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Q8QGV6

- NLK2_XENLA

UniProt

Q8QGV6 - NLK2_XENLA

Protein

Serine/threonine-protein kinase NLK2

Gene

nlk.2

Organism
Xenopus laevis (African clawed frog)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 77 (01 Oct 2014)
      Sequence version 1 (01 Jun 2002)
      Previous versions | rss
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    Functioni

    Negatively regulates Wnt/beta-catenin-signaling during development. Plays a role together with sox11 in neural induction during early embryogenesis. Involved in TGFbeta-mediated mesoderm induction in early embryos, acting downstream of map3k7/tak1 to phosphorylate stat3.1. Augments the rnf138/narf-directed ubiquitination and degradation of tcf/lef by enhancing the association of rnf138/narf and tcf/lef. Phosphorylates mef2a to play a role in anterior neural development, including eye formation.4 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.1 Publication

    Cofactori

    Magnesium.By similarity

    Enzyme regulationi

    Activated by tyrosine and threonine phosphorylation.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei89 – 891ATPCurated
    Active sitei186 – 1861Proton acceptorBy similarityPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi66 – 749ATPBy similarityPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB
    2. magnesium ion binding Source: UniProtKB
    3. MAP kinase activity Source: UniProtKB-EC
    4. protein binding Source: UniProtKB
    5. protein serine/threonine kinase activity Source: UniProtKB
    6. transcription factor binding Source: UniProtKB
    7. ubiquitin protein ligase binding Source: UniProtKB

    GO - Biological processi

    1. anterior/posterior pattern specification Source: UniProtKB
    2. mesoderm formation Source: UniProtKB
    3. nervous system development Source: UniProtKB
    4. peptidyl-serine phosphorylation Source: UniProtKB
    5. peptidyl-threonine phosphorylation Source: UniProtKB
    6. positive regulation of protein ubiquitination Source: UniProtKB
    7. regulation of transcription, DNA-templated Source: UniProtKB-KW
    8. serine phosphorylation of STAT3 protein Source: UniProtKB
    9. transcription, DNA-templated Source: UniProtKB-KW
    10. transforming growth factor beta receptor signaling pathway Source: UniProtKB
    11. Wnt signaling pathway Source: UniProtKB-KW

    Keywords - Molecular functioni

    Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Transcription, Transcription regulation, Ubl conjugation pathway, Wnt signaling pathway

    Keywords - Ligandi

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

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serine/threonine-protein kinase NLK2 (EC:2.7.11.24)
    Alternative name(s):
    Nemo-like kinase 2
    Short name:
    Nlk.2
    Short name:
    xNLK3 Publications
    Gene namesi
    Name:nlk.2
    Synonyms:nlk4 Publications
    OrganismiXenopus laevis (African clawed frog)
    Taxonomic identifieri8355 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiAmphibiaBatrachiaAnuraPipoideaPipidaeXenopodinaeXenopusXenopus

    Organism-specific databases

    XenbaseiXB-GENE-1218927. nlk.2.

    Subcellular locationi

    Nucleus By similarity. Cytoplasm By similarity

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi89 – 891K → R: Kinase inactive. Does not enhance rnf138/narf-mediated ubiquitination or association of rnf138/narf and tcf/lef. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 447447Serine/threonine-protein kinase NLK2PRO_0000370235Add
    BLAST

    Keywords - PTMi

    Phosphoprotein

    Expressioni

    Tissue specificityi

    Expressed widely in the ectoderm during early gastrula stage when neural induction is taking place. Expressed in the head region of neurula stage embryos. At the end of neurulation, expression becomes localized to the nervous system, and is restricted to the central nervous system, eye and head neural crest cells by the early tadpole stages.2 Publications

    Developmental stagei

    Expressed maternally and throughout embryonic development through to the tadpole stage.1 Publication

    Interactioni

    Subunit structurei

    Interacts with sox11, hmgxb4/hmg2l1, rnf138/narf, stat3.1 and mef2a.5 Publications

    Protein-protein interaction databases

    BioGridi99628. 1 interaction.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8QGV6.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini60 – 349290Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    KOiK04468.

    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.

    Q8QGV6-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAFPGSGRSI PGQLCAGVFS GLIQPPLGQK FYCPNGGGAV PSPLPQALSA    50
    PQCNGEGRDP EPDRPIGYGA FGVVWSVTDP RDGKRVALKK MPNVFQNLVS 100
    CKRVFRELKM LCFFKHDNVL SALDILQPPQ IDCFEEIYVI TELMQTDLHK 150
    VIVSPQPLSS DHIKVFLYQI LRGLKYLHSA GILHRDIKPG NLLVNSNCVL 200
    KICDFGLARV EELDESQHMT QEVVTQYYRA PEILMGSRHY RSAIDIWSVG 250
    CIFAELLGRR ILFQAQSPIQ QLDLITDLLG TPPLTAMRSA CEGARAHILR 300
    GPHKPPSLSV LYMLSGEATH EAVHLLCRML LFDPLKRISA KDALAHPYLE 350
    EGRLRYHTCM CHCCYSVSSG RVYTADFEPT ATNRFDDSYE KSLTSVWQVK 400
    ELVHRFITDQ HQGKRPPLCI NPHSAAFKTF IRSTAWHSSK VSKKEER 447
    Length:447
    Mass (Da):50,138
    Last modified:June 1, 2002 - v1
    Checksum:iF05DE96445D0FAE9
    GO

    Sequence cautioni

    The sequence AAH77759.1 differs from that shown. Reason: Frameshift at position 128.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti20 – 201S → G in AAH77759. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB071285 mRNA. Translation: BAB85870.1.
    BC077759 mRNA. Translation: AAH77759.1. Frameshift.
    RefSeqiNP_001082214.1. NM_001088745.1.
    UniGeneiXl.7148.

    Genome annotation databases

    GeneIDi398295.
    KEGGixla:398295.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB071285 mRNA. Translation: BAB85870.1 .
    BC077759 mRNA. Translation: AAH77759.1 . Frameshift.
    RefSeqi NP_001082214.1. NM_001088745.1.
    UniGenei Xl.7148.

    3D structure databases

    ProteinModelPortali Q8QGV6.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 99628. 1 interaction.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 398295.
    KEGGi xla:398295.

    Organism-specific databases

    CTDi 398295.
    Xenbasei XB-GENE-1218927. nlk.2.

    Phylogenomic databases

    KOi K04468.

    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. "Involvement of NLK and Sox11 in neural induction in Xenopus development."
      Hyodo-Miura J., Urushiyama S., Nagai S., Nishita M., Ueno N., Shibuya H.
      Genes Cells 7:487-496(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH SOX11, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
      Tissue: Oocyte1 Publication.
    2. NIH - Xenopus Gene Collection (XGC) project
      Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: EmbryoImported.
    3. "Negative regulation of Wnt signalling by HMG2L1, a novel NLK-binding protein."
      Yamada M., Ohkawara B., Ichimura N., Hyodo-Miura J., Urushiyama S., Shirakabe K., Shibuya H.
      Genes Cells 8:677-684(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HMGXB4.
    4. "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] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH STAT3.1.
    5. "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] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH RNF138, MUTAGENESIS OF LYS-89.
    6. "Nemo-like kinase-myocyte enhancer factor 2A signaling regulates anterior formation in Xenopus development."
      Satoh K., Ohnishi J., Sato A., Takeyama M., Iemura S., Natsume T., Shibuya H.
      Mol. Cell. Biol. 27:7623-7630(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH MEF2A, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiNLK2_XENLA
    AccessioniPrimary (citable) accession number: Q8QGV6
    Secondary accession number(s): Q6DD67
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 14, 2009
    Last sequence update: June 1, 2002
    Last modified: October 1, 2014
    This is version 77 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3