CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-022820
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Serine/threonine-protein kinase NLK 
Protein Synonyms/Alias
 Nemo-like kinase; Protein LAK1 
Gene Name
 NLK 
Gene Synonyms/Alias
 LAK1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
373RTACEGAKAHILRGPubiquitination[1]
419PSKRISAKDALAHPYubiquitination[1]
462FEPVTNPKFDDTFEKubiquitination[1]
469KFDDTFEKNLSSVRQubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 Serine/threonine-protein kinase that regulates a number of 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. 
Sequence Annotation
 DOMAIN 138 427 Protein kinase.
 NP_BIND 144 152 ATP (By similarity).
 REGION 1 304 Required for interaction with TAB2 (By
 REGION 1 125 Sufficient for interaction with DAPK3.
 REGION 124 416 Sufficient for interaction with DAPK3.
 REGION 428 527 Required for homodimerization and kinase
 REGION 434 527 Required for interaction with TAB2 (By
 MOTIF 298 300 TQE.
 ACT_SITE 264 264 Proton acceptor (By similarity).
 BINDING 167 167 ATP (Probable).
 MOD_RES 298 298 Phosphothreonine; by autocatalysis.
 MOD_RES 522 522 Phosphoserine.  
Keyword
 ATP-binding; Complete proteome; Cytoplasm; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transcription; Transcription regulation; Transferase; Wnt signaling pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 527 AA 
Protein Sequence
MSLCGARANA 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 
Gene Ontology
 GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; ISS:UniProtKB.
 GO:0005524; F:ATP binding; ISS:UniProtKB.
 GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
 GO:0004707; F:MAP kinase activity; ISS:UniProtKB.
 GO:0042169; F:SH2 domain binding; ISS:UniProtKB.
 GO:0030178; P:negative regulation of Wnt receptor signaling pathway; ISS:UniProtKB.
 GO:0018107; P:peptidyl-threonine phosphorylation; ISS:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IEA:Compara.
 GO:0006355; P:regulation of transcription, DNA-dependent; ISS:UniProtKB.
 GO:0033136; P:serine phosphorylation of STAT3 protein; ISS:UniProtKB.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:UniProtKB.
 GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW. 
Interpro
 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 
SMART
 SM00220; S_TKc 
PROSITE
 PS01351; MAPK
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS