UniProt functional annotation for Q9HBH9



	UniProt functional annotation for Q9HBH9

UniProt code: Q9HBH9.

Organism: Homo sapiens (Human).

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

Function: Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A- inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal. {ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11463832, ECO:0000269|PubMed:12897141, ECO:0000269|PubMed:16111636, ECO:0000269|PubMed:17965020, ECO:0000269|PubMed:18299328, ECO:0000269|PubMed:20823271, ECO:0000269|PubMed:20927323, ECO:0000269|PubMed:21149447}.

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:11463832};

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:11463832};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:11463832};

Cofactor: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per subunit.;

Activity regulation: Inhibited by CGP57380 and staurosporine. Activated by phosphorylation in a negative-feedback regulatory manner in response to chemotherapy (e.g. cytarabine) and thus impairs the generation of antileukemic responses. {ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:16111636, ECO:0000269|PubMed:16917500, ECO:0000269|PubMed:20664001, ECO:0000269|PubMed:20722422, ECO:0000269|PubMed:20927323}.

Subunit: Monomer. Interacts with the C-terminal regions of EIF4G1 and EIF4G2; this interaction is promoted when MAPK pathways are repressed but repressed upon ERK proteins activation. Also binds to dephosphorylated MAPK3/ERK1 and MAPK1/ERK2. Isoform 1 interaction with phosphorylated MAPK3/ERK1 and MAPK1/ERK2 protects it from dephosphorylation and inactivation. Isoform 2 interacts with ESR2 and EIF4E in the nucleus. {ECO:0000269|PubMed:11013076, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:12897141, ECO:0000269|PubMed:16216586, ECO:0000269|PubMed:16917500, ECO:0000269|PubMed:20823271}.

Subcellular location: [Isoform 2]: Nucleus, PML body.

Subcellular location: [Isoform 1]: Cytoplasm.

Tissue specificity: Ubiquitously expressed in all tissues examined. Isoform 2 is expressed at higher levels in the ovary than is isoform 1. {ECO:0000269|PubMed:11013076}.

Ptm: Dual phosphorylation of Thr-244 and Thr-249 activates the kinase. Phosphorylation of Thr-379 activates the kinase. Phosphorylated upon arsenic trioxide As(2)O(3) treatment. Phosphorylated by MAPK1/ERK2, MAPK11 and MAPK14. Dephosphorylated by PP2A. {ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11463832, ECO:0000269|PubMed:12897141, ECO:0000269|PubMed:18299328}.

Similarity: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase 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:		Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A- inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal. {ECO:0000269\|PubMed:11154262, ECO:0000269\|PubMed:11463832, ECO:0000269\|PubMed:12897141, ECO:0000269\|PubMed:16111636, ECO:0000269\|PubMed:17965020, ECO:0000269\|PubMed:18299328, ECO:0000269\|PubMed:20823271, ECO:0000269\|PubMed:20927323, ECO:0000269\|PubMed:21149447}.


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:11463832};
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:11463832};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:11463832};
Cofactor:		Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per subunit.;
Activity regulation:		Inhibited by CGP57380 and staurosporine. Activated by phosphorylation in a negative-feedback regulatory manner in response to chemotherapy (e.g. cytarabine) and thus impairs the generation of antileukemic responses. {ECO:0000269\|PubMed:11154262, ECO:0000269\|PubMed:16111636, ECO:0000269\|PubMed:16917500, ECO:0000269\|PubMed:20664001, ECO:0000269\|PubMed:20722422, ECO:0000269\|PubMed:20927323}.
Subunit:		Monomer. Interacts with the C-terminal regions of EIF4G1 and EIF4G2; this interaction is promoted when MAPK pathways are repressed but repressed upon ERK proteins activation. Also binds to dephosphorylated MAPK3/ERK1 and MAPK1/ERK2. Isoform 1 interaction with phosphorylated MAPK3/ERK1 and MAPK1/ERK2 protects it from dephosphorylation and inactivation. Isoform 2 interacts with ESR2 and EIF4E in the nucleus. {ECO:0000269\|PubMed:11013076, ECO:0000269\|PubMed:11154262, ECO:0000269\|PubMed:12897141, ECO:0000269\|PubMed:16216586, ECO:0000269\|PubMed:16917500, ECO:0000269\|PubMed:20823271}.
Subcellular location:		[Isoform 2]: Nucleus, PML body.
Subcellular location:		[Isoform 1]: Cytoplasm.
Tissue specificity:		Ubiquitously expressed in all tissues examined. Isoform 2 is expressed at higher levels in the ovary than is isoform 1. {ECO:0000269\|PubMed:11013076}.
Ptm:		Dual phosphorylation of Thr-244 and Thr-249 activates the kinase. Phosphorylation of Thr-379 activates the kinase. Phosphorylated upon arsenic trioxide As(2)O(3) treatment. Phosphorylated by MAPK1/ERK2, MAPK11 and MAPK14. Dephosphorylated by PP2A. {ECO:0000269\|PubMed:11154262, ECO:0000269\|PubMed:11463832, ECO:0000269\|PubMed:12897141, ECO:0000269\|PubMed:18299328}.
Similarity:		Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. {ECO:0000305}.