P23229 · ITA6_HUMAN

  • Protein
    Integrin alpha-6
  • Gene
    ITGA6
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Integrin alpha-6/beta-1 (ITGA6:ITGB1) is a receptor for laminin on platelets (By similarity).
Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion (By similarity).
Integrin alpha-6/beta-4 (ITGA6:ITGB4) is a receptor for laminin in epithelial cells and it plays a critical structural role in the hemidesmosome (By similarity).
ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778).
ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:22351760).
ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464).

Features

Showing features for binding site, site.

111301002003004005006007008009001,0001,100
TypeIDPosition(s)Description
Binding site363Ca2+ 1 (UniProtKB | ChEBI)
Binding site365Ca2+ 1 (UniProtKB | ChEBI)
Binding site367Ca2+ 1 (UniProtKB | ChEBI)
Binding site371Ca2+ 1 (UniProtKB | ChEBI)
Binding site425Ca2+ 2 (UniProtKB | ChEBI)
Binding site427Ca2+ 2 (UniProtKB | ChEBI)
Binding site429Ca2+ 2 (UniProtKB | ChEBI)
Binding site431Ca2+ 2 (UniProtKB | ChEBI)
Binding site433Ca2+ 2 (UniProtKB | ChEBI)
Binding site480Ca2+ 3 (UniProtKB | ChEBI)
Binding site482Ca2+ 3 (UniProtKB | ChEBI)
Binding site484Ca2+ 3 (UniProtKB | ChEBI)
Binding site486Ca2+ 3 (UniProtKB | ChEBI)
Binding site488Ca2+ 3 (UniProtKB | ChEBI)
Site634-635Cleavage; by PLAU in invasive prostate cancer

GO annotations

AspectTerm
Cellular Componentadherens junction
Cellular Componentcell surface
Cellular Componentexternal side of plasma membrane
Cellular Componentfilopodium
Cellular Componentfocal adhesion
Cellular Componentintegrin alpha6-beta1 complex
Cellular Componentintegrin alpha6-beta4 complex
Cellular Componentintegrin complex
Cellular Componentplasma membrane
Molecular Functioncadherin binding
Molecular Functioninsulin-like growth factor I binding
Molecular Functionintegrin binding
Molecular Functionlaminin binding
Molecular Functionmetal ion binding
Molecular Functionneuregulin binding
Biological Processcell adhesion mediated by integrin
Biological Processcell-cell adhesion
Biological Processcell-matrix adhesion
Biological Processcell-substrate adhesion
Biological Processcell-substrate junction assembly
Biological Processcellular response to organic cyclic compound
Biological Processectodermal cell differentiation
Biological Processintegrin-mediated signaling pathway
Biological Processleukocyte migration
Biological Processnail development
Biological Processnegative regulation of extrinsic apoptotic signaling pathway
Biological Processpositive regulation of apoptotic process
Biological Processpositive regulation of cell migration
Biological Processpositive regulation of cell-substrate adhesion
Biological Processpositive regulation of GTPase activity
Biological Processpositive regulation of neuron projection development
Biological Processpositive regulation of phosphorylation
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processskin morphogenesis

Keywords

Enzyme and pathway databases

Protein family/group databases

Community curation (1)

Integrin a6b1 is trafficked specifically by Rab11-FIP5 proteins. The internalization and recycling of a6 integrin by Rab11-FIP5 is specific for the alpha 6 subunit and not observed with a3 integrin or other unrelated type I membrane spanning receptors.

Names & Taxonomy

Protein names

Gene names

    • Name
      ITGA6
Community curation (1)

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P23229
  • Secondary accessions
    • B2RMU9
    • B4DG69
    • B4DKB8
    • C4AM96
    • G5E9H1

Proteomes

Organism-specific databases

Subcellular Location

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain24-1050Extracellular
Transmembrane1051-1076Helical
Topological domain1077-1130Cytoplasmic

Keywords

Disease & Variants

Involvement in disease

Epidermolysis bullosa, junctional 6, with pyloric atresia (JEB6)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. JEB6 is an autosomal recessive form in which blistering lesions occur between the epidermis and the dermis at the lamina lucida level of the basement membrane zone. Clinical manifestations include severe blistering, atrophic scarring, nail dystrophy, and pyloric atresia. Congenital absence of skin (aplasia cutis congenita) is common, and ear anomalies are also relatively common. Disease course is usually severe and often lethal in the neonatal period.
  • See also
    MIM:619817

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 1,228 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for signal, chain, glycosylation, disulfide bond, modified residue (large scale data), modified residue, lipidation.

TypeIDPosition(s)SourceDescription
Signal1-23UniProt
ChainPRO_000001625924-938UniProtIntegrin alpha-6 heavy chain
ChainPRO_000001625824-1130UniProtIntegrin alpha-6
Glycosylation78UniProtN-linked (GlcNAc...) asparagine
Disulfide bond86↔94UniProt
Disulfide bond131↔154UniProt
Disulfide bond175↔188UniProt
Glycosylation223UniProtN-linked (GlcNAc...) asparagine
Glycosylation323UniProtN-linked (GlcNAc...) asparagine
Glycosylation409UniProtN-linked (GlcNAc...) asparagine
Disulfide bond528↔535UniProt
Disulfide bond541↔601UniProt
ChainPRO_0000425742636-1130UniProtProcessed integrin alpha-6
Modified residue (large scale data)638PRIDEPhosphoserine
Disulfide bond665↔671UniProt
Disulfide bond765↔776UniProt
Glycosylation770UniProtN-linked (GlcNAc...) asparagine
Glycosylation787UniProtN-linked (GlcNAc...) asparagine
Disulfide bond920↔967UniProtInterchain (between heavy and light chains)
Glycosylation930UniProtN-linked (GlcNAc...) asparagine
ChainPRO_0000016260942-1130UniProtIntegrin alpha-6 light chain
Glycosylation966UniProtN-linked (GlcNAc...) asparagine
Disulfide bond973↔978UniProt
Glycosylation997UniProtN-linked (GlcNAc...) asparagine
Modified residue1059UniProtIn isoform P23229-4; Phosphoserine
Modified residue1064UniProtIn isoform P23229-2; Phosphoserine
Lipidation1078UniProtS-palmitoyl cysteine; by DHHC3
Modified residue1103UniProtIn isoform P23229-6; Phosphoserine

Post-translational modification

Isoforms containing segment A, but not segment B, are the major targets for PMA-induced phosphorylation. Phosphorylation occurs on 'Ser-1103' of isoform alpha-6X1X2A. Phosphorylation is not required for the induction of integrin alpha-6A/beta-1 high affinity but may reduce the affinity for ligand.
Undergoes PLAU-mediated cleavage at residues Arg-634-635-Arg in a time-dependent manner to produce processed integrin alpha-6 (alpha6p) (PubMed:11359780, PubMed:15023541, PubMed:17303120).
Production of alpha6p enhances prostate cancer cell invasion and migration (PubMed:17303120).
Palmitoylation by DHHC3 enhances stability and cell surface expression.

Keywords

Proteomic databases

2D gel databases

PTM databases

Expression

Tissue specificity

Integrin alpha-6/beta-4 is predominantly expressed by epithelia. Isoforms containing segment X1 are ubiquitously expressed. Isoforms containing segment X1X2 are expressed in heart, kidney, placenta, colon, duodenum, myoblasts and myotubes, and in a limited number of cell lines; they are always coexpressed with the ubiquitous isoform containing segment X1. In some tissues (e.g. Salivary gland), isoforms containing cytoplasmic segment A and isoforms containing segment B are detected while in others, only isoforms containing one cytoplasmic segment are found (segment A in epidermis and segment B in kidney). Processed integrin alpha-6: Expressed at low levels in normal prostate tissue with elevated levels in prostate cancer tissue (at protein level) (PubMed:15023541).

Gene expression databases

Organism-specific databases

Interaction

Subunit

Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of a heavy and a light chain linked by a disulfide bond (By similarity).
Alpha-6 associates with either beta-1 (ITGB1) or beta-4 (ITGB4) to form ITGA6:ITGB1 and ITGA6:ITGB4, respectively (By similarity).
ITGA6:ITGB1 is found in a complex with CD9; interaction takes place in oocytes and is involved in sperm-egg fusion (By similarity).
ITGA6:ITGB4 is found in a ternary complex with NRG1 and ERBB3 (PubMed:20682778).
ITGA6:ITGB4 is found in a ternary complex with IGF1 and IGF1R (PubMed:22351760).
ITGA6:ITGB4 interacts with IGF2 (PubMed:28873464).
Interacts with ADAM9 (By similarity).
Interacts with RAB21 (PubMed:16754960).
Interacts with MDK (PubMed:15466886).
ITGA6:ITGB1 interacts with MDK; this interaction mediates MDK-induced neurite outgrowth (PubMed:15466886).
Interacts with CD82; this interaction down-regulates ITGA6-mediated cell adhesion (PubMed:15557282).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY P23229CD151 P485095EBI-2436548, EBI-10210332
BINARY P23229ITGB1 P055562EBI-2436548, EBI-703066
BINARY P23229ITGB4 P161446EBI-2436548, EBI-948678

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for repeat, region, motif.

TypeIDPosition(s)Description
Repeat30-95FG-GAP 1
Repeat101-166FG-GAP 2
Repeat176-229FG-GAP 3
Repeat283-339FG-GAP 4
Repeat340-402FG-GAP 5
Repeat403-458FG-GAP 6
Repeat459-518FG-GAP 7
Region1077-1083Interaction with HPS5
Motif1079-1083GFFKR motif

Sequence similarities

Belongs to the integrin alpha chain family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (8)
  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.

This entry describes 8 isoforms produced by Alternative splicing. Additional isoforms seem to exist. There is a combination of at least four alternatively spliced domains, two extracellular (X1 and X2) and two cytoplasmic (A and B). So far detected are isoform Alpha-6X1A, isoform Alpha-6X1B and isoform Alpha-6X1X2A (minor). Experimental confirmation may be lacking for some isoforms.

P23229-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Name
    Alpha-6X1X2B
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    1,130
  • Mass (Da)
    126,606
  • Last updated
    2013-06-26 v5
  • Checksum
    B53712888B7FE3B6
MAAAGQLCLLYLSAGLLSRLGAAFNLDTREDNVIRKYGDPGSLFGFSLAMHWQLQPEDKRLLLVGAPRAEALPLQRANRTGGLYSCDITARGPCTRIEFDNDADPTSESKEDQWMGVTVQSQGPGGKVVTCAHRYEKRQHVNTKQESRDIFGRCYVLSQNLRIEDDMDGGDWSFCDGRLRGHEKFGSCQQGVAATFTKDFHYIVFGAPGTYNWKGIVRVEQKNNTFFDMNIFEDGPYEVGGETEHDESLVPVPANSYLGLLFLTSVSYTDPDQFVYKTRPPREQPDTFPDVMMNSYLGFSLDSGKGIVSKDEITFVSGAPRANHSGAVVLLKRDMKSAHLLPEHIFDGEGLASSFGYDVAVVDLNKDGWQDIVIGAPQYFDRDGEVGGAVYVYMNQQGRWNNVKPIRLNGTKDSMFGIAVKNIGDINQDGYPDIAVGAPYDDLGKVFIYHGSANGINTKPTQVLKGISPYFGYSIAGNMDLDRNSYPDVAVGSLSDSVTIFRSRPVINIQKTITVTPNRIDLRQKTACGAPSGICLQVKSCFEYTANPAGYNPSISIVGTLEAEKERRKSGLSSRVQFRNQGSEPKYTQELTLKRQKQKVCMEETLWLQDNIRDKLRPIPITASVEIQEPSSRRRVNSLPEVLPILNSDEPKTAHIDVHFLKEGCGDDNVCNSNLKLEYKFCTREGNQDKFSYLPIQKGVPELVLKDQKDIALEITVTNSPSNPRNPTKDGDDAHEAKLIATFPDTLTYSAYRELRAFPEKQLSCVANQNGSQADCELGNPFKRNSNVTFYLVLSTTEVTFDTPDLDINLKLETTSNQDNLAPITAKAKVVIELLLSVSGVAKPSQVYFGGTVVGEQAMKSEDEVGSLIEYEFRVINLGKPLTNLGTATLNIQWPKEISNGKWLLYLVKVESKGLEKVTCEPQKEINSLNLTESHNSRKKREITEKQIDDNRKFSLFAERKYQTLNCSVNVNCVNIRCPLRGLDSKASLILRSRLWNSTFLEEYSKLNYLDILMRAFIDVTAAAENIRLPNAGTQVRVTVFPSKTVAQYSGVPWWIILVAILAGILMLALLVFILWKCGFFKRSRYDDSVPRYHAVRIRKEEREIKDEKYIDNLEKKQWITKWNENESYS

P23229-2

  • Name
    Alpha-6X1A
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 259-297: Missing
    • 1084-1130: SRYDDSVPRYHAVRIRKEEREIKDEKYIDNLEKKQWITKWNENESYS → NKKDHYDATYHKAEIHAQPSDKERLTSDA

P23229-3

  • Name
    Alpha-6X1B
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

P23229-4

  • Name
    Alpha-6X2A
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 215-258: Missing
    • 1084-1130: SRYDDSVPRYHAVRIRKEEREIKDEKYIDNLEKKQWITKWNENESYS → NKKDHYDATYHKAEIHAQPSDKERLTSDA

P23229-5

  • Name
    Alpha-6X2B
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

P23229-6

  • Name
    Alpha-6X1X2A
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1084-1130: SRYDDSVPRYHAVRIRKEEREIKDEKYIDNLEKKQWITKWNENESYS → NKKDHYDATYHKAEIHAQPSDKERLTSDA

P23229-7

  • Name
    7
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1-114: Missing
    • 215-258: Missing
    • 1084-1130: SRYDDSVPRYHAVRIRKEEREIKDEKYIDNLEKKQWITKWNENESYS → NKKDHYDATYHKAEIHAQPSDKERLTSDA

P23229-9

  • Name
    9
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 918-932: Missing
    • 1084-1130: SRYDDSVPRYHAVRIRKEEREIKDEKYIDNLEKKQWITKWNENESYS → NKKDHYDATYHKAEIHAQPSDKERLTSDA

Computationally mapped potential isoform sequences

There are 4 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0AAQ5BID9A0AAQ5BID9_HUMANITGA6977
C9JXX7C9JXX7_HUMANITGA6231
A0A8C8KBL6A0A8C8KBL6_HUMANITGA61058
H7BZ97H7BZ97_HUMANITGA6258

Sequence caution

The sequence BAG57680.1 differs from that shown. Reason: Erroneous initiation Truncated N-terminus.

Features

Showing features for alternative sequence, sequence conflict.

TypeIDPosition(s)Description
Alternative sequenceVSP_0364061-114in isoform 7
Sequence conflict69in Ref. 1; CAA37655 and 8; CAA42099
Alternative sequenceVSP_002723215-258in isoform Alpha-6X2A, isoform Alpha-6X2B and isoform 7
Alternative sequenceVSP_002724259-297in isoform Alpha-6X1A and isoform Alpha-6X1B
Sequence conflict419in Ref. 4; BAG59130 and 7; AAI36456/AAI36457
Sequence conflict501in Ref. 8; CAA42099
Sequence conflict805in Ref. 1; CAA37655 and 3; AAD48469
Alternative sequenceVSP_036407918-932in isoform 9
Alternative sequenceVSP_0027251084-1130in isoform Alpha-6X1A, isoform Alpha-6X2A, isoform Alpha-6X1X2A, isoform 7 and isoform 9
Sequence conflict1125in Ref. 1; AAB20355

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
X53586
EMBL· GenBank· DDBJ
CAA37655.1
EMBL· GenBank· DDBJ
mRNA
AF166343
EMBL· GenBank· DDBJ
AAD48469.1
EMBL· GenBank· DDBJ
Genomic DNA
AF166335
EMBL· GenBank· DDBJ
AAD48469.1
EMBL· GenBank· DDBJ
Genomic DNA
AF166336
EMBL· GenBank· DDBJ
AAD48469.1
EMBL· GenBank· DDBJ
Genomic DNA
AF166337
EMBL· GenBank· DDBJ
AAD48469.1
EMBL· GenBank· DDBJ
Genomic DNA
AF166338
EMBL· GenBank· DDBJ
AAD48469.1
EMBL· GenBank· DDBJ
Genomic DNA
AF166339
EMBL· GenBank· DDBJ
AAD48469.1
EMBL· GenBank· DDBJ
Genomic DNA
AF166340
EMBL· GenBank· DDBJ
AAD48469.1
EMBL· GenBank· DDBJ
Genomic DNA
AF166341
EMBL· GenBank· DDBJ
AAD48469.1
EMBL· GenBank· DDBJ
Genomic DNA
AF166342
EMBL· GenBank· DDBJ
AAD48469.1
EMBL· GenBank· DDBJ
Genomic DNA
AK294436
EMBL· GenBank· DDBJ
BAG57680.1
EMBL· GenBank· DDBJ
mRNA Different initiation
AK296496
EMBL· GenBank· DDBJ
BAG59130.1
EMBL· GenBank· DDBJ
mRNA
AC078883
EMBL· GenBank· DDBJ
AAX93133.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471058
EMBL· GenBank· DDBJ
EAX11176.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471058
EMBL· GenBank· DDBJ
EAX11177.1
EMBL· GenBank· DDBJ
Genomic DNA
BC050585
EMBL· GenBank· DDBJ
AAH50585.1
EMBL· GenBank· DDBJ
mRNA
BC136455
EMBL· GenBank· DDBJ
AAI36456.1
EMBL· GenBank· DDBJ
mRNA
BC136456
EMBL· GenBank· DDBJ
AAI36457.1
EMBL· GenBank· DDBJ
mRNA
X59512
EMBL· GenBank· DDBJ
CAA42099.1
EMBL· GenBank· DDBJ
mRNA
S66213
EMBL· GenBank· DDBJ
AAB20355.1
EMBL· GenBank· DDBJ
mRNA
S66196
EMBL· GenBank· DDBJ
AAB20354.1
EMBL· GenBank· DDBJ
mRNA
S52135
EMBL· GenBank· DDBJ
AAB24829.1
EMBL· GenBank· DDBJ
Genomic DNA
L40385
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AB208842
EMBL· GenBank· DDBJ
BAD92079.1
EMBL· GenBank· DDBJ
mRNA
DQ858220
EMBL· GenBank· DDBJ
ABH11650.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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