MELK_XENTR
ID MELK_XENTR Reviewed; 652 AA.
AC Q28GW8; A4IGU0; F7BW48; F7BW55;
DT 19-OCT-2011, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Maternal embryonic leucine zipper kinase;
DE EC=2.7.11.1;
GN Name=melk; ORFNames=TEgg058f04.1;
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Egg;
RG Sanger Xenopus tropicalis EST/cDNA project;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=20431018; DOI=10.1126/science.1183670;
RA Hellsten U., Harland R.M., Gilchrist M.J., Hendrix D., Jurka J.,
RA Kapitonov V., Ovcharenko I., Putnam N.H., Shu S., Taher L., Blitz I.L.,
RA Blumberg B., Dichmann D.S., Dubchak I., Amaya E., Detter J.C., Fletcher R.,
RA Gerhard D.S., Goodstein D., Graves T., Grigoriev I.V., Grimwood J.,
RA Kawashima T., Lindquist E., Lucas S.M., Mead P.E., Mitros T., Ogino H.,
RA Ohta Y., Poliakov A.V., Pollet N., Robert J., Salamov A., Sater A.K.,
RA Schmutz J., Terry A., Vize P.D., Warren W.C., Wells D., Wills A.,
RA Wilson R.K., Zimmerman L.B., Zorn A.M., Grainger R., Grammer T.,
RA Khokha M.K., Richardson P.M., Rokhsar D.S.;
RT "The genome of the Western clawed frog Xenopus tropicalis.";
RL Science 328:633-636(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
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. Plays a role in cytokinesis during early development (By
CC similarity). {ECO:0000250}.
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:0000250}; Peripheral membrane
CC protein {ECO:0000250}.
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. Phosphorylated by the
CC maturation promoting factor (MPF), composed of cdk1 and a cyclin-B.
CC Also phosphorylated by some MAPK. Phosphorylated during oocyte
CC maturation. Dephosphorylation destabilizes the protein (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Degraded when cells exit mitosis. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. SNF1 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI35246.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; CR761185; CAJ81864.1; -; mRNA.
DR EMBL; AAMC01051129; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01051130; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01051131; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC135245; AAI35246.1; ALT_SEQ; mRNA.
DR RefSeq; NP_001016390.1; NM_001016390.2.
DR RefSeq; XP_017948689.1; XM_018093200.1.
DR AlphaFoldDB; Q28GW8; -.
DR SMR; Q28GW8; -.
DR STRING; 8364.ENSXETP00000014336; -.
DR PaxDb; Q28GW8; -.
DR DNASU; 549144; -.
DR GeneID; 549144; -.
DR KEGG; xtr:549144; -.
DR CTD; 9833; -.
DR Xenbase; XB-GENE-987654; melk.
DR eggNOG; KOG0583; Eukaryota.
DR InParanoid; Q28GW8; -.
DR OrthoDB; 1127668at2759; -.
DR Proteomes; UP000008143; Chromosome 1.
DR Proteomes; UP000790000; Unplaced.
DR Bgee; ENSXETG00000006551; Expressed in ovary and 10 other tissues.
DR GO; GO:0005938; C:cell cortex; ISS: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:0048821; P:erythrocyte development; IEA:Ensembl.
DR GO; GO:0030097; P:hemopoiesis; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
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 GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0008016; P:regulation of heart contraction; IEA:Ensembl.
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 2: Evidence at transcript 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..652
FT /note="Maternal embryonic leucine zipper kinase"
FT /id="PRO_0000413431"
FT DOMAIN 13..265
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 603..652
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..652
FT /note="Autoinhibitory region"
FT /evidence="ECO:0000250"
FT REGION 443..492
FT /note="Disordered"
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 415
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250"
FT MOD_RES 450
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250"
FT MOD_RES 452
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250"
FT MOD_RES 482
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250"
FT MOD_RES 484
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250"
FT MOD_RES 499
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT MOD_RES 506
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT MOD_RES 518
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 652 AA; 74276 MW; 81BEBB0F76999EB3 CRC64;
MAVDDYEELL KYYELHETIG TGGFAKVKLA SHLTTGEKVA IKIMDKESLG DDLPRVKTEI
DAMKNLSHQH VCRLYHVIET PNKIFMVLEY CPGGELFDYI IAKDRLTEDE ARVFFRQIVS
AVAYIHSQGY AHRDLKPENL LIDEDQNLKL IDFGLCAKPK GGLDYHLMTC CGSPAYAAPE
LIQGKAYIGS EADIWSMGVL MYALMCGYLP FDDDNVMVLY KKIMRGKYEI PKWLSPGSVL
LLSQMLQVDP KKRISVKHLL SHPWLMQGYS CPVEWQSKYP LGYVDEDCVT ELSVFYKCSR
TSTSRLISEW NYDHITASYL LLHSKKSHGK PVRLKRPLAV GDQPVTSFKE LRPKSTLDFE
EPNCGEIAYV FGSMEFSDDE LFSEDFAYSC FEPHTPKEYV KGRSEFHSVD SAPSTPVVQR
YARHKSEDKE NCDAALGKDE NVFLHPAPWT PTPRRKQNEK KGILTTPNKN SHTKEKNQSK
ETPTKKPITT GEELANVISP ERRCRSVELD LNQAHVDSAQ KKKGAKVFGS LERGLDKMIT
MLTPSKRKGY AREGPRKLRA HYNVTTTNIM NPEQLLNQIV KVLPSKNVDY VQKGYTLKCK
TQSDFGKVTM QFELEVCQLS KSEMVGIRRQ RLKGDAWVYK RLVEDILSSC KV
