ITGA6

Protein identityUniProt · HPA

UniProt accession

P23229

Gene

ITGA6

Ensembl

ENSG00000091409

Chromosome

2

Canonical length

1130 aa

Protein class

Cancer-related genes, CD markers, Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

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 6 subunit. This subunit may associate with a beta 1 or beta 4 subunit to form an integrin that interacts with extracellular matrix proteins including members of the laminin family. The alpha 6 beta 4 integrin may promote tumorigenesis, while the alpha 6 beta 1 integrin may negatively regulate erbB2/HER2 signaling. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

Canonical amino-acid sequenceUniProt

1130 residues, UniProt reviewed canonical sequence.

>P23229|ITGA6
     1  MAAAGQLCLL YLSAGLLSRL GAAFNLDTRE DNVIRKYGDP GSLFGFSLAM HWQLQPEDKR
    61  LLLVGAPRAE ALPLQRANRT GGLYSCDITA RGPCTRIEFD NDADPTSESK EDQWMGVTVQ
   121  SQGPGGKVVT CAHRYEKRQH VNTKQESRDI FGRCYVLSQN LRIEDDMDGG DWSFCDGRLR
   181  GHEKFGSCQQ GVAATFTKDF HYIVFGAPGT YNWKGIVRVE QKNNTFFDMN IFEDGPYEVG
   241  GETEHDESLV PVPANSYLGL LFLTSVSYTD PDQFVYKTRP PREQPDTFPD VMMNSYLGFS
   301  LDSGKGIVSK DEITFVSGAP RANHSGAVVL LKRDMKSAHL LPEHIFDGEG LASSFGYDVA
   361  VVDLNKDGWQ DIVIGAPQYF DRDGEVGGAV YVYMNQQGRW NNVKPIRLNG TKDSMFGIAV
   421  KNIGDINQDG YPDIAVGAPY DDLGKVFIYH GSANGINTKP TQVLKGISPY FGYSIAGNMD
   481  LDRNSYPDVA VGSLSDSVTI FRSRPVINIQ KTITVTPNRI DLRQKTACGA PSGICLQVKS
   541  CFEYTANPAG YNPSISIVGT LEAEKERRKS GLSSRVQFRN QGSEPKYTQE LTLKRQKQKV
   601  CMEETLWLQD NIRDKLRPIP ITASVEIQEP SSRRRVNSLP EVLPILNSDE PKTAHIDVHF
   661  LKEGCGDDNV CNSNLKLEYK FCTREGNQDK FSYLPIQKGV PELVLKDQKD IALEITVTNS
   721  PSNPRNPTKD GDDAHEAKLI ATFPDTLTYS AYRELRAFPE KQLSCVANQN GSQADCELGN
   781  PFKRNSNVTF YLVLSTTEVT FDTPDLDINL KLETTSNQDN LAPITAKAKV VIELLLSVSG
   841  VAKPSQVYFG GTVVGEQAMK SEDEVGSLIE YEFRVINLGK PLTNLGTATL NIQWPKEISN
   901  GKWLLYLVKV ESKGLEKVTC EPQKEINSLN LTESHNSRKK REITEKQIDD NRKFSLFAER
   961  KYQTLNCSVN VNCVNIRCPL RGLDSKASLI LRSRLWNSTF LEEYSKLNYL DILMRAFIDV
  1021  TAAAENIRLP NAGTQVRVTV FPSKTVAQYS GVPWWIILVA ILAGILMLAL LVFILWKCGF
  1081  FKRSRYDDSV PRYHAVRIRK EEREIKDEKY IDNLEKKQWI TKWNENESYS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ITGA6 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)

0.31

Highest tissue expression

76 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ITGA6.

Disease | AllUniProt

Conditions ITGA6 is implicated in, by any mechanism.

• Epidermolysis bullosa, junctional 6, with pyloric atresia (JEB6) MIM:619817

Disease | GeneticClinVar

54 pathogenic / likely-pathogenic of 853 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Epidermolysis bullosa, junctional 6, with pyloric atresia
• Junctional epidermolysis bullosa with pyloric atresia
• Childhood-onset schizophrenia
• Junctional epidermolysis bullosa
• Epidermolysis bullosa

Disease | ImmuneIEDB

Conditions an epitope on ITGA6 was assayed in.

• pemphigus B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against ITGA6 are reported. Each links to that disease's full target list.

• Pemphigoid, Bullous 3

ReferencesPubMed · IEDB

Publications for ITGA6 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. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). 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)

0.53

gnomAD pLI

0

gnomAD missense Z

1.65

DepMap mean gene effect

-0.12

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

• cell-cell adhesion
• cell-matrix adhesion
• cell-substrate adhesion
• cell-substrate junction assembly
• ectodermal cell differentiation
• integrin-mediated signaling pathway
• leukocyte migration
• nail development
• negative regulation of extrinsic apoptotic signaling pathway
• positive regulation of apoptotic process
• positive regulation of cell migration
• positive regulation of GTPase activity
• positive regulation of neuron projection development
• positive regulation of transcription by RNA polymerase II
• skin morphogenesis

Molecular functions

• cadherin binding
• insulin-like growth factor I binding
• metal ion binding
• neuregulin binding
• signaling receptor activity

Cellular components

• cell surface
• focal adhesion
• integrin alpha6-beta1 complex
• plasma membrane
• integrin alpha6-beta4 complex

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
• Cell membrane
• Cleavage on pair of basic residues
• Disulfide bond
• Epidermolysis bullosa
• Glycoprotein
• Integrin
• Lipoprotein
• Membrane
• Metal-binding
• Palmitate
• Phosphoprotein
• Receptor
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of ITGA6 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ADAM9
• CD82
• IGF2
• MDK
• RAB21
• CD151
• ITGB1