Mitogen-activated protein kinase kinase kinase 6

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Reviewed, UniProtKB/Swiss-Prot Q9WTR2 (M3K6_MOUSE)

Last modified February 9, 2010. Version 72. History...

Clusters with 100%, 90%, 50% identity |

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase kinase kinase 6
    EC=2.7.11.25
Alternative name(s):
    Apoptosis signal-regulating kinase 2

Gene names

Name:	Map3k6
Synonyms:	Ask2, Mapkkk6, Mekk6

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

Sequence length	1291 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Component of a protein kinase signal transduction cascade. Activates the JNK, but not ERK or p38 kinase pathways. Ref.1
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.1
Cofactor	Magnesium. Ref.1
Enzyme regulation	Activated by phosphorylation on Thr-807. Catalytically active only when complexed with MAP3K5, with MAP3K5 supporting the stability and the active configuration of MAP3K6 and MAP3K6 activating MAP3K5 by direct phosphorylation. Ref.1
Subunit structure	Binds both upstream activators and downstream substrates in multimolecular complexes. Ref.1
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. Contains 1 protein kinase domain.

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Ontologies

Keywords
Domain	Coiled coil
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase kinase activity Inferred from electronic annotation. Source: EC magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.1 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
MAP3K5	Q99683	1	EBI-1254790,EBI-476263	From a different organism.
Map3k5	O35099	1	EBI-1254790,EBI-777493

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1291

1291

Mitogen-activated protein kinase kinase kinase 6

PRO_0000291648

Regions

Domain

649 – 907

259

Protein kinase

Nucleotide binding

655 – 663

ATP By similarity UniProtKB P28523

Coiled coil

1006 – 1069

Potential

Coiled coil

1164 – 1195

Potential

Sites

Active site

772

Proton acceptor By similarity UniProtKB P28523

Binding site

678

ATP Ref.1

Amino acid modifications

Modified residue

805

Phosphothreonine By similarity

Modified residue

807

Phosphothreonine Ref.1

Modified residue

965

Phosphoserine By similarity

Modified residue

985

Phosphoserine By similarity

Experimental info

Mutagenesis

678

K → M: Loss of kinase activity. Ref.1

Sequence conflict

R → G in CAM21067. Ref.3

Sequence conflict

R → G in CAM18232. Ref.3

Sequence conflict

P → L in CAM21067. Ref.3

Sequence conflict

P → L in CAM18232. Ref.3

Sequence conflict

550 – 552

MSA → VST in CAM21067. Ref.3

Sequence conflict

550 – 552

MSA → VST in CAM18232. Ref.3

Sequence conflict

559

E → D in CAM21067. Ref.3

Sequence conflict

559

E → D in CAM18232. Ref.3

Sequence conflict

1114

L → M in CAM21067. Ref.3

Sequence conflict

1114

L → M in CAM18232. Ref.3

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Sequences

Sequence

Length

Mass (Da)

Tools

Q9WTR2-1 [UniParc].

Last modified June 26, 2007. Version 4.
Checksum: FC61A90935A7465D
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FASTA

1,291

143,055

        10         20         30         40         50         60 
MAGPCPRAGV LERAGSCWQD PLAEALSRGR SSPAVTGRGC ARSRPLSVVY VLTREPGPGV 

        70         80         90        100        110        120 
EPGSGTEAEP LPLRCLREAC AQLQGTRPPP QLRSLPFATL ALGDTAALDS FYNADVVVLE 

       130        140        150        160        170        180 
VSSSLAQPSL FYHLGVRESF SMTNNVLLCS QAELPDLQAL REDVFQKNSD CVGSYTLIPY 

       190        200        210        220        230        240 
VVTATGRVLC GDAGLLRGIA DGLVQAGAGT EALLTPLVGR LVRLLEATPT DSCGYFRETI 

       250        260        270        280        290        300 
RQDIRQARER FSGQQLRQEL ARLQRRLDSV ELLSPDIVMN LLLSYRDVQD YSAIIELVET 

       310        320        330        340        350        360 
LQALPTCDVA EQHNVCFHYT FALNRRNRPG DREKALAVLL PLVKYEGPVA PDLYCMCGRI 

       370        380        390        400        410        420 
YKDMFFTSGF QNAGHLEQAY HWYRKAFDVE PSLHSGINAA VLLIAAGQHF EDSEELRLIG 

       430        440        450        460        470        480 
MKLACLLARK GCVEKMQYYW DVGFYLGAQI LANDPIQVVL AAEQLYKLNA PIWYLVSVME 

       490        500        510        520        530        540 
TFLLYQHFRP TPEPSGGPPL RAHFWLHFLL QSCQPFKMAP PQEDQCLVLV LEINKVLLPA 

       550        560        570        580        590        600 
RLEIQGTDPM SAVTLSLLEP ETQEDPSSWT FPVTSICGIS TSKLDQRCCF LYALPPAQDV 

       610        620        630        640        650        660 
QLCFPSVERC QRFCGLIQVL VMNPDSSAPT EEAEGAREVL EFDYEYSETG ERLVLGRGTY 

       670        680        690        700        710        720 
GVVYAGRDRH TRVRIAIKEI PERDSRFSQP LHEEIALHKR LRHKNIVRYL GSASQGGYLK 

       730        740        750        760        770        780 
IFMEEVPGGS LSSLLRSVWG PLKDNESTIS FYTRQILQGL SYLHENRIVH RDIKGDNVLI 

       790        800        810        820        830        840 
NTFSGLLKIS DFGTSKRLAG ITPCTETFTG TLQYMAPEII DQGPRGYGKA ADIWSLGCTV 

       850        860        870        880        890        900 
IEMATGRPPF HELGSPQAAM FQVGMYKVHP PVPGSLSAEA QAFLLRTFEP DPRLRASAQE 

       910        920        930        940        950        960 
LLGDPFLQPG KRSRSPGSPR HTPRPSGAPS GPSSPSADSA TQSQTFPRPQ APSQHPPSPP 

       970        980        990       1000       1010       1020 
KRCLSYGDTS QLRVPEEPAA EEPASPEESS GLSLLHQESK RRAMLAAVLE QEVPTLAENL 

      1030       1040       1050       1060       1070       1080 
LEQEQDSRLS KIHVELLLRC LGAQIHTPNR RQLAQELRTL QAQLRAQSLG PALLKGPLFA 

      1090       1100       1110       1120       1130       1140 
FPDAVKQILR RRQIRPHWMF VLDSLLSRAV RAALAVLDAE SEKKAVLPRS EESSKEESQQ 

      1150       1160       1170       1180       1190       1200 
KPQESQALQS QLPPEQGPPS LMVELGLLRA ETDRLRDLLA EKERECQALV QQALHRVHAE 

      1210       1220       1230       1240       1250       1260 
TRKYAPASET PATLPKDQNL VRWLQELSVD PATIQTLLSH SFTLQTLLTC ATQDDLVYTR 

      1270       1280       1290 
IRGGMVCRIW RAILAQRAGA TSVTPVPRDA E

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Apoptosis signal-regulating kinase (ASK) 2 functions as a mitogen-activated protein kinase kinase kinase in a heteromeric complex with ASK1." Takeda K., Shimozono R., Noguchi T., Umeda T., Morimoto Y., Naguro I., Tobiume K., Saitoh M., Matsuzawa A., Ichijo H. J. Biol. Chem. 282:7522-7531(2007) [PubMed: 17210579] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ENZYME REGULATION, INTERACTION WITH MAP3K5, PHOSPHORYLATION AT THR-807, MUTAGENESIS OF LYS-678. Tissue: Fibroblast.
[2]	Saitoh M., Ichijo H. Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 1003. Tissue: Fibroblast.
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
EMBL GenBank DDBJ	AB021861 mRNA. Translation: BAA78532.4. AL671882, AL837525 Genomic DNA. Translation: CAM21067.1. AL837525, AL671882 Genomic DNA. Translation: CAM18232.1. BC120565 mRNA. Translation: AAI20566.1. BC125577 mRNA. Translation: AAI25578.1.
IPI	IPI00123741.
RefSeq	NP_057902.5.
UniGene	Mm.36640
3D structure databases
HSSP	HSSP built from PDB template 2CLQ based on UniProtKB Q99683.
SMR	Q9WTR2. Positions 639-908.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9WTR2. 2 interactions.
STRING	Q9WTR2.
PTM databases
PhosphoSite	Q9WTR2.
Proteomic databases
PRIDE	Q9WTR2.
Genome annotation databases
Ensembl	ENSMUST00000030677; ENSMUSP00000030677; ENSMUSG00000028862; Mus musculus. [Genome view]
GeneID	53608.
KEGG	mmu:53608.
Organism-specific databases
CTD	53608.
MGI	MGI:1855691. Map3k6.
Phylogenomic databases
eggNOG	roNOG04875.
HOGENOM	HBG380040.
HOVERGEN	Q9WTR2.
InParanoid	Q9WTR2.
Enzyme and pathway databases
BRENDA	2.7.11.25. 244.
Gene expression databases
ArrayExpress	Q9WTR2.
Bgee	Q9WTR2.
CleanEx	MM_MAP3K6.
Genevestigator	Q9WTR2.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR010993. SAM_homology. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. IPR002290. Ser/Thr_prot_kinase_dom. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	310311.
SOURCE	Search...

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Entry information

Entry name

M3K6_MOUSE

Accession

Primary (citable) accession number: Q9WTR2
Secondary accession number(s): A2AE93, Q0VBN3

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 26, 2007
Last sequence update:	June 26, 2007
Last modified:	February 9, 2010
This is version 72 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents