UniProt functional annotation for P16144



	UniProt functional annotation for P16144

UniProt code: P16144.

Organism: Homo sapiens (Human).

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

Function: Integrin alpha-6/beta-4 is a receptor for laminin. Plays a critical structural role in the hemidesmosome of epithelial cells. Is required for the regulation of keratinocyte polarity and motility. 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). {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:28873464}.

Subunit: Heterodimer of an alpha and a beta subunit. Beta-4 associates with alpha-6. Interacts (via cytoplasmic region) with COL17A1 (via cytoplasmic region). Interacts (via cytoplasmic region) with DST isoform 3 (via N-terminus). Isoform beta-4a interacts (via cytoplasmic domain) with DST (via N-terminus). Interacts with RAC1. 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). {ECO:0000269|PubMed:10637308, ECO:0000269|PubMed:11375975, ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:28873464}.

Subcellular location: Cell membrane; Single-pass type I membrane protein. Cell membrane; Lipid-anchor. Cell junction, hemidesmosome. Note=Colocalizes with DST at the leading edge of migrating keratinocytes.

Tissue specificity: Integrin alpha-6/beta-4 is predominantly expressed by epithelia. Isoform beta-4D is also expressed in colon and placenta. Isoform beta-4E is also expressed in epidermis, lung, duodenum, heart, spleen and stomach.

Domain: The fibronectin type-III-like domains bind BPAG1 and plectin and probably also recruit BP230.

Ptm: Palmitoylated by DHHC3 at several cysteines of the membrane- proximal region, enhancing stability and cell surface expression. Palmitoylation also promotes secondary association with tertaspanins. {ECO:0000269|PubMed:15611341, ECO:0000269|PubMed:22314500}.

Disease: Epidermolysis bullosa letalis, with pyloric atresia (EB-PA) [MIM:226730]: An autosomal recessive, frequently lethal, epidermolysis bullosa with variable involvement of skin, nails, mucosa, and with variable effects on the digestive system. It is characterized by mucocutaneous fragility, aplasia cutis congenita, and gastrointestinal atresia, which most commonly affects the pylorus. Pyloric atresia is a primary manifestation rather than a scarring process secondary to epidermolysis bullosa. {ECO:0000269|PubMed:10873890, ECO:0000269|PubMed:11251584, ECO:0000269|PubMed:11328943, ECO:0000269|PubMed:9422533, ECO:0000269|PubMed:9546354, ECO:0000269|PubMed:9792864, ECO:0000269|PubMed:9892956}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Generalized atrophic benign epidermolysis bullosa (GABEB) [MIM:226650]: A non-lethal, adult form of junctional epidermolysis bullosa characterized by life-long blistering of the skin, associated with hair and tooth abnormalities. {ECO:0000269|PubMed:10792571}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Epidermolysis bullosa simplex, Weber-Cockayne type (WC-EBS) [MIM:131800]: A form of intraepidermal epidermolysis bullosa characterized by blistering limited to palmar and plantar areas of the skin. {ECO:0000269|PubMed:12485428}. Note=The disease is caused by variants affecting the gene represented in this entry.

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

Sequence caution: Sequence=CAA37656.1; 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:		Integrin alpha-6/beta-4 is a receptor for laminin. Plays a critical structural role in the hemidesmosome of epithelial cells. Is required for the regulation of keratinocyte polarity and motility. 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). {ECO:0000269\|PubMed:12482924, ECO:0000269\|PubMed:19403692, ECO:0000269\|PubMed:20682778, ECO:0000269\|PubMed:22351760, ECO:0000269\|PubMed:28873464}.


Subunit:		Heterodimer of an alpha and a beta subunit. Beta-4 associates with alpha-6. Interacts (via cytoplasmic region) with COL17A1 (via cytoplasmic region). Interacts (via cytoplasmic region) with DST isoform 3 (via N-terminus). Isoform beta-4a interacts (via cytoplasmic domain) with DST (via N-terminus). Interacts with RAC1. 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). {ECO:0000269\|PubMed:10637308, ECO:0000269\|PubMed:11375975, ECO:0000269\|PubMed:12482924, ECO:0000269\|PubMed:19403692, ECO:0000269\|PubMed:20682778, ECO:0000269\|PubMed:22351760, ECO:0000269\|PubMed:28873464}.
Subcellular location:		Cell membrane; Single-pass type I membrane protein. Cell membrane; Lipid-anchor. Cell junction, hemidesmosome. Note=Colocalizes with DST at the leading edge of migrating keratinocytes.
Tissue specificity:		Integrin alpha-6/beta-4 is predominantly expressed by epithelia. Isoform beta-4D is also expressed in colon and placenta. Isoform beta-4E is also expressed in epidermis, lung, duodenum, heart, spleen and stomach.
Domain:		The fibronectin type-III-like domains bind BPAG1 and plectin and probably also recruit BP230.
Ptm:		Palmitoylated by DHHC3 at several cysteines of the membrane- proximal region, enhancing stability and cell surface expression. Palmitoylation also promotes secondary association with tertaspanins. {ECO:0000269\|PubMed:15611341, ECO:0000269\|PubMed:22314500}.
Disease:		Epidermolysis bullosa letalis, with pyloric atresia (EB-PA) [MIM:226730]: An autosomal recessive, frequently lethal, epidermolysis bullosa with variable involvement of skin, nails, mucosa, and with variable effects on the digestive system. It is characterized by mucocutaneous fragility, aplasia cutis congenita, and gastrointestinal atresia, which most commonly affects the pylorus. Pyloric atresia is a primary manifestation rather than a scarring process secondary to epidermolysis bullosa. {ECO:0000269\|PubMed:10873890, ECO:0000269\|PubMed:11251584, ECO:0000269\|PubMed:11328943, ECO:0000269\|PubMed:9422533, ECO:0000269\|PubMed:9546354, ECO:0000269\|PubMed:9792864, ECO:0000269\|PubMed:9892956}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Generalized atrophic benign epidermolysis bullosa (GABEB) [MIM:226650]: A non-lethal, adult form of junctional epidermolysis bullosa characterized by life-long blistering of the skin, associated with hair and tooth abnormalities. {ECO:0000269\|PubMed:10792571}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Epidermolysis bullosa simplex, Weber-Cockayne type (WC-EBS) [MIM:131800]: A form of intraepidermal epidermolysis bullosa characterized by blistering limited to palmar and plantar areas of the skin. {ECO:0000269\|PubMed:12485428}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the integrin beta chain family. {ECO:0000305}.
Sequence caution:		Sequence=CAA37656.1; Type=Frameshift; Evidence={ECO:0000305};