Mitogen-activated protein kinase 10 - Rattus norvegicus (Rat)

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P49187 (MK10_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 117. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase 10
Short name=MAP kinase 10
Short name=MAPK 10
EC=2.7.11.24

Alternative name(s):
SAPK-beta
Stress-activated protein kinase JNK3
c-Jun N-terminal kinase 3
p54-beta

Gene names

Name:	Mapk10
Synonyms:	Jnk3, Prkm10

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	464 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 beta-amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons By similarity. Ref.4 Ref.5
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme 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 for the enzyme. MAP2K4 then phosphorylates Tyr-223 resulting in a further increase in Vmax. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by HDAC9 By similarity.
Subunit structure	Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4. These proteins also bind other components of the JNK signaling pathway. Interacts with HDAC9 and MAPKBP1 By similarity. Interacts with ARRB2; the interaction enhances MAPK10 activation by MAP3K5. Interacts with SARM1 By similarity. Ref.3 Ref.6
Subcellular location	Cytoplasm. Membrane; Lipid-anchor. Nucleus. Mitochondrion. Note: Palmitoylation regulates MAPK10 trafficking to cytoskeleton By similarity. Recruited to the mitochondria in the presence of SARM1 By similarity.
Domain	The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Post-translational modification	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 By similarity. Palmitoylation regulates subcellular location and axonal development By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. Contains 1 protein kinase domain.
Sequence caution	The sequence AAA42110.1 differs from that shown. Reason: Frameshift at position 22.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane Mitochondrion Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	mitochondrion Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from direct assay PubMed 10051439. Source: RGD JUN kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 464

464

Mitogen-activated protein kinase 10

PRO_0000186279

Regions

Domain

64 – 359

296

Protein kinase

Nucleotide binding

70 – 78

ATP By similarity

Motif

221 – 223

TXY

Sites

Active site

189

Proton acceptor By similarity

Binding site

ATP By similarity

Amino acid modifications

Modified residue

221

Phosphothreonine; by MAP2K7 By similarity

Modified residue

223

Phosphotyrosine; by MAP2K4 By similarity

Lipidation

462

S-palmitoyl cysteine By similarity

Lipidation

463

S-palmitoyl cysteine By similarity

Sequences

Sequence

Length

Mass (Da)

Tools

P49187 [UniParc].

Last modified November 1, 1997. Version 2.
Checksum: 6D6279D7C3E68AF9
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FASTA

464

52,530

        10         20         30         40         50         60 
MSLHFLYYCS EPTLDVKIAF CQGFDKHVDV SSVVKHYNMS KSKVDNQFYS VEVGDSTFTV 

        70         80         90        100        110        120 
LKRYQNLKPI GSGAQGIVCA AYDAVLDRNV AIKKLSRPFQ NQTHAKRAYR ELVLMKCVNH 

       130        140        150        160        170        180 
KNIISLLNVF TPQKTLEEFQ DVYLVMELMD ANLCQVIQME LDHERMSYLL YQMLSAIKHL 

       190        200        210        220        230        240 
HSAGIIHRDL KPSNIVVKSD CTLKILDFGL ARTAGTSFMM TPYVVTRYYR APEVILGMGY 

       250        260        270        280        290        300 
KENVDIWSVG CIMGEMVRHK ILFPGRDYID QWNKVIEQLG TPCPEFMKKL QPTVRNYVEN 

       310        320        330        340        350        360 
RPKYAGLTFP KLFPDSLFPA DSEHNKLKAS QARDLLSKML VIDPAKRISV DDALQHPYIN 

       370        380        390        400        410        420 
VWYDPAEVEA PPPQIYDKQL DEREHTIEEW KELIYKEVMN SEEKTKNGVV KGQPSPSGAA 

       430        440        450        460 
VNSSESLPPS SSVNDISSMS TDQTLASDTD SSLEASAGPL GCCR

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References

[1]	"The stress-activated protein kinase subfamily of c-Jun kinases." Kyriakis J.M., Banerjee P., Nikolakaki E., Dai T., Rubie E.A., Ahmad M.F., Avruch J., Woodgett J.R. Nature 369:156-160(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	Hulo-Demole C., Braconi-Quintaje S. Unpublished observations (MAR-1997) Cited for: IDENTIFICATION OF PROBABLE FRAMESHIFT.
[3]	"Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3." McDonald P.H., Chow C.W., Miller W.E., Laporte S.A., Field M.E., Lin F.-T., Davis R.J., Lefkowitz R.J. Science 290:1574-1577(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARRB2.
[4]	"JNK3 contributes to c-jun induction and apoptosis in 4-hydroxynonenal-treated sympathetic neurons." Bruckner S.R., Estus S. J. Neurosci. Res. 70:665-670(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[5]	"Physiological regulation of the beta-amyloid precursor protein signaling domain by c-Jun N-terminal kinase JNK3 during neuronal differentiation." Kimberly W.T., Zheng J.B., Town T., Flavell R.A., Selkoe D.J. J. Neurosci. 25:5533-5543(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF APP.
[6]	"The beta-arrestin-2 scaffold protein promotes c-Jun N-terminal kinase-3 activation by binding to its nonconserved N terminus." Guo C., Whitmarsh A.J. J. Biol. Chem. 283:15903-15911(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARRB2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L27128 mRNA. Translation: AAA42110.1. Frameshift.
IPI	IPI00191810.
PIR	S43969.
RefSeq	NP_036938.2. NM_012806.2.
UniGene	Rn.9911.
3D structure databases
ProteinModelPortal	P49187.
SMR	P49187. Positions 45-400.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-151503.
PTM databases
PhosphoSite	P49187.
Proteomic databases
PaxDb	P49187.
PRIDE	P49187.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	25272.
KEGG	rno:25272.
Organism-specific databases
CTD	5602.
RGD	3663. Mapk10.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233024.
HOVERGEN	HBG014652.
InParanoid	P49187.
KO	K04440.
Enzyme and pathway databases
BRENDA	2.7.11.24. 5301.
Gene expression databases
ArrayExpress	P49187.
Genevestigator	P49187.
GermOnline	ENSRNOG00000002079. Rattus norvegicus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR003527. MAP_kinase_CS. IPR008351. MAPK_JNK. IPR000719. Prot_kinase_cat_dom. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PRINTS	PR01772. JNKMAPKINASE.
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS01351. MAPK. 1 hit. PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P49187.
ChEMBL	CHEMBL4092.
NextBio	605961.

Entry information

Entry name

MK10_RAT

Accession

Primary (citable) accession number: P49187

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	November 1, 1997
Last modified:	April 3, 2013
This is version 117 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents