Mitogen-activated protein kinase kinase kinase 14

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Reviewed, UniProtKB/Swiss-Prot Q99558 (M3K14_HUMAN)

Last modified February 9, 2010. Version 100. History...

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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 14
    EC=2.7.11.25
Alternative name(s):
    Serine/threonine-protein kinase NIK
    NF-kappa-beta-inducing kinase
      Short name=HsNIK

Gene names

Name:	MAP3K14
Synonyms:	NIK

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

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Protein attributes

Sequence length	947 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Induces the processing of NF-kappa-B 2/P100. Could act in a receptor-selective manner By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Binds to TRAF2, TRAF5, TRAF6, IKKA and NF-kappa-B 2/P100 By similarity. Interacts with PELI3. Interacts with NIBP; the interaction is direct. Interacts with ARRB1 and ARRB2. Ref.4 Ref.5 Ref.6
Subcellular location	Cytoplasm.
Tissue specificity	Weakly expressed in testis, small intestine, spleen, thymus, peripheral blood leukocytes, prostate, ovary and colon. Ref.1
Post-translational modification	Autophosphorylated.
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
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype. Source: UniProtKB protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase kinase activity Inferred from electronic annotation. Source: EC protein binding Ref.4 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
BIRC2	Q13490	1	EBI-358011,EBI-514538
CHUK	O15111	2	EBI-358011,EBI-81249
Chuk	Q60680	1	EBI-358011,EBI-646245	From a different organism.
Chuk	Q60680-2	2	EBI-358011,EBI-646264	From a different organism.
EDAR	Q9UNE0	1	EBI-358011,EBI-529289
IKBKB	O14920	2	EBI-358011,EBI-81266
MAP3K7	O43318-3	1	EBI-358011,EBI-358704
PELI3	Q8N2H9-1	1	EBI-358011,EBI-448466
PELI3	Q8N2H9-2	1	EBI-358011,EBI-448472
TRAF6	Q9Y4K3	1	EBI-358011,EBI-359276

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 947

947

Mitogen-activated protein kinase kinase kinase 14

PRO_0000086266

Regions

Domain

400 – 655

256

Protein kinase

Nucleotide binding

406 – 414

ATP By similarity

Sites

Active site

515

Proton acceptor By similarity

Binding site

429

ATP By similarity

Natural variations

Natural variant

140

S → N: dbSNP rs11574819. Ref.7

VAR_040711

Natural variant

255

T → M: dbSNP rs11574820.

VAR_051641

Natural variant

514

G → K in a lung neuroendocrine carcinoma sample; somatic mutation; requires 2 nucleotide substitutions. Ref.7

VAR_040712

Natural variant

674

H → Y: dbSNP rs11867907.

VAR_051642

Natural variant

764

T → A: dbSNP rs56302559. Ref.7

VAR_040713

Natural variant

852

T → I in an ovarian mucinous carcinoma sample; somatic mutation. Ref.7

VAR_040714

Natural variant

928

P → H: dbSNP rs56036201. Ref.7

VAR_040715

Experimental info

Mutagenesis

429 – 430

KK → AA: Loss of autophosphorylation. Ref.1

Sequence conflict

A → P in CAA71306. Ref.1

Sequence conflict

348

G → S in CAA71306. Ref.1

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Sequences

Sequence

Length

Mass (Da)

Tools

Q99558-1 [UniParc].

Last modified April 4, 2006. Version 2.
Checksum: C9D10F67FF7F48AC
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FASTA

947

104,042

        10         20         30         40         50         60 
MAVMEMACPG APGSAVGQQK ELPKAKEKTP PLGKKQSSVY KLEAVEKSPV FCGKWEILND 

        70         80         90        100        110        120 
VITKGTAKEG SEAGPAAISI IAQAECENSQ EFSPTFSERI FIAGSKQYSQ SESLDQIPNN 

       130        140        150        160        170        180 
VAHATEGKMA RVCWKGKRRS KARKKRKKKS SKSLAHAGVA LAKPLPRTPE QESCTIPVQE 

       190        200        210        220        230        240 
DESPLGAPYV RNTPQFTKPL KEPGLGQLCF KQLGEGLRPA LPRSELHKLI SPLQCLNHVW 

       250        260        270        280        290        300 
KLHHPQDGGP LPLPTHPFPY SRLPHPFPFH PLQPWKPHPL ESFLGKLACV DSQKPLPDPH 

       310        320        330        340        350        360 
LSKLACVDSP KPLPGPHLEP SCLSRGAHEK FSVEEYLVHA LQGSVSSGQA HSLTSLAKTW 

       370        380        390        400        410        420 
AARGSRSREP SPKTEDNEGV LLTEKLKPVD YEYREEVHWA THQLRLGRGS FGEVHRMEDK 

       430        440        450        460        470        480 
QTGFQCAVKK VRLEVFRAEE LMACAGLTSP RIVPLYGAVR EGPWVNIFME LLEGGSLGQL 

       490        500        510        520        530        540 
VKEQGCLPED RALYYLGQAL EGLEYLHSRR ILHGDVKADN VLLSSDGSHA ALCDFGHAVC 

       550        560        570        580        590        600 
LQPDGLGKSL LTGDYIPGTE THMAPEVVLG RSCDAKVDVW SSCCMMLHML NGCHPWTQFF 

       610        620        630        640        650        660 
RGPLCLKIAS EPPPVREIPP SCAPLTAQAI QEGLRKEPIH RVSAAELGGK VNRALQQVGG 

       670        680        690        700        710        720 
LKSPWRGEYK EPRHPPPNQA NYHQTLHAQP RELSPRAPGP RPAEETTGRA PKLQPPLPPE 

       730        740        750        760        770        780 
PPEPNKSPPL TLSKEESGMW EPLPLSSLEP APARNPSSPE RKATVPEQEL QQLEIELFLN 

       790        800        810        820        830        840 
SLSQPFSLEE QEQILSCLSI DSLSLSDDSE KNPSKASQSS RDTLSSGVHS WSSQAEARSS 

       850        860        870        880        890        900 
SWNMVLARGR PTDTPSYFNG VKVQIQSLNG EHLHIREFHR VKVGDIATGI SSQIPAAAFS 

       910        920        930        940 
LVTKDGQPVR YDMEVPDSGI DLQCTLAPDG SFAWSWRVKH GQLENRP

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1." Malinin N.L., Boldin M.P., Kovalenko A.V., Wallach D. Nature 385:540-544(1997) [PubMed: 9020361] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF 429-LYS-LYS-430, TISSUE SPECIFICITY.
[2]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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: Lymph.
[4]	"Pellino3, a novel member of the Pellino protein family, promotes activation of c-Jun and Elk-1 and may act as a scaffolding protein." Jensen L.E., Whitehead A.S. J. Immunol. 171:1500-1506(2003) [PubMed: 12874243] [Abstract] Cited for: INTERACTION WITH PELI3.
[5]	"beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha." Witherow D.S., Garrison T.R., Miller W.E., Lefkowitz R.J. Proc. Natl. Acad. Sci. U.S.A. 101:8603-8607(2004) [PubMed: 15173580] [Abstract] Cited for: INTERACTION WITH ARRB1 AND ARRB2.
[6]	"NIBP, a novel NIK and IKK(beta)-binding protein that enhances NF-(kappa)B activation." Hu W.-H., Pendergast J.S., Mo X.-M., Brambilla R., Bracchi-Ricard V., Li F., Walters W.M., Blits B., He L., Schaal S.M., Bethea J.R. J. Biol. Chem. 280:29233-29241(2005) [PubMed: 15951441] [Abstract] Cited for: INTERACTION WITH NIBP.
[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. Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASN-140; LYS-514; ALA-764; ILE-852 AND HIS-928.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
EMBL GenBank DDBJ	Y10256 mRNA. Translation: CAA71306.1. DQ314874 Genomic DNA. Translation: ABC40733.1. BC035576 mRNA. Translation: AAH35576.1.
IPI	IPI00016099.
RefSeq	NP_003945.2.
UniGene	Hs.404183
3D structure databases
SMR	Q99558. Positions 403-669.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-27522N.
IntAct	Q99558. 118 interactions.
STRING	Q99558.
PTM databases
PhosphoSite	Q99558.
Proteomic databases
PRIDE	Q99558.
Genome annotation databases
Ensembl	ENST00000344686; ENSP00000342059; ENSG00000006062; Homo sapiens. [Genome view]
GeneID	9020.
KEGG	hsa:9020.
Organism-specific databases
CTD	9020.
GeneCards	GC17M040696.
HGNC	HGNC:6853. MAP3K14.
HPA	CAB004518.
MIM	604655. gene.
PharmGKB	PA30597.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG507202.
HOVERGEN	Q99558.
InParanoid	Q99558.
Enzyme and pathway databases
BRENDA	2.7.11.25. 247.
Pathway_Interaction_DB	nfkappabalternativepathway. Alternative NF-kappaB pathway. hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha. avb3_opn_pathway. Osteopontin-mediated events. tcrpathway. TCR signaling in naive CD4+ T cells. cd8tcrpathway. TCR signaling in naive CD8+ T cells.
Reactome	REACT_6900. Signaling in Immune system.
Gene expression databases
Bgee	Q99558.
CleanEx	HS_MAP3K14.
Genevestigator	Q99558.
GermOnline	ENSG00000006062. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR017425. MAPKKK14. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PIRSF	PIRSF038175. MAPKKK14. 1 hit.
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	33793.
SOURCE	Search...

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Entry information

Entry name

M3K14_HUMAN

Accession

Primary (citable) accession number: Q99558
Secondary accession number(s): Q8IYN1

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 2001
Last sequence update:	April 4, 2006
Last modified:	February 9, 2010
This is version 100 of the entry and version 2 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.

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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

Natural variations

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