Reviewed, UniProtKB/Swiss-Prot Q9UBE8 (NLK_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine protein kinase NLK
    EC=2.7.11.24
Alternative name(s):
    Nemo-like kinase
    Protein LAK1

Gene names

Name:	NLK
Synonyms:	LAK1

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	527 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Role in cell fate determination, required for differentiation of bone marrow stromal cells. Acts downstream of MAP3K7 and HIPK2 to negatively regulate the canonical Wnt/beta-catenin signaling pathway and the phosphorylation and destruction of the MYB transcription factor. May suppress a wide range of transcription factors by phosphorylation of the coactivator, CREBBP By similarity. Involved in TGFbeta-mediated mesoderm induction, acting downstream of MAP3K7/TAK1 to phosphorylate STAT3. Ref.6 UniProtKB O54949
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. UniProtKB O54949
Cofactor	Magnesium By similarity. UniProtKB O54949
Enzyme regulation	Activated by tyrosine and threonine phosphorylation By similarity. Activated by activin. Ref.6 UniProtKB Q16539
Subunit structure	Interacts with STAT3 By similarity. Interacts with RNF138/NARF and TCF7L2/TCF4. Interacts with HIPK2 and MYB. Ref.7 Ref.8
Subcellular location	Nucleus By similarity. Cytoplasm By similarity. Note: Predominantly nuclear. A smaller fraction is cytoplasmic By similarity.
Post-translational modification	Dually phosphorylated on Thr-303 and Tyr-305, which activates the enzyme By similarity. Ref.10
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. Contains 1 protein kinase domain.
Sequence caution	The sequence AAD56013.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAF04857.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence ABC40748.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAG37718.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Wnt signaling pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of Wnt receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-threonine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of transcription Inferred from sequence or structural similarity. Source: UniProtKB serine phosphorylation of STAT3 protein Inferred from sequence or structural similarity. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW transforming growth factor beta receptor signaling pathway Ref.6 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleolus Inferred from direct assay. Source: HPA
Molecular function	ATP binding Inferred from sequence or structural similarity. Source: UniProtKB MAP kinase activity Inferred from sequence or structural similarity. Source: UniProtKB SH2 domain binding Inferred from sequence or structural similarity. Source: UniProtKB magnesium ion binding Inferred from sequence or structural similarity. Source: UniProtKB transcription factor binding Ref.8 Inferred from physical interaction. Source: UniProtKB ubiquitin protein ligase binding Ref.8 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MYB	P10242	1	EBI-366978,EBI-298355
Nr4a2	Q06219	1	EBI-366978,EBI-2337255	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 527	527	Serine/threonine protein kinase NLK		PRO_0000186336
Regions
	Domain	138 – 427	290	Protein kinase
	Nucleotide binding	144 – 152	9	ATP By similarity
	Compositional bias	22 – 25	4	Poly-Ala
	Compositional bias	27 – 34	8	Poly-His
	Compositional bias	42 – 48	7	Poly-His
	Compositional bias	71 – 83	13	Poly-Ala
	Compositional bias	106 – 111	6	Poly-Ala
	Compositional bias	115 – 119	5	Poly-Ala
Sites
	Active site	264	1	Proton acceptor By similarity
	Binding site	167	1	ATP By similarity
Amino acid modifications
	Modified residue	298	1	Phosphothreonine Ref.10
	Modified residue	303	1	Phosphothreonine By similarity
	Modified residue	305	1	Phosphotyrosine By similarity
	Modified residue	522	1	Phosphoserine
Natural variations
	Natural variant	177	1	V → A: dbSNP rs11871287.		VAR_019549
	Natural variant	343	1	A → T in a glioblastoma multiforme sample; somatic mutation. Ref.11		VAR_042273
Experimental info
	Sequence conflict	25	1	A → T in AAH64663. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q9UBE8-1 [UniParc]. Last modified November 3, 2009. Version 2. Checksum: CE6AEBA7D8133989	FASTA	527	58,283
	10 20 30 40 50 60 MSLCGARANA KMMAAYNGGT SAAAAGHHHH HHHHLPHLPP PHLHHHHHPQ HHLHPGSAAA 70 80 90 100 110 120 VHPVQQHTSS AAAAAAAAAA AAAMLNPGQQ QPYFPSPAPG QAPGPAAAAP AQVQAAAAAT 130 140 150 160 170 180 VKAHHHQHSH HPQQQLDIEP DRPIGYGAFG VVWSVTDPRD GKRVALKKMP NVFQNLVSCK 190 200 210 220 230 240 RVFRELKMLC FFKHDNVLSA LDILQPPHID YFEEIYVVTE LMQSDLHKII VSPQPLSSDH 250 260 270 280 290 300 VKVFLYQILR GLKYLHSAGI LHRDIKPGNL LVNSNCVLKI CDFGLARVEE LDESRHMTQE 310 320 330 340 350 360 VVTQYYRAPE ILMGSRHYSN AIDIWSVGCI FAELLGRRIL FQAQSPIQQL DLITDLLGTP 370 380 390 400 410 420 SLEAMRTACE GAKAHILRGP HKQPSLPVLY TLSSQATHEA VHLLCRMLVF DPSKRISAKD 430 440 450 460 470 480 ALAHPYLDEG RLRYHTCMCK CCFSTSTGRV YTSDFEPVTN PKFDDTFEKN LSSVRQVKEI 490 500 510 520 IHQFILEQQK GNRVPLCINP QSAAFKSFIS STVAQPSEMP PSPLVWE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of the Fugu rubripes NLK and FN5 genes flanking the NF1 (Neurofibromatosis type 1) gene in the 5' direction and mapping of the human counterparts." Kehrer-Sawatzki H., Moschgath E., Maier C., Legius E., Elgar G., Krone W. Gene 251:63-71(2000) [PubMed: 10863097] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"Cloning of human LAK1 cDNA." Wang C., Lo H. Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: T-cell.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Amygdala.
[4]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"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: Uterus.
[6]	"Role of the TAK1-NLK-STAT3 pathway in TGF-beta-mediated mesoderm induction." Ohkawara B., Shirakabe K., Hyodo-Miura J., Matsuo R., Ueno N., Matsumoto K., Shibuya H. Genes Dev. 18:381-386(2004) [PubMed: 15004007] [Abstract] Cited for: FUNCTION, ENZYME REGULATION.
[7]	"Wnt-1 signal induces phosphorylation and degradation of c-Myb protein via TAK1, HIPK2, and NLK." Kanei-Ishii C., Ninomiya-Tsuji J., Tanikawa J., Nomura T., Ishitani T., Kishida S., Kokura K., Kurahashi T., Ichikawa-Iwata E., Kim Y., Matsumoto K., Ishii S. Genes Dev. 18:816-829(2004) [PubMed: 15082531] [Abstract] Cited for: INTERACTION WITH MYB AND HIPK2.
[8]	"NARF, an nemo-like kinase (NLK)-associated ring finger protein regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF)." Yamada M., Ohnishi J., Ohkawara B., Iemura S., Satoh K., Hyodo-Miura J., Kawachi K., Natsume T., Shibuya H. J. Biol. Chem. 281:20749-20760(2006) [PubMed: 16714285] [Abstract] Cited for: INTERACTION WITH RNF138 AND TCF7L2.
[9]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-298 AND SER-522, MASS SPECTROMETRY.
[10]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-298, MASS SPECTROMETRY. Tissue: T-cell.
[11]	"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: VARIANT [LARGE SCALE ANALYSIS] THR-343.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF197898 mRNA. Translation: AAF04857.1. Different initiation. AF180819 mRNA. Translation: AAD56013.1. Different initiation. AK315315 mRNA. Translation: BAG37718.1. Different initiation. DQ316259 Genomic DNA. Translation: ABC40748.1. Different initiation. BC064663 mRNA. Translation: AAH64663.2.
IPI	IPI00936281.
RefSeq	NP_057315.3.
UniGene	Hs.208759
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UBE8. 11 interactions.
STRING	Q9UBE8.
PTM databases
PhosphoSite	Q9UBE8.
Proteomic databases
PRIDE	Q9UBE8.
Genome annotation databases
Ensembl	ENST00000262393; ENSP00000262393; ENSG00000087095; Homo sapiens. [Genome view] ENST00000407008; ENSP00000384625; ENSG00000087095; Homo sapiens. [Genome view]
GeneID	51701.
KEGG	hsa:51701.
Organism-specific databases
CTD	51701.
GeneCards	GC17P023393.
H-InvDB	HIX0013640.
HGNC	HGNC:29858. NLK.
HPA	HPA018192.
MIM	609476. gene.
PharmGKB	PA134914500.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG06633.
HOGENOM	HBG755340.
HOVERGEN	Q9UBE8.
InParanoid	Q9UBE8.
OrthoDB	EOG9577RS.
PhylomeDB	Q9UBE8.
Enzyme and pathway databases
BRENDA	2.7.11.24. 247.
Pathway_Interaction_DB	wnt_canonical_pathway. Canonical Wnt signaling pathway. wnt_calcium_pathway. Noncanonical Wnt signaling pathway. ps1pathway. Presenilin action in Notch and Wnt signaling.
Gene expression databases
ArrayExpress	Q9UBE8.
Bgee	Q9UBE8.
CleanEx	HS_NLK.
Genevestigator	Q9UBE8.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR003527. MAP_kinase_CS. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. 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	PS01351. MAPK. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

NLK_HUMAN

Accession

Primary (citable) accession number: Q9UBE8
Secondary accession number(s): B2RCX1, Q2PNI9, Q6P2A3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	November 3, 2009
Last modified:	February 9, 2010
This is version 88 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.