UniProt functional annotation for P20936



	UniProt functional annotation for P20936

UniProt code: P20936.

Organism: Homo sapiens (Human).

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

Function: Inhibitory regulator of the Ras-cyclic AMP pathway. Stimulates the GTPase of normal but not oncogenic Ras p21; this stimulation may be further increased in the presence of NCK1. {ECO:0000269|PubMed:11389730, ECO:0000269|PubMed:8360177}.

Subunit: Interacts with SQSTM1. Interacts with SPSB1; the interaction does not promote degradation. Interacts with CAV2 (tyrosine phosphorylated form). Directly interacts with NCK1. Interacts with PDGFRB (tyrosine phosphorylated). Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1. Interacts with tyrosine- phosphorylated EPHB4 (PubMed:8955277). {ECO:0000269|PubMed:12091389, ECO:0000269|PubMed:1375321, ECO:0000269|PubMed:15504032, ECO:0000269|PubMed:15713673, ECO:0000269|PubMed:18024423, ECO:0000269|PubMed:21664272, ECO:0000269|PubMed:8618896, ECO:0000269|PubMed:8955277, ECO:0000269|PubMed:9219684}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:8360177}.

Tissue specificity: In placental villi, detected only in the trophoblast layer (cytotrophoblast and syncytiotrophoblast). Not detected in stromal, endothelial or Hofbauer cells (at protein level). {ECO:0000269|PubMed:8360177}.

Ptm: The N-terminus is blocked.

Ptm: Phosphorylated by SRC and LCK. The phosphorylation SRC inhibits its ability to stimulate the Ras-GTPase activity, whereas phosphorylation by LCK does not display any effect on stimulation activity. {ECO:0000269|PubMed:11389730}.

Disease: Note=Mutations in the SH2 domain of RASA seem to be oncogenic and cause basal cell carcinomas.

Disease: Capillary malformation-arteriovenous malformation 1 (CMAVM1) [MIM:608354]: A disorder characterized by atypical capillary malformations that are multiple, small, round to oval in shape and pinkish red in color. These capillary malformations are associated with either arteriovenous malformation, arteriovenous fistula, or Parkes Weber syndrome. CMAVM1 inheritance is autosomal dominant. {ECO:0000269|PubMed:14639529, ECO:0000269|PubMed:24038909}. Note=The disease is caused by variants affecting the gene represented in this entry.

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:		Inhibitory regulator of the Ras-cyclic AMP pathway. Stimulates the GTPase of normal but not oncogenic Ras p21; this stimulation may be further increased in the presence of NCK1. {ECO:0000269\|PubMed:11389730, ECO:0000269\|PubMed:8360177}.


Subunit:		Interacts with SQSTM1. Interacts with SPSB1; the interaction does not promote degradation. Interacts with CAV2 (tyrosine phosphorylated form). Directly interacts with NCK1. Interacts with PDGFRB (tyrosine phosphorylated). Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1. Interacts with tyrosine- phosphorylated EPHB4 (PubMed:8955277). {ECO:0000269\|PubMed:12091389, ECO:0000269\|PubMed:1375321, ECO:0000269\|PubMed:15504032, ECO:0000269\|PubMed:15713673, ECO:0000269\|PubMed:18024423, ECO:0000269\|PubMed:21664272, ECO:0000269\|PubMed:8618896, ECO:0000269\|PubMed:8955277, ECO:0000269\|PubMed:9219684}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:8360177}.
Tissue specificity:		In placental villi, detected only in the trophoblast layer (cytotrophoblast and syncytiotrophoblast). Not detected in stromal, endothelial or Hofbauer cells (at protein level). {ECO:0000269\|PubMed:8360177}.
Ptm:		The N-terminus is blocked.
Ptm:		Phosphorylated by SRC and LCK. The phosphorylation SRC inhibits its ability to stimulate the Ras-GTPase activity, whereas phosphorylation by LCK does not display any effect on stimulation activity. {ECO:0000269\|PubMed:11389730}.
Disease:		Note=Mutations in the SH2 domain of RASA seem to be oncogenic and cause basal cell carcinomas.
Disease:		Capillary malformation-arteriovenous malformation 1 (CMAVM1) [MIM:608354]: A disorder characterized by atypical capillary malformations that are multiple, small, round to oval in shape and pinkish red in color. These capillary malformations are associated with either arteriovenous malformation, arteriovenous fistula, or Parkes Weber syndrome. CMAVM1 inheritance is autosomal dominant. {ECO:0000269\|PubMed:14639529, ECO:0000269\|PubMed:24038909}. Note=The disease is caused by variants affecting the gene represented in this entry.