UniProt functional annotation for Q14449



	UniProt functional annotation for Q14449

UniProt code: Q14449.

Organism: Homo sapiens (Human).

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

Function: Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibitor of insulin-stimulated MAPK3 phosphorylation. Plays a critical role regulating PDPK1 membrane translocation in response to insulin stimulation and serves as an adapter protein to recruit PDPK1 to activated insulin receptor, thus promoting PKB/AKT1 phosphorylation and transduction of the insulin signal. {ECO:0000269|PubMed:15210700, ECO:0000269|PubMed:19648926}.

Subunit: Interacts with the cytoplasmic domain of the autophosphorylated insulin receptor (INSR), through the SH2 domain (By similarity). Interacts with GRB14 (via BPS domain); this interaction protects the tyrosines in the activation loop on INSR from dephosphorylation. Binds to the ankyrin repeat region of TNKS2 via its N-terminus. Interacts with activated NRAS. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). {ECO:0000250, ECO:0000269|PubMed:11726652, ECO:0000269|PubMed:15210700, ECO:0000269|PubMed:16246733, ECO:0000269|PubMed:19648926, ECO:0000269|PubMed:20973951}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:15210700, ECO:0000269|PubMed:19648926}. Endosome membrane {ECO:0000269|PubMed:15210700, ECO:0000269|PubMed:19648926}; Peripheral membrane protein {ECO:0000269|PubMed:15210700, ECO:0000269|PubMed:19648926}. Note=Upon insulin stimulation, translocates to the plasma membrane. {ECO:0000269|PubMed:15210700, ECO:0000269|PubMed:19648926}.

Tissue specificity: Expressed at high levels in the liver, kidney, pancreas, testis, ovary, heart and skeletal muscle.

Domain: The PH domain binds relatively non-specifically and with low affinity to several phosphoinositides, the best binder being PI(3,4,5)P3. {ECO:0000269|PubMed:19648926}.

Ptm: Phosphorylated on serine residues. Phosphorylated on tyrosine residues by TEK/TIE2. {ECO:0000269|PubMed:20973951}.

Similarity: Belongs to the GRB7/10/14 family. {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:		Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibitor of insulin-stimulated MAPK3 phosphorylation. Plays a critical role regulating PDPK1 membrane translocation in response to insulin stimulation and serves as an adapter protein to recruit PDPK1 to activated insulin receptor, thus promoting PKB/AKT1 phosphorylation and transduction of the insulin signal. {ECO:0000269\|PubMed:15210700, ECO:0000269\|PubMed:19648926}.


Subunit:		Interacts with the cytoplasmic domain of the autophosphorylated insulin receptor (INSR), through the SH2 domain (By similarity). Interacts with GRB14 (via BPS domain); this interaction protects the tyrosines in the activation loop on INSR from dephosphorylation. Binds to the ankyrin repeat region of TNKS2 via its N-terminus. Interacts with activated NRAS. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). {ECO:0000250, ECO:0000269\|PubMed:11726652, ECO:0000269\|PubMed:15210700, ECO:0000269\|PubMed:16246733, ECO:0000269\|PubMed:19648926, ECO:0000269\|PubMed:20973951}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:15210700, ECO:0000269\|PubMed:19648926}. Endosome membrane {ECO:0000269\|PubMed:15210700, ECO:0000269\|PubMed:19648926}; Peripheral membrane protein {ECO:0000269\|PubMed:15210700, ECO:0000269\|PubMed:19648926}. Note=Upon insulin stimulation, translocates to the plasma membrane. {ECO:0000269\|PubMed:15210700, ECO:0000269\|PubMed:19648926}.
Tissue specificity:		Expressed at high levels in the liver, kidney, pancreas, testis, ovary, heart and skeletal muscle.
Domain:		The PH domain binds relatively non-specifically and with low affinity to several phosphoinositides, the best binder being PI(3,4,5)P3. {ECO:0000269\|PubMed:19648926}.
Ptm:		Phosphorylated on serine residues. Phosphorylated on tyrosine residues by TEK/TIE2. {ECO:0000269\|PubMed:20973951}.
Similarity:		Belongs to the GRB7/10/14 family. {ECO:0000305}.