MELK_DANRE
ID MELK_DANRE Reviewed; 676 AA.
AC F1QGZ6; Q7ZU72; Q7ZZN5;
DT 19-OCT-2011, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Maternal embryonic leucine zipper kinase;
DE Short=zMelk;
DE EC=2.7.11.1;
DE AltName: Full=Protein kinase PK38;
GN Name=melk;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16024803; DOI=10.1128/mcb.25.15.6682-6693.2005;
RA Saito R., Tabata Y., Muto A., Arai K., Watanabe S.;
RT "Melk-like kinase plays a role in hematopoiesis in the zebra fish.";
RL Mol. Cell. Biol. 25:6682-6693(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2003) 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 (By similarity). Also plays a role in primitive
CC hematopoiesis, possibly by affecting the expression of genes critical
CC for hematopoiesis. {ECO:0000250, ECO:0000269|PubMed:16024803}.
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.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in the eye, gill, kidney,
CC spleen, muscle, ovary and testis and weakly in the heart, liver, and
CC gut. Expressed in the brain and lateral mesoderm at 12 hours post-
CC fertilization (hpf). {ECO:0000269|PubMed:16024803}.
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. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. SNF1 subfamily. {ECO:0000305}.
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DR EMBL; AB108827; BAC75706.1; -; mRNA.
DR EMBL; CU929184; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FP017148; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC050520; AAH50520.1; -; mRNA.
DR RefSeq; NP_996771.2; NM_206888.2.
DR AlphaFoldDB; F1QGZ6; -.
DR SMR; F1QGZ6; -.
DR STRING; 7955.ENSDARP00000109117; -.
DR PaxDb; F1QGZ6; -.
DR Ensembl; ENSDART00000047728; ENSDARP00000047727; ENSDARG00000030759.
DR GeneID; 30724; -.
DR KEGG; dre:30724; -.
DR CTD; 9833; -.
DR ZFIN; ZDB-GENE-990603-5; melk.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00940000154889; -.
DR HOGENOM; CLU_000288_157_8_1; -.
DR InParanoid; F1QGZ6; -.
DR OMA; LRAHYNV; -.
DR OrthoDB; 1127668at2759; -.
DR PhylomeDB; F1QGZ6; -.
DR TreeFam; TF314032; -.
DR PRO; PR:F1QGZ6; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 1.
DR Bgee; ENSDARG00000030759; Expressed in mature ovarian follicle and 34 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; IMP:ZFIN.
DR GO; GO:0030097; P:hemopoiesis; IMP: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; IMP:ZFIN.
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..676
FT /note="Maternal embryonic leucine zipper kinase"
FT /id="PRO_0000413429"
FT DOMAIN 13..265
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 624..673
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..673
FT /note="Autoinhibitory region"
FT /evidence="ECO:0000250"
FT REGION 423..518
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 426..446
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 464..494
FT /note="Polar 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 CONFLICT 11
FT /note="K -> R (in Ref. 3; AAH50520)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="V -> A (in Ref. 3; AAH50520)"
FT /evidence="ECO:0000305"
FT CONFLICT 436
FT /note="E -> D (in Ref. 3; AAH50520)"
FT /evidence="ECO:0000305"
FT CONFLICT 465..466
FT /note="SS -> YN (in Ref. 1; BAC75706)"
FT /evidence="ECO:0000305"
FT CONFLICT 519
FT /note="I -> M (in Ref. 1; BAC75706 and 3; AAH50520)"
FT /evidence="ECO:0000305"
FT CONFLICT 580
FT /note="K -> R (in Ref. 1; BAC75706)"
FT /evidence="ECO:0000305"
FT CONFLICT 663
FT /note="L -> P (in Ref. 3; AAH50520)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 676 AA; 76805 MW; 36319A846217A3A1 CRC64;
MPVDSTSELL KHYEVYETIG SGGFAKVKLG RHKLTGEKVA IKIMEKKDLG DDLPRVKIEI
EAMKNLSHQH VCRLYHVIET TSKIYMVLEY CPGGELFDYI IAKDRLSEEE TRVFFRQIIS
ALAYVHSQGY AHRDLKPENL LIDEDHNLKL IDFGLCAKPK GGLGFELLTC CGSPAYAAPE
LIQGKAYIGS EADVWSMGVL LYALLCGFLP FDDDNCMVLY RKITRGKYSN PHWLSPSSIL
LLNQMMQVDP KRRLTVKHLL DHPWVMRGYS TPVEWHSKYP LGHIDEDCIT EMAVTFKQSK
QRTIQLVSEW KYDQITATYL LLLAKKRQGR PVRLRAECPV IDIVCSPLQD MQLKKSLRFT
EDDDGVHPVV LGSMVFPPDC YDDENPWTPL TPKNTHTTNT PRMKLYPETT EKWNEMAYSP
VIEHSRPCRQ KPERRERTKE NKENLAVPGT DGDVFALPAP RTPTSSRKVK SNRTVMTTPN
HNNNKSSEVN KGAGSATKEG SRRREVEQQQ NGQQGELNIL AFSPERRSRS LDLAGCQVDS
GQKRKGGKVF GSLERGLDKV ITMLTPSKKR GPRDGPRKIK AQYNVTLTNQ TNADQVLNQI
LSILPEKNVD FVQKGYTLKC HTQSDFGKVT MQFELEVCLL QKPEVVGIRR QRLKGDAWVY
KHLVEDILSS SSQWSA
