Integrin alpha-4

Details

Name
Integrin alpha-4
Synonyms
  • CD49 antigen-like family member D
  • CD49D
  • Integrin alpha-IV
  • VLA-4 subunit alpha
Gene Name
ITGA4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037051|Integrin alpha-4
MAWEARREPGPRRAAVRETVMLLLCLGVPTGRPYNVDTESALLYQGPHNTLFGYSVVLHS
HGANRWLLVGAPTANWLANASVINPGAIYRCRIGKNPGQTCEQLQLGSPNGEPCGKTCLE
ERDNQWLGVTLSRQPGENGSIVTCGHRWKNIFYIKNENKLPTGGCYGVPPDLRTELSKRI
APCYQDYVKKFGENFASCQAGISSFYTKDLIVMGAPGSSYWTGSLFVYNITTNKYKAFLD
KQNQVKFGSYLGYSVGAGHFRSQHTTEVVGGAPQHEQIGKAYIFSIDEKELNILHEMKGK
KLGSYFGASVCAVDLNADGFSDLLVGAPMQSTIREEGRVFVYINSGSGAVMNAMETNLVG
SDKYAARFGESIVNLGDIDNDGFEDVAIGAPQEDDLQGAIYIYNGRADGISSTFSQRIEG
LQISKSLSMFGQSISGQIDADNNGYVDVAVGAFRSDSAVLLRTRPVVIVDASLSHPESVN
RTKFDCVENGWPSVCIDLTLCFSYKGKEVPGYIVLFYNMSLDVNRKAESPPRFYFSSNGT
SDVITGSIQVSSREANCRTHQAFMRKDVRDILTPIQIEAAYHLGPHVISKRSTEEFPPLQ
PILQQKKEKDIMKKTINFARFCAHENCSADLQVSAKIGFLKPHENKTYLAVGSMKTLMLN
VSLFNAGDDAYETTLHVKLPVGLYFIKILELEEKQINCEVTDNSGVVQLDCSIGYIYVDH
LSRIDISFLLDVSSLSRAEEDLSITVHATCENEEEMDNLKHSRVTVAIPLKYEVKLTVHG
FVNPTSFVYGSNDENEPETCMVEKMNLTFHVINTGNSMAPNVSVEIMVPNSFSPQTDKLF
NILDVQTTTGECHFENYQRVCALEQQKSAMQTLKGIVRFLSKTDKRLLYCIKADPHCLNF
LCNFGKMESGKEASVHIQLEGRPSILEMDETSALKFEIRATGFPEPNPRVIELNKDENVA
HVLLEGLHHQRPKRYFTIVIISSSLLLGLIVLLLISYVMWKAGFFKRQYKSILQEENRRD
SWSYINSKSNDD
Number of residues
1032
Molecular Weight
114898.745
Theoretical pI
6.32
GO Classification
Functions
cell adhesion molecule binding / metal ion binding
Processes
B cell differentiation / blood coagulation / blood vessel remodeling / cell-matrix adhesion / cell-matrix adhesion involved in ameboidal cell migration / cellular response to cytokine stimulus / chorio-allantoic fusion / diapedesis / endodermal cell differentiation / extracellular matrix organization / face development / heart development / heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules / heterotypic cell-cell adhesion / import into cell / integrin-mediated signaling pathway / leukocyte cell-cell adhesion / leukocyte migration / leukocyte tethering or rolling / negative regulation of protein homodimerization activity / positive regulation of leukocyte tethering or rolling / positive regulation of T cell migration / receptor clustering / regulation of immune response / substrate adhesion-dependent cell spreading / T cell migration
Components
cell surface / cell-cell junction / external side of plasma membrane / extracellular exosome / focal adhesion / integrin alpha4-beta7 complex / membrane / plasma membrane
General Function
Metal ion binding
Specific Function
Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are also receptors for VCAM1. Integrin alpha-4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On activated endothelial cells integrin VLA-4 triggers homotypic aggregation for most VLA-4-positive leukocyte cell lines. It may also participate in cytolytic T-cell interactions with target cells.
Pfam Domain Function
Transmembrane Regions
978-1001
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0010411|Integrin alpha-4 (ITGA4)
ATGGCTTGGGAAGCGAGGCGCGAACCCGGCCCCCGAAGGGCCGCCGTCCGGGAGACGGTG
ATGCTGTTGCTGTGCCTGGGGGTCCCGACCGGCCGCCCCTACAACGTGGACACTGAGAGC
GCGCTGCTTTACCAGGGCCCCCACAACACGCTGTTCGGCTACTCGGTCGTGCTGCACAGC
CACGGGGCGAACCGATGGCTCCTAGTGGGTGCGCCCACTGCCAACTGGCTCGCCAACGCT
TCAGTGATCAATCCCGGGGCGATTTACAGATGCAGGATCGGAAAGAATCCCGGCCAGACG
TGCGAACAGCTCCAGCTGGGTAGCCCTAATGGAGAACCTTGTGGAAAGACTTGTTTGGAA
GAGAGAGACAATCAGTGGTTGGGGGTCACACTTTCCAGACAGCCAGGAGAAAATGGATCC
ATCGTGACTTGTGGGCATAGATGGAAAAATATATTTTACATAAAGAATGAAAATAAGCTC
CCCACTGGTGGTTGCTATGGAGTGCCCCCTGATTTACGAACAGAACTGAGTAAAAGAATA
GCTCCGTGTTATCAAGATTATGTGAAAAAATTTGGAGAAAATTTTGCATCATGTCAAGCT
GGAATATCCAGTTTTTACACAAAGGATTTAATTGTGATGGGGGCCCCAGGATCATCTTAC
TGGACTGGCTCTCTTTTTGTCTACAATATAACTACAAATAAATACAAGGCTTTTTTAGAC
AAACAAAATCAAGTAAAATTTGGAAGTTATTTAGGATATTCAGTCGGAGCTGGTCATTTT
CGGAGCCAGCATACTACCGAAGTAGTCGGAGGAGCTCCTCAACATGAGCAGATTGGTAAG
GCATATATATTCAGCATTGATGAAAAAGAACTAAATATCTTACATGAAATGAAAGGTAAA
AAGCTTGGATCGTACTTTGGAGCTTCTGTCTGTGCTGTGGACCTCAATGCAGATGGCTTC
TCAGATCTGCTCGTGGGAGCACCCATGCAGAGCACCATCAGAGAGGAAGGAAGAGTGTTT
GTGTACATCAACTCTGGCTCGGGAGCAGTAATGAATGCAATGGAAACAAACCTCGTTGGA
AGTGACAAATATGCTGCAAGATTTGGGGAATCTATAGTTAATCTTGGCGACATTGACAAT
GATGGCTTTGAAGATGTTGCTATCGGAGCTCCACAAGAAGATGACTTGCAAGGTGCTATT
TATATTTACAATGGCCGTGCAGATGGGATCTCGTCAACCTTCTCACAGAGAATTGAAGGA
CTTCAGATCAGCAAATCGTTAAGTATGTTTGGACAGTCTATATCAGGACAAATTGATGCA
GATAATAATGGCTATGTAGATGTAGCAGTTGGTGCTTTTCGGTCTGATTCTGCTGTCTTG
CTAAGGACAAGACCTGTAGTAATTGTTGACGCTTCTTTAAGCCACCCTGAGTCAGTAAAT
AGAACGAAATTTGACTGTGTTGAAAATGGATGGCCTTCTGTGTGCATAGATCTAACACTT
TGTTTCTCATATAAGGGCAAGGAAGTTCCAGGTTACATTGTTTTGTTTTATAACATGAGT
TTGGATGTGAACAGAAAGGCAGAGTCTCCACCAAGATTCTATTTCTCTTCTAATGGAACT
TCTGACGTGATTACAGGAAGCATACAGGTGTCCAGCAGAGAAGCTAACTGTAGAACACAT
CAAGCATTTATGCGGAAAGATGTGCGGGACATCCTCACCCCAATTCAGATTGAAGCTGCT
TACCACCTTGGTCCTCATGTCATCAGTAAACGAAGTACAGAGGAATTCCCACCACTTCAG
CCAATTCTTCAGCAGAAGAAAGAAAAAGACATAATGAAAAAAACAATAAACTTTGCAAGG
TTTTGTGCCCATGAAAATTGTTCTGCTGATTTACAGGTTTCTGCAAAGATTGGGTTTTTG
AAGCCCCATGAAAATAAAACATATCTTGCTGTTGGGAGTATGAAGACATTGATGTTGAAT
GTGTCCTTGTTTAATGCTGGAGATGATGCATATGAAACGACTCTACATGTCAAACTACCC
GTGGGTCTTTATTTCATTAAGATTTTAGAGCTGGAAGAGAAGCAAATAAACTGTGAAGTC
ACAGATAACTCTGGCGTGGTACAACTTGACTGCAGTATTGGCTATATATATGTAGATCAT
CTCTCAAGGATAGATATTAGCTTTCTCCTGGATGTGAGCTCACTCAGCAGAGCGGAAGAG
GACCTCAGTATCACAGTGCATGCTACCTGTGAAAATGAAGAGGAAATGGACAATCTAAAG
CACAGCAGAGTGACTGTAGCAATACCTTTAAAATATGAGGTTAAGCTGACTGTTCATGGG
TTTGTAAACCCAACTTCATTTGTGTATGGATCAAATGATGAAAATGAGCCTGAAACGTGC
ATGGTGGAGAAAATGAACTTAACTTTCCATGTTATCAACACTGGCAATAGTATGGCTCCC
AATGTTAGTGTGGAAATAATGGTACCAAATTCTTTTAGCCCCCAAACTGATAAGCTGTTC
AACATTTTGGATGTCCAGACTACTACTGGAGAATGCCACTTTGAAAATTATCAAAGAGTG
TGTGCATTAGAGCAGCAAAAGAGTGCAATGCAGACCTTGAAAGGCATAGTCCGGTTCTTG
TCCAAGACTGATAAGAGGCTATTGTACTGCATAAAAGCTGATCCACATTGTTTAAATTTC
TTGTGTAATTTTGGGAAAATGGAAAGTGGAAAAGAAGCCAGTGTTCATATCCAACTGGAA
GGCCGGCCATCCATTTTAGAAATGGATGAGACTTCAGCACTCAAGTTTGAAATAAGAGCA
ACAGGTTTTCCAGAGCCAAATCCAAGAGTAATTGAACTAAACAAGGATGAGAATGTTGCG
CATGTTCTACTGGAAGGACTACATCATCAAAGACCCAAACGTTATTTCACCATAGTGATT
ATTTCAAGTAGCTTGCTACTTGGACTTATTGTACTTCTGTTGATCTCATATGTTATGTGG
AAGGCTGGCTTCTTTAAAAGACAATACAAATCTATCCTACAAGAAGAAAACAGAAGAGAC
AGTTGGAGTTATATCAACAGTAAAAGCAATGATGATTAA
Chromosome Location
2
Locus
2q31.3
External Identifiers
ResourceLink
UniProtKB IDP13612
UniProtKB Entry NameITA4_HUMAN
GenBank Protein ID33946
GenBank Gene IDX16983
GenAtlas IDITGA4
HGNC IDHGNC:6140
General References
  1. Takada Y, Elices MJ, Crouse C, Hemler ME: The primary structure of the alpha 4 subunit of VLA-4: homology to other integrins and a possible cell-cell adhesion function. EMBO J. 1989 May;8(5):1361-8. [Article]
  2. Rubio M, Nueda A, Vara A, Corbi Lopez AL: A single mRNA encodes the alpha 150 and alpha 80/70 forms of the alpha subunit of VLA4. Eur J Immunol. 1992 Apr;22(4):1099-102. [Article]
  3. Szabo M, McIntyre BW: Identification of two variants of the human integrin alpha 4 subunit. Mol Immunol. 1995 Dec;32(17-18):1453-4. [Article]
  4. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, 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 EA, 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 SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [Article]
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  6. Rosen GD, Birkenmeier TM, Dean DC: Characterization of the alpha 4 integrin gene promoter. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4094-8. [Article]
  7. Takada Y, Strominger JL, Hemler ME: The very late antigen family of heterodimers is part of a superfamily of molecules involved in adhesion and embryogenesis. Proc Natl Acad Sci U S A. 1987 May;84(10):3239-43. [Article]
  8. Teixido J, Parker CM, Kassner PD, Hemler ME: Functional and structural analysis of VLA-4 integrin alpha 4 subunit cleavage. J Biol Chem. 1992 Jan 25;267(3):1786-91. [Article]
  9. Iida J, Meijne AM, Oegema TR Jr, Yednock TA, Kovach NL, Furcht LT, McCarthy JB: A role of chondroitin sulfate glycosaminoglycan binding site in alpha4beta1 integrin-mediated melanoma cell adhesion. J Biol Chem. 1998 Mar 6;273(10):5955-62. [Article]
  10. Liu S, Thomas SM, Woodside DG, Rose DM, Kiosses WB, Pfaff M, Ginsberg MH: Binding of paxillin to alpha4 integrins modifies integrin-dependent biological responses. Nature. 1999 Dec 9;402(6762):676-81. [Article]
  11. Han J, Liu S, Rose DM, Schlaepfer DD, McDonald H, Ginsberg MH: Phosphorylation of the integrin alpha 4 cytoplasmic domain regulates paxillin binding. J Biol Chem. 2001 Nov 2;276(44):40903-9. Epub 2001 Aug 30. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00108Natalizumabapproved, investigationalyesantibodyDetails
DB04997ATL1102investigationalunknownDetails
DB05092CDP323investigationalunknownDetails
DB05122R1295investigationalunknownDetails
DB05468R411investigationalunknownDetails
DB06822TinzaparinapprovedunknowninhibitorDetails
DB09033VedolizumabapprovedyesantibodyDetails
DB15791MK-0668experimentalunknownDetails