UniProt functional annotation for P53779



	UniProt functional annotation for P53779

UniProt code: P53779.

Organism: Homo sapiens (Human).

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

Function: Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the amyloid-beta precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock (PubMed:22441692). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296). {ECO:0000269|PubMed:11718727, ECO:0000269|PubMed:22327296, ECO:0000269|PubMed:22441692}.

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=2.7.11.24;

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=2.7.11.24;

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:10715136};

Activity regulation: Activated by threonine and tyrosine phosphorylation by two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K7 phosphorylates MAPK10 on Thr-221 causing a conformational change and a large increase in Vmax. MAP2K4 then phosphorylates Tyr-223 resulting in a further increase in Vmax. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by HDAC9. {ECO:0000269|PubMed:11062067, ECO:0000269|PubMed:16611996}.

Subunit: Interacts with MAPKBP1 (By similarity). Interacts with MAPK8IP1/JIP-1 and MAPK8IP3/JIP-3/JSAP1 (By similarity). Interacts with SPAG9/MAPK8IP4/JIP4 (PubMed:15693750). Interacts with HDAC9 (PubMed:16611996). Interacts with ARRB2; the interaction enhances MAPK10 activation by MAP3K5 (PubMed:18435604). Interacts with SARM1 (By similarity). Interacts with JUND; interaction is inhibited in the presence of MEN1 (PubMed:22327296). {ECO:0000250|UniProtKB:P49187, ECO:0000250|UniProtKB:Q61831, ECO:0000269|PubMed:15693750, ECO:0000269|PubMed:16611996, ECO:0000269|PubMed:18435604, ECO:0000269|PubMed:22327296}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:16737965}. Membrane {ECO:0000269|PubMed:16737965}; Lipid-anchor {ECO:0000269|PubMed:16737965}. Nucleus {ECO:0000269|PubMed:16737965}. Mitochondrion {ECO:0000269|PubMed:16737965}. Note=Palmitoylation regulates MAPK10 trafficking to cytoskeleton. Recruited to the mitochondria in the presence of SARM1 (By similarity). {ECO:0000250}.

Tissue specificity: Specific to a subset of neurons in the nervous system. Present in the hippocampus and areas, cerebellum, striatum, brain stem, and weakly in the spinal cord. Very weak expression in testis and kidney.

Domain: The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

Ptm: Dually phosphorylated on Thr-221 and Tyr-223 by MAP2K4 and MAP2K7, which activates the enzyme. MAP2K7 shows a strong preference for Thr- 221 while MAP2K4 phosphorylates Tyr-223 preferentially. Weakly autophosphorylated on threonine and tyrosine residues in vitro. {ECO:0000269|PubMed:10715136}.

Ptm: Palmitoylation regulates subcellular location and axonal development. {ECO:0000269|PubMed:21941371}.

Mass spectrometry: Mass=44070; Method=Electrospray; Evidence={ECO:0000269|PubMed:10715136};

Disease: Note=A chromosomal aberration involving MAPK10 has been found in a single patient with pharmacoresistant epileptic encephalopathy. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation. {ECO:0000269|PubMed:16249883}.

Similarity: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. {ECO:0000305}.

Sequence caution: Sequence=BAG51956.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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:		Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the amyloid-beta precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock (PubMed:22441692). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296). {ECO:0000269\|PubMed:11718727, ECO:0000269\|PubMed:22327296, ECO:0000269\|PubMed:22441692}.


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=2.7.11.24;
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=2.7.11.24;
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:10715136};
Activity regulation:		Activated by threonine and tyrosine phosphorylation by two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K7 phosphorylates MAPK10 on Thr-221 causing a conformational change and a large increase in Vmax. MAP2K4 then phosphorylates Tyr-223 resulting in a further increase in Vmax. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by HDAC9. {ECO:0000269\|PubMed:11062067, ECO:0000269\|PubMed:16611996}.
Subunit:		Interacts with MAPKBP1 (By similarity). Interacts with MAPK8IP1/JIP-1 and MAPK8IP3/JIP-3/JSAP1 (By similarity). Interacts with SPAG9/MAPK8IP4/JIP4 (PubMed:15693750). Interacts with HDAC9 (PubMed:16611996). Interacts with ARRB2; the interaction enhances MAPK10 activation by MAP3K5 (PubMed:18435604). Interacts with SARM1 (By similarity). Interacts with JUND; interaction is inhibited in the presence of MEN1 (PubMed:22327296). {ECO:0000250\|UniProtKB:P49187, ECO:0000250\|UniProtKB:Q61831, ECO:0000269\|PubMed:15693750, ECO:0000269\|PubMed:16611996, ECO:0000269\|PubMed:18435604, ECO:0000269\|PubMed:22327296}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:16737965}. Membrane {ECO:0000269\|PubMed:16737965}; Lipid-anchor {ECO:0000269\|PubMed:16737965}. Nucleus {ECO:0000269\|PubMed:16737965}. Mitochondrion {ECO:0000269\|PubMed:16737965}. Note=Palmitoylation regulates MAPK10 trafficking to cytoskeleton. Recruited to the mitochondria in the presence of SARM1 (By similarity). {ECO:0000250}.
Tissue specificity:		Specific to a subset of neurons in the nervous system. Present in the hippocampus and areas, cerebellum, striatum, brain stem, and weakly in the spinal cord. Very weak expression in testis and kidney.
Domain:		The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Ptm:		Dually phosphorylated on Thr-221 and Tyr-223 by MAP2K4 and MAP2K7, which activates the enzyme. MAP2K7 shows a strong preference for Thr- 221 while MAP2K4 phosphorylates Tyr-223 preferentially. Weakly autophosphorylated on threonine and tyrosine residues in vitro. {ECO:0000269\|PubMed:10715136}.
Ptm:		Palmitoylation regulates subcellular location and axonal development. {ECO:0000269\|PubMed:21941371}.
Mass spectrometry:		Mass=44070; Method=Electrospray; Evidence={ECO:0000269\|PubMed:10715136};
Disease:		Note=A chromosomal aberration involving MAPK10 has been found in a single patient with pharmacoresistant epileptic encephalopathy. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation. {ECO:0000269\|PubMed:16249883}.
Similarity:		Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. {ECO:0000305}.
Sequence caution:		Sequence=BAG51956.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};