UniProt functional annotation for Q9H0H5



	UniProt functional annotation for Q9H0H5

UniProt code: Q9H0H5.

Organism: Homo sapiens (Human).

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

Function: Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Required for proper attachment of the midbody to the cell membrane during cytokinesis. Plays key roles in controlling cell growth and differentiation of hematopoietic cells through mechanisms other than regulating Rac GTPase activity. Also involved in the regulation of growth-related processes in adipocytes and myoblasts. May be involved in regulating spermatogenesis and in the RACGAP1 pathway in neuronal proliferation. Shows strong GAP (GTPase activation) activity towards CDC42 and RAC1 and less towards RHOA. Essential for the early stages of embryogenesis. May play a role in regulating cortical activity through RHOA during cytokinesis. May participate in the regulation of sulfate transport in male germ cells. {ECO:0000269|PubMed:10979956, ECO:0000269|PubMed:11085985, ECO:0000269|PubMed:11278976, ECO:0000269|PubMed:11782313, ECO:0000269|PubMed:14729465, ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16129829, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:23235882, ECO:0000269|PubMed:9497316}.

Subunit: Heterotetramer of two molecules each of RACGAP1 and KIF23. Found in the centralspindlin complex. Associates with alpha-, beta- and gamma-tubulin and microtubules. Interacts via its Rho-GAP domain with RND2. Associates with AURKB during M phase. Interacts via its Rho-GAP domain and basic region with PRC1. The interaction with PRC1 inhibits its GAP activity towards CDC42 in vitro, which may be required for maintaining normal spindle morphology. Interacts with SLC26A8 via its N-terminus. Interacts with RAB11FIP3. Interacts with ECT2; the interaction is direct, occurs at anaphase and during cytokinesis in a microtubule-dependent manner, is enhanced by phosphorylation by PLK1 and phosphorylation at Ser-164 plays a major role in mediating binding (PubMed:25068414). Interacts with KIF23; the interaction is direct. {ECO:0000269|PubMed:11085985, ECO:0000269|PubMed:11278976, ECO:0000269|PubMed:11782313, ECO:0000269|PubMed:12590651, ECO:0000269|PubMed:12689593, ECO:0000269|PubMed:14744859, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16129829, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:18511905, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:23235882, ECO:0000269|PubMed:25068414}.

Subcellular location: Nucleus {ECO:0000269|PubMed:18445686}. Cytoplasm. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:18445686}. Cytoplasmic vesicle, secretory vesicle, acrosome. Cleavage furrow. Midbody, Midbody ring {ECO:0000269|PubMed:16213214}. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note=Colocalizes with RND2 in Golgi-derived proacrosomal vesicles and the acrosome (By similarity). During interphase, localized to the nucleus and cytoplasm along with microtubules, in anaphase, is redistributed to the central spindle and, in telophase and cytokinesis, to the midbody ring, also called Flemming body. Colocalizes with RHOA at the myosin contractile ring during cytokinesis. Colocalizes with ECT2 to the mitotic spindles during anaphase/metaphase, the cleavage furrow during telophase and at the midbody at the end of cytokinesis. Colocalizes with Cdc42 to spindle microtubules from prometaphase to telophase. {ECO:0000250}.

Tissue specificity: Highly expressed in testis, thymus and placenta. Expressed at lower levels in spleen and peripheral blood lymphocytes. In testis, expression is restricted to germ cells with the highest levels of expression found in spermatocytes. Expression is regulated in a cell cycle-dependent manner and peaks during G2/M phase. {ECO:0000269|PubMed:10979956, ECO:0000269|PubMed:11278976, ECO:0000269|PubMed:12590651, ECO:0000269|PubMed:9497316}.

Induction: Expression is down-regulated during macrophage differention of HL-60 cells. {ECO:0000269|PubMed:10979956}.

Domain: The coiled coil region is indispensible for localization to the midbody during cytokinesis. {ECO:0000269|PubMed:11085985}.

Domain: The phorbol-ester/DAG-type zinc finger domain mediates interaction with membranes enriched in phosphatidylinositol 3,4,5- trisphosphate and is required during mitotic cytokinesis for normal attachment of the midbody to the cell membrane.

Ptm: Phosphorylated at multiple sites in the midbody during cytokinesis (PubMed:12689593). Phosphorylation by AURKB on Ser-387 at the midbody is, at least in part, responsible for exerting its latent GAP activity towards RhoA (PubMed:12689593). Phosphorylation on multiple serine residues by PLK1 enhances its association with ECT2 and is critical for cleavage furrow formation (PubMed:19468302, PubMed:19468300). Phosphorylation on Ser-164 plays a major role in mediating interaction with ECT2 (PubMed:25068414). Phosphorylation on Ser-157 does not appear to contribute to binding to ECT2 (PubMed:25068414). {ECO:0000269|PubMed:12689593, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:25068414}.

Sequence caution: Sequence=AAH24144.1; Type=Frameshift; Evidence={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:		Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Required for proper attachment of the midbody to the cell membrane during cytokinesis. Plays key roles in controlling cell growth and differentiation of hematopoietic cells through mechanisms other than regulating Rac GTPase activity. Also involved in the regulation of growth-related processes in adipocytes and myoblasts. May be involved in regulating spermatogenesis and in the RACGAP1 pathway in neuronal proliferation. Shows strong GAP (GTPase activation) activity towards CDC42 and RAC1 and less towards RHOA. Essential for the early stages of embryogenesis. May play a role in regulating cortical activity through RHOA during cytokinesis. May participate in the regulation of sulfate transport in male germ cells. {ECO:0000269\|PubMed:10979956, ECO:0000269\|PubMed:11085985, ECO:0000269\|PubMed:11278976, ECO:0000269\|PubMed:11782313, ECO:0000269\|PubMed:14729465, ECO:0000269\|PubMed:15642749, ECO:0000269\|PubMed:16103226, ECO:0000269\|PubMed:16129829, ECO:0000269\|PubMed:16236794, ECO:0000269\|PubMed:19468300, ECO:0000269\|PubMed:19468302, ECO:0000269\|PubMed:23235882, ECO:0000269\|PubMed:9497316}.


Subunit:		Heterotetramer of two molecules each of RACGAP1 and KIF23. Found in the centralspindlin complex. Associates with alpha-, beta- and gamma-tubulin and microtubules. Interacts via its Rho-GAP domain with RND2. Associates with AURKB during M phase. Interacts via its Rho-GAP domain and basic region with PRC1. The interaction with PRC1 inhibits its GAP activity towards CDC42 in vitro, which may be required for maintaining normal spindle morphology. Interacts with SLC26A8 via its N-terminus. Interacts with RAB11FIP3. Interacts with ECT2; the interaction is direct, occurs at anaphase and during cytokinesis in a microtubule-dependent manner, is enhanced by phosphorylation by PLK1 and phosphorylation at Ser-164 plays a major role in mediating binding (PubMed:25068414). Interacts with KIF23; the interaction is direct. {ECO:0000269\|PubMed:11085985, ECO:0000269\|PubMed:11278976, ECO:0000269\|PubMed:11782313, ECO:0000269\|PubMed:12590651, ECO:0000269\|PubMed:12689593, ECO:0000269\|PubMed:14744859, ECO:0000269\|PubMed:16103226, ECO:0000269\|PubMed:16129829, ECO:0000269\|PubMed:16236794, ECO:0000269\|PubMed:18511905, ECO:0000269\|PubMed:19468300, ECO:0000269\|PubMed:23235882, ECO:0000269\|PubMed:25068414}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:18445686}. Cytoplasm. Cytoplasm, cytoskeleton, spindle {ECO:0000269\|PubMed:18445686}. Cytoplasmic vesicle, secretory vesicle, acrosome. Cleavage furrow. Midbody, Midbody ring {ECO:0000269\|PubMed:16213214}. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note=Colocalizes with RND2 in Golgi-derived proacrosomal vesicles and the acrosome (By similarity). During interphase, localized to the nucleus and cytoplasm along with microtubules, in anaphase, is redistributed to the central spindle and, in telophase and cytokinesis, to the midbody ring, also called Flemming body. Colocalizes with RHOA at the myosin contractile ring during cytokinesis. Colocalizes with ECT2 to the mitotic spindles during anaphase/metaphase, the cleavage furrow during telophase and at the midbody at the end of cytokinesis. Colocalizes with Cdc42 to spindle microtubules from prometaphase to telophase. {ECO:0000250}.
Tissue specificity:		Highly expressed in testis, thymus and placenta. Expressed at lower levels in spleen and peripheral blood lymphocytes. In testis, expression is restricted to germ cells with the highest levels of expression found in spermatocytes. Expression is regulated in a cell cycle-dependent manner and peaks during G2/M phase. {ECO:0000269\|PubMed:10979956, ECO:0000269\|PubMed:11278976, ECO:0000269\|PubMed:12590651, ECO:0000269\|PubMed:9497316}.
Induction:		Expression is down-regulated during macrophage differention of HL-60 cells. {ECO:0000269\|PubMed:10979956}.
Domain:		The coiled coil region is indispensible for localization to the midbody during cytokinesis. {ECO:0000269\|PubMed:11085985}.
Domain:		The phorbol-ester/DAG-type zinc finger domain mediates interaction with membranes enriched in phosphatidylinositol 3,4,5- trisphosphate and is required during mitotic cytokinesis for normal attachment of the midbody to the cell membrane.
Ptm:		Phosphorylated at multiple sites in the midbody during cytokinesis (PubMed:12689593). Phosphorylation by AURKB on Ser-387 at the midbody is, at least in part, responsible for exerting its latent GAP activity towards RhoA (PubMed:12689593). Phosphorylation on multiple serine residues by PLK1 enhances its association with ECT2 and is critical for cleavage furrow formation (PubMed:19468302, PubMed:19468300). Phosphorylation on Ser-164 plays a major role in mediating interaction with ECT2 (PubMed:25068414). Phosphorylation on Ser-157 does not appear to contribute to binding to ECT2 (PubMed:25068414). {ECO:0000269\|PubMed:12689593, ECO:0000269\|PubMed:19468300, ECO:0000269\|PubMed:19468302, ECO:0000269\|PubMed:25068414}.
Sequence caution:		Sequence=AAH24144.1; Type=Frameshift; Evidence={ECO:0000305};