UniProt functional annotation for P13612



	UniProt functional annotation for P13612

UniProt code: P13612.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415). ITGA4:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). {ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:19064666, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:25398877}.

Subunit: Heterodimer of an alpha and a beta subunit. The alpha subunit can sometimes be cleaved into two non-covalently associated fragments. Alpha-4 associates with either beta-1 or beta-7. Alpha-4 interacts with PXN, LPXN, and TGFB1I1/HIC5. Interacts with CSPG4 through CSPG4 chondroitin sulfate glycosaminoglycan. Interacts with JAML; integrin alpha-4/beta-1 may regulate leukocyte to endothelial cells adhesion by controlling JAML homodimerization. ITGA4:ITGB1 is found in a ternary complex with CX3CR1 and CX3CL1 (PubMed:23125415). Interacts with MDK (PubMed:15466886). ITGA4:ITGB1 interacts with MDK; this interaction mediates MDK-induced osteoblast cells migration through PXN phosphorylation (PubMed:15466886). {ECO:0000269|PubMed:10604475, ECO:0000269|PubMed:15466886, ECO:0000269|PubMed:19064666, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:9488735}.

Subcellular location: Membrane; Single-pass type I membrane protein.

Domain: The SG1 motif is involved in binding to chondroitin sulfate glycosaminoglycan and cell adhesion. {ECO:0000269|PubMed:9488735}.

Ptm: Phosphorylation on Ser-1027 inhibits PXN binding. {ECO:0000269|PubMed:11533025}.

Similarity: Belongs to the integrin alpha chain family. {ECO:0000305}.

Sequence caution: Sequence=AAB59613.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=CAA34852.1; Type=Frameshift; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415). ITGA4:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). {ECO:0000269\|PubMed:18635536, ECO:0000269\|PubMed:19064666, ECO:0000269\|PubMed:23125415, ECO:0000269\|PubMed:25398877}.


Subunit:		Heterodimer of an alpha and a beta subunit. The alpha subunit can sometimes be cleaved into two non-covalently associated fragments. Alpha-4 associates with either beta-1 or beta-7. Alpha-4 interacts with PXN, LPXN, and TGFB1I1/HIC5. Interacts with CSPG4 through CSPG4 chondroitin sulfate glycosaminoglycan. Interacts with JAML; integrin alpha-4/beta-1 may regulate leukocyte to endothelial cells adhesion by controlling JAML homodimerization. ITGA4:ITGB1 is found in a ternary complex with CX3CR1 and CX3CL1 (PubMed:23125415). Interacts with MDK (PubMed:15466886). ITGA4:ITGB1 interacts with MDK; this interaction mediates MDK-induced osteoblast cells migration through PXN phosphorylation (PubMed:15466886). {ECO:0000269\|PubMed:10604475, ECO:0000269\|PubMed:15466886, ECO:0000269\|PubMed:19064666, ECO:0000269\|PubMed:23125415, ECO:0000269\|PubMed:9488735}.
Subcellular location:		Membrane; Single-pass type I membrane protein.
Domain:		The SG1 motif is involved in binding to chondroitin sulfate glycosaminoglycan and cell adhesion. {ECO:0000269\|PubMed:9488735}.
Ptm:		Phosphorylation on Ser-1027 inhibits PXN binding. {ECO:0000269\|PubMed:11533025}.
Similarity:		Belongs to the integrin alpha chain family. {ECO:0000305}.
Sequence caution:		Sequence=AAB59613.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=CAA34852.1; Type=Frameshift; Evidence={ECO:0000305};