MELK_XENLA
ID MELK_XENLA Reviewed; 651 AA.
AC Q91821; Q498M1;
DT 19-OCT-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Maternal embryonic leucine zipper kinase;
DE Short=MELK;
DE EC=2.7.11.1;
DE AltName: Full=Protein kinase Eg3;
DE Short=pEg3 kinase;
GN Name=melk;
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]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Egg;
RA Roghi C., Le Guellec R., Paris J., Couturier A., Philippe M.;
RT "Eg3, selected by differential screening encodes a new Xenopus protein
RT kinase.";
RL Submitted (OCT-1992) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo, and Oocyte;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PHOSPHORYLATION.
RX PubMed=11784115; DOI=10.1006/dbio.2001.0525;
RA Blot J., Chartrain I., Roghi C., Philippe M., Tassan J.P.;
RT "Cell cycle regulation of pEg3, a new Xenopus protein kinase of the
RT KIN1/PAR-1/MARK family.";
RL Dev. Biol. 241:327-338(2002).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=16159311; DOI=10.1042/bc20050041;
RA Chartrain I., Couturier A., Tassan J.P.;
RT "Cell-cycle-dependent cortical localization of pEg3 protein kinase in
RT Xenopus and human cells.";
RL Biol. Cell 98:253-263(2006).
RN [5]
RP PHOSPHORYLATION AT THR-414; THR-449; THR-451; THR-481; THR-483; SER-498;
RP SER-505 AND SER-517.
RX PubMed=16628004; DOI=10.4161/cc.5.8.2683;
RA Badouel C., Korner R., Frank-Vaillant M., Couturier A., Nigg E.A.,
RA Tassan J.P.;
RT "M-phase MELK activity is regulated by MPF and MAPK.";
RL Cell Cycle 5:883-889(2006).
RN [6]
RP PHOSPHORYLATION, AND PROTEIN DEGRADATION.
RX PubMed=20420823; DOI=10.1016/j.yexcr.2010.04.019;
RA Badouel C., Chartrain I., Blot J., Tassan J.P.;
RT "Maternal embryonic leucine zipper kinase is stabilized in mitosis by
RT phosphorylation and is partially degraded upon mitotic exit.";
RL Exp. Cell Res. 316:2166-2173(2010).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21378312; DOI=10.1242/jcs.069567;
RA Le Page Y., Chartrain I., Badouel C., Tassan J.P.;
RT "A functional analysis of MELK in cell division reveals a transition in the
RT mode of cytokinesis during Xenopus development.";
RL J. Cell Sci. 124:958-968(2011).
CC -!- FUNCTION: Serine/threonine-protein kinase involved in various processes
CC such as cell cycle regulation, self-renewal of stem cells, apoptosis
CC and splicing regulation. Also plays a role in primitive hematopoiesis,
CC possibly by affecting the expression of genes critical for
CC hematopoiesis (By similarity). Plays a role in cytokinesis during early
CC development. {ECO:0000250, ECO:0000269|PubMed:21378312}.
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=2.7.11.1;
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=2.7.11.1;
CC -!- ACTIVITY REGULATION: Activated by autophosphorylation of the T-loop at
CC Thr-169 and Ser-173: in contrast to other members of the SNF1
CC subfamily, phosphorylation at Thr-169 is not mediated by STK11/LKB1 but
CC via autophosphorylation instead. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16159311,
CC ECO:0000269|PubMed:21378312}; Peripheral membrane protein
CC {ECO:0000269|PubMed:16159311, ECO:0000269|PubMed:21378312}.
CC -!- DOMAIN: The KA1 domain mediates binding to phospholipids and targeting
CC to membranes. {ECO:0000250}.
CC -!- PTM: Autophosphorylated: autophosphorylation of the T-loop at Thr-169
CC and Ser-173 is required for activation (By similarity). Phosphorylated
CC by the maturation promoting factor (MPF), composed of cdk1 and a
CC cyclin-B. Also phosphorylated by some MAPK. Phosphorylated during
CC oocyte maturation. Dephosphorylation destabilizes the protein. There is
CC some ambiguity for some phosphosites: Thr-481/Thr-483 and Ser-505/Ser-
CC 517. {ECO:0000250, ECO:0000269|PubMed:11784115,
CC ECO:0000269|PubMed:16628004, ECO:0000269|PubMed:20420823}.
CC -!- PTM: Degraded when cells exit mitosis. {ECO:0000269|PubMed:20420823}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. SNF1 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI00162.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; Z17205; CAA78913.2; -; mRNA.
DR EMBL; BC106635; AAI06636.1; -; mRNA.
DR EMBL; BC100161; AAI00162.1; ALT_SEQ; mRNA.
DR PIR; S52244; S52244.
DR RefSeq; NP_001081569.1; NM_001088100.2.
DR RefSeq; XP_018087768.1; XM_018232279.1.
DR AlphaFoldDB; Q91821; -.
DR SMR; Q91821; -.
DR BioGRID; 99263; 2.
DR IntAct; Q91821; 1.
DR iPTMnet; Q91821; -.
DR MaxQB; Q91821; -.
DR DNASU; 397927; -.
DR GeneID; 397927; -.
DR KEGG; xla:397927; -.
DR CTD; 397927; -.
DR Xenbase; XB-GENE-987660; melk.L.
DR OMA; LRAHYNV; -.
DR OrthoDB; 1127668at2759; -.
DR Proteomes; UP000186698; Chromosome 1L.
DR Bgee; 397927; Expressed in egg cell and 16 other tissues.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0008283; P:cell population proliferation; ISS:UniProtKB.
DR GO; GO:0030097; P:hemopoiesis; ISS:UniProtKB.
DR GO; GO:0061351; P:neural precursor cell proliferation; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR CDD; cd14078; STKc_MELK; 1.
DR InterPro; IPR028375; KA1/Ssp2_C.
DR InterPro; IPR001772; KA1_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR034673; MELK.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF02149; KA1; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF103243; SSF103243; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50032; KA1; 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 Apoptosis; ATP-binding; Cell cycle; Cell membrane; Kinase; Lipid-binding;
KW Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..651
FT /note="Maternal embryonic leucine zipper kinase"
FT /id="PRO_0000413430"
FT DOMAIN 13..265
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 602..651
FT /note="KA1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00565"
FT REGION 284..323
FT /note="UBA-like"
FT /evidence="ECO:0000250"
FT REGION 328..651
FT /note="Autoinhibitory region"
FT /evidence="ECO:0000250"
FT REGION 410..490
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 420..434
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 134
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 19..27
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 42
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 169
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 173
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 414
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:16628004"
FT MOD_RES 449
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:16628004"
FT MOD_RES 451
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:16628004"
FT MOD_RES 481
FT /note="Phosphothreonine"
FT /evidence="ECO:0000305|PubMed:16628004"
FT MOD_RES 483
FT /note="Phosphothreonine"
FT /evidence="ECO:0000305|PubMed:16628004"
FT MOD_RES 498
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16628004"
FT MOD_RES 505
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:16628004"
FT MOD_RES 517
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:16628004"
SQ SEQUENCE 651 AA; 74307 MW; A21B397D0F1A9C9A CRC64;
MAVDDYEELL KYYELHETVG TGGFAKVKLA SHLITGEKVA IKIMDKESLG DDLPRVKTEI
DAMKNLSHQH VCRLYHVIET PKKIFMVLEY CPGGELFDYI IAKDRLTEEE ARVFFRQIVS
AVAYIHSQGY AHRDLKPENL LIDEDQNLKL IDFGLCAKPK GGLDYHLMTC CGSPAYAAPE
LIQGKAYIGS EADIWSMGVL MYALMCGYLP FDDDNVMVLY KKIMRGKYEI PKWLSPGSVL
LLSQMMQVDP KKRITVKHLL NHPWLMHGYS CPVEWQSKYP LGYIDEDCVT ELSVFYKYSR
TSTTRLISEW SYDHITASYL LLHSKKSHGK AVRLKHPLAV GDQAVTSFKE LRPKSKLDFE
EPNGEIAYVF GSMDFSDEEL FSEDFTYSSF EPHTPKEYVK GRLEFNSVDS APATPVVQRN
ARHKNEDKEN SNTAVARDEN VFLHPAPWTP TPRRKQNEKK GILTTPNKNT QTKEKNQSKE
TPTKKPIGTG EEFANVISPE RRCRSVELDL NQAHIDSAQK KKGAKVFGSL ERGLDKMITM
LTPSKRKGYT REGPRKLRAH YNVTTTNIVN PEQLLNQIVR VLPSKNVDYV QKGYTLKCKT
QSDFGKVTMQ FELEVCQLSK SEVVGIRRQR LKGDAWVYKR LVEDILSSCK V
