UniProt functional annotation for Q16512



	UniProt functional annotation for Q16512

UniProt code: Q16512.

Organism: Homo sapiens (Human).

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

Function: PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. {ECO:0000269|PubMed:11104762, ECO:0000269|PubMed:12514133, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:18066052, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:24248594, ECO:0000269|PubMed:8557118, ECO:0000269|PubMed:8621664, ECO:0000269|PubMed:9175763}.

Catalytic activity: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.13; Evidence={ECO:0000269|PubMed:18066052};

Catalytic activity: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.13; Evidence={ECO:0000269|PubMed:18066052};

Activity regulation: Kinase activity is activated upon binding to Rho proteins (RHOA, RHOB and RAC1). Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids. Activated by caspase-3 (CASP3) cleavage during apoptosis. Two specific sites, Thr-774 (activation loop of the kinase domain) and Ser-916 (turn motif), need to be phosphorylated for its full activation. {ECO:0000269|PubMed:8571126, ECO:0000269|PubMed:9751706}.

Biophysicochemical properties: Kinetic parameters: KM=20.6 uM for HDAC5 {ECO:0000269|PubMed:20188095};

Subunit: Interacts with ZFAND6 (By similarity). Interacts with AR (PubMed:12514133). Interacts with PRKCB (PubMed:20228790). Interacts (via REM 1 and REM 2 repeats) with RAC1 (PubMed:14514689, PubMed:18006505). Interacts (via REM 1 repeat) with RHOA (PubMed:10619026, PubMed:8571126). Interacts with RHOB (PubMed:9478917). Interacts (via C-terminus) with PDPK1 (PubMed:10792047). Interacts with CCNT2; enhances MYOD1-dependent transcription (PubMed:16331689). Component of a signaling complex containing at least AKAP13, PKN1, MAPK14, ZAK and MAP2K3. Within this complex, AKAP13 interacts directly with PKN1, which in turn recruits MAPK14, MAP2K3 and ZAK (PubMed:21224381). {ECO:0000250|UniProtKB:P70268, ECO:0000269|PubMed:10619026, ECO:0000269|PubMed:10792047, ECO:0000269|PubMed:12514133, ECO:0000269|PubMed:14514689, ECO:0000269|PubMed:16331689, ECO:0000269|PubMed:18006505, ECO:0000269|PubMed:20228790, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:8571126, ECO:0000269|PubMed:9478917}.

Subunit: (Microbial infection) Interacts (via the second REM repeat) with S.typhimurium E3 ubiquitin-protein ligase SspH1 (via the leucine- rich repeat region) (PubMed:16611232, PubMed:24248594). {ECO:0000269|PubMed:16611232, ECO:0000269|PubMed:24248594}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:9478917}. Nucleus {ECO:0000269|PubMed:12514133}. Endosome {ECO:0000269|PubMed:9478917}. Cell membrane {ECO:0000250|UniProtKB:Q63433}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q63433}. Cleavage furrow {ECO:0000269|PubMed:17332740}. Midbody {ECO:0000269|PubMed:17332740}. Note=Associates with chromatin in a ligand-dependent manner. Localization to endosomes is mediated via its interaction with RHOB. Association to the cell membrane is dependent on Ser-377 phosphorylation. Accumulates during telophase at the cleavage furrow and finally concentrates around the midbody in cytokinesis. {ECO:0000250|UniProtKB:Q63433, ECO:0000269|PubMed:17332740}.

Tissue specificity: Found ubiquitously. Expressed in heart, brain, placenta, lung, skeletal muscle, kidney and pancreas. Expressed in numerous tumor cell lines, especially in breast tumor cells. {ECO:0000269|PubMed:21754995}.

Domain: The C1 domain does not bind the diacylglycerol (DAG).

Ptm: Autophosphorylated; preferably on serine. Phosphorylated during mitosis. {ECO:0000269|PubMed:10792047, ECO:0000269|PubMed:17332740}.

Ptm: Activated by limited proteolysis with trypsin. {ECO:0000250}.

Ptm: (Microbial infection) In case of infection, polyubiquitinated by the bacterial E3 ubiquitin-protein ligase SspH1, leading to its proteasomal degradation. {ECO:0000269|PubMed:24248594}.

Similarity: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. {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:		PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. {ECO:0000269\|PubMed:11104762, ECO:0000269\|PubMed:12514133, ECO:0000269\|PubMed:17332740, ECO:0000269\|PubMed:18066052, ECO:0000269\|PubMed:20188095, ECO:0000269\|PubMed:21224381, ECO:0000269\|PubMed:21754995, ECO:0000269\|PubMed:24248594, ECO:0000269\|PubMed:8557118, ECO:0000269\|PubMed:8621664, ECO:0000269\|PubMed:9175763}.


Catalytic activity:		Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.13; Evidence={ECO:0000269\|PubMed:18066052};
Catalytic activity:		Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.13; Evidence={ECO:0000269\|PubMed:18066052};
Activity regulation:		Kinase activity is activated upon binding to Rho proteins (RHOA, RHOB and RAC1). Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids. Activated by caspase-3 (CASP3) cleavage during apoptosis. Two specific sites, Thr-774 (activation loop of the kinase domain) and Ser-916 (turn motif), need to be phosphorylated for its full activation. {ECO:0000269\|PubMed:8571126, ECO:0000269\|PubMed:9751706}.
Biophysicochemical properties:		Kinetic parameters: KM=20.6 uM for HDAC5 {ECO:0000269\|PubMed:20188095};
Subunit:		Interacts with ZFAND6 (By similarity). Interacts with AR (PubMed:12514133). Interacts with PRKCB (PubMed:20228790). Interacts (via REM 1 and REM 2 repeats) with RAC1 (PubMed:14514689, PubMed:18006505). Interacts (via REM 1 repeat) with RHOA (PubMed:10619026, PubMed:8571126). Interacts with RHOB (PubMed:9478917). Interacts (via C-terminus) with PDPK1 (PubMed:10792047). Interacts with CCNT2; enhances MYOD1-dependent transcription (PubMed:16331689). Component of a signaling complex containing at least AKAP13, PKN1, MAPK14, ZAK and MAP2K3. Within this complex, AKAP13 interacts directly with PKN1, which in turn recruits MAPK14, MAP2K3 and ZAK (PubMed:21224381). {ECO:0000250\|UniProtKB:P70268, ECO:0000269\|PubMed:10619026, ECO:0000269\|PubMed:10792047, ECO:0000269\|PubMed:12514133, ECO:0000269\|PubMed:14514689, ECO:0000269\|PubMed:16331689, ECO:0000269\|PubMed:18006505, ECO:0000269\|PubMed:20228790, ECO:0000269\|PubMed:21224381, ECO:0000269\|PubMed:8571126, ECO:0000269\|PubMed:9478917}.
Subunit:		(Microbial infection) Interacts (via the second REM repeat) with S.typhimurium E3 ubiquitin-protein ligase SspH1 (via the leucine- rich repeat region) (PubMed:16611232, PubMed:24248594). {ECO:0000269\|PubMed:16611232, ECO:0000269\|PubMed:24248594}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:17332740, ECO:0000269\|PubMed:9478917}. Nucleus {ECO:0000269\|PubMed:12514133}. Endosome {ECO:0000269\|PubMed:9478917}. Cell membrane {ECO:0000250\|UniProtKB:Q63433}; Peripheral membrane protein {ECO:0000250\|UniProtKB:Q63433}. Cleavage furrow {ECO:0000269\|PubMed:17332740}. Midbody {ECO:0000269\|PubMed:17332740}. Note=Associates with chromatin in a ligand-dependent manner. Localization to endosomes is mediated via its interaction with RHOB. Association to the cell membrane is dependent on Ser-377 phosphorylation. Accumulates during telophase at the cleavage furrow and finally concentrates around the midbody in cytokinesis. {ECO:0000250\|UniProtKB:Q63433, ECO:0000269\|PubMed:17332740}.
Tissue specificity:		Found ubiquitously. Expressed in heart, brain, placenta, lung, skeletal muscle, kidney and pancreas. Expressed in numerous tumor cell lines, especially in breast tumor cells. {ECO:0000269\|PubMed:21754995}.
Domain:		The C1 domain does not bind the diacylglycerol (DAG).
Ptm:		Autophosphorylated; preferably on serine. Phosphorylated during mitosis. {ECO:0000269\|PubMed:10792047, ECO:0000269\|PubMed:17332740}.
Ptm:		Activated by limited proteolysis with trypsin. {ECO:0000250}.
Ptm:		(Microbial infection) In case of infection, polyubiquitinated by the bacterial E3 ubiquitin-protein ligase SspH1, leading to its proteasomal degradation. {ECO:0000269\|PubMed:24248594}.
Similarity:		Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. {ECO:0000305}.