Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q02779 (M3K10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitogen-activated protein kinase kinase kinase 10

EC=2.7.11.25
Alternative name(s):
Mixed lineage kinase 2
Protein kinase MST
Gene names
Name:MAP3K10
Synonyms:MLK2, MST
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length954 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Activates the JUN N-terminal pathway By similarity.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Enzyme regulation

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

Subunit structure

Homodimer By similarity.

Tissue specificity

Expressed in brain and skeletal muscle.

Post-translational modification

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

Sequence similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.

Contains 1 protein kinase domain.

Contains 1 SH3 domain.

Ontologies

Keywords
   Coding sequence diversityPolymorphism
   DomainRepeat
SH3 domain
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processJNK cascade

Traceable author statement PubMed 10801775. Source: ProtInc

activation of JNKK activity

Inferred from sequence or structural similarity. Source: GOC

activation of JUN kinase activity

Inferred from sequence or structural similarity PubMed 8195146. Source: UniProtKB

apoptotic process

Traceable author statement PubMed 10801775. Source: ProtInc

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from mutant phenotype PubMed 19801649. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 19801649. Source: UniProtKB

peptidyl-serine phosphorylation

Inferred from direct assay PubMed 19801649. Source: UniProtKB

peptidyl-threonine phosphorylation

Inferred from direct assay PubMed 19801649. Source: UniProtKB

positive regulation of JNK cascade

Inferred from mutant phenotype PubMed 17584736. Source: UniProtKB

positive regulation of JUN kinase activity

Inferred from mutant phenotype PubMed 17584736. Source: UniProtKB

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from sequence or structural similarity PubMed 8195146. Source: UniProtKB

signal transduction

Traceable author statement PubMed 10801775. Source: ProtInc

smoothened signaling pathway

Inferred from mutant phenotype PubMed 18455992. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 18455992. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

JUN kinase kinase kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

bHLH transcription factor binding

Inferred from physical interaction PubMed 19801649. Source: UniProtKB

protein homodimerization activity

Inferred from sequence or structural similarity PubMed 8195146. Source: UniProtKB

protein kinase activity

Traceable author statement PubMed 10801775Ref.1. Source: ProtInc

protein serine/threonine kinase activity

Inferred from direct assay PubMed 19801649. Source: UniProtKB

transcription corepressor activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 954954Mitogen-activated protein kinase kinase kinase 10
PRO_0000086259

Regions

Domain16 – 8166SH3
Domain98 – 360263Protein kinase
Nucleotide binding104 – 1129ATP By similarity
Region384 – 40522Leucine-zipper 1
Region419 – 44022Leucine-zipper 2
Compositional bias2 – 54Poly-Glu
Compositional bias449 – 46315Arg/Lys-rich (basic)

Sites

Active site2221Proton acceptor By similarity
Binding site1251ATP By similarity

Amino acid modifications

Modified residue2581Phosphothreonine; by autocatalysis By similarity
Modified residue2621Phosphoserine; by autocatalysis and MAP4K1 By similarity
Modified residue4981Phosphoserine Ref.4
Modified residue5021Phosphoserine Ref.4
Modified residue5061Phosphoserine Ref.5
Modified residue5581Phosphothreonine Ref.4

Natural variations

Natural variant1071G → E in a metastatic melanoma sample; somatic mutation. Ref.6
VAR_040702
Natural variant1681P → Q.
Corresponds to variant rs36102209 [ dbSNP | Ensembl ].
VAR_051639

Experimental info

Sequence conflict462 – 4643SRL → AV in CAA88531. Ref.2
Sequence conflict465 – 48016LKLRE…LPSGF → AQAAGRRQPHQPALWL Ref.3
Sequence conflict4711G → S in CAA88531. Ref.2
Sequence conflict8071R → G in CAA62351. Ref.1
Sequence conflict8181A → V in CAA62351. Ref.1

Secondary structure

............ 954
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q02779 [UniParc].

Last modified April 17, 2007. Version 3.
Checksum: 59A7596B05751981

FASTA954103,694
        10         20         30         40         50         60 
MEEEEGAVAK EWGTTPAGPV WTAVFDYEAA GDEELTLRRG DRVQVLSQDC AVSGDEGWWT 

        70         80         90        100        110        120 
GQLPSGRVGV FPSNYVAPGA PAAPAGLQLP QEIPFHELQL EEIIGVGGFG KVYRALWRGE 

       130        140        150        160        170        180 
EVAVKAARLD PEKDPAVTAE QVCQEARLFG ALQHPNIIAL RGACLNPPHL CLVMEYARGG 

       190        200        210        220        230        240 
ALSRVLAGRR VPPHVLVNWA VQVARGMNYL HNDAPVPIIH RDLKSINILI LEAIENHNLA 

       250        260        270        280        290        300 
DTVLKITDFG LAREWHKTTK MSAAGTYAWM APEVIRLSLF SKSSDVWSFG VLLWELLTGE 

       310        320        330        340        350        360 
VPYREIDALA VAYGVAMNKL TLPIPSTCPE PFARLLEECW DPDPHGRPDF GSILKRLEVI 

       370        380        390        400        410        420 
EQSALFQMPL ESFHSLQEDW KLEIQHMFDD LRTKEKELRS REEELLRAAQ EQRFQEEQLR 

       430        440        450        460        470        480 
RREQELAERE MDIVERELHL LMCQLSQEKP RVRKRKGNFK RSRLLKLREG GSHISLPSGF 

       490        500        510        520        530        540 
EHKITVQASP TLDKRKGSDG ASPPASPSII PRLRAIRLTP VDCGGSSSGS SSGGSGTWSR 

       550        560        570        580        590        600 
GGPPKKEELV GGKKKGRTWG PSSTLQKERV GGEERLKGLG EGSKQWSSSA PNLGKSPKHT 

       610        620        630        640        650        660 
PIAPGFASLN EMEEFAEAED GGSSVPPSPY STPSYLSVPL PAEPSPGARA PWEPTPSAPP 

       670        680        690        700        710        720 
ARWGHGARRR CDLALLGCAT LLGAVGLGAD VAEARAADGE EQRRWLDGLF FPRAGRFPRG 

       730        740        750        760        770        780 
LSPPARPHGR REDVGPGLGL APSATLVSLS SVSDCNSTRS LLRSDSDEAA PAAPSPPPSP 

       790        800        810        820        830        840 
PAPTPTPSPS TNPLVDLELE SFKKDPRQSL TPTHVTAACA VSRGHRRTPS DGALGQRGPP 

       850        860        870        880        890        900 
EPAGHGPGPR DLLDFPRLPD PQALFPARRR PPEFPGRPTT LTFAPRPRPA ASRPRLDPWK 

       910        920        930        940        950 
LVSFGRTLTI SPPSRPDTPE SPGPPSVQPT LLDMDMEGQN QDSTVPLCGA HGSH 

« Hide

References

« Hide 'large scale' references
[1]"Complete nucleotide sequence, expression, and chromosomal localisation of human mixed-lineage kinase 2."
Dorow D.S., Devereux L., Tu G.F., Price G., Nicholl J.K., Sutherland G.R., Simpson R.J.
Eur. J. Biochem. 234:492-500(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[2]"Cloning and characterization of MST, a novel (putative) serine/threonine kinase with SH3 domain."
Katoh M., Hirai M., Sugimura T., Terada M.
Oncogene 10:1447-1451(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[3]"Identification of a new family of human epithelial protein kinases containing two leucine/isoleucine-zipper domains."
Dorow D.S., Devereux L., Dietzsch E., de Kretser T.
Eur. J. Biochem. 213:701-710(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 244-480.
Tissue: Colon epithelium.
[4]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-498; SER-502 AND THR-558, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[5]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-506, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[6]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-107.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X90846 mRNA. Translation: CAA62351.1.
Z48615 mRNA. Translation: CAA88531.1.
CCDSCCDS12549.1.
PIRS68178.
RefSeqNP_002437.2. NM_002446.3.
UniGeneHs.466743.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2RF0X-ray2.00A/B/C/D13-78[»]
ProteinModelPortalQ02779.
SMRQ02779. Positions 17-78, 92-385.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110440. 25 interactions.
IntActQ02779. 3 interactions.
STRING9606.ENSP00000253055.

Chemistry

BindingDBQ02779.
ChEMBLCHEMBL2873.
GuidetoPHARMACOLOGY2070.

PTM databases

PhosphoSiteQ02779.

Polymorphism databases

DMDM145559494.

Proteomic databases

PaxDbQ02779.
PRIDEQ02779.

Protocols and materials databases

DNASU4294.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000253055; ENSP00000253055; ENSG00000130758.
GeneID4294.
KEGGhsa:4294.
UCSCuc002ona.3. human.

Organism-specific databases

CTD4294.
GeneCardsGC19P040697.
H-InvDBHIX0040140.
HGNCHGNC:6849. MAP3K10.
HPAHPA007039.
MIM600137. gene.
neXtProtNX_Q02779.
PharmGKBPA30593.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000060081.
HOVERGENHBG067662.
InParanoidQ02779.
KOK04418.
OMAKGHFKKS.
OrthoDBEOG7D85VN.
PhylomeDBQ02779.
TreeFamTF105118.

Enzyme and pathway databases

SignaLinkQ02779.

Gene expression databases

ArrayExpressQ02779.
BgeeQ02779.
CleanExHS_MAP3K10.
GenevestigatorQ02779.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR015785. MAP3K10.
IPR016231. MAPKKK9/10/11.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR001452. SH3_domain.
[Graphical view]
PANTHERPTHR23257:SF370. PTHR23257:SF370. 1 hit.
PfamPF07714. Pkinase_Tyr. 1 hit.
PF14604. SH3_9. 1 hit.
[Graphical view]
PIRSFPIRSF000556. MAPKKK9_11. 1 hit.
PRINTSPR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTSM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMAP3K10. human.
EvolutionaryTraceQ02779.
GeneWikiMAP3K10.
GenomeRNAi4294.
NextBio16901.
PROQ02779.
SOURCESearch...

Entry information

Entry nameM3K10_HUMAN
AccessionPrimary (citable) accession number: Q02779
Secondary accession number(s): Q12761, Q14871
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: April 17, 2007
Last modified: July 9, 2014
This is version 145 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM