Q9WUL6 (M3K14_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase kinase kinase 14
EC=2.7.11.25

Alternative name(s):
NF-kappa-beta-inducing kinase
Serine/threonine-protein kinase NIK

Gene names

Name:	Map3k14
Synonyms:	Nik

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 › Mus

Protein attributes

Sequence length	942 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. Promotes proteolytic processing of NFKB2/P100, which leads to activation of NF-kappa-B via the non-canonical pathway. Could act in a receptor-selective manner. Ref.2
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Interacts with TRAF2, TRAF3, TRAF5, TRAF6, IKKA and NF-kappa-B2/P100. Interacts with PELI3. Interacts with NIBP; the interaction is direct. Interacts with ARRB1 and ARRB2. Interacts with GRB10. Interacts with ZFP91 By similarity.
Subcellular location	Cytoplasm.
Post-translational modification	Phosphorylation at Thr-561 is required to activates its kinase activity and 'Lys-63'-linked polyubiquitination. Phosphorylated by CHUK/IKKA leading to MAP3K14 destabilization By similarity. Autophosphorylated. Ref.2 Ubiquitinated. Undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. 'Lys-48'-linked polyubiquitination leads to its degradation by the proteasome, while 'Lys-63'-linked polyubiquitination stabilizes and activates it By similarity.
Disruption phenotype	Mice display the alymphoplasia phenotype (aly), which is characterized by systemic absence of lymph nodes and Peyer patches and disorganized splenic and thymic structures with immunodeficiency. 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.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	I-kappaB kinase/NF-kappaB cascade Inferred from direct assay Ref.2. Source: UniProtKB immune response Inferred from direct assay Ref.2. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase kinase activity Inferred from electronic annotation. Source: EC NF-kappaB-inducing kinase activity Inferred from direct assay Ref.2. Source: UniProtKB protein binding Inferred from physical interaction Ref.2. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 942	942	Mitogen-activated protein kinase kinase kinase 14		PRO_0000086267
Regions
	Domain	402 – 657	256	Protein kinase
	Nucleotide binding	408 – 416	9	ATP By similarity
	Region	403 – 655	253	Interaction with ZFP91 By similarity
Sites
	Active site	517	1	Proton acceptor By similarity
	Binding site	431	1	ATP By similarity
Amino acid modifications
	Modified residue	561	1	Phosphothreonine By similarity
Experimental info
	Mutagenesis	855	1	G → R in ALY; no binding to IKKA. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9WUL6 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 3BE4E4BA2D25C200	FASTA	942	103,080
	10 20 30 40 50 60 MAVMEVACPG TPGSAVGQQK ELAKAKEKTQ SLGKKQSCIF KLEAVEKSPV FCGKWEILND 70 80 90 100 110 120 VITKGTAKDG SEGGPPAISI IAQAECENSQ EFSPTFSERI FIAGSQQYSQ SESLDQIPNN 130 140 150 160 170 180 VAHATEGKMA RVCRRGKRHG KARKKRRKKR SKSLAQAGVA LAKPLPRTPE QESCTIPVQE 190 200 210 220 230 240 DESPLGNLYA RNVSQFTKPL GGPGLGHLCF KKQDEGLRPV LPRPELHKLI SPLQCLNHVW 250 260 270 280 290 300 KLHHPQATGP RPHPTHPFPY SGMPHPFPFY PLEPWKPYML DSAVLDKLAG VSGQRPLPGP 310 320 330 340 350 360 PHLSQLAHGD SQKPLPGPHL ESSCPSRGAL EKVPVEEYLV HALQGSVSSG QAHSLASLAK 370 380 390 400 410 420 TWSSGSAKLQ RLGPETEDNE GVLLTEKLKP VDYEYREEVH WMTHQPRVGR GSFGEVHRMK 430 440 450 460 470 480 DKQTGFQCAV KKVRLEVFRV EELVACAGLS SPRIVPLYGA VREGPWVNIF MELLEGGSLG 490 500 510 520 530 540 QLIKQMGCLP EDRALYYLGQ ALEGLEYLHT RRILHGDVKA DNVLLSSDGS RAALCDFGHA 550 560 570 580 590 600 LCLQPDGLGK SLLTGDYIPG TETHMAPEVV MGKPCDAKVD IWSSCCMMLH MLNGCHPWTQ 610 620 630 640 650 660 YFRGPLCLKI ASEPPPIREI PPSCAPLTAQ AIQEGLRKEP VHRASAMELR RKVGKALQEV 670 680 690 700 710 720 GGLKSPWKGE YKEPRPPPQD QATCHQTLPT PPRENPPAKA NTDGAPEPQP PLPPEPPEPS 730 740 750 760 770 780 KAPALNLSKE ESGTWEPLPL SSLDPATAKG PSFPDRRATL PELELQQLEI ELFLNSLSQP 790 800 810 820 830 840 FSLEEQEQIL SCLSIDSLSL SDDSEKNPSK ASQSSRDTLS SGVHSWNSQA EARTCSCSTA 850 860 870 880 890 900 LARGRPTDIP SYFNGVKVQI QSLNGEHLHI REFHRVKVGD IATGISSQIP ATAFSLVTKD 910 920 930 940 GQPVCYDMEV PDSGIDLQCT LAPDGSFAWT WRVKHGQLEN RP

References

[1]	"Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-kappa b-inducing kinase." Shinkura R., Kitada K., Matsuda F., Tashiro K., Ikuta K., Suzuki M., Kogishi K., Serikawa T., Honjo T. Nat. Genet. 22:74-77(1999) [PubMed: 10319865] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], DISRUPTION PHENOTYPE, MUTAGENESIS OF GLY-855. Strain: C57BL/6. Tissue: Spleen.
[2]	"NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100." Xiao G., Harhaj E.W., Sun S.-C. Mol. Cell 7:401-409(2001) [PubMed: 11239468] [Abstract] Cited for: FUNCTION, AUTOPHOSPHORYLATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF143094 mRNA. Translation: AAD31512.1.
IPI	IPI00124786.
RefSeq	NP_058592.1. NM_016896.3.
UniGene	Mm.158981.
3D structure databases
ProteinModelPortal	Q9WUL6.
SMR	Q9WUL6. Positions 403-655.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9WUL6.
PTM databases
PhosphoSite	Q9WUL6.
Proteomic databases
PRIDE	Q9WUL6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000021324; ENSMUSP00000021324; ENSMUSG00000020941.
GeneID	53859.
KEGG	mmu:53859.
Organism-specific databases
CTD	9020.
MGI	MGI:1858204. Map3k14.
Phylogenomic databases
GeneTree	ENSGT00600000084293.
HOGENOM	HBG507202.
HOVERGEN	HBG052384.
InParanoid	Q9WUL6.
OMA	HGQLENR.
OrthoDB	EOG44MXRB.
PhylomeDB	Q9WUL6.
Gene expression databases
ArrayExpress	Q9WUL6.
Bgee	Q9WUL6.
CleanEx	MM_MAP3K14.
Genevestigator	Q9WUL6.
GermOnline	ENSMUSG00000020941. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR017425. MAPKKK14. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
KO	K04466.
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PIRSF	PIRSF038175. MAPKKK14. 1 hit.
SUPFAM	SSF56112. Kinase_like. 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
NextBio	310697.
SOURCE	Search...

Entry information

Entry name

M3K14_MOUSE

Accession

Primary (citable) accession number: Q9WUL6

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 2001
Last sequence update:	November 1, 1999
Last modified:	December 14, 2011
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program