UniProt functional annotation for Q13009



	UniProt functional annotation for Q13009

UniProt code: Q13009.

Organism: Homo sapiens (Human).

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

Function: Guanyl-nucleotide exchange factor that activates RHO-like proteins and connects extracellular signals to cytoskeletal activities. Activates RAC1, CDC42, and to a lesser extent RHOA and their downstream signaling to regulate processes like cell adhesion and cell migration. {ECO:0000269|PubMed:20361982, ECO:0000269|PubMed:25684205}.

Subunit: Component of the Par polarity complex, composed of at least phosphorylated PRKCZ, PARD3 and TIAM1. Interacts with NTRK2; mediates the activation of RAC1 by BDNF. Interacts with MAPK8IP2 and CD44 (By similarity). Interacts with BAIAP2. Interacts with EPHA8; regulates clathrin-mediated endocytosis of EPHA8. Interacts with PARD3. Interacts (via PDZ domain) with CNTNAP4, SDC1 and SDC3 (via C-terminus). {ECO:0000250, ECO:0000269|PubMed:15899863, ECO:0000269|PubMed:20332120, ECO:0000269|PubMed:20361982, ECO:0000269|PubMed:20496116, ECO:0000269|PubMed:23395182, ECO:0000269|PubMed:23832200, ECO:0000269|PubMed:7753201}.

Subcellular location: Cell junction. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note=Detected at the boundary between cells with actin-rich protrusions (By similarity). Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction. {ECO:0000250}.

Tissue specificity: Found in virtually all analyzed tumor cell lines including B- and T-lymphomas, neuroblastomas, melanomas and carcinomas.

Domain: The first PH domain mediates interaction with membranes enriched in phosphoinositides. {ECO:0000250}.

Ptm: Ubiquitinated. Undergoes 'Lys-48' ubiquitination at Lys-1404 and Lys-1420 by a CUL3(KBTBD6/7) E3 ubiquitin ligase complex composed of CUL3, RBX1, KBTBD6 and KBTBD7. 'Lys-48' ubiquitination at Lys-1404 and Lys-1420 triggers proteasomal degradation (PubMed:25684205). Ubiquitination at Lys-1404 and Lys-1420 by CUL3(KBTBD6/7) also requires the membrane-associated protein GABARAP and may therefore be spatially restricted within the cell (PubMed:25684205). {ECO:0000269|PubMed:25684205}.

Similarity: Belongs to the TIAM 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:		Guanyl-nucleotide exchange factor that activates RHO-like proteins and connects extracellular signals to cytoskeletal activities. Activates RAC1, CDC42, and to a lesser extent RHOA and their downstream signaling to regulate processes like cell adhesion and cell migration. {ECO:0000269\|PubMed:20361982, ECO:0000269\|PubMed:25684205}.


Subunit:		Component of the Par polarity complex, composed of at least phosphorylated PRKCZ, PARD3 and TIAM1. Interacts with NTRK2; mediates the activation of RAC1 by BDNF. Interacts with MAPK8IP2 and CD44 (By similarity). Interacts with BAIAP2. Interacts with EPHA8; regulates clathrin-mediated endocytosis of EPHA8. Interacts with PARD3. Interacts (via PDZ domain) with CNTNAP4, SDC1 and SDC3 (via C-terminus). {ECO:0000250, ECO:0000269\|PubMed:15899863, ECO:0000269\|PubMed:20332120, ECO:0000269\|PubMed:20361982, ECO:0000269\|PubMed:20496116, ECO:0000269\|PubMed:23395182, ECO:0000269\|PubMed:23832200, ECO:0000269\|PubMed:7753201}.
Subcellular location:		Cell junction. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note=Detected at the boundary between cells with actin-rich protrusions (By similarity). Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction. {ECO:0000250}.
Tissue specificity:		Found in virtually all analyzed tumor cell lines including B- and T-lymphomas, neuroblastomas, melanomas and carcinomas.
Domain:		The first PH domain mediates interaction with membranes enriched in phosphoinositides. {ECO:0000250}.
Ptm:		Ubiquitinated. Undergoes 'Lys-48' ubiquitination at Lys-1404 and Lys-1420 by a CUL3(KBTBD6/7) E3 ubiquitin ligase complex composed of CUL3, RBX1, KBTBD6 and KBTBD7. 'Lys-48' ubiquitination at Lys-1404 and Lys-1420 triggers proteasomal degradation (PubMed:25684205). Ubiquitination at Lys-1404 and Lys-1420 by CUL3(KBTBD6/7) also requires the membrane-associated protein GABARAP and may therefore be spatially restricted within the cell (PubMed:25684205). {ECO:0000269\|PubMed:25684205}.
Similarity:		Belongs to the TIAM family. {ECO:0000305}.