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UniProtKB/Swiss-Prot entry P35611


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name ADDA_HUMAN
Primary accession number P35611
Secondary accession numbers Q13734 Q14729 Q16156 Q9UJB6
Integrated into Swiss-Prot on June 1, 1994
Sequence was last modified on December 1, 2000 (Sequence version 2)
Annotations were last modified on    June 16, 2009 (Entry version 94)
Name and origin of the protein
Protein name Alpha-adducin
Synonym Erythrocyte adducin subunit alpha
Gene name
Name: ADD1
Synonyms: ADDA
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 24-36; 41-47; 516-569 AND 722-729, AND VARIANT CYS-586.
TISSUE=Reticulocyte;
DOI=10.1083/jcb.115.3.665; PubMed=1840603 [NCBI, ExPASy, EBI, Israel, Japan]
Joshi R.L., Gilligan D.M., Otto E., McLaughlin T., Bennett V.D.;
"Primary structure and domain organization of human alpha and beta adducin.";
J. Cell Biol. 115:665-675(1991).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
DOI=10.1016/0888-7543(95)80113-Z; PubMed=7774961 [NCBI, ExPASy, EBI, Israel, Japan]
Lin B., Nasir J., McDonald H., Graham R., Rommens J.M., Goldberg Y.P., Hayden M.R.;
"Genomic organization of the human alpha-adducin gene and its alternately spliced isoforms.";
Genomics 25:93-99(1995).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature03466; PubMed=15815621 [NCBI, ExPASy, EBI, Israel, Japan]
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.;
"Generation and annotation of the DNA sequences of human chromosomes 2 and 4.";
Nature 434:724-731(2005).
[4]
NUCLEOTIDE SEQUENCE [MRNA] OF 531-737.
DOI=10.1038/ng1192-223; PubMed=1345173 [NCBI, ExPASy, EBI, Israel, Japan]
Taylor S.A., Snell R.G., Buckler A., Ambrose C., Duyao M., Church D., Lin C.S., Altherr M., Bates G.P., Groot N.;
"Cloning of the alpha-adducin gene from the Huntington's disease candidate region of chromosome 4 by exon amplification.";
Nat. Genet. 2:223-227(1992).
[5]
PHOSPHORYLATION AT SER-59; SER-408; SER-436; SER-481; SER-716 AND SER-726, AND PARTIAL PROTEIN SEQUENCE.
DOI=10.1074/jbc.271.41.25157; PubMed=8810272 [NCBI, ExPASy, EBI, Israel, Japan]
Matsuoka Y., Hughes C.A., Bennett V.;
"Adducin regulation. Definition of the calmodulin-binding domain and sites of phosphorylation by protein kinases A and C.";
J. Biol. Chem. 271:25157-25166(1996).
[6]
PHOSPHORYLATION AT THR-445 AND THR-480, AND MUTAGENESIS OF THR-445 AND THR-480.
DOI=10.1083/jcb.145.2.347; PubMed=10209029 [NCBI, ExPASy, EBI, Israel, Japan]
Fukata Y., Oshiro N., Kinoshita N., Kawano Y., Matsuoka Y., Bennett V., Matsuura Y., Kaibuchi K.;
"Phosphorylation of adducin by Rho-kinase plays a crucial role in cell motility.";
J. Cell Biol. 145:347-361(1999).
[7]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-358 AND SER-465, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1073/pnas.0404720101; PubMed=15302935 [NCBI, ExPASy, EBI, Israel, Japan]
Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P.;
"Large-scale characterization of HeLa cell nuclear phosphoproteins.";
Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
[8]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-355 AND SER-358, AND MASS SPECTROMETRY.
TISSUE=Brain cortex;
DOI=10.1021/pr0498436; PubMed=15822905 [NCBI, ExPASy, EBI, Israel, Japan]
DeGiorgis J.A., Jaffe H., Moreira J.E., Carlotti C.G. Jr., Leite J.P., Pant H.C., Dosemeci A.;
"Phosphoproteomic analysis of synaptosomes from human cerebral cortex.";
J. Proteome Res. 4:306-315(2005).
[9]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-707; SER-710 AND SER-716, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1016/j.cell.2006.09.026; PubMed=17081983 [NCBI, ExPASy, EBI, Israel, Japan]
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.";
Cell 127:635-648(2006).
[10]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-353; SER-355; SER-358 AND SER-465, AND MASS SPECTROMETRY.
DOI=10.1073/pnas.0611217104; PubMed=17287340 [NCBI, ExPASy, EBI, Israel, Japan]
Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.;
"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry.";
Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007).
[11]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12 AND SER-358, AND MASS SPECTROMETRY.
TISSUE=Platelet;
DOI=10.1021/pr0704130; PubMed=18088087 [NCBI, ExPASy, EBI, Israel, Japan]
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.;
"Phosphoproteome of resting human platelets.";
J. Proteome Res. 7:526-534(2008).
[12]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12; THR-331; SER-334; SER-358; SER-431; SER-436 AND SER-465, AND MASS SPECTROMETRY.
DOI=10.1073/pnas.0805139105; PubMed=18669648 [NCBI, ExPASy, EBI, Israel, Japan]
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[13]
VARIANT TRP-460.
PubMed=9674650 [NCBI, ExPASy, EBI, Israel, Japan]
Kamitani A., Wong Z.Y., Fraser R., Davies D.L., Connor J.M., Foy C.J., Watt G.C., Harrap S.B.;
"Human alpha-adducin gene, blood pressure, and sodium metabolism.";
Hypertension 32:138-143(1998).
[14]
VARIANTS TRP-460 AND CYS-586.
DOI=10.1038/10297; PubMed=10391210 [NCBI, ExPASy, EBI, Israel, Japan]
Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A.;
"Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis.";
Nat. Genet. 22:239-247(1999).
Comments
  • FUNCTION: Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to calmodulin.
  • SUBUNIT: Heterodimer of an alpha and a beta subunit or an alpha and a gamma subunit. Binds ROCK1.
  • SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein; Cytoplasmic side.
  • ALTERNATIVE PRODUCTS: 3 named isoforms [FASTA] produced by alternative splicing. Additional isoforms seem to exist.
    Name1
    Isoform IDP35611-1
    This is the isoform sequence displayed in this entry.
    Name2
    Isoform IDP35611-2
    Features which should be applied to build the isoform sequence: VSP_000175, VSP_000176.
    Name3
    Isoform IDP35611-3
    Features which should be applied to build the isoform sequence: VSP_000174.
  • TISSUE SPECIFICITY: Expressed in all tissues. Found in much higher levels in reticulocytes than the beta subunit.
  • DOMAIN: Each subunit is comprised of three regions: a NH2-terminal protease-resistant globular head region, a short connecting subdomain, and a protease-sensitive tail region.
  • PTM: The N-terminus is blocked.
  • SIMILARITY: Belongs to the aldolase class II family. Adducin subfamily.
  • SEQUENCE CAUTION:
    • Sequence=CAA98970.1; Type=Erroneous gene model prediction;
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
X58141; CAA41149.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L29296; AAB05645.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L29286; AAB05645.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L29287; AAB05645.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L29289; AAB05645.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L29290; AAB05645.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L29291; AAB05645.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L29292; AAB05645.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L29293; AAB05645.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L29294; AAB05645.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L29295; AAB05645.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L29297; AAB05645.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L29298; AAB05645.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
Z74617; CAA98970.1; ALT_SEQ; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
Z68280; -; NOT_ANNOTATED_CDS; Genomic_DNA.[EMBL / GenBank / DDBJ]
S70314; AAB30914.2; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00019901; -.
IPI00220158; -.
IPI00253279; -.
PIR S18207; S18207.
RefSeq NP_001110.2; -.
NP_054908.2; -.
NP_054909.2; -.
UniGene Hs.183706
3D structure databases
DisProt DP00240; -.
ModBase P35611.
PTM databases
PhosphoSite P35611; -.
Enzyme and pathway databases
Reactome REACT_578; Apoptosis.
Organism-specific databases
GeneCards GC04P002882; -.
HGNC HGNC:243; ADD1.
GenAtlas ADD1.
HPA CAB009794; -.
MIM 102680; gene. [NCBI / EBI]
PharmGKB PA31; -.
Gene expression databases
ArrayExpress P35611; -.
Bgee P35611; -.
CleanEx HS_ADD1; -.
Ontologies
GO
GO:0005829; Cellular component: cytosol (inferred from experiment from Reactome).
GO:0008290; Cellular component: F-actin capping protein complex (inferred from direct assay from UniProtKB).
GO:0005634; Cellular component: nucleus (inferred from direct assay from UniProtKB).
GO:0005886; Cellular component: plasma membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0051015; Molecular function: actin filament binding (inferred from direct assay from UniProtKB).
GO:0005516; Molecular function: calmodulin binding (inferred from electronic annotation from UniProtKB-KW).
GO:0046872; Molecular function: metal ion binding (inferred from electronic annotation from InterPro).
GO:0046982; Molecular function: protein heterodimerization activity (inferred from physical interaction from UniProtKB).
GO:0042803; Molecular function: protein homodimerization activity (inferred from physical interaction from UniProtKB).
GO:0030507; Molecular function: spectrin binding (inferred from direct assay from UniProtKB).
GO:0008134; Molecular function: transcription factor binding (inferred from physical interaction from UniProtKB).
GO:0051017; Biological process: actin filament bundle formation (inferred from direct assay from UniProtKB).
GO:0051016; Biological process: barbed-end actin filament capping (inferred from direct assay from UniProtKB).
GO:0032092; Biological process: positive regulation of protein binding (inferred from direct assay from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR001303; Aldolase_II/adducin_N.
Graphical view of domain structure.
Gene3D G3DSA:3.40.225.10; Aldolase_II/adducin_N; 1.
Pfam PF00596; Aldolase_II; 1.
Pfam graphical view of domain structure.
Proteomic databases
PRIDE P35611; -.
Genome annotation databases
Ensembl ENSG00000087274; Homo sapiens. [Contig view]
GeneID 118; -.
KEGG hsa:118; -.
Phylogenomic databases
HOVERGEN P35611; -.
OMA P35611; NSGRGDE.
Other
NextBio 459; -.
PMAP-CutDB P35611; -.
SOURCE ADD1; Homo sapiens.
ProtoNet P35611.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Actin-binding; Alternative splicing; Calmodulin-binding; Cell membrane; Cytoplasm; Cytoskeleton; Direct protein sequencing; Membrane; Phosphoprotein; Polymorphism.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   737  737     Alpha-adducin. PRO_0000218530
REGION   717   734  18     Interaction with calmodulin (Potential). 
MOD_RES   12    12        Phosphoserine. 
MOD_RES   59    59        Phosphoserine; by PKA. 
MOD_RES   331   331        Phosphothreonine. 
MOD_RES   334   334        Phosphoserine. 
MOD_RES   353   353        Phosphoserine. 
MOD_RES   355   355        Phosphoserine. 
MOD_RES   358   358        Phosphoserine. 
MOD_RES   408   408        Phosphoserine; by PKA. 
MOD_RES   431   431        Phosphoserine. 
MOD_RES   436   436        Phosphoserine; by PKA. 
MOD_RES   445   445        Phosphothreonine; by ROCK1. 
MOD_RES   465   465        Phosphoserine. 
MOD_RES   480   480        Phosphothreonine; by ROCK1. 
MOD_RES   481   481        Phosphoserine; by PKA. 
MOD_RES   483   483        Phosphoserine (By similarity). 
MOD_RES   586   586        Phosphoserine (By similarity). 
MOD_RES   614   614        Phosphothreonine (By similarity). 
MOD_RES   707   707        Phosphoserine. 
MOD_RES   710   710        Phosphoserine. 
MOD_RES   716   716        Phosphoserine; by PKC. 
MOD_RES   726   726        Phosphoserine; by PKA and PKC. 
VAR_SEQ   471   471        K -> KVWTNITHDHVKPLLQSLSSGVCVPSCITNCL (in isoform 3). VSP_000174
VAR_SEQ   621   631        DLVPEPTTGDD -> GDGCAREYLLP (in isoform 2). VSP_000175
VAR_SEQ   632   737        Missing (in isoform 2). VSP_000176
VARIANT   6     6  1     R -> C (in dbSNP:rs2295497 [NCBI]). VAR_022108 
VARIANT   270   270  1     Y -> N (in dbSNP:rs4971 [NCBI]). VAR_014863 
VARIANT   376   376  1     E -> D (in dbSNP:rs4972 [NCBI]). VAR_014864 
VARIANT   460   460  1     G -> W (in dbSNP:rs4961 [NCBI]). VAR_014184 
VARIANT   510   510  1     N -> I (in dbSNP:rs4962 [NCBI]). VAR_014865 
VARIANT   586   586  1     S -> C (in dbSNP:rs4963 [NCBI]). VAR_014185 
MUTAGEN   445   445        T->D: Abolishes phosphorylation by ROCK1; when associated with D-480. 
MUTAGEN   480   480        T->D: Abolishes phosphorylation by ROCK1; when associated with D-445. 
CONFLICT   606   606        A -> E (in Ref. 2; AAB05645). 
Sequence information
Length: 737 AA [This is the length of the unprocessed precursor] Molecular weight: 80955 Da [This is the MW of the unprocessed precursor] CRC64: DF13AB30B12F20B6 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MNGDSRAAVV TSPPPTTAPH KERYFDRVDE NNPEYLRERN MAPDLRQDFN MMEQKKRVSM 

        70         80         90        100        110        120 
ILQSPAFCEE LESMIQEQFK KGKNPTGLLA LQQIADFMTT NVPNVYPAAP QGGMAALNMS 

       130        140        150        160        170        180 
LGMVTPVNDL RGSDSIAYDK GEKLLRCKLA AFYRLADLFG WSQLIYNHIT TRVNSEQEHF 

       190        200        210        220        230        240 
LIVPFGLLYS EVTASSLVKI NLQGDIVDRG STNLGVNQAG FTLHSAIYAA RPDVKCVVHI 

       250        260        270        280        290        300 
HTPAGAAVSA MKCGLLPISP EALSLGEVAY HDYHGILVDE EEKVLIQKNL GPKSKVLILR 

       310        320        330        340        350        360 
NHGLVSVGES VEEAFYYIHN LVVACEIQVR TLASAGGPDN LVLLNPEKYK AKSRSPGSPV 

       370        380        390        400        410        420 
GEGTGSPPKW QIGEQEFEAL MRMLDNLGYR TGYPYRYPAL REKSKKYSDV EVPASVTGYS 

       430        440        450        460        470        480 
FASDGDSGTC SPLRHSFQKQ QREKTRWLNS GRGDEASEEG QNGSSPKSKT KWTKEDGHRT 

       490        500        510        520        530        540 
STSAVPNLFV PLNTNPKEVQ EMRNKIREQN LQDIKTAGPQ SQVLCGVVMD RSLVQGELVT 

       550        560        570        580        590        600 
ASKAIIEKEY QPHVIVSTTG PNPFTTLTDR ELEEYRREVE RKQKGSEENL DEAREQKEKS 

       610        620        630        640        650        660 
PPDQPAVPHP PPSTPIKLEE DLVPEPTTGD DSDAATFKPT LPDLSPDEPS EALGFPMLEK 

       670        680        690        700        710        720 
EEEAHRPPSP TEAPTEASPE PAPDPAPVAE EAAPSAVEEG AAADPGSDGS PGKSPSKKKK 

       730 
KFRTPSFLKK SKKKSDS 

P35611 in FASTA format

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