MYLK3_HUMAN
ID MYLK3_HUMAN Reviewed; 819 AA.
AC Q32MK0; B5BUL9; B7Z5U8; Q32MK1; Q96DV1;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 3.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Myosin light chain kinase 3;
DE EC=2.7.11.18;
DE AltName: Full=Cardiac-MyBP-C-associated Ca/CaM kinase;
DE Short=Cardiac-MLCK;
GN Name=MYLK3; Synonyms=MLCK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT LEU-180.
RC TISSUE=Cardiac myocyte;
RA Mues A., Seidel R., Gautel M.;
RT "The cardiac-MyBP-C associated Ca/CaM kinase is a novel MLCK with cardiac-
RT specific domains.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-180.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=17885681; DOI=10.1172/jci30804;
RA Seguchi O., Takashima S., Yamazaki S., Asakura M., Asano Y., Shintani Y.,
RA Wakeno M., Minamino T., Kondo H., Furukawa H., Nakamaru K., Naito A.,
RA Takahashi T., Ohtsuka T., Kawakami K., Isomura T., Kitamura S., Tomoike H.,
RA Mochizuki N., Kitakaze M.;
RT "A cardiac myosin light chain kinase regulates sarcomere assembly in the
RT vertebrate heart.";
RL J. Clin. Invest. 117:2812-2824(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-401 AND SER-408, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [8]
RP VARIANT [LARGE SCALE ANALYSIS] ARG-390.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Kinase that phosphorylates MYL2 in vitro. Promotes sarcomere
CC formation in cardiomyocytes and increases cardiomyocyte contractility
CC (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[myosin light chain] = ADP + H(+) + O-phospho-L-
CC seryl-[myosin light chain]; Xref=Rhea:RHEA:22004, Rhea:RHEA-
CC COMP:13684, Rhea:RHEA-COMP:13685, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421,
CC ChEBI:CHEBI:456216; EC=2.7.11.18;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[myosin light chain] = ADP + H(+) + O-
CC phospho-L-threonyl-[myosin light chain]; Xref=Rhea:RHEA:53900,
CC Rhea:RHEA-COMP:13686, Rhea:RHEA-COMP:13687, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977,
CC ChEBI:CHEBI:456216; EC=2.7.11.18;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q32MK0-3; Sequence=Displayed;
CC Name=2;
CC IsoId=Q32MK0-4; Sequence=VSP_044312;
CC -!- TISSUE SPECIFICITY: Restricted to heart. {ECO:0000269|PubMed:17885681}.
CC -!- PTM: Phosphorylated on serine residues. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI09098.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAC42766.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ247087; CAC42766.1; ALT_INIT; mRNA.
DR EMBL; AK299443; BAH13034.1; -; mRNA.
DR EMBL; AB451455; BAG70269.1; -; mRNA.
DR EMBL; AC007225; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC109097; AAI09098.2; ALT_INIT; mRNA.
DR CCDS; CCDS10723.2; -. [Q32MK0-3]
DR CCDS; CCDS76861.1; -. [Q32MK0-4]
DR RefSeq; NP_001295230.1; NM_001308301.1. [Q32MK0-4]
DR RefSeq; NP_872299.2; NM_182493.2. [Q32MK0-3]
DR RefSeq; XP_006721397.1; XM_006721334.3. [Q32MK0-4]
DR AlphaFoldDB; Q32MK0; -.
DR SMR; Q32MK0; -.
DR BioGRID; 124881; 11.
DR IntAct; Q32MK0; 5.
DR STRING; 9606.ENSP00000378288; -.
DR BindingDB; Q32MK0; -.
DR ChEMBL; CHEMBL4627; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q32MK0; -.
DR iPTMnet; Q32MK0; -.
DR PhosphoSitePlus; Q32MK0; -.
DR BioMuta; MYLK3; -.
DR DMDM; 254763411; -.
DR jPOST; Q32MK0; -.
DR MassIVE; Q32MK0; -.
DR MaxQB; Q32MK0; -.
DR PaxDb; Q32MK0; -.
DR PeptideAtlas; Q32MK0; -.
DR PRIDE; Q32MK0; -.
DR ProteomicsDB; 61603; -. [Q32MK0-3]
DR ProteomicsDB; 6721; -.
DR Antibodypedia; 28053; 270 antibodies from 26 providers.
DR DNASU; 91807; -.
DR Ensembl; ENST00000394809.9; ENSP00000378288.4; ENSG00000140795.13. [Q32MK0-3]
DR Ensembl; ENST00000536476.5; ENSP00000439297.1; ENSG00000140795.13. [Q32MK0-4]
DR GeneID; 91807; -.
DR KEGG; hsa:91807; -.
DR MANE-Select; ENST00000394809.9; ENSP00000378288.4; NM_182493.3; NP_872299.2.
DR UCSC; uc002eei.5; human. [Q32MK0-3]
DR CTD; 91807; -.
DR DisGeNET; 91807; -.
DR GeneCards; MYLK3; -.
DR HGNC; HGNC:29826; MYLK3.
DR HPA; ENSG00000140795; Group enriched (heart muscle, skeletal muscle, tongue).
DR MIM; 612147; gene.
DR neXtProt; NX_Q32MK0; -.
DR OpenTargets; ENSG00000140795; -.
DR PharmGKB; PA162396375; -.
DR VEuPathDB; HostDB:ENSG00000140795; -.
DR eggNOG; KOG0032; Eukaryota.
DR GeneTree; ENSGT00940000160007; -.
DR HOGENOM; CLU_000288_90_0_1; -.
DR InParanoid; Q32MK0; -.
DR OMA; DPWPLEE; -.
DR OrthoDB; 218222at2759; -.
DR PhylomeDB; Q32MK0; -.
DR TreeFam; TF314166; -.
DR PathwayCommons; Q32MK0; -.
DR SignaLink; Q32MK0; -.
DR SIGNOR; Q32MK0; -.
DR BioGRID-ORCS; 91807; 16 hits in 1107 CRISPR screens.
DR ChiTaRS; MYLK3; human.
DR GeneWiki; MYLK3; -.
DR GenomeRNAi; 91807; -.
DR Pharos; Q32MK0; Tchem.
DR PRO; PR:Q32MK0; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q32MK0; protein.
DR Bgee; ENSG00000140795; Expressed in cardiac muscle of right atrium and 138 other tissues.
DR Genevisible; Q32MK0; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; ISS:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; ISS:BHF-UCL.
DR GO; GO:0004687; F:myosin light chain kinase activity; ISS:BHF-UCL.
DR GO; GO:0055003; P:cardiac myofibril assembly; ISS:BHF-UCL.
DR GO; GO:0071347; P:cellular response to interleukin-1; IMP:BHF-UCL.
DR GO; GO:0060298; P:positive regulation of sarcomere organization; ISS:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; ISS:BHF-UCL.
DR GO; GO:0002528; P:regulation of vascular permeability involved in acute inflammatory response; IMP:BHF-UCL.
DR GO; GO:0045214; P:sarcomere organization; ISS:BHF-UCL.
DR GO; GO:0048769; P:sarcomerogenesis; ISS:BHF-UCL.
DR InterPro; IPR011009; Kinase-like_dom_sf.
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; 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 Alternative splicing; ATP-binding; Cytoplasm; Kinase; Magnesium;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..819
FT /note="Myosin light chain kinase 3"
FT /id="PRO_0000272200"
FT DOMAIN 515..770
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 146..334
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 347..462
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 152..172
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 636
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 521..529
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 544
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 152
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT87"
FT MOD_RES 355
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT87"
FT MOD_RES 401
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..341
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044312"
FT VARIANT 70
FT /note="S -> T (in dbSNP:rs9923813)"
FT /id="VAR_058335"
FT VARIANT 180
FT /note="V -> L (in dbSNP:rs28407821)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.1"
FT /id="VAR_058336"
FT VARIANT 390
FT /note="G -> R (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs141602742)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035630"
FT CONFLICT 149
FT /note="R -> G (in Ref. 2; BAG70269)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="G -> R (in Ref. 1; CAC42766)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 819 AA; 88393 MW; 21148BBACB0FF0D9 CRC64;
MSGTSKESLG HGGLPGLGKT CLTTMDTKLN MLNEKVDQLL HFQEDVTEKL QSMCRDMGHL
ERGLHRLEAS RAPGPGGADG VPHIDTQAGW PEVLELVRAM QQDAAQHGAR LEALFRMVAA
VDRAIALVGA TFQKSKVADF LMQGRVPWRR GSPGDSPEEN KERVEEEGGK PKHVLSTSGV
QSDAREPGEE SQKADVLEGT AERLPPIRAS GLGADPAQAV VSPGQGDGVP GPAQAFPGHL
PLPTKVEAKA PETPSENLRT GLELAPAPGR VNVVSPSLEV APGAGQGASS SRPDPEPLEE
GTRLTPGPGP QCPGPPGLPA QARATHSGGE TPPRISIHIQ EMDTPGEMLM TGRGSLGPTL
TTEAPAAAQP GKQGPPGTGR CLQAPGTEPG EQTPEGAREL SPLQESSSPG GVKAEEEQRA
GAEPGTRPSL ARSDDNDHEV GALGLQQGKS PGAGNPEPEQ DCAARAPVRA EAVRRMPPGA
EAGSVVLDDS PAPPAPFEHR VVSVKETSIS AGYEVCQHEV LGGGRFGQVH RCTEKSTGLP
LAAKIIKVKS AKDREDVKNE INIMNQLSHV NLIQLYDAFE SKHSCTLVME YVDGGELFDR
ITDEKYHLTE LDVVLFTRQI CEGVHYLHQH YILHLDLKPE NILCVNQTGH QIKIIDFGLA
RRYKPREKLK VNFGTPEFLA PEVVNYEFVS FPTDMWSVGV ITYMLLSGLS PFLGETDAET
MNFIVNCSWD FDADTFEGLS EEAKDFVSRL LVKEKSCRMS ATQCLKHEWL NNLPAKASRS
KTRLKSQLLL QKYIAQRKWK KHFYVVTAAN RLRKFPTSP
