ITGA4

Protein identityUniProt · HPA

UniProt accession

P13612

Gene

ITGA4

Ensembl

ENSG00000115232

Chromosome

2

Canonical length

1032 aa

Protein class

Cancer-related genes, CD markers, FDA approved drug targets, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Plasma membrane

Secretome location

Intracellular and membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 4 subunit. This subunit associates with a beta 1 or beta 7 subunit to form an integrin that may play a role in cell motility and migration. This integrin is a therapeutic target for the treatment of multiple sclerosis, Crohn's disease and inflammatory bowel disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

Canonical amino-acid sequenceUniProt

1032 residues, UniProt reviewed canonical sequence.

>P13612|ITGA4
     1  MAWEARREPG PRRAAVRETV MLLLCLGVPT GRPYNVDTES ALLYQGPHNT LFGYSVVLHS
    61  HGANRWLLVG APTANWLANA SVINPGAIYR CRIGKNPGQT CEQLQLGSPN GEPCGKTCLE
   121  ERDNQWLGVT LSRQPGENGS IVTCGHRWKN IFYIKNENKL PTGGCYGVPP DLRTELSKRI
   181  APCYQDYVKK FGENFASCQA GISSFYTKDL IVMGAPGSSY WTGSLFVYNI TTNKYKAFLD
   241  KQNQVKFGSY LGYSVGAGHF RSQHTTEVVG GAPQHEQIGK AYIFSIDEKE LNILHEMKGK
   301  KLGSYFGASV CAVDLNADGF SDLLVGAPMQ STIREEGRVF VYINSGSGAV MNAMETNLVG
   361  SDKYAARFGE SIVNLGDIDN DGFEDVAIGA PQEDDLQGAI YIYNGRADGI SSTFSQRIEG
   421  LQISKSLSMF GQSISGQIDA DNNGYVDVAV GAFRSDSAVL LRTRPVVIVD ASLSHPESVN
   481  RTKFDCVENG WPSVCIDLTL CFSYKGKEVP GYIVLFYNMS LDVNRKAESP PRFYFSSNGT
   541  SDVITGSIQV SSREANCRTH QAFMRKDVRD ILTPIQIEAA YHLGPHVISK RSTEEFPPLQ
   601  PILQQKKEKD IMKKTINFAR FCAHENCSAD LQVSAKIGFL KPHENKTYLA VGSMKTLMLN
   661  VSLFNAGDDA YETTLHVKLP VGLYFIKILE LEEKQINCEV TDNSGVVQLD CSIGYIYVDH
   721  LSRIDISFLL DVSSLSRAEE DLSITVHATC ENEEEMDNLK HSRVTVAIPL KYEVKLTVHG
   781  FVNPTSFVYG SNDENEPETC MVEKMNLTFH VINTGNSMAP NVSVEIMVPN SFSPQTDKLF
   841  NILDVQTTTG ECHFENYQRV CALEQQKSAM QTLKGIVRFL SKTDKRLLYC IKADPHCLNF
   901  LCNFGKMESG KEASVHIQLE GRPSILEMDE TSALKFEIRA TGFPEPNPRV IELNKDENVA
   961  HVLLEGLHHQ RPKRYFTIVI ISSSLLLGLI VLLLISYVMW KAGFFKRQYK SILQEENRRD
  1021  SWSYINSKSN DD

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ITGA4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

69 nTPM

Expression across tissuesHPA

ReferencesPubMed · IEDB

Publications for ITGA4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.47

gnomAD pLI

0

gnomAD missense Z

1.64

DepMap mean gene effect

-0.1

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• axonogenesis involved in innervation
• B cell differentiation
• cell-cell adhesion
• cell-cell adhesion mediated by integrin
• cell-matrix adhesion
• cell-matrix adhesion involved in ameboidal cell migration
• cellular response to amyloid-beta
• cellular response to cytokine stimulus
• diapedesis
• endodermal cell differentiation
• heterotypic cell-cell adhesion
• immune response in gut-associated lymphoid tissue
• integrin-mediated signaling pathway
• leukocyte cell-cell adhesion
• leukocyte tethering or rolling
• negative regulation of vasoconstriction
• neuron projection extension
• positive regulation of endothelial cell apoptotic process
• positive regulation of leukocyte tethering or rolling
• positive regulation of T cell migration
• positive regulation of vascular endothelial cell proliferation
• receptor clustering
• substrate adhesion-dependent cell spreading
• clathrin-dependent extracellular exosome endocytosis
• negative regulation of protein homodimerization activity

Molecular functions

• cell adhesion molecule binding
• coreceptor activity
• fibronectin binding
• integrin binding
• metal ion binding
• protein antigen binding
• signaling receptor activity

Cellular components

• cell surface
• extracellular exosome
• focal adhesion
• growth cone
• integrin alpha4-beta1 complex
• integrin alpha4-beta7 complex
• membrane
• neuronal cell body
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Integrin alpha chain
• FG-GAP repeat
• Integrin alpha beta-propellor
• Integrin alpha, first immunoglubulin-like domain
• Integrin alpha chain, C-terminal cytoplasmic region, conserved site
• Integrin alpha, N-terminal
• Integrin domain superfamily
• Integrin alpha, second immunoglobulin-like domain
• Integrin alpha, third immunoglobulin-like domain
• FG-GAP repeat
• Integrin alpha Ig-like domain 1
• Integrin alpha Ig-like domain 2
• Integrin alpha Ig-like domain 3

KeywordsUniProt

• Calcium
• Cell adhesion
• Disulfide bond
• Glycoprotein
• Integrin
• Membrane
• Metal-binding
• Phosphoprotein
• Receptor
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of ITGA4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BCAM
• JAML
• LPXN
• MDK
• PXN
• SELP
• SVEP1
• CD82