NLK2_XENLA
ID NLK2_XENLA Reviewed; 447 AA.
AC Q8QGV6; Q6DD67;
DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Serine/threonine-protein kinase NLK2;
DE EC=2.7.11.24;
DE AltName: Full=Nemo-like kinase 2;
DE Short=Nlk.2;
DE Short=xNLK {ECO:0000303|PubMed:12047350, ECO:0000303|PubMed:12875653, ECO:0000303|PubMed:17785444};
GN Name=nlk.2;
GN Synonyms=nlk {ECO:0000303|PubMed:12047350, ECO:0000303|PubMed:12875653,
GN ECO:0000303|PubMed:15004007, ECO:0000303|PubMed:17785444};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000305, ECO:0000312|EMBL:BAB85870.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH SOX11, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Oocyte {ECO:0000269|PubMed:12047350};
RX PubMed=12047350; DOI=10.1046/j.1365-2443.2002.00536.x;
RA Hyodo-Miura J., Urushiyama S., Nagai S., Nishita M., Ueno N., Shibuya H.;
RT "Involvement of NLK and Sox11 in neural induction in Xenopus development.";
RL Genes Cells 7:487-496(2002).
RN [2] {ECO:0000312|EMBL:AAH77759.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo {ECO:0000312|EMBL:AAH77759.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP INTERACTION WITH HMGXB4.
RX PubMed=12875653; DOI=10.1046/j.1365-2443.2003.00666.x;
RA Yamada M., Ohkawara B., Ichimura N., Hyodo-Miura J., Urushiyama S.,
RA Shirakabe K., Shibuya H.;
RT "Negative regulation of Wnt signalling by HMG2L1, a novel NLK-binding
RT protein.";
RL Genes Cells 8:677-684(2003).
RN [4] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH STAT3.1.
RX PubMed=15004007; DOI=10.1101/gad.1166904;
RA Ohkawara B., Shirakabe K., Hyodo-Miura J., Matsuo R., Ueno N.,
RA Matsumoto K., Shibuya H.;
RT "Role of the TAK1-NLK-STAT3 pathway in TGF-beta-mediated mesoderm
RT induction.";
RL Genes Dev. 18:381-386(2004).
RN [5] {ECO:0000305}
RP FUNCTION, INTERACTION WITH RNF138, AND MUTAGENESIS OF LYS-89.
RX PubMed=16714285; DOI=10.1074/jbc.m602089200;
RA Yamada M., Ohnishi J., Ohkawara B., Iemura S., Satoh K., Hyodo-Miura J.,
RA Kawachi K., Natsume T., Shibuya H.;
RT "NARF, an nemo-like kinase (NLK)-associated ring finger protein regulates
RT the ubiquitylation and degradation of T cell factor/lymphoid enhancer
RT factor (TCF/LEF).";
RL J. Biol. Chem. 281:20749-20760(2006).
RN [6] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH MEF2A, AND TISSUE
RP SPECIFICITY.
RX PubMed=17785444; DOI=10.1128/mcb.01481-07;
RA Satoh K., Ohnishi J., Sato A., Takeyama M., Iemura S., Natsume T.,
RA Shibuya H.;
RT "Nemo-like kinase-myocyte enhancer factor 2A signaling regulates anterior
RT formation in Xenopus development.";
RL Mol. Cell. Biol. 27:7623-7630(2007).
CC -!- FUNCTION: Negatively regulates Wnt/beta-catenin-signaling during
CC development. Plays a role together with sox11 in neural induction
CC during early embryogenesis. Involved in TGFbeta-mediated mesoderm
CC induction in early embryos, acting downstream of map3k7/tak1 to
CC phosphorylate stat3.1. Augments the rnf138/narf-directed ubiquitination
CC and degradation of tcf/lef by enhancing the association of rnf138/narf
CC and tcf/lef. Phosphorylates mef2a to play a role in anterior neural
CC development, including eye formation. {ECO:0000269|PubMed:12047350,
CC ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:16714285,
CC ECO:0000269|PubMed:17785444}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.24;
CC Evidence={ECO:0000269|PubMed:17785444};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.24; Evidence={ECO:0000269|PubMed:17785444};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O54949};
CC -!- ACTIVITY REGULATION: Activated by tyrosine and threonine
CC phosphorylation. {ECO:0000250|UniProtKB:Q63844}.
CC -!- SUBUNIT: Interacts with sox11, hmgxb4/hmg2l1, rnf138/narf, stat3.1 and
CC mef2a. {ECO:0000269|PubMed:12047350, ECO:0000269|PubMed:12875653,
CC ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:16714285,
CC ECO:0000269|PubMed:17785444}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O54949}. Cytoplasm
CC {ECO:0000250|UniProtKB:O54949}.
CC -!- TISSUE SPECIFICITY: Expressed widely in the ectoderm during early
CC gastrula stage when neural induction is taking place. Expressed in the
CC head region of neurula stage embryos. At the end of neurulation,
CC expression becomes localized to the nervous system, and is restricted
CC to the central nervous system, eye and head neural crest cells by the
CC early tadpole stages. {ECO:0000269|PubMed:12047350,
CC ECO:0000269|PubMed:17785444}.
CC -!- DEVELOPMENTAL STAGE: Expressed maternally and throughout embryonic
CC development through to the tadpole stage.
CC {ECO:0000269|PubMed:12047350}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MAP kinase subfamily. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH77759.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB071285; BAB85870.1; -; mRNA.
DR EMBL; BC077759; AAH77759.1; ALT_FRAME; mRNA.
DR RefSeq; NP_001082214.1; NM_001088745.1.
DR AlphaFoldDB; Q8QGV6; -.
DR SMR; Q8QGV6; -.
DR BioGRID; 99628; 1.
DR DNASU; 398295; -.
DR GeneID; 398295; -.
DR KEGG; xla:398295; -.
DR CTD; 398295; -.
DR Xenbase; XB-GENE-1218927; nlk.2.S.
DR OrthoDB; 741207at2759; -.
DR Proteomes; UP000186698; Chromosome 9_10S.
DR Bgee; 398295; Expressed in blastula and 19 other tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0004707; F:MAP kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:UniProtKB.
DR GO; GO:0001707; P:mesoderm formation; IMP:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IGI:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IPI:UniProtKB.
DR GO; GO:0042501; P:serine phosphorylation of STAT protein; IMP:UniProtKB.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR003527; MAP_kinase_CS.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS01351; MAPK; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Developmental protein; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation pathway;
KW Wnt signaling pathway.
FT CHAIN 1..447
FT /note="Serine/threonine-protein kinase NLK2"
FT /id="PRO_0000370235"
FT DOMAIN 60..349
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 186
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P53779,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 66..74
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P53779,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 89
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MUTAGEN 89
FT /note="K->R: Kinase inactive. Does not enhance rnf138/narf-
FT mediated ubiquitination or association of rnf138/narf and
FT tcf/lef."
FT /evidence="ECO:0000269|PubMed:16714285"
FT CONFLICT 20
FT /note="S -> G (in Ref. 2; AAH77759)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 447 AA; 50138 MW; F05DE96445D0FAE9 CRC64;
MAFPGSGRSI PGQLCAGVFS GLIQPPLGQK FYCPNGGGAV PSPLPQALSA PQCNGEGRDP
EPDRPIGYGA FGVVWSVTDP RDGKRVALKK MPNVFQNLVS CKRVFRELKM LCFFKHDNVL
SALDILQPPQ IDCFEEIYVI TELMQTDLHK VIVSPQPLSS DHIKVFLYQI LRGLKYLHSA
GILHRDIKPG NLLVNSNCVL KICDFGLARV EELDESQHMT QEVVTQYYRA PEILMGSRHY
RSAIDIWSVG CIFAELLGRR ILFQAQSPIQ QLDLITDLLG TPPLTAMRSA CEGARAHILR
GPHKPPSLSV LYMLSGEATH EAVHLLCRML LFDPLKRISA KDALAHPYLE EGRLRYHTCM
CHCCYSVSSG RVYTADFEPT ATNRFDDSYE KSLTSVWQVK ELVHRFITDQ HQGKRPPLCI
NPHSAAFKTF IRSTAWHSSK VSKKEER
