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Protein

Mitogen-activated protein kinase kinase kinase 10

Gene

MAP3K10

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Activates the JUN N-terminal pathway.By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

Homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei125ATPPROSITE-ProRule annotation1
Active sitei222Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi104 – 112ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • bHLH transcription factor binding Source: UniProtKB
  • JUN kinase kinase kinase activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • protein kinase activity Source: ProtInc
  • protein serine/threonine kinase activity Source: UniProtKB
  • transcription corepressor activity Source: UniProtKB

GO - Biological processi

  • activation of JUN kinase activity Source: UniProtKB
  • apoptotic process Source: ProtInc
  • JNK cascade Source: ProtInc
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • peptidyl-serine phosphorylation Source: UniProtKB
  • peptidyl-threonine phosphorylation Source: UniProtKB
  • positive regulation of apoptotic process Source: GO_Central
  • positive regulation of JNK cascade Source: UniProtKB
  • positive regulation of JUN kinase activity Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • signal transduction Source: ProtInc
  • smoothened signaling pathway Source: UniProtKB

Keywordsi

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

Enzyme and pathway databases

SignaLinkiQ02779.
SIGNORiQ02779.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase kinase kinase 10 (EC:2.7.11.25)
Alternative name(s):
Mixed lineage kinase 2
Protein kinase MST
Gene namesi
Name:MAP3K10
Synonyms:MLK2, MST
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000130758.7.
HGNCiHGNC:6849. MAP3K10.

Subcellular locationi

Pathology & Biotechi

Organism-specific databases

DisGeNETi4294.
OpenTargetsiENSG00000130758.
PharmGKBiPA30593.

Chemistry databases

ChEMBLiCHEMBL2873.
GuidetoPHARMACOLOGYi2070.

Polymorphism and mutation databases

BioMutaiMAP3K10.
DMDMi145559494.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862591 – 954Mitogen-activated protein kinase kinase kinase 10Add BLAST954

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei258Phosphothreonine; by autocatalysisBy similarity1
Modified residuei262Phosphoserine; by autocatalysis and MAP4K1By similarity1
Modified residuei498PhosphoserineCombined sources1
Modified residuei502PhosphoserineCombined sources1
Modified residuei506PhosphoserineCombined sources1
Modified residuei558PhosphothreonineCombined sources1
Modified residuei857Omega-N-methylarginineBy similarity1

Post-translational modificationi

Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation.By similarity

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

MaxQBiQ02779.
PaxDbiQ02779.
PeptideAtlasiQ02779.
PRIDEiQ02779.
TopDownProteomicsiQ02779.

PTM databases

iPTMnetiQ02779.
PhosphoSitePlusiQ02779.

Expressioni

Tissue specificityi

Expressed in brain and skeletal muscle.

Gene expression databases

BgeeiENSG00000130758.
CleanExiHS_MAP3K10.
ExpressionAtlasiQ02779. baseline and differential.
GenevisibleiQ02779. HS.

Organism-specific databases

HPAiHPA007039.

Interactioni

Subunit structurei

Homodimer.By similarity

GO - Molecular functioni

  • bHLH transcription factor binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi110440. 25 interactors.
ELMiQ02779.
IntActiQ02779. 3 interactors.
STRINGi9606.ENSP00000253055.

Chemistry databases

BindingDBiQ02779.

Structurei

Secondary structure

1954
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi20 – 23Combined sources4
Beta strandi42 – 47Combined sources6
Helixi50 – 53Combined sources4
Beta strandi58 – 62Combined sources5
Beta strandi68 – 72Combined sources5
Helixi73 – 75Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2RF0X-ray2.00A/B/C/D13-78[»]
ProteinModelPortaliQ02779.
SMRiQ02779.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ02779.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 81SH3PROSITE-ProRule annotationAdd BLAST66
Domaini98 – 360Protein kinasePROSITE-ProRule annotationAdd BLAST263

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni384 – 405Leucine-zipper 1Add BLAST22
Regioni419 – 440Leucine-zipper 2Add BLAST22

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi2 – 5Poly-Glu4
Compositional biasi449 – 463Arg/Lys-rich (basic)Add BLAST15

Sequence similaritiesi

Keywords - Domaini

Repeat, SH3 domain

Phylogenomic databases

eggNOGiKOG0192. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00900000140790.
HOGENOMiHOG000060081.
HOVERGENiHBG067662.
InParanoidiQ02779.
KOiK04418.
OMAiIEQSAMF.
OrthoDBiEOG091G0JNI.
PhylomeDBiQ02779.
TreeFamiTF105118.

Family and domain databases

CDDicd12059. SH3_MLK1-3. 1 hit.
InterProiView protein in InterPro
IPR011009. Kinase-like_dom.
IPR015785. MAP3K10.
IPR035779. MLK1-3_SH3.
IPR016231. MLK1-4.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR036028. SH3-like_dom.
IPR001452. SH3_domain.
PANTHERiPTHR43997:SF5. PTHR43997:SF5. 1 hit.
PfamiView protein in Pfam
PF07714. Pkinase_Tyr. 1 hit.
PF14604. SH3_9. 1 hit.
PIRSFiPIRSF000556. MAPKKK9_11. 1 hit.
PRINTSiPR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiView protein in SMART
SM00220. S_TKc. 1 hit.
SM00326. SH3. 1 hit.
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50002. SH3. 1 hit.

Sequencei

Sequence statusi: Complete.

Q02779-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEEEEGAVAK EWGTTPAGPV WTAVFDYEAA GDEELTLRRG DRVQVLSQDC
60 70 80 90 100
AVSGDEGWWT GQLPSGRVGV FPSNYVAPGA PAAPAGLQLP QEIPFHELQL
110 120 130 140 150
EEIIGVGGFG KVYRALWRGE EVAVKAARLD PEKDPAVTAE QVCQEARLFG
160 170 180 190 200
ALQHPNIIAL RGACLNPPHL CLVMEYARGG ALSRVLAGRR VPPHVLVNWA
210 220 230 240 250
VQVARGMNYL HNDAPVPIIH RDLKSINILI LEAIENHNLA DTVLKITDFG
260 270 280 290 300
LAREWHKTTK MSAAGTYAWM APEVIRLSLF SKSSDVWSFG VLLWELLTGE
310 320 330 340 350
VPYREIDALA VAYGVAMNKL TLPIPSTCPE PFARLLEECW DPDPHGRPDF
360 370 380 390 400
GSILKRLEVI EQSALFQMPL ESFHSLQEDW KLEIQHMFDD LRTKEKELRS
410 420 430 440 450
REEELLRAAQ EQRFQEEQLR RREQELAERE MDIVERELHL LMCQLSQEKP
460 470 480 490 500
RVRKRKGNFK RSRLLKLREG GSHISLPSGF EHKITVQASP TLDKRKGSDG
510 520 530 540 550
ASPPASPSII PRLRAIRLTP VDCGGSSSGS SSGGSGTWSR GGPPKKEELV
560 570 580 590 600
GGKKKGRTWG PSSTLQKERV GGEERLKGLG EGSKQWSSSA PNLGKSPKHT
610 620 630 640 650
PIAPGFASLN EMEEFAEAED GGSSVPPSPY STPSYLSVPL PAEPSPGARA
660 670 680 690 700
PWEPTPSAPP ARWGHGARRR CDLALLGCAT LLGAVGLGAD VAEARAADGE
710 720 730 740 750
EQRRWLDGLF FPRAGRFPRG LSPPARPHGR REDVGPGLGL APSATLVSLS
760 770 780 790 800
SVSDCNSTRS LLRSDSDEAA PAAPSPPPSP PAPTPTPSPS TNPLVDLELE
810 820 830 840 850
SFKKDPRQSL TPTHVTAACA VSRGHRRTPS DGALGQRGPP EPAGHGPGPR
860 870 880 890 900
DLLDFPRLPD PQALFPARRR PPEFPGRPTT LTFAPRPRPA ASRPRLDPWK
910 920 930 940 950
LVSFGRTLTI SPPSRPDTPE SPGPPSVQPT LLDMDMEGQN QDSTVPLCGA

HGSH
Length:954
Mass (Da):103,694
Last modified:April 17, 2007 - v3
Checksum:i59A7596B05751981
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti462 – 464SRL → AV in CAA88531 (PubMed:7731697).Curated3
Sequence conflicti465 – 480LKLRE…LPSGF → AQAAGRRQPHQPALWL (PubMed:8477742).CuratedAdd BLAST16
Sequence conflicti471G → S in CAA88531 (PubMed:7731697).Curated1
Sequence conflicti807R → G in CAA62351 (PubMed:8536694).Curated1
Sequence conflicti818A → V in CAA62351 (PubMed:8536694).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040702107G → E in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_051639168P → Q. Corresponds to variant dbSNP:rs36102209Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X90846 mRNA. Translation: CAA62351.1.
Z48615 mRNA. Translation: CAA88531.1.
CCDSiCCDS12549.1.
PIRiS68178.
RefSeqiNP_002437.2. NM_002446.3.
UniGeneiHs.466743.

Genome annotation databases

EnsembliENST00000253055; ENSP00000253055; ENSG00000130758.
GeneIDi4294.
KEGGihsa:4294.
UCSCiuc002ona.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiM3K10_HUMAN
AccessioniPrimary (citable) accession number: Q02779
Secondary accession number(s): Q12761, Q14871
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: April 17, 2007
Last modified: October 25, 2017
This is version 171 of the entry and version 3 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, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families