Reviewed, UniProtKB/Swiss-Prot Q99558 (M3K14_HUMAN)

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

Protein attributes

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

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.

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...

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

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	9	ATP By similarity
Sites
	Active site	515	1	Proton acceptor By similarity
	Binding site	429	1	ATP By similarity
Natural variations
	Natural variant	140	1	S → N: dbSNP rs11574819. Ref.7		VAR_040711
	Natural variant	255	1	T → M: dbSNP rs11574820.		VAR_051641
	Natural variant	514	1	G → K in a lung neuroendocrine carcinoma sample; somatic mutation; requires 2 nucleotide substitutions. Ref.7		VAR_040712
	Natural variant	674	1	H → Y: dbSNP rs11867907.		VAR_051642
	Natural variant	764	1	T → A: dbSNP rs56302559. Ref.7		VAR_040713
	Natural variant	852	1	T → I in an ovarian mucinous carcinoma sample; somatic mutation. Ref.7		VAR_040714
	Natural variant	928	1	P → H: dbSNP rs56036201. Ref.7		VAR_040715
Experimental info
	Mutagenesis	429 – 430	2	KK → AA: Loss of autophosphorylation. Ref.1
	Sequence conflict	25	1	A → P in CAA71306. Ref.1
	Sequence conflict	348	1	G → S in CAA71306. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q99558-1 [UniParc]. Last modified April 4, 2006. Version 2. Checksum: C9D10F67FF7F48AC	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

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. , 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: VARIANTS [LARGE SCALE ANALYSIS] ASN-140; LYS-514; ALA-764; ILE-852 AND HIS-928.
+	Additional computationally mapped references.

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...

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.