UniProt functional annotation for Q9UIK4



	UniProt functional annotation for Q9UIK4

UniProt code: Q9UIK4.

Organism: Homo sapiens (Human).

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

Function: Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell death signals, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Acts as a mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation (PubMed:17347302). Regulates granulocytic motility by controlling cell spreading and polarization (PubMed:24163421). {ECO:0000269|PubMed:17347302, ECO:0000269|PubMed:24163421, ECO:0000269|PubMed:26047703}.

Function: Isoform 2 is not regulated by calmodulin. It can phosphorylate MYL9. It can induce membrane blebbing and autophagic cell death.

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=2.7.11.1; Evidence={ECO:0000269|PubMed:10376525, ECO:0000269|PubMed:26047703};

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=2.7.11.1; Evidence={ECO:0000269|PubMed:10376525, ECO:0000269|PubMed:26047703};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:10376525, ECO:0000269|PubMed:10629061, ECO:0000269|PubMed:11230133};

Activity regulation: Activated by Ca(2+)/calmodulin. Regulated by a double locking mechanism, involving autophosphorylation at Ser-318, calmodulin binding, and dimerization. In the inactive state, Ser-318 is phosphorylated, and the kinase is dimeric. Activation involves: dephosphorylation at Ser-318, release-of-autoinhibition mechanism where calmodulin binding induces a conformational change that relieves the steric block of the active site by the autoinhibitory domain, and generation of the monomeric active form of the kinase. {ECO:0000269|PubMed:10376525}.

Subunit: Homodimer in its autoinhibited state. Active as monomer (By similarity). Isoform 2 but not isoform 1 can interact with ATF4. Interacts with 14-3-3 proteins YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ and SFN; the interaction requires DAPK2 phosphorylation at Thr-369 and suppresses DAPK2 kinase activity and DAPK2-induced apoptosis (PubMed:26047703). {ECO:0000250, ECO:0000269|PubMed:26047703}.

Subcellular location: Cytoplasm. Cytoplasmic vesicle, autophagosome lumen.

Tissue specificity: Expressed in neutrophils and eosinophils (PubMed:24163421). Isoform 2 is expressed in embryonic stem cells (at protein level). Isoform 1 is ubiquitously expressed in all tissue types examined with high levels in heart, lung and skeletal muscle. {ECO:0000269|PubMed:10376525, ECO:0000269|PubMed:17347302, ECO:0000269|PubMed:21408167, ECO:0000269|PubMed:24163421}.

Induction: Up-regulated during granulocytic maturation (PubMed:17347302, PubMed:24163421). {ECO:0000269|PubMed:17347302, ECO:0000269|PubMed:24163421}.

Domain: The autoinhibitory domain sterically blocks the substrate peptide-binding site by making both hydrophobic and electrostatic contacts with the kinase core. {ECO:0000250}.

Ptm: Autophosphorylation at Ser-318 inhibits its catalytic activity. Dephosphorylated at Ser-318 in response to activated Fas and TNF-alpha receptors. {ECO:0000269|PubMed:11230133}.

Similarity: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase 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:		Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell death signals, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Acts as a mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation (PubMed:17347302). Regulates granulocytic motility by controlling cell spreading and polarization (PubMed:24163421). {ECO:0000269\|PubMed:17347302, ECO:0000269\|PubMed:24163421, ECO:0000269\|PubMed:26047703}.



Function:		Isoform 2 is not regulated by calmodulin. It can phosphorylate MYL9. It can induce membrane blebbing and autophagic cell death.


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=2.7.11.1; Evidence={ECO:0000269\|PubMed:10376525, ECO:0000269\|PubMed:26047703};
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=2.7.11.1; Evidence={ECO:0000269\|PubMed:10376525, ECO:0000269\|PubMed:26047703};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:10376525, ECO:0000269\|PubMed:10629061, ECO:0000269\|PubMed:11230133};
Activity regulation:		Activated by Ca(2+)/calmodulin. Regulated by a double locking mechanism, involving autophosphorylation at Ser-318, calmodulin binding, and dimerization. In the inactive state, Ser-318 is phosphorylated, and the kinase is dimeric. Activation involves: dephosphorylation at Ser-318, release-of-autoinhibition mechanism where calmodulin binding induces a conformational change that relieves the steric block of the active site by the autoinhibitory domain, and generation of the monomeric active form of the kinase. {ECO:0000269\|PubMed:10376525}.
Subunit:		Homodimer in its autoinhibited state. Active as monomer (By similarity). Isoform 2 but not isoform 1 can interact with ATF4. Interacts with 14-3-3 proteins YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ and SFN; the interaction requires DAPK2 phosphorylation at Thr-369 and suppresses DAPK2 kinase activity and DAPK2-induced apoptosis (PubMed:26047703). {ECO:0000250, ECO:0000269\|PubMed:26047703}.
Subcellular location:		Cytoplasm. Cytoplasmic vesicle, autophagosome lumen.
Tissue specificity:		Expressed in neutrophils and eosinophils (PubMed:24163421). Isoform 2 is expressed in embryonic stem cells (at protein level). Isoform 1 is ubiquitously expressed in all tissue types examined with high levels in heart, lung and skeletal muscle. {ECO:0000269\|PubMed:10376525, ECO:0000269\|PubMed:17347302, ECO:0000269\|PubMed:21408167, ECO:0000269\|PubMed:24163421}.
Induction:		Up-regulated during granulocytic maturation (PubMed:17347302, PubMed:24163421). {ECO:0000269\|PubMed:17347302, ECO:0000269\|PubMed:24163421}.
Domain:		The autoinhibitory domain sterically blocks the substrate peptide-binding site by making both hydrophobic and electrostatic contacts with the kinase core. {ECO:0000250}.
Ptm:		Autophosphorylation at Ser-318 inhibits its catalytic activity. Dephosphorylated at Ser-318 in response to activated Fas and TNF-alpha receptors. {ECO:0000269\|PubMed:11230133}.
Similarity:		Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily. {ECO:0000305}.