Reviewed, UniProtKB/Swiss-Prot Q02779 (M3K10_HUMAN)

Names and origin

Protein names

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 names

Name:	MAP3K10
Synonyms:	MLK2, MST

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	954 AA.
Sequence status	Complete.
Protein existence	Evidence 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 diversity	Polymorphism
Domain	Repeat SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	activation of JUN kinase activity Inferred from sequence or structural similarity. Source: UniProtKB induction of apoptosis Traceable author statement. Source: ProtInc protein amino acid autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW JUN kinase kinase kinase activity Inferred from sequence or structural similarity. Source: UniProtKB protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB protein tyrosine kinase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 954

954

Mitogen-activated protein kinase kinase kinase 10

PRO_0000086259

Regions

Domain

16 – 81

66

SH3

Domain

98 – 360

263

Protein kinase

Domain

384 – 405

22

Leucine-zipper 1

Domain

419 – 440

22

Leucine-zipper 2

Nucleotide binding

104 – 112

9

ATP By similarity

Compositional bias

2 – 5

4

Poly-Glu

Compositional bias

449 – 463

15

Arg/Lys-rich (basic)

Sites

Active site

222

1

Proton acceptor By similarity

Binding site

125

1

ATP By similarity

Amino acid modifications

Modified residue

258

1

Phosphothreonine; by autocatalysis By similarity

Modified residue

262

1

Phosphoserine; by autocatalysis and MAP4K1 By similarity

Modified residue

489

1

Phosphoserine Ref.4

Modified residue

498

1

Phosphoserine

Modified residue

502

1

Phosphoserine

Modified residue

506

1

Phosphoserine Ref.6

Modified residue

508

1

Phosphoserine

Modified residue

558

1

Phosphothreonine

Modified residue

588

1

Phosphoserine

Modified residue

589

1

Phosphoserine

Modified residue

828

1

Phosphothreonine

Modified residue

830

1

Phosphoserine

Natural variations

Natural variant

107

1

G → E in a metastatic melanoma sample; somatic mutation. Ref.7

VAR_040702

Natural variant

168

1

P → Q: dbSNP rs36102209.

VAR_051639

Experimental info

Sequence conflict

462 – 464

3

SRL → AV in CAA88531. Ref.2

Sequence conflict

465 – 480

16

LKLRE…LPSGF → AQAAGRRQPHQPALWL Ref.3

Sequence conflict

471

1

G → S in CAA88531. Ref.2

Sequence conflict

807

1

R → G in CAA62351. Ref.1

Sequence conflict

818

1

A → V in CAA62351. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

954

Helix Strand Turn

Details...

Beta strand

20 – 23

4

Beta strand

42 – 44

3

Turn

50 – 52

3

Helix

73 – 75

3

Sequences

	Sequence		Length	Mass (Da)
	Q02779-1 [UniParc]. Last modified April 17, 2007. Version 3. Checksum: 59A7596B05751981	FASTA	954	103,694
	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

References

	« Hide 'large scale' referencesShow '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: 8536694] [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: 7731697] [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: 8477742] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 244-480. Tissue: Colon epithelium.
[4]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-489, MASS SPECTROMETRY.
[5]	"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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-489; SER-498; SER-502; SER-506; SER-508; THR-558; SER-588; SER-589; THR-828 AND SER-830, MASS SPECTROMETRY.
[6]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-506, MASS SPECTROMETRY. Tissue: T-cell.
[7]	"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. , 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: 17344846] [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.

IPI

IPI00295401.

PIR

S68178.

RefSeq

NP_002437.2.

UniGene

Hs.466743

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2RF0	X-ray	2.00	A/B/C/D	13-78	[»]

SMR

Q02779. Positions 19-359, 90-360.

ModBase

Search...

Protein-protein interaction databases

STRING

Q02779.

PTM databases

PhosphoSite

Q02779.

Proteomic databases

PRIDE

Q02779.

Genome annotation databases

Ensembl

ENST00000253055; ENSP00000253055; ENSG00000130758; Homo sapiens. [Genome view]

GeneID

4294.

KEGG

hsa:4294.

UCSC

uc002ona.1. human.

Organism-specific databases

CTD

4294.

GeneCards

GC19P045389.

HGNC

HGNC:6849. MAP3K10.

HPA

HPA007039.

MIM

600137. gene.

PharmGKB

PA30593.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG09571.

HOGENOM

HBG716519.

HOVERGEN

Q02779.

InParanoid

Q02779.

OMA

REGSSHI.

OrthoDB

EOG9QC3RC.

PhylomeDB

Q02779.

Enzyme and pathway databases

BRENDA

2.7.11.25. 247.

Pathway_Interaction_DB

p38_mkk3_6pathway. p38 MAPK signaling pathway.

Gene expression databases

ArrayExpress

Q02779.

Bgee

Q02779.

CleanEx

HS_MAP3K10.

Genevestigator

Q02779.

GermOnline

ENSG00000130758. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR015785. MAPKKK-like.
IPR016231. MAPKKK9/10/11.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_prot_kinase_AS.
IPR011511. SH3_2.
IPR001452. SH3_domain.
IPR020473. SH3_region.
[Graphical view]

PANTHER

PTHR23257:SF87. MAPKKK-like. 1 hit.

Pfam

PF07653. SH3_2. 1 hit.
[Graphical view]

PIRSF

PIRSF000556. MAPKKK9_11. 1 hit.

PRINTS

PR00452. SH3DOMAIN.

SMART

SM00326. SH3. 1 hit.
[Graphical view]

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

BindingDB

Q02779.

NextBio

16901.

SOURCE

Search...

Entry information

Entry name

M3K10_HUMAN

Accession

Primary (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:	February 9, 2010
This is version 99 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.