Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

E1BMN8

- NLK_BOVIN

UniProt

E1BMN8 - NLK_BOVIN

Protein

Serine/threonine-protein kinase NLK

Gene

NLK

Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 4 out of 5- Protein inferred from homologyi
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 23 (01 Oct 2014)
      Sequence version 2 (19 Oct 2011)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    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 By similarity.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Magnesium.By similarity

    Enzyme regulationi

    Activated by the non-canonical Wnt signaling pathway, in which WNT5A leads to activation of MAP3K7/TAK1 and HIPK2, which subsequently phosphorylates and activates this protein. Activated by dimerization and subsequent intermolecular autophosphorylation on Thr-305. Other cytokines such as IL6 may also activate this regulatory circuit By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei174 – 1741ATPPROSITE-ProRule annotation
    Active sitei271 – 2711Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi151 – 1599ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. MAP kinase activity Source: UniProtKB-EC
    3. metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    1. regulation of transcription, DNA-templated Source: UniProtKB-KW
    2. transcription, DNA-templated Source: UniProtKB-KW
    3. Wnt signaling pathway Source: UniProtKB-KW

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Transcription, Transcription regulation, Wnt signaling pathway

    Keywords - Ligandi

    ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serine/threonine-protein kinase NLK (EC:2.7.11.24)
    Alternative name(s):
    Nemo-like kinase
    Gene namesi
    Name:NLK
    OrganismiBos taurus (Bovine)
    Taxonomic identifieri9913 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
    ProteomesiUP000009136: Unplaced

    Subcellular locationi

    Nucleus By similarity. Cytoplasm By similarity
    Note: Predominantly nuclear. A smaller fraction is cytoplasmic By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 534534Serine/threonine-protein kinase NLKPRO_0000413529Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei305 – 3051Phosphothreonine; by autocatalysisBy similarity
    Modified residuei529 – 5291PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylated on Thr-305. Intermolecular autophosphorylation on Thr-305 activates the enzyme By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Interactioni

    Subunit structurei

    Homodimer. Homodimerization is required for intermolecular autophosphorylation, kinase activation and nuclear localization. Interacts with the upstream activating kinases HIPK2 and MAP3K7/TAK1. Interaction with MAP3K7/TAK1 seems to be indirect, and may be mediated by other proteins such as STAT3, TAB1 and TAB2. Interacts with and phosphorylates a number of transcription factors including FOXO1, FOXO3, FOXO4, LEF1, MYB, MYBL1, MYBL2, NOTCH1 and TCF7L2/TCF4. Interacts with DAPK3/ZIPK, and this interaction may disrupt interaction with transcription factors such as TCF7L2/TCF. Forms a complex with CHD7, PPARG and SETDB1 in response to WNT5A signaling. May interact with components of cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes. Interacts with RNF138/NARF. Interacts with MEF2A By similarity.By similarity

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini145 – 434290Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni8 – 311304Required for interaction with TAB2By similarityAdd
    BLAST
    Regioni8 – 132125Sufficient for interaction with DAPK3By similarityAdd
    BLAST
    Regioni131 – 423293Sufficient for interaction with DAPK3By similarityAdd
    BLAST
    Regioni435 – 534100Required for homodimerization and kinase activation and localization to the nucleusBy similarityAdd
    BLAST
    Regioni441 – 53494Required for interaction with TAB2By similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi305 – 3073TQE

    Domaini

    Contains a TQE activation loop motif in which autophosphorylation of the threonine residue (Thr-305) is sufficient for kinase activation. This mode of activation contrasts with that of classical MAP kinases, which contain a TXY activation loop motif in which phosphorylation of both the threonine and tyrosine residues is required for kinase activation (By similarity).By similarity

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR003527. MAP_kinase_CS.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS01351. MAPK. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    E1BMN8-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPNVFQNLVS CKRVFRELKM AAYNGGTSAA AAGHHHHHHH HLPHLPPPHL    50
    HHHHHPQHHL HPGSAAAVHP VQQHTSSAAA AAAAAAAAAA MLNPGQQQPY 100
    FPSPAPGQAP GPAAAAPAQV QAAAAATVKA HHHQHSHHPQ QQLDIEPDRP 150
    IGYGAFGVVW SVTDPRDGKR VALKKMPNVF QNLVSCKRVF RELKMLCFFK 200
    HDNVLSALDI LQPPHIDYFE EIYVVTELMQ SDLHKIIVSP QPLSSDHVKV 250
    FLYQILRGLK YLHSAGILHR DIKPGNLLVN SNCVLKICDF GLARVEELDE 300
    SRHMTQEVVT QYYRAPEILM GSRHYSNAID IWSVGCIFAE LLGRRILFQA 350
    QSPIQQLDLI TDLLGTPSLE AMRTACEGAK AHILRGPHKQ PSLPVLYTLS 400
    SQATHEAVHL LCRMLVFDPS KRISAKDALA HPYLDEGRLR YHTCMCKCCF 450
    STSTGRVYTS DFEPVTNPKF DDTFEKNLSS VRQVKEIIHQ FILEQQKGNR 500
    VPLCINPQSA AFKSFISSTV AQPSEMPPSP LVWE 534
    Length:534
    Mass (Da):59,339
    Last modified:October 19, 2011 - v2
    Checksum:i02F602E8141D57BF
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AAFC03038599 Genomic DNA. No translation available.
    AAFC03038600 Genomic DNA. No translation available.
    AAFC03038601 Genomic DNA. No translation available.
    AAFC03117551 Genomic DNA. No translation available.
    AAFC03125057 Genomic DNA. No translation available.
    UniGeneiBt.43996.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AAFC03038599 Genomic DNA. No translation available.
    AAFC03038600 Genomic DNA. No translation available.
    AAFC03038601 Genomic DNA. No translation available.
    AAFC03117551 Genomic DNA. No translation available.
    AAFC03125057 Genomic DNA. No translation available.
    UniGenei Bt.43996.

    3D structure databases

    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi E1BMN8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR003527. MAP_kinase_CS.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS01351. MAPK. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The genome sequence of taurine cattle: a window to ruminant biology and evolution."
      The bovine genome sequencing and analysis consortium
      Science 324:522-528(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: Hereford.

    Entry informationi

    Entry nameiNLK_BOVIN
    AccessioniPrimary (citable) accession number: E1BMN8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 19, 2011
    Last sequence update: October 19, 2011
    Last modified: October 1, 2014
    This is version 23 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3