UniProt functional annotation for P62745



	UniProt functional annotation for P62745

UniProt code: P62745.

Organism: Homo sapiens (Human).

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

Function: Mediates apoptosis in neoplastically transformed cells after DNA damage. Not essential for development but affects cell adhesion and growth factor signaling in transformed cells. Plays a negative role in tumorigenesis as deletion causes tumor formation. Involved in intracellular protein trafficking of a number of proteins. Targets PKN1 to endosomes and is involved in trafficking of the EGF receptor from late endosomes to lysosomes. Also required for stability and nuclear trafficking of AKT1/AKT which promotes endothelial cell survival during vascular development. Serves as a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Required for genotoxic stress-induced cell death in breast cancer cells. {ECO:0000269|PubMed:10508588, ECO:0000269|PubMed:15226397, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:21373644, ECO:0000269|PubMed:9478917}.

Subunit: Binds ROCK1 and ROCK2 (By similarity). Also binds PKN1/PRK1 (PubMed:9478917). Interacts with ARGGEF3 (PubMed:12221096). Interacts with RTKN (By similarity). Interacts with AKAP13 (PubMed:11546812). Interacts with RIPOR1 (PubMed:27807006). {ECO:0000250|UniProtKB:P62746, ECO:0000250|UniProtKB:P62747, ECO:0000269|PubMed:11546812, ECO:0000269|PubMed:12221096, ECO:0000269|PubMed:27807006, ECO:0000269|PubMed:9478917}.

Subcellular location: Late endosome membrane; Lipid-anchor. Cell membrane; Lipid-anchor. Nucleus. Cleavage furrow. Note=Late endosomal membrane (geranylgeranylated form). Plasma membrane (farnesylated form). Also detected at the nuclear margin and in the nucleus. Translocates to the equatorial region before furrow formation in a ECT2-dependent manner.

Induction: Up-regulated by DNA damaging agents like H(2)O(2) or ionizing radiation (IR). {ECO:0000269|PubMed:21373644}.

Ptm: Prenylation specifies the subcellular location of RHOB. The farnesylated form is localized to the plasma membrane while the geranylgeranylated form is localized to the endosome. {ECO:0000269|PubMed:1400319, ECO:0000269|PubMed:7713879}.

Ptm: (Microbial infection) Glycosylated at Tyr-34 by Photorhabdus asymbiotica toxin PAU_02230. Mono-O-GlcNAcylation by PAU_02230 inhibits downstream signaling by an impaired interaction with diverse regulator and effector proteins of Rho and leads to actin disassembly. {ECO:0000269|PubMed:24141704}.

Ptm: (Microbial infection) Glucosylated at Thr-37 by C.difficile toxins TcdA and TcdB in the colonic epithelium (PubMed:24905543). Monoglucosylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption (PubMed:24905543). {ECO:0000269|PubMed:24905543}.

Miscellaneous: RHOB is one of the targets of farnesyltransferase inhibitors which are currently under investigation as cancer therapeutics. These elevate the levels of geranylgeranylated RHOB and cause mislocalization, leading to apoptosis and antineoplastic effects.

Similarity: Belongs to the small GTPase superfamily. Rho 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:		Mediates apoptosis in neoplastically transformed cells after DNA damage. Not essential for development but affects cell adhesion and growth factor signaling in transformed cells. Plays a negative role in tumorigenesis as deletion causes tumor formation. Involved in intracellular protein trafficking of a number of proteins. Targets PKN1 to endosomes and is involved in trafficking of the EGF receptor from late endosomes to lysosomes. Also required for stability and nuclear trafficking of AKT1/AKT which promotes endothelial cell survival during vascular development. Serves as a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Required for genotoxic stress-induced cell death in breast cancer cells. {ECO:0000269\|PubMed:10508588, ECO:0000269\|PubMed:15226397, ECO:0000269\|PubMed:16236794, ECO:0000269\|PubMed:21373644, ECO:0000269\|PubMed:9478917}.


Subunit:		Binds ROCK1 and ROCK2 (By similarity). Also binds PKN1/PRK1 (PubMed:9478917). Interacts with ARGGEF3 (PubMed:12221096). Interacts with RTKN (By similarity). Interacts with AKAP13 (PubMed:11546812). Interacts with RIPOR1 (PubMed:27807006). {ECO:0000250\|UniProtKB:P62746, ECO:0000250\|UniProtKB:P62747, ECO:0000269\|PubMed:11546812, ECO:0000269\|PubMed:12221096, ECO:0000269\|PubMed:27807006, ECO:0000269\|PubMed:9478917}.
Subcellular location:		Late endosome membrane; Lipid-anchor. Cell membrane; Lipid-anchor. Nucleus. Cleavage furrow. Note=Late endosomal membrane (geranylgeranylated form). Plasma membrane (farnesylated form). Also detected at the nuclear margin and in the nucleus. Translocates to the equatorial region before furrow formation in a ECT2-dependent manner.
Induction:		Up-regulated by DNA damaging agents like H(2)O(2) or ionizing radiation (IR). {ECO:0000269\|PubMed:21373644}.
Ptm:		Prenylation specifies the subcellular location of RHOB. The farnesylated form is localized to the plasma membrane while the geranylgeranylated form is localized to the endosome. {ECO:0000269\|PubMed:1400319, ECO:0000269\|PubMed:7713879}.
Ptm:		(Microbial infection) Glycosylated at Tyr-34 by Photorhabdus asymbiotica toxin PAU_02230. Mono-O-GlcNAcylation by PAU_02230 inhibits downstream signaling by an impaired interaction with diverse regulator and effector proteins of Rho and leads to actin disassembly. {ECO:0000269\|PubMed:24141704}.
Ptm:		(Microbial infection) Glucosylated at Thr-37 by C.difficile toxins TcdA and TcdB in the colonic epithelium (PubMed:24905543). Monoglucosylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption (PubMed:24905543). {ECO:0000269\|PubMed:24905543}.
Miscellaneous:		RHOB is one of the targets of farnesyltransferase inhibitors which are currently under investigation as cancer therapeutics. These elevate the levels of geranylgeranylated RHOB and cause mislocalization, leading to apoptosis and antineoplastic effects.
Similarity:		Belongs to the small GTPase superfamily. Rho family. {ECO:0000305}.