Full text data of ADD2
ADD2
(ADDB)
[Confidence: high (present in two of the MS resources)]
Beta-adducin (Erythrocyte adducin subunit beta)
Beta-adducin (Erythrocyte adducin subunit beta)
hRBCD
IPI00019904
IPI00019904 Splice isoform 1 of P35612 Beta adducin Splice isoform 1 of P35612 Beta adducin membrane 3 7 3 1 4 2 3 1 2 n/a 8 8 n/a 7 2 4 7 8 5 7 cytoskeleton n/a found at its expected molecular weight found at molecular weight
IPI00019904 Splice isoform 1 of P35612 Beta adducin Splice isoform 1 of P35612 Beta adducin membrane 3 7 3 1 4 2 3 1 2 n/a 8 8 n/a 7 2 4 7 8 5 7 cytoskeleton n/a found at its expected molecular weight found at molecular weight
UniProt
P35612
ID ADDB_HUMAN Reviewed; 726 AA.
AC P35612; A8K4P2; B4DM17; D6W5G7; D6W5G8; Q13482; Q16412; Q59G82;
read moreAC Q5U5P4; Q6P0P2; Q6PGQ4; Q7Z688; Q7Z689; Q7Z690; Q7Z691;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 129.
DE RecName: Full=Beta-adducin;
DE AltName: Full=Erythrocyte adducin subunit beta;
GN Name=ADD2; Synonyms=ADDB;
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.
RC TISSUE=Reticulocyte;
RX PubMed=1840603; DOI=10.1083/jcb.115.3.665;
RA Joshi R.L., Gilligan D.M., Otto E., McLaughlin T., Bennett V.D.;
RT "Primary structure and domain organization of human alpha and beta
RT adducin.";
RL J. Cell Biol. 115:665-675(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4; 5; 6 AND 7), TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Fetal kidney, and Umbilical vein endothelial cell;
RX PubMed=12951058; DOI=10.1016/j.bbrc.2003.08.011;
RA Citterio L., Tizzoni L., Catalano M., Zerbini G., Bianchi G.,
RA Barlassina C.;
RT "Expression analysis of the human adducin gene family and evidence of
RT ADD2 beta4 multiple splicing variants.";
RL Biochem. Biophys. Res. Commun. 309:359-367(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 8).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=21697133; DOI=10.1167/iovs.11-7479;
RA Oshikawa M., Tsutsui C., Ikegami T., Fuchida Y., Matsubara M.,
RA Toyama S., Usami R., Ohtoko K., Kato S.;
RT "Full-length transcriptome analysis of human retina-derived cell lines
RT ARPE-19 and Y79 using the vector-capping method.";
RL Invest. Ophthalmol. Vis. Sci. 52:6662-6670(2011).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP ALA-439.
RC TISSUE=Eye;
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 332-726 (ISOFORM 3).
RC TISSUE=Bone marrow;
RA Sinard J.H., Stewart G.W., Argent A.C., Gilligan D.M., Morrow J.S.;
RT "A novel isoform of beta adducin utilizes an alternatively spliced
RT exon near the C-terminus.";
RL Mol. Biol. Cell 6:269-269(1995).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 462-559 (ISOFORM 2), AND
RP ALTERNATIVE SPLICING.
RX PubMed=8566798; DOI=10.1016/0378-1119(95)00591-9;
RA Tisminetzky S., Devescovi G., Tripodi G., Muro A., Bianchi G.,
RA Colombi M., Moro L., Barlati S., Tuteja R., Baralle F.E.;
RT "Genomic organisation and chromosomal localisation of the gene
RT encoding human beta adducin.";
RL Gene 167:313-316(1995).
RN [11]
RP PHOSPHORYLATION AT THR-55; SER-703 AND SER-713, AND PARTIAL PROTEIN
RP SEQUENCE.
RX PubMed=8810272; DOI=10.1074/jbc.271.41.25157;
RA Matsuoka Y., Hughes C.A., Bennett V.;
RT "Adducin regulation. Definition of the calmodulin-binding domain and
RT sites of phosphorylation by protein kinases A and C.";
RL J. Biol. Chem. 271:25157-25166(1996).
RN [12]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH DMTN AND SLC2A1, AND
RP INTERACTION WITH SLC2A1.
RX PubMed=18347014; DOI=10.1074/jbc.M707818200;
RA Khan A.A., Hanada T., Mohseni M., Jeong J.J., Zeng L., Gaetani M.,
RA Li D., Reed B.C., Speicher D.W., Chishti A.H.;
RT "Dematin and adducin provide a novel link between the spectrin
RT cytoskeleton and human erythrocyte membrane by directly interacting
RT with glucose transporter-1.";
RL J. Biol. Chem. 283:14600-14609(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-530; SER-592; SER-596;
RP SER-600; SER-604; THR-611; SER-613; SER-617; SER-693 AND SER-697, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Membrane-cytoskeleton-associated protein that promotes
CC the assembly of the spectrin-actin network. Binds to the
CC erythrocyte membrane receptor SLC2A1/GLUT1 and may therefore
CC provide a link between the spectrin cytoskeleton to the plasma
CC membrane. Binds to calmodulin. Calmodulin binds preferentially to
CC the beta subunit.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. Found in a
CC complex with ADD2, DMTN and SLC2A1. Interacts with SLC2A1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cell membrane;
CC Peripheral membrane protein; Cytoplasmic side.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Comment=Additional isoforms seem to exist;
CC Name=1;
CC IsoId=P35612-1; Sequence=Displayed;
CC Name=2; Synonyms=Adducin 63;
CC IsoId=P35612-2; Sequence=VSP_000181, VSP_000182;
CC Name=3; Synonyms=Beta-4, E;
CC IsoId=P35612-3; Sequence=VSP_000183;
CC Name=4; Synonyms=Beta-4a;
CC IsoId=P35612-4; Sequence=VSP_017244, VSP_017246;
CC Name=5; Synonyms=Beta-4b;
CC IsoId=P35612-5; Sequence=VSP_017242, VSP_017243, VSP_017245;
CC Name=6; Synonyms=Beta-4c;
CC IsoId=P35612-6; Sequence=VSP_017242, VSP_017244, VSP_017246;
CC Name=7; Synonyms=Beta-4d;
CC IsoId=P35612-7; Sequence=VSP_017241, VSP_017244, VSP_017246;
CC Name=8;
CC IsoId=P35612-8; Sequence=VSP_043625, VSP_000181, VSP_000182;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed mainly in brain, spleen, kidney
CC cortex and medulla, and heart. Also expressed in human umbilical
CC vein endothelial cells, human vascular smooth muscle cells, kidney
CC tubular cells and K-562 cell line.
CC -!- DEVELOPMENTAL STAGE: Fetal kidney expresses isoforms 3, 4, 5, 6
CC and 7, and fetal liver expresses isoforms 3 and 4.
CC -!- DOMAIN: Each subunit is comprised of three regions: a NH2-terminal
CC protease-resistant globular head region, a short connecting
CC subdomain, and a protease-sensitive tail region.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the aldolase class II family. Adducin
CC subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92464.1; Type=Erroneous initiation;
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DR EMBL; X58199; CAA41176.1; -; mRNA.
DR EMBL; AF486420; AAP71863.1; -; mRNA.
DR EMBL; AF486421; AAP71864.1; -; mRNA.
DR EMBL; AF486422; AAP71865.1; -; mRNA.
DR EMBL; AF486423; AAP71866.1; -; mRNA.
DR EMBL; AK291007; BAF83696.1; -; mRNA.
DR EMBL; AK297250; BAG59729.1; -; mRNA.
DR EMBL; AB209227; BAD92464.1; ALT_INIT; mRNA.
DR EMBL; AB593080; BAJ84020.1; -; mRNA.
DR EMBL; AC005234; AAD12715.1; -; Genomic_DNA.
DR EMBL; AC007395; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471053; EAW99801.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99806.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99807.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99808.1; -; Genomic_DNA.
DR EMBL; BC041666; AAH41666.1; -; mRNA.
DR EMBL; BC051882; AAH51882.1; -; mRNA.
DR EMBL; BC056881; AAH56881.1; -; mRNA.
DR EMBL; BC065525; AAH65525.1; -; mRNA.
DR EMBL; U43959; AAA86421.1; -; mRNA.
DR EMBL; S81079; AAD14349.1; -; Genomic_DNA.
DR EMBL; S81077; AAD14349.1; JOINED; Genomic_DNA.
DR PIR; S18208; S18208.
DR RefSeq; NP_001171983.1; NM_001185054.1.
DR RefSeq; NP_001171984.1; NM_001185055.1.
DR RefSeq; NP_001608.1; NM_001617.3.
DR RefSeq; NP_059516.2; NM_017482.3.
DR RefSeq; NP_059522.1; NM_017488.3.
DR UniGene; Hs.188528; -.
DR DisProt; DP00241; -.
DR ProteinModelPortal; P35612; -.
DR SMR; P35612; 149-353.
DR PhosphoSite; P35612; -.
DR DMDM; 543774; -.
DR PaxDb; P35612; -.
DR PRIDE; P35612; -.
DR Ensembl; ENST00000264436; ENSP00000264436; ENSG00000075340.
DR Ensembl; ENST00000355733; ENSP00000347972; ENSG00000075340.
DR Ensembl; ENST00000403045; ENSP00000384303; ENSG00000075340.
DR Ensembl; ENST00000407644; ENSP00000384677; ENSG00000075340.
DR Ensembl; ENST00000413157; ENSP00000388072; ENSG00000075340.
DR Ensembl; ENST00000430656; ENSP00000398112; ENSG00000075340.
DR Ensembl; ENST00000522886; ENSP00000430243; ENSG00000075340.
DR Ensembl; ENST00000606038; ENSP00000475223; ENSG00000271760.
DR Ensembl; ENST00000606120; ENSP00000476220; ENSG00000271760.
DR Ensembl; ENST00000606312; ENSP00000475774; ENSG00000271760.
DR Ensembl; ENST00000606698; ENSP00000475993; ENSG00000271760.
DR Ensembl; ENST00000607267; ENSP00000475838; ENSG00000271760.
DR Ensembl; ENST00000607524; ENSP00000475332; ENSG00000271760.
DR Ensembl; ENST00000607677; ENSP00000475595; ENSG00000271760.
DR GeneID; 119; -.
DR KEGG; hsa:119; -.
DR UCSC; uc002sgz.3; human.
DR CTD; 119; -.
DR GeneCards; GC02M070800; -.
DR HGNC; HGNC:244; ADD2.
DR HPA; CAB009796; -.
DR MIM; 102681; gene.
DR neXtProt; NX_P35612; -.
DR PharmGKB; PA24566; -.
DR eggNOG; COG0235; -.
DR HOVERGEN; HBG004180; -.
DR InParanoid; P35612; -.
DR OMA; SGPMSPE; -.
DR OrthoDB; EOG7HF1HR; -.
DR PhylomeDB; P35612; -.
DR GeneWiki; ADD2; -.
DR GenomeRNAi; 119; -.
DR NextBio; 469; -.
DR PRO; PR:P35612; -.
DR ArrayExpress; P35612; -.
DR Bgee; P35612; -.
DR Genevestigator; P35612; -.
DR GO; GO:0016023; C:cytoplasmic membrane-bounded vesicle; IDA:UniProtKB.
DR GO; GO:0008290; C:F-actin capping protein complex; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0051015; F:actin filament binding; IDA:BHF-UCL.
DR GO; GO:0030507; F:spectrin binding; IDA:BHF-UCL.
DR GO; GO:0005198; F:structural molecule activity; IEA:Ensembl.
DR GO; GO:0051017; P:actin filament bundle assembly; IDA:BHF-UCL.
DR GO; GO:0051016; P:barbed-end actin filament capping; IDA:BHF-UCL.
DR GO; GO:0030097; P:hemopoiesis; IEA:Ensembl.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL.
DR GO; GO:0006461; P:protein complex assembly; IDA:UniProtKB.
DR Gene3D; 3.40.225.10; -; 1.
DR InterPro; IPR027773; ADD2.
DR InterPro; IPR001303; Aldolase_II/adducin_N.
DR PANTHER; PTHR10672:SF6; PTHR10672:SF6; 1.
DR Pfam; PF00596; Aldolase_II; 1.
DR SMART; SM01007; Aldolase_II; 1.
DR SUPFAM; SSF53639; SSF53639; 1.
PE 1: Evidence at protein level;
KW Actin-binding; Alternative splicing; Calmodulin-binding;
KW Cell membrane; Complete proteome; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Membrane; Phosphoprotein; Polymorphism;
KW Reference proteome.
FT CHAIN 1 726 Beta-adducin.
FT /FTId=PRO_0000218533.
FT REGION 425 444 Interaction with calmodulin (Potential).
FT REGION 704 721 Interaction with calmodulin (Potential).
FT MOD_RES 55 55 Phosphothreonine; by PKA.
FT MOD_RES 530 530 Phosphoserine.
FT MOD_RES 532 532 Phosphoserine (By similarity).
FT MOD_RES 535 535 Phosphoserine (By similarity).
FT MOD_RES 561 561 Phosphothreonine (By similarity).
FT MOD_RES 592 592 Phosphoserine.
FT MOD_RES 596 596 Phosphoserine.
FT MOD_RES 600 600 Phosphoserine.
FT MOD_RES 604 604 Phosphoserine.
FT MOD_RES 611 611 Phosphothreonine.
FT MOD_RES 613 613 Phosphoserine.
FT MOD_RES 617 617 Phosphoserine.
FT MOD_RES 693 693 Phosphoserine.
FT MOD_RES 697 697 Phosphoserine.
FT MOD_RES 703 703 Phosphoserine; by PKC.
FT MOD_RES 713 713 Phosphoserine; by PKA and PKC.
FT VAR_SEQ 1 1 M -> MPRRRVPGANCKPTGK (in isoform 8).
FT /FTId=VSP_043625.
FT VAR_SEQ 78 566 Missing (in isoform 7).
FT /FTId=VSP_017241.
FT VAR_SEQ 188 493 Missing (in isoform 5 and isoform 6).
FT /FTId=VSP_017242.
FT VAR_SEQ 532 559 STESQLMSKGDEDTKDDSEETVPNPFSQ -> VEQRLPLTG
FT GETCLPSGSSVPGAGLQDP (in isoform 2 and
FT isoform 8).
FT /FTId=VSP_000181.
FT VAR_SEQ 560 726 Missing (in isoform 2 and isoform 8).
FT /FTId=VSP_000182.
FT VAR_SEQ 581 726 GEKETAPEEPGSPAKSAPASPVQSPAKEAETKSPLVSPSKS
FT LEEGTKKTETSKAATTEPETTQPEGVVVNGREEEQTAEEIL
FT SKGLSQMTTSADTDVDTSKDKTESVTSGPMSPEGSPSKSPS
FT KKKKKFRTPSFLKKSKKKEKVES -> ETGQEREPGSGPAV
FT CEFFSVALHIWSNILERKKLPQKSLAHLQSLHLLLQCRAQR
FT RRQRQRAL (in isoform 3).
FT /FTId=VSP_000183.
FT VAR_SEQ 581 587 GEKETAP -> APGWFSS (in isoform 4, isoform
FT 6 and isoform 7).
FT /FTId=VSP_017244.
FT VAR_SEQ 581 586 GEKETA -> ETGQER (in isoform 5).
FT /FTId=VSP_017243.
FT VAR_SEQ 587 726 Missing (in isoform 5).
FT /FTId=VSP_017245.
FT VAR_SEQ 588 726 Missing (in isoform 4, isoform 6 and
FT isoform 7).
FT /FTId=VSP_017246.
FT VARIANT 28 28 D -> N (in dbSNP:rs4986).
FT /FTId=VAR_014866.
FT VARIANT 98 98 S -> C (in dbSNP:rs4987).
FT /FTId=VAR_048195.
FT VARIANT 335 335 E -> D (in dbSNP:rs4982).
FT /FTId=VAR_014867.
FT VARIANT 439 439 T -> A (in dbSNP:rs17855969).
FT /FTId=VAR_025318.
FT VARIANT 663 663 S -> R (in dbSNP:rs4985).
FT /FTId=VAR_014868.
SQ SEQUENCE 726 AA; 80854 MW; B07F7303D929DBA4 CRC64;
MSEETVPEAA SPPPPQGQPY FDRFSEDDPE YMRLRNRAAD LRQDFNLMEQ KKRVTMILQS
PSFREELEGL IQEQMKKGNN SSNIWALRQI ADFMASTSHA VFPTSSMNVS MMTPINDLHT
ADSLNLAKGE RLMRCKISSV YRLLDLYGWA QLSDTYVTLR VSKEQDHFLI SPKGVSCSEV
TASSLIKVNI LGEVVEKGSS CFPVDTTGFC LHSAIYAARP DVRCIIHLHT PATAAVSAMK
WGLLPVSHNA LLVGDMAYYD FNGEMEQEAD RINLQKCLGP TCKILVLRNH GVVALGDTVE
EAFYKIFHLQ AACEIQVSAL SSAGGVENLI LLEQEKHRPH EVGSVQWAGS TFGPMQKSRL
GEHEFEALMR MLDNLGYRTG YTYRHPFVQE KTKHKSEVEI PATVTAFVFE EDGAPVPALR
QHAQKQQKEK TRWLNTPNTY LRVNVADEVQ RSMGSPRPKT TWMKADEVEK SSSGMPIRIE
NPNQFVPLYT DPQEVLEMRN KIREQNRQDV KSAGPQSQLL ASVIAEKSRS PSTESQLMSK
GDEDTKDDSE ETVPNPFSQL TDQELEEYKK EVERKKLELD GEKETAPEEP GSPAKSAPAS
PVQSPAKEAE TKSPLVSPSK SLEEGTKKTE TSKAATTEPE TTQPEGVVVN GREEEQTAEE
ILSKGLSQMT TSADTDVDTS KDKTESVTSG PMSPEGSPSK SPSKKKKKFR TPSFLKKSKK
KEKVES
//
ID ADDB_HUMAN Reviewed; 726 AA.
AC P35612; A8K4P2; B4DM17; D6W5G7; D6W5G8; Q13482; Q16412; Q59G82;
read moreAC Q5U5P4; Q6P0P2; Q6PGQ4; Q7Z688; Q7Z689; Q7Z690; Q7Z691;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 129.
DE RecName: Full=Beta-adducin;
DE AltName: Full=Erythrocyte adducin subunit beta;
GN Name=ADD2; Synonyms=ADDB;
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.
RC TISSUE=Reticulocyte;
RX PubMed=1840603; DOI=10.1083/jcb.115.3.665;
RA Joshi R.L., Gilligan D.M., Otto E., McLaughlin T., Bennett V.D.;
RT "Primary structure and domain organization of human alpha and beta
RT adducin.";
RL J. Cell Biol. 115:665-675(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4; 5; 6 AND 7), TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Fetal kidney, and Umbilical vein endothelial cell;
RX PubMed=12951058; DOI=10.1016/j.bbrc.2003.08.011;
RA Citterio L., Tizzoni L., Catalano M., Zerbini G., Bianchi G.,
RA Barlassina C.;
RT "Expression analysis of the human adducin gene family and evidence of
RT ADD2 beta4 multiple splicing variants.";
RL Biochem. Biophys. Res. Commun. 309:359-367(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 8).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=21697133; DOI=10.1167/iovs.11-7479;
RA Oshikawa M., Tsutsui C., Ikegami T., Fuchida Y., Matsubara M.,
RA Toyama S., Usami R., Ohtoko K., Kato S.;
RT "Full-length transcriptome analysis of human retina-derived cell lines
RT ARPE-19 and Y79 using the vector-capping method.";
RL Invest. Ophthalmol. Vis. Sci. 52:6662-6670(2011).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP ALA-439.
RC TISSUE=Eye;
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 332-726 (ISOFORM 3).
RC TISSUE=Bone marrow;
RA Sinard J.H., Stewart G.W., Argent A.C., Gilligan D.M., Morrow J.S.;
RT "A novel isoform of beta adducin utilizes an alternatively spliced
RT exon near the C-terminus.";
RL Mol. Biol. Cell 6:269-269(1995).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 462-559 (ISOFORM 2), AND
RP ALTERNATIVE SPLICING.
RX PubMed=8566798; DOI=10.1016/0378-1119(95)00591-9;
RA Tisminetzky S., Devescovi G., Tripodi G., Muro A., Bianchi G.,
RA Colombi M., Moro L., Barlati S., Tuteja R., Baralle F.E.;
RT "Genomic organisation and chromosomal localisation of the gene
RT encoding human beta adducin.";
RL Gene 167:313-316(1995).
RN [11]
RP PHOSPHORYLATION AT THR-55; SER-703 AND SER-713, AND PARTIAL PROTEIN
RP SEQUENCE.
RX PubMed=8810272; DOI=10.1074/jbc.271.41.25157;
RA Matsuoka Y., Hughes C.A., Bennett V.;
RT "Adducin regulation. Definition of the calmodulin-binding domain and
RT sites of phosphorylation by protein kinases A and C.";
RL J. Biol. Chem. 271:25157-25166(1996).
RN [12]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH DMTN AND SLC2A1, AND
RP INTERACTION WITH SLC2A1.
RX PubMed=18347014; DOI=10.1074/jbc.M707818200;
RA Khan A.A., Hanada T., Mohseni M., Jeong J.J., Zeng L., Gaetani M.,
RA Li D., Reed B.C., Speicher D.W., Chishti A.H.;
RT "Dematin and adducin provide a novel link between the spectrin
RT cytoskeleton and human erythrocyte membrane by directly interacting
RT with glucose transporter-1.";
RL J. Biol. Chem. 283:14600-14609(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-530; SER-592; SER-596;
RP SER-600; SER-604; THR-611; SER-613; SER-617; SER-693 AND SER-697, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Membrane-cytoskeleton-associated protein that promotes
CC the assembly of the spectrin-actin network. Binds to the
CC erythrocyte membrane receptor SLC2A1/GLUT1 and may therefore
CC provide a link between the spectrin cytoskeleton to the plasma
CC membrane. Binds to calmodulin. Calmodulin binds preferentially to
CC the beta subunit.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. Found in a
CC complex with ADD2, DMTN and SLC2A1. Interacts with SLC2A1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cell membrane;
CC Peripheral membrane protein; Cytoplasmic side.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Comment=Additional isoforms seem to exist;
CC Name=1;
CC IsoId=P35612-1; Sequence=Displayed;
CC Name=2; Synonyms=Adducin 63;
CC IsoId=P35612-2; Sequence=VSP_000181, VSP_000182;
CC Name=3; Synonyms=Beta-4, E;
CC IsoId=P35612-3; Sequence=VSP_000183;
CC Name=4; Synonyms=Beta-4a;
CC IsoId=P35612-4; Sequence=VSP_017244, VSP_017246;
CC Name=5; Synonyms=Beta-4b;
CC IsoId=P35612-5; Sequence=VSP_017242, VSP_017243, VSP_017245;
CC Name=6; Synonyms=Beta-4c;
CC IsoId=P35612-6; Sequence=VSP_017242, VSP_017244, VSP_017246;
CC Name=7; Synonyms=Beta-4d;
CC IsoId=P35612-7; Sequence=VSP_017241, VSP_017244, VSP_017246;
CC Name=8;
CC IsoId=P35612-8; Sequence=VSP_043625, VSP_000181, VSP_000182;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed mainly in brain, spleen, kidney
CC cortex and medulla, and heart. Also expressed in human umbilical
CC vein endothelial cells, human vascular smooth muscle cells, kidney
CC tubular cells and K-562 cell line.
CC -!- DEVELOPMENTAL STAGE: Fetal kidney expresses isoforms 3, 4, 5, 6
CC and 7, and fetal liver expresses isoforms 3 and 4.
CC -!- DOMAIN: Each subunit is comprised of three regions: a NH2-terminal
CC protease-resistant globular head region, a short connecting
CC subdomain, and a protease-sensitive tail region.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the aldolase class II family. Adducin
CC subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92464.1; Type=Erroneous initiation;
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DR EMBL; X58199; CAA41176.1; -; mRNA.
DR EMBL; AF486420; AAP71863.1; -; mRNA.
DR EMBL; AF486421; AAP71864.1; -; mRNA.
DR EMBL; AF486422; AAP71865.1; -; mRNA.
DR EMBL; AF486423; AAP71866.1; -; mRNA.
DR EMBL; AK291007; BAF83696.1; -; mRNA.
DR EMBL; AK297250; BAG59729.1; -; mRNA.
DR EMBL; AB209227; BAD92464.1; ALT_INIT; mRNA.
DR EMBL; AB593080; BAJ84020.1; -; mRNA.
DR EMBL; AC005234; AAD12715.1; -; Genomic_DNA.
DR EMBL; AC007395; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471053; EAW99801.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99806.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99807.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99808.1; -; Genomic_DNA.
DR EMBL; BC041666; AAH41666.1; -; mRNA.
DR EMBL; BC051882; AAH51882.1; -; mRNA.
DR EMBL; BC056881; AAH56881.1; -; mRNA.
DR EMBL; BC065525; AAH65525.1; -; mRNA.
DR EMBL; U43959; AAA86421.1; -; mRNA.
DR EMBL; S81079; AAD14349.1; -; Genomic_DNA.
DR EMBL; S81077; AAD14349.1; JOINED; Genomic_DNA.
DR PIR; S18208; S18208.
DR RefSeq; NP_001171983.1; NM_001185054.1.
DR RefSeq; NP_001171984.1; NM_001185055.1.
DR RefSeq; NP_001608.1; NM_001617.3.
DR RefSeq; NP_059516.2; NM_017482.3.
DR RefSeq; NP_059522.1; NM_017488.3.
DR UniGene; Hs.188528; -.
DR DisProt; DP00241; -.
DR ProteinModelPortal; P35612; -.
DR SMR; P35612; 149-353.
DR PhosphoSite; P35612; -.
DR DMDM; 543774; -.
DR PaxDb; P35612; -.
DR PRIDE; P35612; -.
DR Ensembl; ENST00000264436; ENSP00000264436; ENSG00000075340.
DR Ensembl; ENST00000355733; ENSP00000347972; ENSG00000075340.
DR Ensembl; ENST00000403045; ENSP00000384303; ENSG00000075340.
DR Ensembl; ENST00000407644; ENSP00000384677; ENSG00000075340.
DR Ensembl; ENST00000413157; ENSP00000388072; ENSG00000075340.
DR Ensembl; ENST00000430656; ENSP00000398112; ENSG00000075340.
DR Ensembl; ENST00000522886; ENSP00000430243; ENSG00000075340.
DR Ensembl; ENST00000606038; ENSP00000475223; ENSG00000271760.
DR Ensembl; ENST00000606120; ENSP00000476220; ENSG00000271760.
DR Ensembl; ENST00000606312; ENSP00000475774; ENSG00000271760.
DR Ensembl; ENST00000606698; ENSP00000475993; ENSG00000271760.
DR Ensembl; ENST00000607267; ENSP00000475838; ENSG00000271760.
DR Ensembl; ENST00000607524; ENSP00000475332; ENSG00000271760.
DR Ensembl; ENST00000607677; ENSP00000475595; ENSG00000271760.
DR GeneID; 119; -.
DR KEGG; hsa:119; -.
DR UCSC; uc002sgz.3; human.
DR CTD; 119; -.
DR GeneCards; GC02M070800; -.
DR HGNC; HGNC:244; ADD2.
DR HPA; CAB009796; -.
DR MIM; 102681; gene.
DR neXtProt; NX_P35612; -.
DR PharmGKB; PA24566; -.
DR eggNOG; COG0235; -.
DR HOVERGEN; HBG004180; -.
DR InParanoid; P35612; -.
DR OMA; SGPMSPE; -.
DR OrthoDB; EOG7HF1HR; -.
DR PhylomeDB; P35612; -.
DR GeneWiki; ADD2; -.
DR GenomeRNAi; 119; -.
DR NextBio; 469; -.
DR PRO; PR:P35612; -.
DR ArrayExpress; P35612; -.
DR Bgee; P35612; -.
DR Genevestigator; P35612; -.
DR GO; GO:0016023; C:cytoplasmic membrane-bounded vesicle; IDA:UniProtKB.
DR GO; GO:0008290; C:F-actin capping protein complex; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0051015; F:actin filament binding; IDA:BHF-UCL.
DR GO; GO:0030507; F:spectrin binding; IDA:BHF-UCL.
DR GO; GO:0005198; F:structural molecule activity; IEA:Ensembl.
DR GO; GO:0051017; P:actin filament bundle assembly; IDA:BHF-UCL.
DR GO; GO:0051016; P:barbed-end actin filament capping; IDA:BHF-UCL.
DR GO; GO:0030097; P:hemopoiesis; IEA:Ensembl.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL.
DR GO; GO:0006461; P:protein complex assembly; IDA:UniProtKB.
DR Gene3D; 3.40.225.10; -; 1.
DR InterPro; IPR027773; ADD2.
DR InterPro; IPR001303; Aldolase_II/adducin_N.
DR PANTHER; PTHR10672:SF6; PTHR10672:SF6; 1.
DR Pfam; PF00596; Aldolase_II; 1.
DR SMART; SM01007; Aldolase_II; 1.
DR SUPFAM; SSF53639; SSF53639; 1.
PE 1: Evidence at protein level;
KW Actin-binding; Alternative splicing; Calmodulin-binding;
KW Cell membrane; Complete proteome; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Membrane; Phosphoprotein; Polymorphism;
KW Reference proteome.
FT CHAIN 1 726 Beta-adducin.
FT /FTId=PRO_0000218533.
FT REGION 425 444 Interaction with calmodulin (Potential).
FT REGION 704 721 Interaction with calmodulin (Potential).
FT MOD_RES 55 55 Phosphothreonine; by PKA.
FT MOD_RES 530 530 Phosphoserine.
FT MOD_RES 532 532 Phosphoserine (By similarity).
FT MOD_RES 535 535 Phosphoserine (By similarity).
FT MOD_RES 561 561 Phosphothreonine (By similarity).
FT MOD_RES 592 592 Phosphoserine.
FT MOD_RES 596 596 Phosphoserine.
FT MOD_RES 600 600 Phosphoserine.
FT MOD_RES 604 604 Phosphoserine.
FT MOD_RES 611 611 Phosphothreonine.
FT MOD_RES 613 613 Phosphoserine.
FT MOD_RES 617 617 Phosphoserine.
FT MOD_RES 693 693 Phosphoserine.
FT MOD_RES 697 697 Phosphoserine.
FT MOD_RES 703 703 Phosphoserine; by PKC.
FT MOD_RES 713 713 Phosphoserine; by PKA and PKC.
FT VAR_SEQ 1 1 M -> MPRRRVPGANCKPTGK (in isoform 8).
FT /FTId=VSP_043625.
FT VAR_SEQ 78 566 Missing (in isoform 7).
FT /FTId=VSP_017241.
FT VAR_SEQ 188 493 Missing (in isoform 5 and isoform 6).
FT /FTId=VSP_017242.
FT VAR_SEQ 532 559 STESQLMSKGDEDTKDDSEETVPNPFSQ -> VEQRLPLTG
FT GETCLPSGSSVPGAGLQDP (in isoform 2 and
FT isoform 8).
FT /FTId=VSP_000181.
FT VAR_SEQ 560 726 Missing (in isoform 2 and isoform 8).
FT /FTId=VSP_000182.
FT VAR_SEQ 581 726 GEKETAPEEPGSPAKSAPASPVQSPAKEAETKSPLVSPSKS
FT LEEGTKKTETSKAATTEPETTQPEGVVVNGREEEQTAEEIL
FT SKGLSQMTTSADTDVDTSKDKTESVTSGPMSPEGSPSKSPS
FT KKKKKFRTPSFLKKSKKKEKVES -> ETGQEREPGSGPAV
FT CEFFSVALHIWSNILERKKLPQKSLAHLQSLHLLLQCRAQR
FT RRQRQRAL (in isoform 3).
FT /FTId=VSP_000183.
FT VAR_SEQ 581 587 GEKETAP -> APGWFSS (in isoform 4, isoform
FT 6 and isoform 7).
FT /FTId=VSP_017244.
FT VAR_SEQ 581 586 GEKETA -> ETGQER (in isoform 5).
FT /FTId=VSP_017243.
FT VAR_SEQ 587 726 Missing (in isoform 5).
FT /FTId=VSP_017245.
FT VAR_SEQ 588 726 Missing (in isoform 4, isoform 6 and
FT isoform 7).
FT /FTId=VSP_017246.
FT VARIANT 28 28 D -> N (in dbSNP:rs4986).
FT /FTId=VAR_014866.
FT VARIANT 98 98 S -> C (in dbSNP:rs4987).
FT /FTId=VAR_048195.
FT VARIANT 335 335 E -> D (in dbSNP:rs4982).
FT /FTId=VAR_014867.
FT VARIANT 439 439 T -> A (in dbSNP:rs17855969).
FT /FTId=VAR_025318.
FT VARIANT 663 663 S -> R (in dbSNP:rs4985).
FT /FTId=VAR_014868.
SQ SEQUENCE 726 AA; 80854 MW; B07F7303D929DBA4 CRC64;
MSEETVPEAA SPPPPQGQPY FDRFSEDDPE YMRLRNRAAD LRQDFNLMEQ KKRVTMILQS
PSFREELEGL IQEQMKKGNN SSNIWALRQI ADFMASTSHA VFPTSSMNVS MMTPINDLHT
ADSLNLAKGE RLMRCKISSV YRLLDLYGWA QLSDTYVTLR VSKEQDHFLI SPKGVSCSEV
TASSLIKVNI LGEVVEKGSS CFPVDTTGFC LHSAIYAARP DVRCIIHLHT PATAAVSAMK
WGLLPVSHNA LLVGDMAYYD FNGEMEQEAD RINLQKCLGP TCKILVLRNH GVVALGDTVE
EAFYKIFHLQ AACEIQVSAL SSAGGVENLI LLEQEKHRPH EVGSVQWAGS TFGPMQKSRL
GEHEFEALMR MLDNLGYRTG YTYRHPFVQE KTKHKSEVEI PATVTAFVFE EDGAPVPALR
QHAQKQQKEK TRWLNTPNTY LRVNVADEVQ RSMGSPRPKT TWMKADEVEK SSSGMPIRIE
NPNQFVPLYT DPQEVLEMRN KIREQNRQDV KSAGPQSQLL ASVIAEKSRS PSTESQLMSK
GDEDTKDDSE ETVPNPFSQL TDQELEEYKK EVERKKLELD GEKETAPEEP GSPAKSAPAS
PVQSPAKEAE TKSPLVSPSK SLEEGTKKTE TSKAATTEPE TTQPEGVVVN GREEEQTAEE
ILSKGLSQMT TSADTDVDTS KDKTESVTSG PMSPEGSPSK SPSKKKKKFR TPSFLKKSKK
KEKVES
//
MIM
102681
*RECORD*
*FIELD* NO
102681
*FIELD* TI
*102681 ADDUCIN 2; ADD2
;;ADDUCIN, BETA
*FIELD* TX
DESCRIPTION
Adducin is a heterodimeric calmodulin (114180)-binding protein of the
read morecell-membrane skeleton that is thought to play a role in assembly of the
spectrin-actin (182860/102560) lattice that underlies the plasma
membrane (Joshi et al., 1991).
CLONING
Joshi et al. (1991) determined the sequence of cDNAs encoding the human
alpha- (ADD1; 102680) and beta-adducins. The 726-amino acid predicted
beta subunit is 49% identical to the alpha-adducin sequence.
Gilligan et al. (1997) described 5 ADD2 splice variants that differed
predominantly in the splicing of 3-prime exons. Some isoforms encoded by
these variants lack the central calmodulin-binding domain or the
lysine-rich C-terminal domain of the full-length protein.
In a comprehensive assay of gene expression, Gilligan et al. (1999)
showed ubiquitous expression of alpha- and gamma-adducin (ADD3; 601568),
in contrast with the restricted expression of beta-adducin. Beta-adducin
was expressed at high levels in brain and hematopoietic tissues (bone
marrow in humans, and spleen in mice).
GENE STRUCTURE
Tisminetzky et al. (1995) determined the genomic organization of the
human beta-adducin gene and showed that it contains 13 exons spanning
approximately 50 kb. The authors showed that alternative splicing
results in the production of several different transcripts.
Gilligan et al. (1997) determined that the ADD2 gene contains 17 exons
and spans over 100 kb. The first 2 exons are noncoding, and coding exons
3 through 6 are common to all splice variants. The promoter region lacks
TATA or CAAT elements, but is GC-rich and contains several binding sites
for transcription factors.
GENE FUNCTION
Ruediger et al. (2011) investigated how mossy fiber terminal complexes
at the entry of hippocampal and cerebellar circuits rearrange upon
learning in mice, and the functional role of the rearrangements.
Ruediger et al. (2011) showed that one-trial and incremental learning
lead to robust, circuit-specific, long-lasting, and reversible increases
in the numbers of filopodial synapses onto fast-spiking interneurons
that trigger feedforward inhibition. The increase in feedforward
inhibition connectivity involved a majority of the presynaptic
terminals, restricted the number of c-Fos (164810)-expressing
postsynaptic neurons at memory retrieval, and correlated temporally with
the quality of the memory. Ruediger et al. (2011) then showed that for
contextual fear conditioning and Morris water maze learning, increased
feedforward inhibition connectivity by hippocampal mossy fibers has a
critical role for the precision of the memory and the learned behavior.
In the absence of mossy fiber long-term potentiation in Rab3a
(179490)-null mice, c-Fos ensemble reorganization and feedforward
inhibition growth were both absent in CA3 upon learning, and the memory
was imprecise. By contrast, in the absence of Add2, c-Fos reorganization
was normal, but feedforward inhibition growth was abolished. In
parallel, c-Fos ensembles in CA3 were greatly enlarged, and the memory
was imprecise. Feedforward inhibition growth and memory precision were
both rescued by re-expression of Add2 specifically in hippocampal mossy
fibers. Ruediger et al. (2011) concluded that their results established
a causal relationship between learning-related increases in the numbers
of defined synapses and the precision of learning and memory in the
adult. The results further related plasticity and feedforward inhibition
growth at hippocampal mossy fibers to the precision of
hippocampus-dependent memories.
MAPPING
By somatic cell hybrid analysis, Joshi et al. (1991) found that the
alpha and beta subunits of adducin are encoded by separate genes, the
alpha gene being located on chromosome 4p16.3 and the beta gene on
chromosome 2. Gilligan et al. (1995) mapped ADD2 to 2p14-p13 by
fluorescence in situ hybridization.
White et al. (1995) mapped the mouse Add2 gene to chromosome 6 by
haplotype analysis in interspecific backcross mice. Mapping of the human
gene to chromosome 2 was confirmed by study of somatic cell hybrid
panels by Southern blotting. The gene was further localized to
2pter-p11.2 by study of somatic cell hybrids containing portions of
chromosome 2. Tisminetzky et al. (1995) regionally mapped ADD2 to
2p15-cen by in situ hybridization.
MOLECULAR GENETICS
Lanzani et al. (2005) analyzed the ADD2 gene in 40 unrelated individuals
and identified a C1797T polymorphism (dbSNP rs4984) in the coding
sequence, located on the alternatively spliced exon 15. The authors then
genotyped 512 newly discovered and never-treated hypertensive patients
(see 145500) for C1797T, but found no association between the
polymorphism and ambulatory blood pressure or plasma levels of renin
activity and endogenous ouabain.
ANIMAL MODEL
To elucidate the role of adducin in vivo, Gilligan et al. (1999) created
Add2-null mice by gene targeting, deleting exons 9 to 13. A 55-kD
chimeric polypeptide was produced from the first 8 exons of Add2 and
part of the neo cassette in spleen, but was not detected in peripheral
red blood cells (RBCs) or brain. Add2-null RBCs were osmotically
fragile, spherocytic, and dehydrated compared with the wildtype,
resembling RBCs from patients with hereditary spherocytosis (see
182900). The lack of beta-adducin in RBCs led to decreased membrane
incorporation of alpha-adducin (30% of normal) and unexpectedly promoted
a 5-fold increase in gamma-adducin incorporation into the RBC membrane
skeleton. This study demonstrated the importance of adducin to RBC
membrane stability in vivo.
Muro et al. (2000) showed that in Add2 -/- mice, targeted disruption of
the beta-adducin gene resulted in an 80% decrease of alpha-adducin and a
4-fold upregulation of gamma-adducin in erythrocytes. Elliptocytes,
ovalocytes, and occasionally spherocytes were found in the blood smears
of -/- mice. Mild hematologic findings were thought to be related to the
amount of adducin remaining in the mutant animals (presumably
alpha-gamma adducin).
The Milan hypertensive strain of rats develops a genetic form of renal
hypertension that, when compared to its normotensive control, shows
renal dysfunction similar to that of a subset of human patients with
primary hypertension. Bianchi et al. (1994) showed that 1 point mutation
in each of the 2 genes coding for adducin is associated with blood
pressure level in this strain of rats. The hypertensive and normal rats
differed, respectively, by the amino acids tyrosine and phenylalanine at
position 316 of the alpha subunit; at the beta-adducin locus, the
hypertensive strain was always homozygous for arginine at position 529,
while the normal strain showed either arginine or glutamine in that
position. The arg/gln heterozygotes showed lower blood pressure than any
of the homozygotes. In vitro phosphorylation studies suggested that both
of these amino acid substitutions occurred within protein kinase
recognition sites. Analysis of an F2 generation demonstrated that Y
(tyrosine) alleles segregated with a significant increment in blood
pressure. This effect was modulated by the presence of the R (arginine)
allele of the beta subunit. Bianchi et al. (1994) stated that, taken
together, these findings strongly supported a role for adducin
polymorphisms in causing variation of blood pressure in the Milan strain
of rats. In the rat, the beta- and alpha-adducin genes were said to be
located on chromosomes 4 and 14, respectively.
Chen et al. (2007) created double-knockout mice lacking beta-adducin and
the headpiece domain of dematin (EPB49; 125305). Double-knockout pups
were pale compared with wildtype pups, but otherwise they appeared
grossly normal. Peripheral blood analysis showed severe hemolytic anemia
with reduced number of erythrocytes/hematocrit/hemoglobin and an
approximately 12-fold increase in the number of circulating
reticulocytes. The presence of a variety of misshapen and fragmented
erythrocytes correlated with increased osmotic fragility and reduced in
vivo life span. Mutant erythrocyte membranes showed weak retention of
spectrin-actin complexes, increased grain size, decreased filament
number, and features consistent with the presence of large protein
aggregates. Chen et al. (2007) concluded that dematin and adducin are
essential for the maintenance of erythrocyte shape and membrane
stability.
*FIELD* RF
1. Bianchi, G.; Tripodi, G.; Casari, G.; Salardi, S.; Barber, B. R.;
Garcia, R.; Leoni, P.; Torielli, L.; Cusi, D.; Ferrandi, M.; Pinna,
L. A.; Baralle, F. E.; Ferrari, P.: Two point mutations within the
adducin genes are involved in blood pressure variation. Proc. Nat.
Acad. Sci. 91: 3999-4003, 1994.
2. Chen, H.; Khan, A. A.; Liu, F.; Gilligan, D. M.; Peters, L. L.;
Messick, J.; Haschek-Hock, W. M.; Li, X.; Ostafin, A. E.; Chishti,
A. H.: Combined deletion of mouse dematin-headpiece and beta-adducin
exerts a novel effect on the spectrin-actin junctions leading to erythrocyte
fragility and hemolytic anemia. J. Biol. Chem. 282: 4124-4135, 2007.
3. Gilligan, D. M.; Lieman, J.; Bennett, V.: Assignment of the human
beta-adducin gene (ADD2) to 2p13-p14 by in situ hybridization. Genomics 28:
610-612, 1995.
4. Gilligan, D. M.; Lozovatsky, L.; Gwynn, B.; Brugnara, C.; Mohandas,
N.; Peters, L. L.: Targeted disruption of the beta adducin gene (Add2)
causes red blood cell spherocytosis in mice. Proc. Nat. Acad. Sci. 96:
10717-10722, 1999.
5. Gilligan, D. M.; Lozovatsky, L.; Silberfein, A.: Organization
of the human beta-adducin gene (ADD2). Genomics 43: 141-148, 1997.
6. Joshi, R.; Gilligan, D. M.; Otto, E.; McLaughlin, T.; Bennett,
V.: Primary structure and domain organization of human alpha and
beta adducin. J. Cell Biol. 115: 665-675, 1991.
7. Lanzani, C.; Citterio, L.; Jankaricova, M.; Sciarrone, M. T.; Barlassina,
C.; Fattori, S.; Messaggio, E.; Di Serio, C.; Zagato, L.; Cusi, D.;
Hamlyn, J. M.; Stella, A.; Bianchi, G.; Manunta, P.: Role of the
adducin family genes in human essential hypertension. J. Hypertension 23:
543-549, 2005.
8. Muro, A. F.; Marro, M. L.; Gajovic, S.; Porro, F.; Luzzatto, L.;
Baralle, F. E.: Mild spherocytic hereditary elliptocytosis and altered
levels of alpha- and gamma-adducins in beta-adducin-deficient mice. Blood 95:
3978-3985, 2000.
9. Ruediger, S.; Vittori, C.; Bednarek, E.; Genoud, C.; Strata, P.;
Sacchetti, B.; Caroni, P.: Learning-related feedforward inhibitory
connectivity growth required for memory precision. Nature 473: 514-518,
2011.
10. Tisminetzky, S.; Devescovi, G.; Tripodi, G.; Muro, A.; Bianchi,
G.; Colombi, M.; Moro, L.; Barlati, S.; Tuteja, R.; Baralle, F. E.
: Genomic organisation and chromosomal localisation of the gene encoding
human beta adducin. Gene 167: 313-316, 1995.
11. White, R. A.; Angeloni, S. V.; Pasztor, L. M.: Chromosomal localization
of the beta-adducin gene to mouse chromosome 6 and human chromosome
2. Mammalian Genome 6: 741-743, 1995.
*FIELD* CN
Ada Hamosh - updated: 6/22/2011
Patricia A. Hartz - updated: 4/10/2009
Marla J. F. O'Neill - updated: 12/2/2008
Victor A. McKusick - updated: 9/27/2000
Victor A. McKusick - updated: 10/29/1999
Alan F. Scott - updated: 5/13/1996
Alan F. Scott - updated: 9/27/1995
*FIELD* CD
Victor A. McKusick: 11/23/1992
*FIELD* ED
alopez: 06/24/2011
terry: 6/22/2011
mgross: 4/13/2009
terry: 4/10/2009
carol: 12/2/2008
terry: 3/11/2005
mcapotos: 10/10/2000
terry: 9/27/2000
mgross: 11/8/1999
terry: 10/29/1999
carol: 2/18/1999
terry: 5/13/1996
mark: 5/13/1996
terry: 4/17/1996
mark: 4/1/1996
mark: 1/21/1996
mark: 11/30/1995
carol: 4/8/1994
carol: 1/4/1993
carol: 11/23/1992
*RECORD*
*FIELD* NO
102681
*FIELD* TI
*102681 ADDUCIN 2; ADD2
;;ADDUCIN, BETA
*FIELD* TX
DESCRIPTION
Adducin is a heterodimeric calmodulin (114180)-binding protein of the
read morecell-membrane skeleton that is thought to play a role in assembly of the
spectrin-actin (182860/102560) lattice that underlies the plasma
membrane (Joshi et al., 1991).
CLONING
Joshi et al. (1991) determined the sequence of cDNAs encoding the human
alpha- (ADD1; 102680) and beta-adducins. The 726-amino acid predicted
beta subunit is 49% identical to the alpha-adducin sequence.
Gilligan et al. (1997) described 5 ADD2 splice variants that differed
predominantly in the splicing of 3-prime exons. Some isoforms encoded by
these variants lack the central calmodulin-binding domain or the
lysine-rich C-terminal domain of the full-length protein.
In a comprehensive assay of gene expression, Gilligan et al. (1999)
showed ubiquitous expression of alpha- and gamma-adducin (ADD3; 601568),
in contrast with the restricted expression of beta-adducin. Beta-adducin
was expressed at high levels in brain and hematopoietic tissues (bone
marrow in humans, and spleen in mice).
GENE STRUCTURE
Tisminetzky et al. (1995) determined the genomic organization of the
human beta-adducin gene and showed that it contains 13 exons spanning
approximately 50 kb. The authors showed that alternative splicing
results in the production of several different transcripts.
Gilligan et al. (1997) determined that the ADD2 gene contains 17 exons
and spans over 100 kb. The first 2 exons are noncoding, and coding exons
3 through 6 are common to all splice variants. The promoter region lacks
TATA or CAAT elements, but is GC-rich and contains several binding sites
for transcription factors.
GENE FUNCTION
Ruediger et al. (2011) investigated how mossy fiber terminal complexes
at the entry of hippocampal and cerebellar circuits rearrange upon
learning in mice, and the functional role of the rearrangements.
Ruediger et al. (2011) showed that one-trial and incremental learning
lead to robust, circuit-specific, long-lasting, and reversible increases
in the numbers of filopodial synapses onto fast-spiking interneurons
that trigger feedforward inhibition. The increase in feedforward
inhibition connectivity involved a majority of the presynaptic
terminals, restricted the number of c-Fos (164810)-expressing
postsynaptic neurons at memory retrieval, and correlated temporally with
the quality of the memory. Ruediger et al. (2011) then showed that for
contextual fear conditioning and Morris water maze learning, increased
feedforward inhibition connectivity by hippocampal mossy fibers has a
critical role for the precision of the memory and the learned behavior.
In the absence of mossy fiber long-term potentiation in Rab3a
(179490)-null mice, c-Fos ensemble reorganization and feedforward
inhibition growth were both absent in CA3 upon learning, and the memory
was imprecise. By contrast, in the absence of Add2, c-Fos reorganization
was normal, but feedforward inhibition growth was abolished. In
parallel, c-Fos ensembles in CA3 were greatly enlarged, and the memory
was imprecise. Feedforward inhibition growth and memory precision were
both rescued by re-expression of Add2 specifically in hippocampal mossy
fibers. Ruediger et al. (2011) concluded that their results established
a causal relationship between learning-related increases in the numbers
of defined synapses and the precision of learning and memory in the
adult. The results further related plasticity and feedforward inhibition
growth at hippocampal mossy fibers to the precision of
hippocampus-dependent memories.
MAPPING
By somatic cell hybrid analysis, Joshi et al. (1991) found that the
alpha and beta subunits of adducin are encoded by separate genes, the
alpha gene being located on chromosome 4p16.3 and the beta gene on
chromosome 2. Gilligan et al. (1995) mapped ADD2 to 2p14-p13 by
fluorescence in situ hybridization.
White et al. (1995) mapped the mouse Add2 gene to chromosome 6 by
haplotype analysis in interspecific backcross mice. Mapping of the human
gene to chromosome 2 was confirmed by study of somatic cell hybrid
panels by Southern blotting. The gene was further localized to
2pter-p11.2 by study of somatic cell hybrids containing portions of
chromosome 2. Tisminetzky et al. (1995) regionally mapped ADD2 to
2p15-cen by in situ hybridization.
MOLECULAR GENETICS
Lanzani et al. (2005) analyzed the ADD2 gene in 40 unrelated individuals
and identified a C1797T polymorphism (dbSNP rs4984) in the coding
sequence, located on the alternatively spliced exon 15. The authors then
genotyped 512 newly discovered and never-treated hypertensive patients
(see 145500) for C1797T, but found no association between the
polymorphism and ambulatory blood pressure or plasma levels of renin
activity and endogenous ouabain.
ANIMAL MODEL
To elucidate the role of adducin in vivo, Gilligan et al. (1999) created
Add2-null mice by gene targeting, deleting exons 9 to 13. A 55-kD
chimeric polypeptide was produced from the first 8 exons of Add2 and
part of the neo cassette in spleen, but was not detected in peripheral
red blood cells (RBCs) or brain. Add2-null RBCs were osmotically
fragile, spherocytic, and dehydrated compared with the wildtype,
resembling RBCs from patients with hereditary spherocytosis (see
182900). The lack of beta-adducin in RBCs led to decreased membrane
incorporation of alpha-adducin (30% of normal) and unexpectedly promoted
a 5-fold increase in gamma-adducin incorporation into the RBC membrane
skeleton. This study demonstrated the importance of adducin to RBC
membrane stability in vivo.
Muro et al. (2000) showed that in Add2 -/- mice, targeted disruption of
the beta-adducin gene resulted in an 80% decrease of alpha-adducin and a
4-fold upregulation of gamma-adducin in erythrocytes. Elliptocytes,
ovalocytes, and occasionally spherocytes were found in the blood smears
of -/- mice. Mild hematologic findings were thought to be related to the
amount of adducin remaining in the mutant animals (presumably
alpha-gamma adducin).
The Milan hypertensive strain of rats develops a genetic form of renal
hypertension that, when compared to its normotensive control, shows
renal dysfunction similar to that of a subset of human patients with
primary hypertension. Bianchi et al. (1994) showed that 1 point mutation
in each of the 2 genes coding for adducin is associated with blood
pressure level in this strain of rats. The hypertensive and normal rats
differed, respectively, by the amino acids tyrosine and phenylalanine at
position 316 of the alpha subunit; at the beta-adducin locus, the
hypertensive strain was always homozygous for arginine at position 529,
while the normal strain showed either arginine or glutamine in that
position. The arg/gln heterozygotes showed lower blood pressure than any
of the homozygotes. In vitro phosphorylation studies suggested that both
of these amino acid substitutions occurred within protein kinase
recognition sites. Analysis of an F2 generation demonstrated that Y
(tyrosine) alleles segregated with a significant increment in blood
pressure. This effect was modulated by the presence of the R (arginine)
allele of the beta subunit. Bianchi et al. (1994) stated that, taken
together, these findings strongly supported a role for adducin
polymorphisms in causing variation of blood pressure in the Milan strain
of rats. In the rat, the beta- and alpha-adducin genes were said to be
located on chromosomes 4 and 14, respectively.
Chen et al. (2007) created double-knockout mice lacking beta-adducin and
the headpiece domain of dematin (EPB49; 125305). Double-knockout pups
were pale compared with wildtype pups, but otherwise they appeared
grossly normal. Peripheral blood analysis showed severe hemolytic anemia
with reduced number of erythrocytes/hematocrit/hemoglobin and an
approximately 12-fold increase in the number of circulating
reticulocytes. The presence of a variety of misshapen and fragmented
erythrocytes correlated with increased osmotic fragility and reduced in
vivo life span. Mutant erythrocyte membranes showed weak retention of
spectrin-actin complexes, increased grain size, decreased filament
number, and features consistent with the presence of large protein
aggregates. Chen et al. (2007) concluded that dematin and adducin are
essential for the maintenance of erythrocyte shape and membrane
stability.
*FIELD* RF
1. Bianchi, G.; Tripodi, G.; Casari, G.; Salardi, S.; Barber, B. R.;
Garcia, R.; Leoni, P.; Torielli, L.; Cusi, D.; Ferrandi, M.; Pinna,
L. A.; Baralle, F. E.; Ferrari, P.: Two point mutations within the
adducin genes are involved in blood pressure variation. Proc. Nat.
Acad. Sci. 91: 3999-4003, 1994.
2. Chen, H.; Khan, A. A.; Liu, F.; Gilligan, D. M.; Peters, L. L.;
Messick, J.; Haschek-Hock, W. M.; Li, X.; Ostafin, A. E.; Chishti,
A. H.: Combined deletion of mouse dematin-headpiece and beta-adducin
exerts a novel effect on the spectrin-actin junctions leading to erythrocyte
fragility and hemolytic anemia. J. Biol. Chem. 282: 4124-4135, 2007.
3. Gilligan, D. M.; Lieman, J.; Bennett, V.: Assignment of the human
beta-adducin gene (ADD2) to 2p13-p14 by in situ hybridization. Genomics 28:
610-612, 1995.
4. Gilligan, D. M.; Lozovatsky, L.; Gwynn, B.; Brugnara, C.; Mohandas,
N.; Peters, L. L.: Targeted disruption of the beta adducin gene (Add2)
causes red blood cell spherocytosis in mice. Proc. Nat. Acad. Sci. 96:
10717-10722, 1999.
5. Gilligan, D. M.; Lozovatsky, L.; Silberfein, A.: Organization
of the human beta-adducin gene (ADD2). Genomics 43: 141-148, 1997.
6. Joshi, R.; Gilligan, D. M.; Otto, E.; McLaughlin, T.; Bennett,
V.: Primary structure and domain organization of human alpha and
beta adducin. J. Cell Biol. 115: 665-675, 1991.
7. Lanzani, C.; Citterio, L.; Jankaricova, M.; Sciarrone, M. T.; Barlassina,
C.; Fattori, S.; Messaggio, E.; Di Serio, C.; Zagato, L.; Cusi, D.;
Hamlyn, J. M.; Stella, A.; Bianchi, G.; Manunta, P.: Role of the
adducin family genes in human essential hypertension. J. Hypertension 23:
543-549, 2005.
8. Muro, A. F.; Marro, M. L.; Gajovic, S.; Porro, F.; Luzzatto, L.;
Baralle, F. E.: Mild spherocytic hereditary elliptocytosis and altered
levels of alpha- and gamma-adducins in beta-adducin-deficient mice. Blood 95:
3978-3985, 2000.
9. Ruediger, S.; Vittori, C.; Bednarek, E.; Genoud, C.; Strata, P.;
Sacchetti, B.; Caroni, P.: Learning-related feedforward inhibitory
connectivity growth required for memory precision. Nature 473: 514-518,
2011.
10. Tisminetzky, S.; Devescovi, G.; Tripodi, G.; Muro, A.; Bianchi,
G.; Colombi, M.; Moro, L.; Barlati, S.; Tuteja, R.; Baralle, F. E.
: Genomic organisation and chromosomal localisation of the gene encoding
human beta adducin. Gene 167: 313-316, 1995.
11. White, R. A.; Angeloni, S. V.; Pasztor, L. M.: Chromosomal localization
of the beta-adducin gene to mouse chromosome 6 and human chromosome
2. Mammalian Genome 6: 741-743, 1995.
*FIELD* CN
Ada Hamosh - updated: 6/22/2011
Patricia A. Hartz - updated: 4/10/2009
Marla J. F. O'Neill - updated: 12/2/2008
Victor A. McKusick - updated: 9/27/2000
Victor A. McKusick - updated: 10/29/1999
Alan F. Scott - updated: 5/13/1996
Alan F. Scott - updated: 9/27/1995
*FIELD* CD
Victor A. McKusick: 11/23/1992
*FIELD* ED
alopez: 06/24/2011
terry: 6/22/2011
mgross: 4/13/2009
terry: 4/10/2009
carol: 12/2/2008
terry: 3/11/2005
mcapotos: 10/10/2000
terry: 9/27/2000
mgross: 11/8/1999
terry: 10/29/1999
carol: 2/18/1999
terry: 5/13/1996
mark: 5/13/1996
terry: 4/17/1996
mark: 4/1/1996
mark: 1/21/1996
mark: 11/30/1995
carol: 4/8/1994
carol: 1/4/1993
carol: 11/23/1992