ITAE_HUMAN
ID ITAE_HUMAN Reviewed; 1179 AA.
AC P38570; Q17RS6; Q9NZU9;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 14-APR-2009, sequence version 3.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Integrin alpha-E;
DE AltName: Full=HML-1 antigen;
DE AltName: Full=Integrin alpha-IEL;
DE AltName: Full=Mucosal lymphocyte 1 antigen;
DE AltName: CD_antigen=CD103;
DE Contains:
DE RecName: Full=Integrin alpha-E light chain;
DE Contains:
DE RecName: Full=Integrin alpha-E heavy chain;
DE Flags: Precursor;
GN Name=ITGAE;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 19-38 AND 179-188, AND
RP VARIANTS VAL-477; GLN-482 AND ALA-1019.
RC TISSUE=Leukemia, and Lymphocyte;
RX PubMed=8119947; DOI=10.1016/s0021-9258(17)37563-4;
RA Shaw S.K., Cepek K.L., Murphy E.A., Russell G.J., Brenner M.B.,
RA Parker C.M.;
RT "Molecular cloning of the human mucosal lymphocyte integrin alpha E
RT subunit. Unusual structure and restricted RNA distribution.";
RL J. Biol. Chem. 269:6016-6025(1994).
RN [2]
RP SEQUENCE REVISION TO 88-114.
RA Parker C.M.;
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-477; GLN-482 AND
RP ALA-1019.
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 53-1179, AND VARIANT TRP-950.
RC TISSUE=Fetal kidney;
RX PubMed=10673275; DOI=10.1101/gr.10.2.165;
RA Touchman J.W., Anikster Y., Dietrich N.L., Maduro V.V.B., McDowell G.,
RA Shotelersuk V., Bouffard G.G., Beckstrom-Sternberg S.M., Gahl W.A.,
RA Green E.D.;
RT "The genomic region encompassing the nephropathic cystinosis gene (CTNS):
RT complete sequencing of a 200-kb segment and discovery of a novel gene
RT within the common cystinosis-causing deletion.";
RL Genome Res. 10:165-173(2000).
RN [6]
RP INTERACTION WITH INTEGRIN BETA-7, AND INDUCTION.
RX PubMed=1542691; DOI=10.1073/pnas.89.5.1924;
RA Parker C.M., Cepek K.L., Russell G.J., Shaw S.K., Posnett D.N.,
RA Schwarting R., Brenner M.B.;
RT "A family of beta 7 integrins on human mucosal lymphocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:1924-1928(1992).
RN [7]
RP MUTAGENESIS OF ASP-208 AND PHE-316.
RX PubMed=10837471; DOI=10.1074/jbc.m001228200;
RA Higgins J.M.G., Cernadas M., Tan K., Irie A., Wang J.-H., Takada Y.,
RA Brenner M.B.;
RT "The role of alpha and beta chains in ligand recognition by beta 7
RT integrins.";
RL J. Biol. Chem. 275:25652-25664(2000).
CC -!- FUNCTION: Integrin alpha-E/beta-7 is a receptor for E-cadherin. It
CC mediates adhesion of intra-epithelial T-lymphocytes to epithelial cell
CC monolayers.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. The alpha subunit
CC is composed of a heavy and a light chains linked by a disulfide bond.
CC Alpha-E associates with beta-7.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed on a subclass of T-lymphocytes known as
CC intra-epithelial lymphocytes which are located between mucosal
CC epithelial cells.
CC -!- INDUCTION: Integrin alpha-E/beta-7 is induced by TGFB1.
CC {ECO:0000269|PubMed:1542691}.
CC -!- DOMAIN: The integrin I-domain (insert) is a VWFA domain. Integrins with
CC I-domains do not undergo protease cleavage.
CC -!- SIMILARITY: Belongs to the integrin alpha chain family. {ECO:0000305}.
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DR EMBL; L25851; AAB59359.2; -; mRNA.
DR EMBL; AC116914; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC113436; AAI13437.1; -; mRNA.
DR EMBL; BC117207; AAI17208.1; -; mRNA.
DR EMBL; AF168787; AAF43107.1; -; Genomic_DNA.
DR CCDS; CCDS32531.1; -.
DR PIR; A53213; A53213.
DR RefSeq; NP_002199.3; NM_002208.4.
DR AlphaFoldDB; P38570; -.
DR SMR; P38570; -.
DR BioGRID; 109888; 5.
DR ComplexPortal; CPX-1824; Integrin alphaE-beta7 complex.
DR CORUM; P38570; -.
DR IntAct; P38570; 2.
DR STRING; 9606.ENSP00000263087; -.
DR GlyGen; P38570; 11 sites.
DR iPTMnet; P38570; -.
DR PhosphoSitePlus; P38570; -.
DR BioMuta; ITGAE; -.
DR DMDM; 226694184; -.
DR EPD; P38570; -.
DR jPOST; P38570; -.
DR MassIVE; P38570; -.
DR PaxDb; P38570; -.
DR PeptideAtlas; P38570; -.
DR PRIDE; P38570; -.
DR ProteomicsDB; 55300; -.
DR Antibodypedia; 10997; 1083 antibodies from 44 providers.
DR CPTC; P38570; 1 antibody.
DR DNASU; 3682; -.
DR Ensembl; ENST00000263087.9; ENSP00000263087.4; ENSG00000083457.12.
DR GeneID; 3682; -.
DR KEGG; hsa:3682; -.
DR MANE-Select; ENST00000263087.9; ENSP00000263087.4; NM_002208.5; NP_002199.3.
DR UCSC; uc002fwo.5; human.
DR CTD; 3682; -.
DR DisGeNET; 3682; -.
DR GeneCards; ITGAE; -.
DR HGNC; HGNC:6147; ITGAE.
DR HPA; ENSG00000083457; Tissue enhanced (bone marrow, intestine, lung, lymphoid tissue).
DR MIM; 604682; gene.
DR neXtProt; NX_P38570; -.
DR OpenTargets; ENSG00000083457; -.
DR PharmGKB; PA29947; -.
DR VEuPathDB; HostDB:ENSG00000083457; -.
DR eggNOG; KOG3637; Eukaryota.
DR GeneTree; ENSGT00940000161532; -.
DR HOGENOM; CLU_004111_0_0_1; -.
DR InParanoid; P38570; -.
DR OMA; QICVPTK; -.
DR OrthoDB; 743479at2759; -.
DR PhylomeDB; P38570; -.
DR TreeFam; TF105391; -.
DR PathwayCommons; P38570; -.
DR Reactome; R-HSA-216083; Integrin cell surface interactions.
DR SignaLink; P38570; -.
DR SIGNOR; P38570; -.
DR BioGRID-ORCS; 3682; 9 hits in 1083 CRISPR screens.
DR ChiTaRS; ITGAE; human.
DR GeneWiki; ITGAE; -.
DR GenomeRNAi; 3682; -.
DR Pharos; P38570; Tbio.
DR PRO; PR:P38570; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P38570; protein.
DR Bgee; ENSG00000083457; Expressed in oocyte and 206 other tissues.
DR ExpressionAtlas; P38570; baseline and differential.
DR Genevisible; P38570; HS.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0008305; C:integrin complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005178; F:integrin binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0033627; P:cell adhesion mediated by integrin; IBA:GO_Central.
DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0007160; P:cell-matrix adhesion; IBA:GO_Central.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IBA:GO_Central.
DR Gene3D; 2.130.10.130; -; 2.
DR Gene3D; 3.40.50.410; -; 1.
DR InterPro; IPR013517; FG-GAP.
DR InterPro; IPR013519; Int_alpha_beta-p.
DR InterPro; IPR000413; Integrin_alpha.
DR InterPro; IPR013649; Integrin_alpha-2.
DR InterPro; IPR018184; Integrin_alpha_C_CS.
DR InterPro; IPR028994; Integrin_alpha_N.
DR InterPro; IPR032695; Integrin_dom_sf.
DR InterPro; IPR002035; VWF_A.
DR InterPro; IPR036465; vWFA_dom_sf.
DR Pfam; PF01839; FG-GAP; 1.
DR Pfam; PF00357; Integrin_alpha; 1.
DR Pfam; PF08441; Integrin_alpha2; 1.
DR Pfam; PF00092; VWA; 1.
DR PRINTS; PR01185; INTEGRINA.
DR SMART; SM00191; Int_alpha; 4.
DR SMART; SM00327; VWA; 1.
DR SUPFAM; SSF53300; SSF53300; 1.
DR SUPFAM; SSF69179; SSF69179; 2.
DR SUPFAM; SSF69318; SSF69318; 1.
DR PROSITE; PS51470; FG_GAP; 5.
DR PROSITE; PS00242; INTEGRIN_ALPHA; 1.
DR PROSITE; PS50234; VWFA; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell adhesion; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Integrin;
KW Magnesium; Membrane; Metal-binding; Receptor; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:8119947"
FT CHAIN 19..1179
FT /note="Integrin alpha-E"
FT /id="PRO_0000016283"
FT CHAIN 19..177
FT /note="Integrin alpha-E light chain"
FT /id="PRO_0000016284"
FT CHAIN 179..1177
FT /note="Integrin alpha-E heavy chain"
FT /id="PRO_0000016285"
FT TOPO_DOM 19..1124
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1125..1147
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1148..1179
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 22..79
FT /note="FG-GAP 1"
FT REPEAT 80..138
FT /note="FG-GAP 2"
FT DOMAIN 200..389
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT REPEAT 390..442
FT /note="FG-GAP 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT REPEAT 447..499
FT /note="FG-GAP 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT REPEAT 500..560
FT /note="FG-GAP 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT REPEAT 563..627
FT /note="FG-GAP 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT REPEAT 631..691
FT /note="FG-GAP 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT REGION 145..199
FT /note="X-domain (extra domain)"
FT REGION 158..200
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1150..1154
FT /note="GFFKR motif"
FT COMPBIAS 158..184
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 185..200
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 522
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 524
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 526
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 530
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 586
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 588
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 590
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 594
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 654
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 656
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 658
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 662
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT CARBOHYD 49
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 271
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 321
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 444
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 726
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 782
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 857
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 934
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 954
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1065
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1096
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 70..79
FT /evidence="ECO:0000250"
FT DISULFID 126..159
FT /evidence="ECO:0000250"
FT DISULFID 706..762
FT /evidence="ECO:0000250"
FT DISULFID 823..829
FT /evidence="ECO:0000250"
FT DISULFID 893..907
FT /evidence="ECO:0000250"
FT DISULFID 1008..1033
FT /evidence="ECO:0000250"
FT DISULFID 1041..1057
FT /evidence="ECO:0000250"
FT VARIANT 360
FT /note="D -> E"
FT /id="VAR_008884"
FT VARIANT 477
FT /note="I -> V (in dbSNP:rs220479)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:8119947"
FT /id="VAR_054889"
FT VARIANT 482
FT /note="R -> Q (in dbSNP:rs2272606)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:8119947"
FT /id="VAR_054890"
FT VARIANT 892
FT /note="Q -> H (in dbSNP:rs3744679)"
FT /id="VAR_020037"
FT VARIANT 950
FT /note="R -> W (in dbSNP:rs1716)"
FT /evidence="ECO:0000269|PubMed:10673275"
FT /id="VAR_034025"
FT VARIANT 1019
FT /note="V -> A (in dbSNP:rs2976230)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:8119947"
FT /id="VAR_054891"
FT VARIANT 1041
FT /note="C -> S"
FT /id="VAR_008885"
FT MUTAGEN 208
FT /note="D->A: Loss of E-cadherin binding."
FT /evidence="ECO:0000269|PubMed:10837471"
FT MUTAGEN 316
FT /note="F->A: Loss of E-cadherin binding."
FT /evidence="ECO:0000269|PubMed:10837471"
SQ SEQUENCE 1179 AA; 130159 MW; 6645F8FFF9A0F045 CRC64;
MWLFHTLLCI ASLALLAAFN VDVARPWLTP KGGAPFVLSS LLHQDPSTNQ TWLLVTSPRT
KRTPGPLHRC SLVQDEILCH PVEHVPIPKG RHRGVTVVRS HHGVLICIQV LVRRPHSLSS
ELTGTCSLLG PDLRPQAQAN FFDLENLLDP DARVDTGDCY SNKEGGGEDD VNTARQRRAL
EKEEEEDKEE EEDEEEEEAG TEIAIILDGS GSIDPPDFQR AKDFISNMMR NFYEKCFECN
FALVQYGGVI QTEFDLRDSQ DVMASLARVQ NITQVGSVTK TASAMQHVLD SIFTSSHGSR
RKASKVMVVL TDGGIFEDPL NLTTVINSPK MQGVERFAIG VGEEFKSART ARELNLIASD
PDETHAFKVT NYMALDGLLS KLRYNIISME GTVGDALHYQ LAQIGFSAQI LDERQVLLGA
VGAFDWSGGA LLYDTRSRRG RFLNQTAAAA ADAEAAQYSY LGYAVAVLHK TCSLSYIAGA
PRYKHHGAVF ELQKEGREAS FLPVLEGEQM GSYFGSELCP VDIDMDGSTD FLLVAAPFYH
VHGEEGRVYV YRLSEQDGSF SLARILSGHP GFTNARFGFA MAAMGDLSQD KLTDVAIGAP
LEGFGADDGA SFGSVYIYNG HWDGLSASPS QRIRASTVAP GLQYFGMSMA GGFDISGDGL
ADITVGTLGQ AVVFRSRPVV RLKVSMAFTP SALPIGFNGV VNVRLCFEIS SVTTASESGL
REALLNFTLD VDVGKQRRRL QCSDVRSCLG CLREWSSGSQ LCEDLLLMPT EGELCEEDCF
SNASVKVSYQ LQTPEGQTDH PQPILDRYTE PFAIFQLPYE KACKNKLFCV AELQLATTVS
QQELVVGLTK ELTLNINLTN SGEDSYMTSM ALNYPRNLQL KRMQKPPSPN IQCDDPQPVA
SVLIMNCRIG HPVLKRSSAH VSVVWQLEEN AFPNRTADIT VTVTNSNERR SLANETHTLQ
FRHGFVAVLS KPSIMYVNTG QGLSHHKEFL FHVHGENLFG AEYQLQICVP TKLRGLQVVA
VKKLTRTQAS TVCTWSQERA CAYSSVQHVE EWHSVSCVIA SDKENVTVAA EISWDHSEEL
LKDVTELQIL GEISFNKSLY EGLNAENHRT KITVVFLKDE KYHSLPIIIK GSVGGLLVLI
VILVILFKCG FFKRKYQQLN LESIRKAQLK SENLLEEEN
