UniProt functional annotation for P62330



	UniProt functional annotation for P62330

UniProt code: P62330.

Organism: Homo sapiens (Human).

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

Function: GTP-binding protein involved in protein trafficking that regulates endocytic recycling and cytoskeleton remodeling (PubMed:11266366, PubMed:21170023, PubMed:16737952, PubMed:7589240, PubMed:18400762). Required for normal completion of mitotic cytokinesis (By similarity). Plays a role in the reorganization of the actin cytoskeleton and the formation of stress fibers (By similarity). Involved in the regulation of dendritic spine development, contributing to the regulation of dendritic branching and filopodia extension (PubMed:14978216). Plays an important role in membrane trafficking, during junctional remodeling and epithelial polarization. Regulates surface levels of adherens junction proteins such as CDH1 (By similarity). Required for NTRK1 sorting to the recycling pathway from early endosomes (By similarity). {ECO:0000250|UniProtKB:P62331, ECO:0000250|UniProtKB:P62332, ECO:0000269|PubMed:11266366, ECO:0000269|PubMed:14978216, ECO:0000269|PubMed:16099990, ECO:0000269|PubMed:16737952, ECO:0000269|PubMed:18400762, ECO:0000269|PubMed:21170023, ECO:0000269|PubMed:7589240}.

Function: (Microbial infection) Functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. {ECO:0000269|PubMed:16099990}.

Activity regulation: Activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). Activated by ASAP3. Inactivated by ACAP1 and ACAP2. Activated by NGF via NTRK1 (By similarity). {ECO:0000250|UniProtKB:P62332, ECO:0000269|PubMed:11062263, ECO:0000269|PubMed:18400762}.

Subunit: Interacts (when activated) with GGA1, GGA2 and GGA3; the interaction is required for proper subcellular location of GGA1, GGA2 and GGA3 (PubMed:11950392). Interacts with PIP5K1C (PubMed:12847086). Interacts with USP6 (via Rab-GAP TBC domain) (PubMed:15509780). Interacts with RAB11FIP3 and RAB11FIP4 (PubMed:16148947, PubMed:17030804, PubMed:17628206). Interacts with HERC1 (PubMed:15642342). Interacts with ARHGAP21 (PubMed:15793564). Interacts with ASAP3; the interaction is stabilized by calcium ions (PubMed:16737952, PubMed:20510928). Interacts with NCS1/FREQ at the plasma membrane (PubMed:17555535). Interacts with TBC1D24 (PubMed:20727515). Interacts with ECPAS (PubMed:20682791). Interacts with MICALL1 (PubMed:21951725). Interacts with SPAG9 homodimers, forming heterotetramers (PubMed:19644450). Interacts with CYTH3 (PubMed:23940353). Interacts with ASAP2 (By similarity). Interacts with UACA (By similarity). Interacts with KIF23, forming heterodimers and heterotetramers (By similarity). Interacts with C9orf72 (By similarity). Interacts (GTP-bound form) with TJAP1/PILT (By similarity). {ECO:0000250|UniProtKB:P62331, ECO:0000250|UniProtKB:P62332, ECO:0000269|PubMed:11950392, ECO:0000269|PubMed:12847086, ECO:0000269|PubMed:15509780, ECO:0000269|PubMed:15642342, ECO:0000269|PubMed:15793564, ECO:0000269|PubMed:16148947, ECO:0000269|PubMed:16737952, ECO:0000269|PubMed:17030804, ECO:0000269|PubMed:17555535, ECO:0000269|PubMed:17628206, ECO:0000269|PubMed:19644450, ECO:0000269|PubMed:20510928, ECO:0000269|PubMed:20682791, ECO:0000269|PubMed:20727515, ECO:0000269|PubMed:21951725, ECO:0000269|PubMed:23940353}.

Subunit: (Microbial infection) Interacts with the V.cholerae enterotoxin subunit A1; this causes a conformation change so that the toxin can bind NAD and catalyze the ADP-ribosylation of Gs alpha. {ECO:0000269|PubMed:16099990}.

Subunit: (Microbial infection) Interacts with EspG from enteropathogenic E.coli. {ECO:0000269|PubMed:21170023, ECO:0000269|PubMed:22939626}.

Subunit: (Microbial infection) Identified in a complex with RAB1A and EspG from enteropathogenic E.coli. {ECO:0000269|PubMed:22939626}.

Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:16737952, ECO:0000269|PubMed:23603394, ECO:0000269|PubMed:7589240}. Cell membrane {ECO:0000269|PubMed:16737952, ECO:0000269|PubMed:17398095, ECO:0000269|PubMed:17555535}; Lipid-anchor {ECO:0000269|PubMed:7589240}. Endosome membrane {ECO:0000269|PubMed:19948740, ECO:0000269|PubMed:20682791, ECO:0000269|PubMed:21951725}; Lipid-anchor. Recycling endosome membrane {ECO:0000305}; Lipid-anchor {ECO:0000305}. Cell projection, filopodium membrane; Lipid-anchor. Cell projection, ruffle {ECO:0000269|PubMed:16737952}. Cleavage furrow {ECO:0000269|PubMed:23603394}. Midbody, Midbody ring {ECO:0000269|PubMed:23603394}. Early endosome membrane {ECO:0000250|UniProtKB:P62331}; Lipid-anchor {ECO:0000250|UniProtKB:P62331}. Golgi apparatus, trans-Golgi network membrane {ECO:0000250|UniProtKB:P62331}; Lipid-anchor {ECO:0000250|UniProtKB:P62331}. Note=Distributed uniformly on the plasma membrane, as well as throughout the cytoplasm during metaphase. Subsequently concentrated at patches in the equatorial region at the onset of cytokinesis, and becomes distributed in the equatorial region concurrent with cleavage furrow ingression. In late stages of cytokinesis, concentrates at the midbody ring/Flemming body (PubMed:23603394). Recruitment to the midbody ring requires both activation by PSD/EFA6A and interaction with KIF23/MKLP1 (By similarity). After abscission of the intercellular bridge, incorporated into one of the daughter cells as a midbody remnant and localizes to punctate structures beneath the plasma membrane (PubMed:23603394). Recruited to the cell membrane in association with CYTH2 and ARL4C. Colocalizes with DAB2IP at the plasma membrane and endocytic vesicles (By similarity). Myristoylation is required for proper localization to membranes (PubMed:7589240). {ECO:0000250, ECO:0000250|UniProtKB:P62331, ECO:0000269|PubMed:23603394, ECO:0000269|PubMed:7589240}.

Tissue specificity: Ubiquitous, with higher levels in heart, substantia nigra, and kidney. {ECO:0000269|PubMed:14659046}.

Similarity: Belongs to the small GTPase superfamily. Arf 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:		GTP-binding protein involved in protein trafficking that regulates endocytic recycling and cytoskeleton remodeling (PubMed:11266366, PubMed:21170023, PubMed:16737952, PubMed:7589240, PubMed:18400762). Required for normal completion of mitotic cytokinesis (By similarity). Plays a role in the reorganization of the actin cytoskeleton and the formation of stress fibers (By similarity). Involved in the regulation of dendritic spine development, contributing to the regulation of dendritic branching and filopodia extension (PubMed:14978216). Plays an important role in membrane trafficking, during junctional remodeling and epithelial polarization. Regulates surface levels of adherens junction proteins such as CDH1 (By similarity). Required for NTRK1 sorting to the recycling pathway from early endosomes (By similarity). {ECO:0000250\|UniProtKB:P62331, ECO:0000250\|UniProtKB:P62332, ECO:0000269\|PubMed:11266366, ECO:0000269\|PubMed:14978216, ECO:0000269\|PubMed:16099990, ECO:0000269\|PubMed:16737952, ECO:0000269\|PubMed:18400762, ECO:0000269\|PubMed:21170023, ECO:0000269\|PubMed:7589240}.



Function:		(Microbial infection) Functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. {ECO:0000269\|PubMed:16099990}.


Activity regulation:		Activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). Activated by ASAP3. Inactivated by ACAP1 and ACAP2. Activated by NGF via NTRK1 (By similarity). {ECO:0000250\|UniProtKB:P62332, ECO:0000269\|PubMed:11062263, ECO:0000269\|PubMed:18400762}.
Subunit:		Interacts (when activated) with GGA1, GGA2 and GGA3; the interaction is required for proper subcellular location of GGA1, GGA2 and GGA3 (PubMed:11950392). Interacts with PIP5K1C (PubMed:12847086). Interacts with USP6 (via Rab-GAP TBC domain) (PubMed:15509780). Interacts with RAB11FIP3 and RAB11FIP4 (PubMed:16148947, PubMed:17030804, PubMed:17628206). Interacts with HERC1 (PubMed:15642342). Interacts with ARHGAP21 (PubMed:15793564). Interacts with ASAP3; the interaction is stabilized by calcium ions (PubMed:16737952, PubMed:20510928). Interacts with NCS1/FREQ at the plasma membrane (PubMed:17555535). Interacts with TBC1D24 (PubMed:20727515). Interacts with ECPAS (PubMed:20682791). Interacts with MICALL1 (PubMed:21951725). Interacts with SPAG9 homodimers, forming heterotetramers (PubMed:19644450). Interacts with CYTH3 (PubMed:23940353). Interacts with ASAP2 (By similarity). Interacts with UACA (By similarity). Interacts with KIF23, forming heterodimers and heterotetramers (By similarity). Interacts with C9orf72 (By similarity). Interacts (GTP-bound form) with TJAP1/PILT (By similarity). {ECO:0000250\|UniProtKB:P62331, ECO:0000250\|UniProtKB:P62332, ECO:0000269\|PubMed:11950392, ECO:0000269\|PubMed:12847086, ECO:0000269\|PubMed:15509780, ECO:0000269\|PubMed:15642342, ECO:0000269\|PubMed:15793564, ECO:0000269\|PubMed:16148947, ECO:0000269\|PubMed:16737952, ECO:0000269\|PubMed:17030804, ECO:0000269\|PubMed:17555535, ECO:0000269\|PubMed:17628206, ECO:0000269\|PubMed:19644450, ECO:0000269\|PubMed:20510928, ECO:0000269\|PubMed:20682791, ECO:0000269\|PubMed:20727515, ECO:0000269\|PubMed:21951725, ECO:0000269\|PubMed:23940353}.
Subunit:		(Microbial infection) Interacts with the V.cholerae enterotoxin subunit A1; this causes a conformation change so that the toxin can bind NAD and catalyze the ADP-ribosylation of Gs alpha. {ECO:0000269\|PubMed:16099990}.
Subunit:		(Microbial infection) Interacts with EspG from enteropathogenic E.coli. {ECO:0000269\|PubMed:21170023, ECO:0000269\|PubMed:22939626}.
Subunit:		(Microbial infection) Identified in a complex with RAB1A and EspG from enteropathogenic E.coli. {ECO:0000269\|PubMed:22939626}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000269\|PubMed:16737952, ECO:0000269\|PubMed:23603394, ECO:0000269\|PubMed:7589240}. Cell membrane {ECO:0000269\|PubMed:16737952, ECO:0000269\|PubMed:17398095, ECO:0000269\|PubMed:17555535}; Lipid-anchor {ECO:0000269\|PubMed:7589240}. Endosome membrane {ECO:0000269\|PubMed:19948740, ECO:0000269\|PubMed:20682791, ECO:0000269\|PubMed:21951725}; Lipid-anchor. Recycling endosome membrane {ECO:0000305}; Lipid-anchor {ECO:0000305}. Cell projection, filopodium membrane; Lipid-anchor. Cell projection, ruffle {ECO:0000269\|PubMed:16737952}. Cleavage furrow {ECO:0000269\|PubMed:23603394}. Midbody, Midbody ring {ECO:0000269\|PubMed:23603394}. Early endosome membrane {ECO:0000250\|UniProtKB:P62331}; Lipid-anchor {ECO:0000250\|UniProtKB:P62331}. Golgi apparatus, trans-Golgi network membrane {ECO:0000250\|UniProtKB:P62331}; Lipid-anchor {ECO:0000250\|UniProtKB:P62331}. Note=Distributed uniformly on the plasma membrane, as well as throughout the cytoplasm during metaphase. Subsequently concentrated at patches in the equatorial region at the onset of cytokinesis, and becomes distributed in the equatorial region concurrent with cleavage furrow ingression. In late stages of cytokinesis, concentrates at the midbody ring/Flemming body (PubMed:23603394). Recruitment to the midbody ring requires both activation by PSD/EFA6A and interaction with KIF23/MKLP1 (By similarity). After abscission of the intercellular bridge, incorporated into one of the daughter cells as a midbody remnant and localizes to punctate structures beneath the plasma membrane (PubMed:23603394). Recruited to the cell membrane in association with CYTH2 and ARL4C. Colocalizes with DAB2IP at the plasma membrane and endocytic vesicles (By similarity). Myristoylation is required for proper localization to membranes (PubMed:7589240). {ECO:0000250, ECO:0000250\|UniProtKB:P62331, ECO:0000269\|PubMed:23603394, ECO:0000269\|PubMed:7589240}.
Tissue specificity:		Ubiquitous, with higher levels in heart, substantia nigra, and kidney. {ECO:0000269\|PubMed:14659046}.
Similarity:		Belongs to the small GTPase superfamily. Arf family. {ECO:0000305}.