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UniProtKB/Swiss-Prot entry P53779


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name MK10_HUMAN
Primary accession number P53779
Secondary accession numbers A6NFS3 Q15707 Q49AP1
Integrated into Swiss-Prot on October 1, 1996
Sequence was last modified on November 1, 1997 (Sequence version 2)
Annotations were last modified on    June 16, 2009 (Entry version 105)
Name and origin of the protein
Protein name Mitogen-activated protein kinase 10
Synonyms EC 2.7.11.24
Stress-activated protein kinase JNK3
c-Jun N-terminal kinase 3
MAP kinase p49 3F12
Gene name
Name: MAPK10
Synonyms: JNK3, JNK3A, PRKM10
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1).
TISSUE=Hippocampus;
DOI=10.1016/0896-6273(95)90241-4; PubMed=7826642 [NCBI, ExPASy, EBI, Israel, Japan]
Mohit A.A., Martin J.H., Miller C.A.;
"p493F12 kinase: a novel MAP kinase expressed in a subset of neurons in the human nervous system.";
Neuron 14:67-78(1995).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-1 AND ALPHA-2).
TISSUE=Brain;
PubMed=8654373 [NCBI, ExPASy, EBI, Israel, Japan]
Gupta S., Barrett T., Whitmarsh A.J., Cavanagh J., Sluss H.K., Derijard B., Davis R.J.;
"Selective interaction of JNK protein kinase isoforms with transcription factors.";
EMBO J. 15:2760-2770(1996).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature03466; PubMed=15815621 [NCBI, ExPASy, EBI, Israel, Japan]
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.;
"Generation and annotation of the DNA sequences of human chromosomes 2 and 4.";
Nature 434:724-731(2005).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-2).
TISSUE=Brain;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
PARTIAL PROTEIN SEQUENCE, REGULATION BY MAP2K4 AND MAP2K7, PHOSPHORYLATION AT THR-221 AND TYR-223, COFACTOR, AND MASS SPECTROMETRY.
DOI=10.1021/bi992410+; PubMed=10715136 [NCBI, ExPASy, EBI, Israel, Japan]
Lisnock J., Griffin P., Calaycay J., Frantz B., Parsons J., O'Keefe S.J., LoGrasso P.;
"Activation of JNK3 alpha 1 requires both MKK4 and MKK7: kinetic characterization of in vitro phosphorylated JNK3 alpha 1.";
Biochemistry 39:3141-3148(2000).
[7]
INTERACTION WITH SPAG9.
DOI=10.1042/BJ20041577; PubMed=15693750 [NCBI, ExPASy, EBI, Israel, Japan]
Jagadish N., Rana R., Selvi R., Mishra D., Garg M., Yadav S., Herr J.C., Okumura K., Hasegawa A., Koyama K., Suri A.;
"Characterization of a novel human sperm-associated antigen 9 (SPAG9) having structural homology with c-Jun N-terminal kinase-interacting protein.";
Biochem. J. 389:73-82(2005).
[8]
CHROMOSOMAL REARRANGEMENT, AND INVOLVEMENT IN EPILEPTIC ENCEPHALOPATHY LENNOX-GASTAUT TYPE.
DOI=10.1007/s00439-005-0084-y; PubMed=16249883 [NCBI, ExPASy, EBI, Israel, Japan]
Shoichet S.A., Duprez L., Hagens O., Waetzig V., Menzel C., Herdegen T., Schweiger S., Dan B., Vamos E., Ropers H.-H., Kalscheuer V.M.;
"Truncation of the CNS-expressed JNK3 in a patient with a severe developmental epileptic encephalopathy.";
Hum. Genet. 118:559-567(2006).
[9]
INTERACTION WITH HDAC9, AND ENZYME REGULATION.
DOI=10.1128/MCB.26.9.3550-3564.2006; PubMed=16611996 [NCBI, ExPASy, EBI, Israel, Japan]
Morrison B.E., Majdzadeh N., Zhang X., Lyles A., Bassel-Duby R., Olson E.N., D'Mello S.R.;
"Neuroprotection by histone deacetylase-related protein.";
Mol. Cell. Biol. 26:3550-3564(2006).
[10]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-223, AND MASS SPECTROMETRY.
DOI=10.1016/j.cell.2007.11.025; PubMed=18083107 [NCBI, ExPASy, EBI, Israel, Japan]
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer.";
Cell 131:1190-1203(2007).
[11]
X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 40-402.
DOI=10.1016/S0969-2126(98)00100-2; PubMed=9739089 [NCBI, ExPASy, EBI, Israel, Japan]
Xie X., Gu Y., Fox T., Coll J.T., Fleming M.A., Markland W., Caron P.R., Wilson K.P., Su M.S.-S.;
"Crystal structure of JNK3: a kinase implicated in neuronal apoptosis.";
Structure 6:983-991(1998).
Comments
  • FUNCTION: Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of AP-1 such as c-Jun and ATF2 and thus regulates AP-1 transcriptional activity. Required for stress-induced neuronal apoptosis and the pathogenesis of glutamate excitotoxicity (By similarity).
  • CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
  • COFACTOR: Magnesium.
  • 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. MAP2K4 then phosphorylates Tyr-223 resulting in a further increase in Vmax. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by HDAC9.
  • SUBUNIT: Interacts with MAPKBP1 (By similarity). 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.
  • SUBCELLULAR LOCATION: Cytoplasm.
  • ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing. A similar low level of binding to substrates is observed for isoform alpha-1 and isoform alpha-2. However, there is no correlation between binding and phosphorylation, which is achieved about at the same efficiency by all isoforms.
    NameAlpha-2
    Isoform IDP53779-1
    This is the isoform sequence displayed in this entry.
    NameAlpha-1
    Isoform IDP53779-2
    Features which should be applied to build the isoform sequence: VSP_004839.
  • 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, which activates the enzyme. Weakly autophosphorylated on threonine and tyrosine residues in vitro.
  • MASS SPECTROMETRY: Mass=44070; Method=Electrospray; Range=1-464; Source=PubMed:10715136;.
  • DISEASE: A chromosomal rearrangement involving MAPK10 is a cause of epileptic encephalopathy Lennox-Gastaut type [MIM:606369]. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation. Epileptic encephalopathies of the Lennox-Gastaut group are childhood epileptic disorders characterized by severe psychomotor delay and seizures.
  • SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.
  • SIMILARITY: Contains 1 protein kinase domain.
  • WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/JNK3ID427.html";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
U07620; AAC50101.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U34819; AAC50604.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U34820; AAC50605.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AC096953; -; NOT_ANNOTATED_CDS; Genomic_DNA.[EMBL / GenBank / DDBJ]
CH471057; EAX05963.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC035057; AAH35057.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00003148; -.
IPI00023547; -.
PIR S71104; S71104.
RefSeq NP_002744.1; -.
NP_620446.1; -.
NP_620447.1; -.
NP_620448.1; -.
UniGene Hs.125503
3D structure databases
PDB
1JNK; X-ray; 2.30 A; A=1-423.[ExPASy / RCSB / EBI]
1PMN; X-ray; 2.20 A; A=40-401.[ExPASy / RCSB / EBI]
1PMQ; X-ray; 2.20 A; A=40-401.[ExPASy / RCSB / EBI]
1PMU; X-ray; 2.70 A; A=40-401.[ExPASy / RCSB / EBI]
1PMV; X-ray; 2.50 A; A=40-401.[ExPASy / RCSB / EBI]
2B1P; X-ray; 1.90 A; A=46-400.[ExPASy / RCSB / EBI]
2EXC; X-ray; 2.75 A; X=45-400.[ExPASy / RCSB / EBI]
2O0U; X-ray; 2.10 A; A=39-402.[ExPASy / RCSB / EBI]
2O2U; X-ray; 2.45 A; A=39-402.[ExPASy / RCSB / EBI]
2OK1; X-ray; 2.40 A; A=40-402.[ExPASy / RCSB / EBI]
2P33; X-ray; 2.40 A; A=40-402.[ExPASy / RCSB / EBI]
2R9S; X-ray; 2.40 A; A/B=46-401.[ExPASy / RCSB / EBI]
2WAJ; X-ray; 2.40 A; A=39-402.[ExPASy / RCSB / EBI]
2ZDT; X-ray; 2.00 A; A=39-402.[ExPASy / RCSB / EBI]
2ZDU; X-ray; 2.50 A; A=39-402.[ExPASy / RCSB / EBI]
3CGF; X-ray; 3.00 A; A=40-402.[ExPASy / RCSB / EBI]
3CGO; X-ray; 3.00 A; A=40-402.[ExPASy / RCSB / EBI]
3DA6; X-ray; 2.00 A; A=39-402.[ExPASy / RCSB / EBI]
3FI2; X-ray; 2.28 A; A=39-402.[ExPASy / RCSB / EBI]
3FI3; X-ray; 2.20 A; A=39-402.[ExPASy / RCSB / EBI]
3FV8; X-ray; 2.28 A; A=39-402.[ExPASy / RCSB / EBI]
3G90; X-ray; 2.40 A; X=40-402.[ExPASy / RCSB / EBI]
3G9L; X-ray; 2.20 A; X=40-402.[ExPASy / RCSB / EBI]
3G9N; X-ray; 2.80 A; A=40-402.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1JNK; -.
1PMN; -.
1PMQ; -.
1PMU; -.
1PMV; -.
2B1P; -.
2EXC; -.
2O0U; -.
2O2U; -.
2OK1; -.
2P33; -.
2R9S; -.
2WAJ; -.
2ZDT; -.
2ZDU; -.
3CGF; -.
3CGO; -.
3DA6; -.
3FI2; -.
3FI3; -.
3FV8; -.
3G90; -.
3G9L; -.
3G9N; -.
ModBase P53779.
Protein-protein interaction databases
DIP DIP:1015N; -.
IntAct P53779; 5.
PTM databases
PhosphoSite P53779; -.
Enzyme and pathway databases
BRENDA 2.7.11.24; 247.
Pathway_Interaction_DB foxopathway; FoxO family signaling.
p75ntrpathway; p75(NTR)-mediated signaling.
Organism-specific databases
GeneCards GC04M087156; -.
H-InvDB HIX0004352; -.
HGNC HGNC:6872; MAPK10.
GenAtlas MAPK10.
MIM 602897; gene. [NCBI / EBI]
606369; phenotype. [NCBI / EBI]
PharmGKB PA30617; -.
Gene expression databases
ArrayExpress P53779; -.
Bgee P53779; -.
CleanEx HS_MAPK10; -.
GermOnline ENSG00000109339; Homo sapiens.
Ontologies
GO
GO:0005737; Cellular component: cytoplasm (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005524; Molecular function: ATP binding (inferred from electronic annotation from UniProtKB-KW).
GO:0004705; Molecular function: JUN kinase activity (inferred from sequence or structural similarity from UniProtKB).
GO:0004708; Molecular function: MAP kinase kinase activity (traceable author statement from ProtInc).
GO:0007254; Biological process: JNK cascade (inferred from sequence or structural similarity from UniProtKB).
GO:0006468; Biological process: protein amino acid phosphorylation (inferred from electronic annotation from InterPro).
QuickGo view.
Family and domain databases
InterPro IPR008351; JNK_MAPK.
IPR003527; MAP_kinase_CS.
IPR000719; Prot_kinase_core.
IPR017441; Protein_kinase_ATP_BS.
IPR017442; Se/Thr_pkinase-rel.
IPR008271; Ser_thr_pkin_AS.
IPR002290; Ser_thr_pkinase.
Graphical view of domain structure.
Pfam PF00069; Pkinase; 1.
Pfam graphical view of domain structure.
PRINTS PR01772; JNKMAPKINASE.
ProDom PD000001; Prot_kinase; 1.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00220; S_TKc; 1.
SMART graphical view of domain structure.
PROSITE PS01351; MAPK; 1.
PS00107; PROTEIN_KINASE_ATP; FALSE_NEG.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00108; PROTEIN_KINASE_ST; 1.
PROSITE graphical view of domain structure (profiles).
Proteomic databases
PRIDE P53779; -.
Genome annotation databases
Ensembl ENSG00000109339; Homo sapiens. [Contig view]
GeneID 5602; -.
KEGG hsa:5602; -.
Phylogenomic databases
HOGENOM P53779; -.
HOVERGEN P53779; -.
OMA P53779; EHNKLKX.
Other
NextBio 21762; -.
SOURCE MAPK10; Homo sapiens.
ProtoNet P53779.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Alternative splicing; ATP-binding; Chromosomal rearrangement; Cytoplasm; Direct protein sequencing; Epilepsy; Kinase; Nucleotide-binding; Phosphoprotein; Serine/threonine-protein kinase; Transferase.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   464  464     Mitogen-activated protein kinase 10. PRO_0000186277
DOMAIN   64   359  296     Protein kinase. 
NP_BIND   70    78  9     ATP. 
MOTIF   221   223  3     TXY. 
ACT_SITE   189   189        Proton acceptor. 
BINDING   93    93        ATP. 
MOD_RES   221   221        Phosphothreonine. 
MOD_RES   223   223        Phosphotyrosine. 
VAR_SEQ   418   464        GAAVNSSESLPPSSSVNDISSMSTDQTLASDTDSSLEASA GPLGCCR -> AQVQQ (in isoform Alpha-1). VSP_004839
STRAND   47    53  7      
STRAND   56    61  6      
STRAND   64    72  9      
STRAND   74    83  10      
TURN   84    87  4      
STRAND   88    97  10      
HELIX   98   100  3      
HELIX   102   117  16      
STRAND   126   130  5      
TURN   136   138  3      
STRAND   141   147  7      
STRAND   150   152  3      
HELIX   153   157  5      
HELIX   163   182  20      
HELIX   192   194  3      
STRAND   195   197  3      
STRAND   203   205  3      
HELIX   232   235  4      
HELIX   244   258  15      
HELIX   268   279  12      
TURN   284   286  3      
HELIX   287   289  3      
HELIX   292   299  8      
HELIX   309   312  4      
HELIX   323   339  17      
TURN   344   346  3      
HELIX   350   354  5      
TURN   357   359  3      
HELIX   360   362  3      
HELIX   365   368  4      
HELIX   389   398  10      
Sequence information
Length: 464 AA [This is the length of the unprocessed precursor] Molecular weight: 52585 Da [This is the MW of the unprocessed precursor] CRC64: 2E20C05EB89CDA66 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MSLHFLYYCS EPTLDVKIAF CQGFDKQVDV SYIAKHYNMS 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 YQMLCGIKHL 

       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 

P53779 in FASTA format

View entry in raw text format (no links)
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