN; HBG106057; -.
DR InParanoid; Q92482; -.
DR KO; K09876; -.
DR OMA; SAGWIVI; -.
DR OrthoDB; EOG7J9VPP; -.
DR PhylomeDB; Q92482; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR ChiTaRS; AQP3; human.
DR GeneWiki; Aquaporin_3; -.
DR GenomeRNAi; 360; -.
DR NextBio; 1505; -.
DR PRO; PR:Q92482; -.
DR Bgee; Q92482; -.
DR CleanEx; HS_AQP3; -.
DR Genevestigator; Q92482; -.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0016021; C:integral to membrane; IC:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0015254; F:glycerol channel activity; IDA:BHF-UCL.
DR GO; GO:0015250; F:water channel activity; TAS:BHF-UCL.
DR GO; GO:0007588; P:excretion; TAS:ProtInc.
DR GO; GO:0042476; P:odontogenesis; IEP:UniProtKB.
DR GO; GO:0002684; P:positive regulation of immune system process; IDA:BHF-UCL.
DR GO; GO:0045616; P:regulation of keratinocyte differentiation; TAS:BHF-UCL.
DR GO; GO:0070295; P:renal water absorption; IEA:Ensembl.
DR GO; GO:0051592; P:response to calcium ion; TAS:BHF-UCL.
DR GO; GO:0032526; P:response to retinoic acid; IDA:BHF-UCL.
DR GO; GO:0033280; P:response to vitamin D; TAS:BHF-UCL.
DR GO; GO:0015840; P:urea transport; IEA:Ensembl.
DR Gene3D; 1.20.1080.10; -; 1.
DR InterPro; IPR023271; Aquaporin-like.
DR InterPro; IPR023275; Aquaporin_3.
DR InterPro; IPR000425; MIP.
DR InterPro; IPR022357; MIP_CS.
DR PANTHER; PTHR19139; PTHR19139; 1.
DR Pfam; PF00230; MIP; 1.
DR PRINTS; PR02015; AQUAPORIN3.
DR PRINTS; PR00783; MINTRINSICP.
DR SUPFAM; SSF81338; SSF81338; 1.
DR TIGRFAMs; TIGR00861; MIP; 1.
DR PROSITE; PS00221; MIP; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Blood group antigen; Cell membrane;
KW Complete proteome; Glycoprotein; Membrane; Polymorphism;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1 292 Aquaporin-3.
FT /FTId=PRO_0000063943.
FT TOPO_DOM 1 28 Cytoplasmic (Potential).
FT TRANSMEM 29 49 Helical; (Potential).
FT TOPO_DOM 50 53 Extracellular (Potential).
FT TRANSMEM 54 74 Helical; (Potential).
FT TOPO_DOM 75 109 Cytoplasmic (Potential).
FT TRANSMEM 110 130 Helical; (Potential).
FT TOPO_DOM 131 157 Extracellular (Potential).
FT TRANSMEM 158 178 Helical; (Potential).
FT TOPO_DOM 179 188 Cytoplasmic (Potential).
FT TRANSMEM 189 209 Helical; (Potential).
FT TOPO_DOM 210 244 Extracellular (Potential).
FT TRANSMEM 245 265 Helical; (Potential).
FT TOPO_DOM 266 292 Cytoplasmic (Potential).
FT MOTIF 83 85 NPA 1.
FT MOTIF 215 217 NPA 2.
FT CARBOHYD 141 141 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 165 281 FIGTASLIVCVLAIVDPYNNPVPRGLEAFTVGLVVLVIGTS
FT MGFNSGYAVNPARDFGPRLFTALAGWGSAVFTTGQHWWWVP
FT IVSPLLGSIAGVFVYQLMIGCHLEQPPPSNEEENV -> DR
FT PALVVGAHRVPTPGLHCGCLRVPADDRLPPGAAPTLQRGRE
FT CEAGPCEAQGADLSGKGHLPLRCPGLEHPLTVQGHSQEAPL
FT HDPPFQAKELPIYPHPTKTAPSGFPLDLAQIAP (in
FT isoform 2).
FT /FTId=VSP_003229.
FT VAR_SEQ 282 292 Missing (in isoform 2).
FT /FTId=VSP_003230.
FT VARIANT 43 43 V -> M (in dbSNP:rs34942735).
FT /FTId=VAR_025089.
FT CONFLICT 23 23 R -> G (in Ref. 6; BAF84897).
FT CONFLICT 137 137 V -> A (in Ref. 4; CAG46822).
SQ SEQUENCE 292 AA; 31544 MW; A9555E9576EABA9C CRC64;
MGRQKELVSR CGEMLHIRYR LLRQALAECL GTLILVMFGC GSVAQVVLSR GTHGGFLTIN
LAFGFAVTLG ILIAGQVSGA HLNPAVTFAM CFLAREPWIK LPIYTLAQTL GAFLGAGIVF
GLYYDAIWHF ADNQLFVSGP NGTAGIFATY PSGHLDMING FFDQFIGTAS LIVCVLAIVD
PYNNPVPRGL EAFTVGLVVL VIGTSMGFNS GYAVNPARDF GPRLFTALAG WGSAVFTTGQ
HWWWVPIVSP LLGSIAGVFV YQLMIGCHLE QPPPSNEEEN VKLAHVKHKE QI
//

MIM 600170
*RECORD*
*FIELD* NO
600170
*FIELD* TI
*600170 AQUAPORIN 3; AQP3
*FIELD* TX

CLONING

By use of a PCR cloning strategy, Ishibashi et al. (1994) cloned a third
read moremember of the major intrinsic protein (MIP) family from rat kidney and
designated it aquaporin-3 (AQP3). See also aquaporin-1 (107776).
Aquaporin-3 is localized at the basal lateral membranes of collecting
duct cells in the kidney.

Using a rat AQP3 probe, Ishibashi et al. (1995) screened a human kidney
cDNA library and isolated a cDNA coding for human AQP3 protein. The
deduced amino acid sequence of AQP3 was 91% identical to rat AQP3. Human
AQP3 mRNA was expressed in colon, kidney, liver, pancreas, lung,
peripheral leukocytes, spleen, and prostate.

Ma et al. (2000) isolated a cDNA encoding mouse Aqp3, which is expressed
in kidney, large airways, eye, urinary bladder, skin, and
gastrointestinal tract. The 292-amino acid protein is 95% identical to
the human sequence.

GENE FUNCTION

By functional expression in Xenopus oocytes, Ishibashi et al. (1994)
confirmed the water-channel function of AQP3. Moreover, AQP3 facilitated
the transport of nonionic small solutes such as urea and glycerol,
albeit to a smaller degree. The results suggested that water channels
can be functionally heterogeneous and possess water and solute
permeation mechanisms.

By Western blot analysis and immunofluorescence microscopy of epidermis,
Sougrat et al. (2002) showed strong expression of an approximately 33-kD
glycosylated AQP3 protein in keratinocyte plasma membranes, 1 layer
below the unstained stratum corneum (SC). In the basal layer of the
epidermis, AQP3 was expressed intracellularly. AQP1, AQP2 (107777), AQP4
(600308), and AQP5 (600442) were not detected in human skin. Osmotically
induced transepidermal water permeability, measured on stripped skin and
reconstructed epidermis, was inhibitable by acid pH or mercuric chloride
and was mediated by AQP3. Sougrat et al. (2002) concluded that below the
water-impermeable SC, viable human epidermis exhibits a high
AQP3-mediated water permeability through keratinocyte plasma membranes.
They proposed that AQP3 provides a short circuit for water, or
water-clamp, between the base of the epidermis and the SC in order to
maintain a constant water content and to prevent the formation of a
continuous water gradient across the epidermis below the SC.

GENE STRUCTURE

Inase et al. (1995) reported the structural organization of the genomic
AQP3 gene. It appeared to exist as a single copy and to comprise 6 exons
distributed over 7 kb. The initiation site of transcription was
identified to be located 64-bp upstream of the first ATG codon by primer
extension analysis and ribonuclease protection assay. The 5-prime
flanking region contained a TATA box, 2 Sp1 sequences, and some
consensus sequences including AP-2 sites.

MAPPING

By fluorescence in situ hybridization, Ishibashi et al. (1995) mapped
the AQP3 gene to 7q36.2-q36.3. In an erratum, the authors stated that
the correct chromosomal assignment of the AQP3 gene is on 9p13.

Mulders et al. (1996) mapped the AQP3 gene to 9p21-p12 by fluorescence
in situ hybridization; they added a note to their paper stating that
after hybridization with another human AQP3 genomic clone and cDNA,
Ishibashi et al. (1995) confirmed the localization to 9p.

MOLECULAR GENETICS

AQP3 is a water and glycerol channel present on human erythrocytes and
in various tissues. By protein and molecular biology analysis, Roudier
et al. (2002) showed that 2 unrelated probands who developed
alloantibodies to the high frequency antigen GIL were found to be
AQP3-deficient. The defect was caused by homozygous mutation affecting
the 5-prime donor splice site of intron 5 of the AQP3 gene. This
mutation caused skipping of exon 5 and generated a frameshift and
premature stop codon. Functional studied by 90 degree light scattering
using a stopped-flow spectrometer revealed the absence of facilitated
glycerol transport across red cell membranes from the probands, but the
water and urea transports were normal. Expression studies in COS-7 cells
followed by flow cytometry analysis showed that only cells transfected
with AQP3 cDNA strongly reacted with anti-GIL antibodies. This was the
first report of AQP3 deficiency in humans and provided the molecular
basis of a new blood group system, GIL, encoded by the AQP3 gene.

As AQP3 protein has a wide tissue distribution in the epithelial cells
of kidney, airways, and skin and in immature dendritic cells, suggesting
a role in water reabsorption, mucosal secretions, allergic diseases, and
cell volume regulation, it was surprising that the Aqp3-null individuals
identified by Roudier et al. (2002) and the reported GIL-negative
individuals (Daniels et al., 1998) suffered no obvious clinical
syndromes. Moreover, AQP3, which efficiently transport glycerol, might
be implicated in energy metabolism. The absence of clinical disorders in
normal life conditions was observed also in Colton-null individuals who
were deficient for AQP1. It is only under stress conditions that a
defective urinary concentrating ability (King et al., 2001) and a
decrease in pulmonary vascular permeability (King et al., 2002) were
detected in Colton-null individuals.

ANIMAL MODEL

Ma et al. (2000) generated Aqp3-deficient mice by targeted gene
disruption. Apart from polyuria, Aqp3 -/- mice were grossly normal. The
deletion resulted in decreased renal cortex expression of Aqp2 but had
little or no effect on Aqp1 or Aqp4 expression, as determined by
immunoblot analysis. Aqp3-null mice consumed 10-fold more fluids than
wildtype littermates, and their urine osmolality was much lower. Water
deprivation or vasopressin treatment resulted in partial urine
concentration. In double-knockout mice that also lacked Aqp4,
urine-concentrating ability was further impaired. Ma et al. (2000)
concluded that these knockout mice established a model of nephrogenic
diabetes insipidus produced by impaired water permeability and urine
concentration in collecting-duct basolateral membrane.

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.

Using Aqp3-deficient mice with the hairless SKH1 background, Ma et al.
(2002) detected markedly reduced SC water content and water holding
capacity in the skin of Aqp3-null mice. Immunofluorescence microscopy
demonstrated high Aqp3 expression in wildtype mice, but no expression in
mutant mice. RT-PCR analysis detected no aquaporins in the
Aqp3-deficient mouse skin. Electron microscopy showed no apparent
differences in skin structure between wildtype and mutant mice. Ma et
al. (2002) concluded that AQP3 is critical to skin physiology and that
its modulation may be useful in the treatment of skin disorders with
abnormally wet, dry, or permeable skin.

Aqp3-deficient mice have reduced SC hydration and skin elasticity, and
impaired barrier recovery after SC removal. SC glycerol content is
reduced 3-fold in Aqp3-null mice, whereas SC structure, protein/lipid
composition, and ion/osmolyte content are not changed. Hara and Verkman
(2003) showed that glycerol replacement corrects each of the defects in
Aqp3-null mice. SC water content, measured by skin conductance and
(3)H2O accumulation, was 3-fold lower in Aqp3-null versus wildtype mice,
but became similar after topical or systemic administration of glycerol
in quantities that normalized SC glycerol content. SC water content was
not corrected by glycerol-like osmolytes such as xylitol, erythritol,
and propanediol. Orally administered glycerol fully corrected the
reduced skin elasticity in Aqp3-null mice as measured by the kinetics of
skin displacement after suction, and the delayed barrier recovery as
measured by transepidermal water loss after tape-stripping. The data
provided functional evidence for a physiologic role of glycerol
transport by an aquaglyceroporin, and indicated that glycerol is a major
determinant of SC water retention and mechanical and biosynthetic
functions. The findings established a scientific basis for the
centuries-old empiric practice of including glycerol in cosmetic and
medicinal skin formulations.

*FIELD* AV
.0001
GIL BLOOD GROUP
AQP3, IVS5, G-A, +1

In 2 unrelated women who developed alloantibodies to the high frequency
antigen GIL (607457) (Daniels et al., 1998), Roudier et al. (2002) found
a homozygous mutation in the AQP3 gene affecting the 5-prime donor
splice site of intron 5: IVS5DS+1G-A. The mutation resulted in skipping
of exon 5, frameshift, and premature termination of translation. One
proband was a white French woman who had had 10 pregnancies before 1979,
when an antibody against the GIL antigen reacting with all red blood
cells (RBCs) except her own was identified following a hemolytic
reaction that occurred during orthopedic surgery. Proband 2 was a white
American woman who had no history of blood transfusion. Red blood cells
from her first child had a weakly positive direct antiglobulin test and
her serum contained an anti-GIL antibody.

*FIELD* RF
1. Daniels, G. L.; Delong, E. N.; Hare, V.; Johnson, S. T.; Lepennec,
P. Y.; Mallory, D.; Marshall, M. J.; Oliver, C.; Spruell, P.: GIL:
a red cell antigen of very high frequency. Immunohematology 14:
49-52, 1998.

2. Hara, M.; Verkman, A. S.: Glycerol replacement corrects defective
skin hydration, elasticity, and barrier function in aquaporin-3-deficient
mice. Proc. Nat. Acad. Sci. 100: 7360-7365, 2003.

3. Inase, N.; Fushimi, K.; Ishibashi, K.; Uchida, S.; Ichioka, M.;
Sasaki, S.; Marumo, F.: Isolation of human aquaporin 3 gene. J.
Biol. Chem. 270: 17913-17916, 1995.

4. Ishibashi, K.; Sasaki, S.; Fushimi, K.; Uchida, S.; Kuwahara, M.;
Saito, H.; Furukawa, T.; Nakajima, K.; Yamaguchi, Y.; Gojobori, T.;
Marumo, F.: Molecular cloning and expression of a member of the aquaporin
family with permeability to glycerol and urea in addition to water
expressed at the basolateral membrane of kidney collecting duct cells. Proc.
Nat. Acad. Sci. 91: 6269-6273, 1994.

5. Ishibashi, K.; Sasaki, S.; Saito, F.; Ikeuchi, T.; Marumo, F.:
Structure and chromosomal localization of a human water channel (AQP3)
gene. Genomics 27: 352-354, 1995. Note: Erratum: Genomics 30: 633
only, 1995.

6. 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.

7. 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.

8. Ma, T.; Hara, M.; Sougrat, R.; Verbavatz, J.-M.; Verkman, A. S.
: Impaired stratum corneum hydration in mice lacking epidermal water
channel aquaporin-3. J. Biol. Chem. 277: 17147-17153, 2002.

9. Ma, T.; Song, Y.; Yang, B.; Gillespie, A.; Carlson, E. J.; Epstein,
C. J.; Verkman, A. S.: Nephrogenic diabetes insipidus in mice lacking
aquaporin-3 water channels. Proc. Nat. Acad. Sci. 97: 4386-4391,
2000.

10. Mulders, S. M.; Olde Weghuis, D.; van Boxtel, J. A. F.; Geurts
van Kessel, A.; Echevarria, M.; van Os, C. H.; Deen, P. M. T.: Localization
of the human gene for aquaporin 3 (AQP3) to chromosome 9, region p21-p12,
using fluorescent in situ hybridization. Cytogenet. Cell Genet. 72:
303-305, 1996.

11. Roudier, N.; Ripoche, P.; Gane, P.; Le Pennec, P. Y.; Daniels,
G.; Cartron, J.-P.; Bailly, P.: AQP3 deficiency in humans and the
molecular basis of a novel blood group system, GIL. J. Biol. Chem. 277:
45854-45859, 2002.

12. Sougrat, R.; Morand, M.; Gondran, C.; Barre, P.; Gobin, R.; Bonte,
F.; Dumas, M.; Verbavatz, J.-M.: Functional expression of AQP3 in
human skin epidermis and reconstructed epidermis. J. Invest. Derm. 118:
678-685, 2002.

13. 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
Victor A. McKusick - updated: 7/14/2003
Victor A. McKusick - updated: 12/26/2002
Paul J. Converse - updated: 6/18/2002

*FIELD* CD
Victor A. McKusick: 10/31/1994

*FIELD* ED
carol: 01/07/2010
terry: 4/4/2005
tkritzer: 7/23/2003
terry: 7/14/2003
alopez: 1/3/2003
terry: 12/26/2002
mgross: 6/18/2002
alopez: 8/2/1998
dkim: 6/30/1998
terry: 6/13/1996
mark: 6/11/1996
mark: 4/1/1996
mark: 10/19/1995
terry: 10/31/1994

MIM 607457
*RECORD*
*FIELD* NO
607457
*FIELD* TI
#607457 GIL BLOOD GROUP
*FIELD* TX
A number sign (#) is used with this entry because the GIL blood group
read morehas been demonstrated to be a characteristic of the aquaporin-3 (AQP3;
600170) molecule on erythrocytes.

Daniels et al. (1998) described 5 cases of alloantibodies to a high
frequency antigen, GIL. AQP1 (107776) and AQP3 were the only 2 proteins
of the aquaporin family identified on human red blood cells (RBCs). As
the AQP1 molecules express Colton blood group antigens (CO; 110450),
Roudier et al. (2002) investigated whether the AQP3 molecule might also
be the basis of a blood group system. Roudier et al. (2002) studied RBCs
from 24 individuals who had developed alloantibodies directed against
unidentified high frequency antigens by immunoblotting with a rat
anti-AQP3 antibody, which crossreacts with human AQP3. Roudier et al.
(2002) found that 2 GIL-negative individuals had a defect in aquaporin-3
(600170.0001). One proband was a white French woman who had had 10
pregnancies before 1979, when an antibody against the GIL antigen
reacting with all RBCs except her own was identified following a
hemolytic reaction that occurred during orthopedic surgery. Proband 2
was a white American woman who had no history of blood transfusion. Red
blood cells from her first child had a weakly positive direct
antiglobulin test and her serum contained an anti-GIL antibody.

Roudier et al. (2002) indicated that the GIL blood group system was
designated as No. 29 by the International Society of Blood Transfusion.

*FIELD* RF
1. Daniels, G. L.; Delong, E. N.; Hare, V.; Johnson, S. T.; Lepennec,
P. Y.; Mallory, D.; Marshall, M. J.; Oliver, C.; Spruell, P.: GIL:
a red cell antigen of very high frequency. Immunohematology 14:
49-52, 1998.

2. Roudier, N.; Ripoche, P.; Gane, P.; Le Pennec, P. Y.; Daniels,
G.; Cartron, J.-P.; Bailly, P.: AQP3 deficiency in humans and the
molecular basis of a novel blood group system, GIL. J. Biol. Chem. 277:
45854-45859, 2002.

*FIELD* CD
Victor A. McKusick: 1/3/2003

*FIELD* ED
carol: 01/07/2010
alopez: 1/3/2003

RBCC Red Blood Cell Collection

Full text data of AQP3