ITGB4

Protein identityUniProt · HPA

UniProt accession

P16144

Gene

ITGB4

Ensembl

ENSG00000132470

Chromosome

17

Canonical length

1822 aa

Protein class

Cancer-related genes, CD markers, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Plasma membrane,Cell Junctions

OverviewNCBI Gene

Integrins are heterodimers comprised of alpha and beta subunits, that are noncovalently associated transmembrane glycoprotein receptors. Different combinations of alpha and beta polypeptides form complexes that vary in their ligand-binding specificities. Integrins mediate cell-matrix or cell-cell adhesion, and transduced signals that regulate gene expression and cell growth. This gene encodes the integrin beta 4 subunit, a receptor for the laminins. This subunit tends to associate with alpha 6 subunit and is likely to play a pivotal role in the biology of invasive carcinoma. Mutations in this gene are associated with epidermolysis bullosa with pyloric atresia. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1822 residues, UniProt reviewed canonical sequence.

>P16144|ITGB4
     1  MAGPRPSPWA RLLLAALISV SLSGTLANRC KKAPVKSCTE CVRVDKDCAY CTDEMFRDRR
    61  CNTQAELLAA GCQRESIVVM ESSFQITEET QIDTTLRRSQ MSPQGLRVRL RPGEERHFEL
   121  EVFEPLESPV DLYILMDFSN SMSDDLDNLK KMGQNLARVL SQLTSDYTIG FGKFVDKVSV
   181  PQTDMRPEKL KEPWPNSDPP FSFKNVISLT EDVDEFRNKL QGERISGNLD APEGGFDAIL
   241  QTAVCTRDIG WRPDSTHLLV FSTESAFHYE ADGANVLAGI MSRNDERCHL DTTGTYTQYR
   301  TQDYPSVPTL VRLLAKHNII PIFAVTNYSY SYYEKLHTYF PVSSLGVLQE DSSNIVELLE
   361  EAFNRIRSNL DIRALDSPRG LRTEVTSKMF QKTRTGSFHI RRGEVGIYQV QLRALEHVDG
   421  THVCQLPEDQ KGNIHLKPSF SDGLKMDAGI ICDVCTCELQ KEVRSARCSF NGDFVCGQCV
   481  CSEGWSGQTC NCSTGSLSDI QPCLREGEDK PCSGRGECQC GHCVCYGEGR YEGQFCEYDN
   541  FQCPRTSGFL CNDRGRCSMG QCVCEPGWTG PSCDCPLSNA TCIDSNGGIC NGRGHCECGR
   601  CHCHQQSLYT DTICEINYSA IHPGLCEDLR SCVQCQAWGT GEKKGRTCEE CNFKVKMVDE
   661  LKRAEEVVVR CSFRDEDDDC TYSYTMEGDG APGPNSTVLV HKKKDCPPGS FWWLIPLLLL
   721  LLPLLALLLL LCWKYCACCK ACLALLPCCN RGHMVGFKED HYMLRENLMA SDHLDTPMLR
   781  SGNLKGRDVV RWKVTNNMQR PGFATHAASI NPTELVPYGL SLRLARLCTE NLLKPDTREC
   841  AQLRQEVEEN LNEVYRQISG VHKLQQTKFR QQPNAGKKQD HTIVDTVLMA PRSAKPALLK
   901  LTEKQVEQRA FHDLKVAPGY YTLTADQDAR GMVEFQEGVE LVDVRVPLFI RPEDDDEKQL
   961  LVEAIDVPAG TATLGRRLVN ITIIKEQARD VVSFEQPEFS VSRGDQVARI PVIRRVLDGG
  1021  KSQVSYRTQD GTAQGNRDYI PVEGELLFQP GEAWKELQVK LLELQEVDSL LRGRQVRRFH
  1081  VQLSNPKFGA HLGQPHSTTI IIRDPDELDR SFTSQMLSSQ PPPHGDLGAP QNPNAKAAGS
  1141  RKIHFNWLPP SGKPMGYRVK YWIQGDSESE AHLLDSKVPS VELTNLYPYC DYEMKVCAYG
  1201  AQGEGPYSSL VSCRTHQEVP SEPGRLAFNV VSSTVTQLSW AEPAETNGEI TAYEVCYGLV
  1261  NDDNRPIGPM KKVLVDNPKN RMLLIENLRE SQPYRYTVKA RNGAGWGPER EAIINLATQP
  1321  KRPMSIPIIP DIPIVDAQSG EDYDSFLMYS DDVLRSPSGS QRPSVSDDTG CGWKFEPLLG
  1381  EELDLRRVTW RLPPELIPRL SASSGRSSDA EAPHGPPDDG GAGGKGGSLP RSATPGPPGE
  1441  HLVNGRMDFA FPGSTNSLHR MTTTSAAAYG THLSPHVPHR VLSTSSTLTR DYNSLTRSEH
  1501  SHSTTLPRDY STLTSVSSHD SRLTAGVPDT PTRLVFSALG PTSLRVSWQE PRCERPLQGY
  1561  SVEYQLLNGG ELHRLNIPNP AQTSVVVEDL LPNHSYVFRV RAQSQEGWGR EREGVITIES
  1621  QVHPQSPLCP LPGSAFTLST PSAPGPLVFT ALSPDSLQLS WERPRRPNGD IVGYLVTCEM
  1681  AQGGGPATAF RVDGDSPESR LTVPGLSENV PYKFKVQART TEGFGPEREG IITIESQDGG
  1741  PFPQLGSRAG LFQHPLQSEY SSITTTHTSA TEPFLVDGLT LGAQHLEAGG SLTRHVTQEF
  1801  VSRTLTTSGT LSTHMDQQFF QT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ITGB4 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)

0.36

Highest tissue expression

199 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ITGB4.

Disease | AllUniProt

Conditions ITGB4 is implicated in, by any mechanism.

• Epidermolysis bullosa, junctional 5A, intermediate (JEB5A) MIM:619816
• Epidermolysis bullosa, junctional 5B, with pyloric atresia (JEB5B) MIM:226730

Disease | GeneticClinVar

158 pathogenic / likely-pathogenic of 1,953 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Junctional epidermolysis bullosa with pyloric atresia
• Epidermolysis bullosa, junctional 5A, intermediate
• ITGB4-related disorder
• Epidermolysis bullosa simplex 1C, localized
• Junctional epidermolysis bullosa

ReferencesPubMed · IEDB

Publications for ITGB4 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)

0.65

gnomAD pLI

0

gnomAD missense Z

0.37

DepMap mean gene effect

-0.13

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• autophagy
• cell adhesion
• cell adhesion mediated by integrin
• cell migration
• cell motility
• cell-cell adhesion
• cell-matrix adhesion
• filopodium assembly
• hemidesmosome assembly
• integrin-mediated signaling pathway
• mesodermal cell differentiation
• nail development
• peripheral nervous system myelin formation
• response to wounding
• skin morphogenesis
• trophoblast cell migration

Molecular functions

• G protein-coupled receptor binding
• integrin binding
• metal ion binding

Cellular components

• basal plasma membrane
• basement membrane
• cell junction
• cell leading edge
• cell surface
• extracellular exosome
• focal adhesion
• hemidesmosome
• integrin complex
• nuclear membrane
• nucleolus
• plasma membrane
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• EGF-like domain
• Integrin beta subunit, VWA domain
• Na-Ca exchanger/integrin-beta4
• Fibronectin type III
• Integrin beta subunit, tail
• Immunoglobulin-like fold
• Integrin beta subunit
• PSI domain
• Integrin beta N-terminal
• Fibronectin type III superfamily
• Integrin beta tail domain superfamily
• von Willebrand factor A-like domain superfamily
• CalX-like domain superfamily
• Integrin beta, epidermal growth factor-like domain 1
• Integrins beta, I-EGF domain, conserved site
• Fibronectin type III domain
• Integrin beta chain VWA domain
• Calx-beta domain
• Integrin beta tail domain
• Integrin plexin domain
• Integrin beta epidermal growth factor like domain 1
• Teneurin-like EGF domain
• Integrin beta-4 subunit

KeywordsUniProt

• Calcium
• Cell adhesion
• Cell junction
• Cell membrane
• Disulfide bond
• EGF-like domain
• Epidermolysis bullosa
• Glycoprotein
• Integrin
• Lipoprotein
• Magnesium
• Membrane
• Metal-binding
• Palmitate
• Phosphoprotein
• Receptor
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of ITGB4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• IGF2
• RAC1
• TMEM268
• ERBIN