EKS-RAN-00481

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-RAN-00481

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
CMGC/MAPK	374.8	3.1E-112	141	427	287

Status

Reviewed

Ensembl Protein

ENSRNOP00000011726

UniProt Accession

D3ZSZ3;

Protein Name

Serine/threonine-protein kinase NLK

Protein Synonyms/Alias

Nemo-like kinase;

Gene Name

Nlk

Gene Synonyms/Alias

Nlk;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSRNOG00000008704	ENSRNOP00000011726	ENSRNOT00000011726

Organism

Rattus norvegicus

Functional Description

Serine/threonine-protein kinase that regulates a numberof transcription factors with key roles in cell fate determination. Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2. Activation of this pathway causes binding to and phosphorylation of the histone methyltransferase SETDB1. The NLK- SETDB1 complex subsequently interacts with PPARG, leading to methylation of PPARG target promoters at histone H3K9 and transcriptional silencing. The resulting loss of PPARG target gene transcription inhibits adipogenesis and promotes osteoblastogenesis in mesenchymal stem cells (MSCs). Negative regulator of the canonical Wnt/beta-catenin signaling pathway. Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1. Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes. Negative regulator of the Notch signaling pathway. Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1. Negative regulator of the MYB family of transcription factors. Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP. Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself. Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1 (By similarity).

Protein Length

527

Protein Sequence
(FASTA)

MSLCGTRANA KMMAAYNGGT SAAAAGHHHH HHHHLPHLPP PHLHHHHHPQ HHLHPGSAAA 60

VHPVQQHTSS AAAAAAAAAA AAAMLNPGQQ QPYFPSPAPG QAPGPAAAAP AQVQAAAAAT 120

VKAHHHQHSH HPQQQLDIEP DRPIGYGAFG VVWSVTDPRD GKRVALKKMP NVFQNLVSCK 180

RVFRELKMLC FFKHDNVLSA LDILQPPHID YFEEIYVVTE LMQSDLHKII VSPQPLSSDH 240

VKVFLYQILR GLKYLHSAGI LHRDIKPGNL LVNSNCVLKI CDFGLARVEE LDESRHMTQE 300

VVTQYYRAPE ILMGSRHYSN AIDIWSVGCI FAELLGRRIL FQAQSPIQQL DLITDLLGTP 360

SLEAMRTACE GAKAHILRGP HKQPSLPVLY TLSSQATHEA VHLLCRMLVF DPSKRISAKD 420

ALAHPYLDEG RLRYHTCMCK CCFSTSTGRV YTSDFEPVTN PKFDDTFEKN LSSVRQVKEI 480

IHQFILEQQK GNRVPLCINP QSAAFKSFIS STVAQPSEMP PSPLVWE 527

Nucleotide Sequence
(FASTA)

ATGTCTCTTT GTGGCACACG AGCCAACGCA AAAATGATGG CGGCTTACAA TGGCGGTACA 60

TCTGCAGCAG CAGCAGGTCA CCACCACCAC CATCACCACC ACCTTCCACA CCTTCCTCCT 120

CCTCACCTTC ACCACCACCA CCACCCTCAA CACCACCTTC ATCCGGGGTC GGCTGCTGCT 180

GTACACCCTG TACAGCAGCA TACGTCTTCG GCAGCTGCGG CAGCCGCAGC GGCAGCTGCG 240

GCCGCAGCCA TGTTAAACCC TGGGCAACAA CAGCCATATT TCCCATCACC GGCACCTGGT 300

CAGGCTCCTG GGCCAGCTGC AGCAGCCCCA GCTCAGGTAC AGGCTGCTGC AGCTGCTACA 360

GTTAAGGCGC ACCATCATCA GCACTCGCAT CATCCGCAAC AGCAGCTGGA CATTGAGCCG 420

GATAGACCTA TTGGATATGG AGCCTTTGGT GTTGTCTGGT CAGTAACAGA TCCAAGAGAT 480

GGAAAGAGAG TAGCACTCAA AAAGATGCCC AACGTCTTCC AGAATCTGGT CTCTTGCAAA 540

AGAGTCTTCC GGGAATTGAA GATGTTGTGT TTTTTTAAAC ATGATAATGT ACTCTCTGCC 600

CTTGACATAC TCCAGCCTCC ACACATTGAC TATTTTGAAG AAATATATGT TGTCACAGAA 660

TTGATGCAGA GTGATCTACA TAAAATTATC GTCTCTCCTC AGCCACTCAG CTCAGATCAT 720

GTCAAAGTTT TTCTTTATCA GATTTTGCGA GGTTTGAAAT ATCTCCATTC AGCTGGCATT 780

TTACATCGCG ACATTAAGCC GGGGAATCTC CTTGTGAACA GCAACTGTGT TCTAAAGATT 840

TGTGATTTTG GATTGGCCAG AGTGGAAGAA TTGGATGAAT CCCGTCACAT GACTCAGGAA 900

GTTGTTACTC AGTATTACCG GGCTCCGGAG ATCCTCATGG GCAGCCGCCA TTACAGCAAT 960

GCTATTGACA TCTGGTCTGT GGGGTGCATC TTTGCAGAGC TGCTGGGCCG AAGGATACTG 1020

TTTCAGGCGC AGAGTCCCAT TCAGCAGTTG GATTTGATCA CAGATCTGTT GGGCACGCCA 1080

TCACTGGAAG CGATGAGGAC AGCTTGTGAA GGTGCTAAGG CACACATACT CAGGGGTCCT 1140

CACAAACAGC CATCTCTCCC TGTACTCTAC ACCCTTTCCA GCCAGGCCAC ACATGAAGCC 1200

GTTCACCTGC TTTGCAGAAT GTTGGTCTTT GATCCATCAA AAAGAATATC CGCTAAGGAT 1260

GCCTTAGCCC ACCCCTACCT AGATGAAGGG CGGCTGAGAT ACCATACATG TATGTGTAAG 1320

TGCTGCTTTT CCACCTCGAC GGGAAGAGTC TACACCAGTG ACTTTGAGCC TGTCACCAAC 1380

CCCAAATTTG ATGACACCTT TGAGAAGAAC CTCAGCTCTG TCCGACAAGT TAAAGAAATT 1440

ATCCACCAGT TCATTTTGGA ACAGCAGAAA GGAAACAGAG TACCTCTCTG CATTAACCCG 1500

CAGTCTGCTG CCTTTAAGAG CTTTATCAGT TCCACCGTCG CTCAGCCGTC TGAGATGCCA 1560

CCGTCTCCTC TGGTGTGGGA GTGA 1584

Domain Profile

S: 4     lkplgeGaygvvvsavdkrteervaikklsrpfqketsakrtlRElkllkelkheNiikl  63

          +p+g Ga+gvv+s++d r+++rva+kk+ ++fq+ +s+kr++RElk+l  +kh+N+++

Q: 141   DRPIGYGAFGVVWSVTDPRDGKRVALKKMPNVFQNLVSCKRVFRELKMLCFFKHDNVLSA  200

         689*********************************************************

S: 64    ldvftpeeeleelkdvYlvtelmetdLkkviksq.klsdehiklllyqilrglkylHsan  122

         ld+++p + ++ ++++Y+vtelm++dL+k+i s   ls++h+k++lyqilrglkylHsa+

Q: 201   LDILQPPH-IDYFEEIYVVTELMQSDLHKIIVSPqPLSSDHVKVFLYQILRGLKYLHSAG  259

         *******9.**********************99879************************

S: 123   viHrDlKPsNllvnedcelkildFGlarsadkekekklteyvatrwYraPeillslkeyt  182

         ++HrD+KP+Nllvn++c lki+dFGlar+++ ++++++t++v+t++YraPeil+ +++y+

Q: 260   ILHRDIKPGNLLVNSNCVLKICDFGLARVEELDESRHMTQEVVTQYYRAPEILMGSRHYS  319

         *********************************999************************

S: 183   kavDiWsvGCIlaElltgkplfpgkdeidqlekilevlgtpseeflkkieseearnyiks  242

         +a+DiWsvGCI+aEll +++lf++++ i+ql++i+++lgtps e +++ ++  a+++i +

Q: 320   NAIDIWSVGCIFAELLGRRILFQAQSPIQQLDLITDLLGTPSLEAMRTACEG-AKAHILR  378

         ************************************************9996.7777777

S: 243   lpkkkkk..dfeelfpkaseealdLleklLvldpdkRisveeaLehpYl  289

          p+k+     + +l ++a++ea++Ll ++Lv+dp+kRis+++aL+hpYl

Q: 379   GPHKQPSlpVLYTLSSQATHEAVHLLCRMLVFDPSKRISAKDALAHPYL  427

         77666644457788888*******************************7

Domain Sequence
(FASTA)

DRPIGYGAFG VVWSVTDPRD GKRVALKKMP NVFQNLVSCK RVFRELKMLC FFKHDNVLSA 60

LDILQPPHID YFEEIYVVTE LMQSDLHKII VSPQPLSSDH VKVFLYQILR GLKYLHSAGI 120

LHRDIKPGNL LVNSNCVLKI CDFGLARVEE LDESRHMTQE VVTQYYRAPE ILMGSRHYSN 180

AIDIWSVGCI FAELLGRRIL FQAQSPIQQL DLITDLLGTP SLEAMRTACE GAKAHILRGP 240

HKQPSLPVLY TLSSQATHEA VHLLCRMLVF DPSKRISAKD ALAHPYL 287

Keyword

ATP-binding; Complete proteome; Cytoplasm; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transcription; Transcription regulation; Transferase; Wnt signaling pathway.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Caenorhabditis elegans"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gadus morhua"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Ochotona princeps"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Pteropus vampyrus"; ?>Sarcophilus harrisii"; ?>Sorex araneus"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tarsius syrichta"; ?>Tetraodon nigroviridis"; ?>Tursiops truncatus"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005737	; C:cytoplasm
GO:0005634	; C:nucleus
GO:0005524	; F:ATP binding
GO:0000287	; F:magnesium ion binding
GO:0004707	; F:MAP kinase activity
GO:0030178	; P:negative regulation of Wnt receptor signaling pathway
GO:0018107	; P:peptidyl-threonine phosphorylation
GO:0046777	; P:protein autophosphorylation
GO:0006355	; P:regulation of transcription, DNA-dependent
GO:0033136	; P:serine phosphorylation of STAT3 protein
GO:0006351	; P:transcription, DNA-dependent
GO:0007179	; P:transforming growth factor beta receptor signaling pathway
GO:0016055	; P:Wnt receptor signaling pathway

KEGG

rno:497961

;

InterPros

IPR011009	; Kinase-like_dom.
IPR003527	; MAP_kinase_CS.
IPR000719	; Prot_kinase_cat_dom.
IPR017441	; Protein_kinase_ATP_BS.
IPR002290	; Ser/Thr_dual-sp_kinase_dom.
IPR008271	; Ser/Thr_kinase_AS.

Pfam

PF00069

; Pkinase; 1.

SMARTs

SM00220

; S_TKc; 1.

Prosites

PS01351	; MAPK; 1.
PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00108	; PROTEIN_KINASE_ST; 1.

Prints

Created Date

20-Feb-2013