Mitogen-activated protein kinase kinase kinase 11

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Q66HA1 (M3K11_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified December 14, 2011. Version 76. History...

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

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase kinase kinase 11
EC=2.7.11.25

Alternative name(s):
Mixed lineage kinase 3

Gene names

Name:	Map3k11
Synonyms:	Mlk3

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	850 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Activates the JUN N-terminal pathway. Required for serum-stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle 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. Interacts with MAP2K7/MKK4 By similarity. Interacts with MAP2K7/MKK7.
Subunit structure	Homodimer; undergoes dimerization during activation By similarity.
Subcellular location	Cytoplasm › cytoskeleton › centrosome. Note: Location is cell cycle dependent By similarity.
Post-translational modification	Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation. Thr-278 is likely to be the main autophosphorylation site. Phosphorylation of Ser-556 and Ser-557 is induced by CDC42 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
Cellular component	Cytoplasm Cytoskeleton
Domain	Repeat SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of JNKK activity Inferred from direct assay. Source: RGD cell death Inferred from mutant phenotype. Source: RGD positive regulation of neuron apoptosis Inferred from mutant phenotype. Source: RGD protein autophosphorylation Inferred from direct assay. Source: RGD
Cellular component	soluble fraction Inferred from direct assay. Source: RGD
Molecular function	ATP binding Inferred from direct assay. Source: RGD JUN kinase kinase kinase activity Inferred from direct assay. Source: RGD Rac GTPase binding Inferred from physical interaction. Source: RGD mitogen-activated protein kinase kinase binding Inferred from physical interaction Ref.3. Source: RGD 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 – 850

850

Mitogen-activated protein kinase kinase kinase 11

PRO_0000277829

Regions

Domain

42 – 106

SH3

Domain

118 – 380

263

Protein kinase

Domain

404 – 425

Leucine-zipper 1

Domain

439 – 460

Leucine-zipper 2

Nucleotide binding

124 – 132

ATP By similarity

Compositional bias

18 – 29

Poly-Gly

Compositional bias

473 – 476

Poly-Arg

Compositional bias

600 – 823

224

Pro-rich

Sites

Active site

242

Proton acceptor By similarity

Binding site

145

ATP By similarity

Amino acid modifications

Modified residue

Phosphoserine By similarity

Modified residue

278

Phosphothreonine; by autocatalysis By similarity

Modified residue

282

Phosphoserine; by autocatalysis and MAP4K1 By similarity

Modified residue

395

Phosphoserine By similarity

Modified residue

494

Phosphoserine By similarity

Modified residue

508

Phosphoserine By similarity

Modified residue

525

Phosphoserine By similarity

Modified residue

549

Phosphoserine By similarity

Modified residue

556

Phosphoserine By similarity

Modified residue

557

Phosphoserine By similarity

Modified residue

570

Phosphoserine By similarity

Modified residue

655

Phosphoserine By similarity

Modified residue

704

Phosphothreonine By similarity

Modified residue

712

Phosphothreonine By similarity

Modified residue

728

Phosphoserine By similarity

Modified residue

731

Phosphoserine By similarity

Modified residue

741

Phosphothreonine By similarity

Modified residue

743

Phosphoserine By similarity

Modified residue

749

Phosphoserine By similarity

Modified residue

751

Phosphoserine By similarity

Modified residue

755

Phosphothreonine By similarity

Modified residue

758

Phosphothreonine By similarity

Modified residue

761

Phosphoserine By similarity

Modified residue

773

Phosphoserine By similarity

Modified residue

792

Phosphoserine By similarity

Modified residue

796

Phosphoserine By similarity

Modified residue

818

Phosphoserine By similarity

Sequences

Sequence

Length

Mass (Da)

Tools

Q66HA1 [UniParc].

Last modified October 11, 2004. Version 1.
Checksum: 81ECA45841BDB379
Show »

FASTA

850

93,109

        10         20         30         40         50         60 
MEPLKNLFLK SPLGSWNGSG SGGGGGSGGV RPEGSPKATA AYANPVWTAL FDYEPNGQDE 

        70         80         90        100        110        120 
LALRKGDRVE VLSRDAAISG DEGWWAGQVG GQVGIFPSNY VSRGGGPPPC EVASFQELRL 

       130        140        150        160        170        180 
EEVIGIGGFG KVYRGSWRGE LVAVKAARQD PDEDISVTAE SVRQEARLFA MLAHPNIIAL 

       190        200        210        220        230        240 
KAVCLEEPNL CLVMEYAAGG PLSRALAGRR VPPHVLVNWA VQIARGMHYL HCEALVPVIH 

       250        260        270        280        290        300 
RDLKSNNILL LQPIEGDDME HKTLKITDFG LAREWHKTTQ MSAAGTYAWM APEVIKASTF 

       310        320        330        340        350        360 
SKGSDVWSFG VLLWELLTGE VPYRGIDCLA VAYGVAVNKL TLPIPSTCPE PFAQLMADCW 

       370        380        390        400        410        420 
AQDPHRRPDF ASILQQLEAL EAQVLREMPR DSFHSMQEGW KREIQGLFDE LRAKEKELLS 

       430        440        450        460        470        480 
REEELTRAAR EQRSQAEQLR RREHLLAQWE LEVFERELTL LLQQVDRERP HVRRRRGTFK 

       490        500        510        520        530        540 
RSKLRARDGG ERISMPLDFK HRITVQASPG LDRRRNVFEV GAGDSPTFPR FRAIQLEPAE 

       550        560        570        580        590        600 
SGQTWGRQSP RRLDDSSNGE RRACWAWGPS SPKPGEAQNG RRRSRMDEAT WYLDSDDSSP 

       610        620        630        640        650        660 
LGSPSTPPAL NGNPPRPSPE PEEPRRSGPT ERGNSSGTPK LIQRALLRGT ALLASLGLGR 

       670        680        690        700        710        720 
DLQPPGGLSR ERGESPTAPP PAQMASPCPP DLPSTPLIHL SQATPDARGP LTPAPLLLDL 

       730        740        750        760        770        780 
GVSSGQPSAK SPRREETRGR TVSPPPGISR SAPGTPGTPR SPPLGLISRP RPSPLRNRID 

       790        800        810        820        830        840 
PWSFVSAGPR PSPLPSPQPA PRRAPWTLFP DSDPFWDSPP ANPFRGGSQD CRTQTKDVGA 

       850 
QAPWAPEAGP

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: Lung.
[2]	"CEP11004, a novel inhibitor of the mixed lineage kinases, suppresses apoptotic death in dopamine neurons of the substantia nigra induced by 6-hydroxydopamine." Ganguly A., Oo T.F., Rzhetskaya M., Pratt R., Yarygina O., Momoi T., Kholodilov N., Burke R.E. J. Neurochem. 88:469-480(2004) [PubMed: 14690535] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 778-850. Strain: Sprague-Dawley.
[3]	"Delayed activation and regulation of MKK7 in hippocampal CA1 region following global cerebral ischemia in rats." Zhang Q., Tian H., Fu X., Zhang G. Life Sci. 74:37-45(2003) [PubMed: 14575811] [Abstract] Cited for: INTERACTION WITH MAP2K7/MKK7.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC081952 mRNA. Translation: AAH81952.1. AY240868 mRNA. Translation: AAO91627.1.
IPI	IPI00471828.
RefSeq	NP_001013168.1. NM_001013150.1.
UniGene	Rn.28235.
3D structure databases
HSSP	HSSP built from PDB template 1U4D based on UniProtKB Q07912.
ProteinModelPortal	Q66HA1.
SMR	Q66HA1. Positions 43-102.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q66HA1. 1 interaction.
STRING	Q66HA1.
Proteomic databases
PRIDE	Q66HA1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	309168.
KEGG	rno:309168.
Organism-specific databases
CTD	4296.
RGD	1359261. Map3k11.
Phylogenomic databases
eggNOG	maNOG17953.
GeneTree	ENSGT00600000084346.
HOVERGEN	HBG067662.
InParanoid	Q66HA1.
OrthoDB	EOG4PNXGN.
Gene expression databases
ArrayExpress	Q66HA1.
Genevestigator	Q66HA1.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR016231. MAPKKK9/10/11. IPR015785. MAPKKK9/10/11-like. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase. IPR008271. Ser/Thr_kinase_AS. IPR011511. SH3_2. IPR001452. SH3_domain. IPR020635. Tyr_kinase_cat_dom. [Graphical view]
KO	K04419.
PANTHER	PTHR23257:SF87. MAPKKK-like. 1 hit.
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF07653. SH3_2. 1 hit. [Graphical view]
PIRSF	PIRSF000556. MAPKKK9_11. 1 hit.
PRINTS	PR00452. SH3DOMAIN. PR00109. TYRKINASE.
SMART	SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF50044. SH3. 1 hit.
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
NextBio	660318.

Entry information

Entry name

M3K11_RAT

Accession

Primary (citable) accession number: Q66HA1
Secondary accession number(s): Q80YF1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 20, 2007
Last sequence update:	October 11, 2004
Last modified:	December 14, 2011
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents