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Protein

Mitogen-activated protein kinase 10

Gene

MAPK10

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+1 Publication

Enzyme regulationi

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 HDAC9.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei93ATP1
Active sitei189Proton acceptor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi70 – 78ATP9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • JUN kinase activity Source: UniProtKB
  • MAP kinase kinase activity Source: ProtInc

GO - Biological processi

  • Fc-epsilon receptor signaling pathway Source: Reactome
  • JNK cascade Source: UniProtKB
  • neuron development Source: GO_Central
  • protein phosphorylation Source: UniProtKB
  • regulation of circadian rhythm Source: UniProtKB
  • regulation of gene expression Source: GO_Central
  • response to light stimulus Source: UniProtKB
  • rhythmic process Source: UniProtKB-KW
  • signal transduction Source: ProtInc

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processBiological rhythms
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.24 2681
ReactomeiR-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-450341 Activation of the AP-1 family of transcription factors
SignaLinkiP53779
SIGNORiP53779

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase 10 (EC:2.7.11.24)
Short name:
MAP kinase 10
Short name:
MAPK 10
Alternative name(s):
MAP kinase p49 3F12
Stress-activated protein kinase 1b
Short name:
SAPK1b
Stress-activated protein kinase JNK3
c-Jun N-terminal kinase 3
Gene namesi
Name:MAPK10
Synonyms:JNK3, JNK3A, PRKM10, SAPK1B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000109339.18
HGNCiHGNC:6872 MAPK10
MIMi602897 gene
neXtProtiNX_P53779

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi462C → S: Loss of palmitoylation. 1 Publication1
Mutagenesisi463C → S: Loss of palmitoylation. 1 Publication1

Keywords - Diseasei

Epilepsy, Mental retardation

Organism-specific databases

DisGeNETi5602
MalaCardsiMAPK10
OpenTargetsiENSG00000109339
Orphaneti2382 Lennox-Gastaut syndrome
PharmGKBiPA30617

Chemistry databases

ChEMBLiCHEMBL2637
DrugBankiDB08005 4-{[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]amino}-N-ethylpiperidine-1-carboxamide
DB08021 5-bromo-N-(3-chloro-2-(4-(prop-2-ynyl)piperazin-1-yl)phenyl)furan-2-carboxamide
DB06933 N-(tert-butyl)-4-[5-(pyridin-2-ylamino)quinolin-3-yl]benzenesulfonamide
DB07010 N-BENZYL-4-[4-(3-CHLOROPHENYL)-1H-PYRAZOL-3-YL]-1H-PYRROLE-2-CARBOXAMIDE
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester
GuidetoPHARMACOLOGYi1498

Polymorphism and mutation databases

BioMutaiMAPK10
DMDMi2507196

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001862771 – 464Mitogen-activated protein kinase 10Add BLAST464

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei221Phosphothreonine; by MAP2K71 Publication1
Modified residuei223Phosphotyrosine; by MAP2K41 Publication1
Lipidationi462S-palmitoyl cysteine1 Publication1
Lipidationi463S-palmitoyl cysteine1 Publication1

Post-translational modificationi

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.1 Publication
Palmitoylation regulates subcellular location and axonal development.1 Publication

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

EPDiP53779
MaxQBiP53779
PaxDbiP53779
PeptideAtlasiP53779
PRIDEiP53779
ProteomicsDBi56616
56617 [P53779-2]
56618 [P53779-3]

PTM databases

iPTMnetiP53779
PhosphoSitePlusiP53779
SwissPalmiP53779

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiENSG00000109339
CleanExiHS_MAPK10
ExpressionAtlasiP53779 baseline and differential
GenevisibleiP53779 HS

Organism-specific databases

HPAiCAB022625

Interactioni

Subunit structurei

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. Interacts with ARRB2; the interaction enhances MAPK10 activation by MAP3K5. Interacts with SARM1 (By similarity).By similarity

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi111588, 49 interactors
CORUMiP53779
DIPiDIP-1015N
ELMiP53779
IntActiP53779, 19 interactors
MINTiP53779
STRINGi9606.ENSP00000352157

Chemistry databases

BindingDBiP53779

Structurei

Secondary structure

1464
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi48 – 53Combined sources6
Beta strandi56 – 61Combined sources6
Beta strandi64 – 69Combined sources6
Beta strandi77 – 83Combined sources7
Turni84 – 87Combined sources4
Beta strandi88 – 97Combined sources10
Helixi98 – 100Combined sources3
Helixi102 – 114Combined sources13
Turni115 – 117Combined sources3
Beta strandi121 – 123Combined sources3
Beta strandi127 – 130Combined sources4
Turni136 – 138Combined sources3
Beta strandi142 – 147Combined sources6
Beta strandi150 – 152Combined sources3
Helixi153 – 157Combined sources5
Helixi163 – 182Combined sources20
Helixi192 – 194Combined sources3
Beta strandi195 – 197Combined sources3
Beta strandi199 – 201Combined sources3
Beta strandi203 – 205Combined sources3
Beta strandi207 – 209Combined sources3
Turni212 – 214Combined sources3
Helixi216 – 219Combined sources4
Beta strandi220 – 222Combined sources3
Helixi227 – 229Combined sources3
Helixi232 – 235Combined sources4
Helixi244 – 258Combined sources15
Helixi268 – 279Combined sources12
Helixi284 – 287Combined sources4
Helixi292 – 299Combined sources8
Helixi309 – 312Combined sources4
Helixi315 – 317Combined sources3
Helixi323 – 339Combined sources17
Turni344 – 346Combined sources3
Helixi350 – 355Combined sources6
Turni357 – 361Combined sources5
Helixi365 – 368Combined sources4
Helixi378 – 382Combined sources5
Helixi387 – 399Combined sources13

3D structure databases

ProteinModelPortaliP53779
SMRiP53779
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP53779

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini64 – 359Protein kinasePROSITE-ProRule annotationAdd BLAST296

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi221 – 223TXY3

Domaini

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0665 Eukaryota
ENOG410XSHI LUCA
GeneTreeiENSGT00550000074271
HOGENOMiHOG000233024
HOVERGENiHBG014652
InParanoidiP53779
KOiK04440
OMAiMSRHFLY
OrthoDBiEOG091G09G2
PhylomeDBiP53779
TreeFamiTF105100

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR003527 MAP_kinase_CS
IPR008351 MAPK_JNK
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PRINTSiPR01772 JNKMAPKINASE
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS01351 MAPK, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: 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.
Isoform Alpha-2 (identifier: P53779-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSLHFLYYCS EPTLDVKIAF CQGFDKQVDV SYIAKHYNMS KSKVDNQFYS
60 70 80 90 100
VEVGDSTFTV LKRYQNLKPI GSGAQGIVCA AYDAVLDRNV AIKKLSRPFQ
110 120 130 140 150
NQTHAKRAYR ELVLMKCVNH KNIISLLNVF TPQKTLEEFQ DVYLVMELMD
160 170 180 190 200
ANLCQVIQME LDHERMSYLL YQMLCGIKHL HSAGIIHRDL KPSNIVVKSD
210 220 230 240 250
CTLKILDFGL ARTAGTSFMM TPYVVTRYYR APEVILGMGY KENVDIWSVG
260 270 280 290 300
CIMGEMVRHK ILFPGRDYID QWNKVIEQLG TPCPEFMKKL QPTVRNYVEN
310 320 330 340 350
RPKYAGLTFP KLFPDSLFPA DSEHNKLKAS QARDLLSKML VIDPAKRISV
360 370 380 390 400
DDALQHPYIN VWYDPAEVEA PPPQIYDKQL DEREHTIEEW KELIYKEVMN
410 420 430 440 450
SEEKTKNGVV KGQPSPSGAA VNSSESLPPS SSVNDISSMS TDQTLASDTD
460
SSLEASAGPL GCCR
Length:464
Mass (Da):52,585
Last modified:November 1, 1997 - v2
Checksum:i2E20C05EB89CDA66
GO
Isoform Alpha-1 (identifier: P53779-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     418-464: GAAVNSSESLPPSSSVNDISSMSTDQTLASDTDSSLEASAGPLGCCR → AQVQQ

Show »
Length:422
Mass (Da):48,554
Checksum:iFCC8C11954481C04
GO
Isoform 3 (identifier: P53779-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: Missing.

Show »
Length:426
Mass (Da):48,128
Checksum:i1022B6AC7774A666
GO

Sequence cautioni

The sequence BAG51956 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti162D → G in BAG51956 (PubMed:14702039).Curated1

Mass spectrometryi

Molecular mass is 44070 Da from positions 1 - 464. Determined by ESI. 1 Publication

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0419111 – 38Missing in isoform 3. 1 PublicationAdd BLAST38
Alternative sequenceiVSP_004839418 – 464GAAVN…LGCCR → AQVQQ in isoform Alpha-1. 3 PublicationsAdd BLAST47

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U07620 mRNA Translation: AAC50101.1
U34819 mRNA Translation: AAC50604.1
U34820 mRNA Translation: AAC50605.1
AK057723 mRNA Translation: BAG51956.1 Different initiation.
AK124791 mRNA Translation: BAG54096.1
AC096953 Genomic DNA No translation available.
AC104059 Genomic DNA No translation available.
AC104827 Genomic DNA No translation available.
AC108054 Genomic DNA No translation available.
AC110076 Genomic DNA No translation available.
CH471057 Genomic DNA Translation: EAX05963.1
BC035057 mRNA Translation: AAH35057.1
CCDSiCCDS34026.1 [P53779-1]
CCDS3612.1 [P53779-3]
CCDS43247.1 [P53779-2]
PIRiS71104
RefSeqiNP_001304996.1, NM_001318067.1
NP_001304997.1, NM_001318068.1
NP_001304998.1, NM_001318069.1
NP_002744.1, NM_002753.4 [P53779-2]
NP_620446.1, NM_138980.3 [P53779-3]
NP_620448.1, NM_138982.3 [P53779-1]
XP_005263186.1, XM_005263129.2 [P53779-1]
XP_005263187.1, XM_005263130.2 [P53779-1]
XP_005263192.1, XM_005263135.3 [P53779-2]
XP_006714331.1, XM_006714268.2 [P53779-3]
XP_011530419.1, XM_011532117.2 [P53779-1]
XP_011530420.1, XM_011532118.2 [P53779-1]
XP_011530422.1, XM_011532120.2 [P53779-3]
XP_011530423.1, XM_011532121.2 [P53779-3]
XP_016863908.1, XM_017008419.1 [P53779-1]
XP_016863909.1, XM_017008420.1 [P53779-1]
XP_016863910.1, XM_017008421.1 [P53779-1]
XP_016863912.1, XM_017008423.1 [P53779-3]
XP_016863913.1, XM_017008424.1 [P53779-3]
XP_016863914.1, XM_017008425.1 [P53779-3]
XP_016863915.1, XM_017008426.1
XP_016863918.1, XM_017008429.1 [P53779-2]
XP_016863919.1, XM_017008430.1 [P53779-2]
XP_016863920.1, XM_017008431.1 [P53779-2]
XP_016863921.1, XM_017008432.1 [P53779-2]
UniGeneiHs.125503
Hs.13438

Genome annotation databases

EnsembliENST00000395157; ENSP00000378586; ENSG00000109339 [P53779-2]
ENST00000395166; ENSP00000378595; ENSG00000109339 [P53779-3]
ENST00000515400; ENSP00000424154; ENSG00000109339 [P53779-1]
ENST00000515650; ENSP00000492204; ENSG00000109339 [P53779-1]
ENST00000638225; ENSP00000491866; ENSG00000109339 [P53779-3]
ENST00000638313; ENSP00000492292; ENSG00000109339 [P53779-1]
ENST00000639175; ENSP00000491160; ENSG00000109339 [P53779-3]
ENST00000639234; ENSP00000491306; ENSG00000109339 [P53779-2]
ENST00000639242; ENSP00000491089; ENSG00000109339 [P53779-3]
ENST00000640858; ENSP00000491122; ENSG00000109339 [P53779-2]
ENST00000640970; ENSP00000492231; ENSG00000109339 [P53779-2]
ENST00000641050; ENSP00000493270; ENSG00000109339 [P53779-2]
ENST00000641051; ENSP00000493275; ENSG00000109339 [P53779-1]
ENST00000641066; ENSP00000493072; ENSG00000109339 [P53779-1]
ENST00000641110; ENSP00000493163; ENSG00000109339 [P53779-3]
ENST00000641157; ENSP00000493363; ENSG00000109339 [P53779-1]
ENST00000641170; ENSP00000493237; ENSG00000109339 [P53779-2]
ENST00000641207; ENSP00000493450; ENSG00000109339 [P53779-1]
ENST00000641274; ENSP00000492929; ENSG00000109339 [P53779-2]
ENST00000641283; ENSP00000493444; ENSG00000109339 [P53779-3]
ENST00000641287; ENSP00000493100; ENSG00000109339 [P53779-3]
ENST00000641297; ENSP00000493092; ENSG00000109339 [P53779-3]
ENST00000641341; ENSP00000493290; ENSG00000109339 [P53779-1]
ENST00000641391; ENSP00000493008; ENSG00000109339 [P53779-3]
ENST00000641410; ENSP00000493208; ENSG00000109339 [P53779-2]
ENST00000641462; ENSP00000493435; ENSG00000109339 [P53779-1]
ENST00000641647; ENSP00000493375; ENSG00000109339 [P53779-1]
ENST00000641657; ENSP00000493105; ENSG00000109339 [P53779-3]
ENST00000641724; ENSP00000493038; ENSG00000109339 [P53779-3]
ENST00000641737; ENSP00000493177; ENSG00000109339 [P53779-3]
ENST00000641803; ENSP00000493049; ENSG00000109339 [P53779-3]
ENST00000641823; ENSP00000493408; ENSG00000109339 [P53779-1]
ENST00000641862; ENSP00000493396; ENSG00000109339 [P53779-2]
ENST00000641902; ENSP00000492903; ENSG00000109339 [P53779-1]
ENST00000641911; ENSP00000493374; ENSG00000109339 [P53779-3]
ENST00000641943; ENSP00000492941; ENSG00000109339 [P53779-3]
ENST00000641952; ENSP00000493013; ENSG00000109339 [P53779-1]
ENST00000641983; ENSP00000493045; ENSG00000109339 [P53779-1]
ENST00000642009; ENSP00000493168; ENSG00000109339 [P53779-3]
ENST00000642015; ENSP00000493040; ENSG00000109339 [P53779-3]
ENST00000642038; ENSP00000492942; ENSG00000109339 [P53779-2]
ENST00000642103; ENSP00000493001; ENSG00000109339 [P53779-3]
GeneIDi5602
KEGGihsa:5602
UCSCiuc003hpp.4 human [P53779-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement

Similar proteinsi

Entry informationi

Entry nameiMK10_HUMAN
AccessioniPrimary (citable) accession number: P53779
Secondary accession number(s): A6NFS3
, A6NG28, B3KQ94, Q15707, Q49AP1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 1, 1997
Last modified: June 20, 2018
This is version 202 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. SIMILARITY comments
    Index of protein domains and families

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