MYLK2_HUMAN
ID MYLK2_HUMAN Reviewed; 596 AA.
AC Q9H1R3; Q569L1; Q96I84;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Myosin light chain kinase 2, skeletal/cardiac muscle;
DE Short=MLCK2;
DE EC=2.7.11.18;
GN Name=MYLK2;
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], FUNCTION, AND VARIANTS CMH VAL-87 AND GLU-95.
RC TISSUE=Skeletal muscle;
RX PubMed=11733062; DOI=10.1016/s0092-8674(01)00586-4;
RA Davis J.S., Hassanzadeh S., Winitsky S., Lin H., Satorius C., Vemuri R.,
RA Aletras A.H., Wen H., Epstein N.D.;
RT "The overall pattern of cardiac contraction depends on a spatial gradient
RT of myosin regulatory light chain phosphorylation.";
RL Cell 107:631-641(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Skeletal muscle;
RA Stanchi F., Lanfranchi G.;
RT "Full-length sequencing of 100 cDNA clones from human adult skeletal
RT muscle.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 [5]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 566-587 IN COMPLEX WITH CENTRIN,
RP AND SUBUNIT.
RA Radu L., Miron S., Durand D., Assairi L., Blouquit Y., Charbonnier J.B.;
RT "Structural features of the complexes formed by Scherffelia dubia
RT centrin.";
RL Submitted (JAN-2011) to the PDB data bank.
RN [6]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-117; VAL-142; ALA-144 AND ASN-324.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Implicated in the level of global muscle contraction and
CC cardiac function. Phosphorylates a specific serine in the N-terminus of
CC a myosin light chain. {ECO:0000269|PubMed:11733062}.
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 -!- SUBUNIT: May interact with centrin. {ECO:0000269|Ref.5}.
CC -!- INTERACTION:
CC Q9H1R3; P08238: HSP90AB1; NbExp=3; IntAct=EBI-356910, EBI-352572;
CC Q9H1R3; Q06413: MEF2C; NbExp=2; IntAct=EBI-356910, EBI-2684075;
CC Q9H1R3; Q9BYV2: TRIM54; NbExp=2; IntAct=EBI-356910, EBI-2130429;
CC Q9H1R3; O76024: WFS1; NbExp=3; IntAct=EBI-356910, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Note=Colocalizes with phosphorylated
CC myosin light chain (RLCP) at filaments of the myofibrils.
CC -!- TISSUE SPECIFICITY: Heart and skeletal muscles. Increased expression in
CC the apical tissue compared to the interventricular septal tissue.
CC -!- DISEASE: Cardiomyopathy, familial hypertrophic (CMH) [MIM:192600]: A
CC hereditary heart disorder characterized by ventricular hypertrophy,
CC which is usually asymmetric and often involves the interventricular
CC septum. The symptoms include dyspnea, syncope, collapse, palpitations,
CC and chest pain. They can be readily provoked by exercise. The disorder
CC has inter- and intrafamilial variability ranging from benign to
CC malignant forms with high risk of cardiac failure and sudden cardiac
CC death. {ECO:0000269|PubMed:11733062}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; AF325549; AAK15494.1; -; mRNA.
DR EMBL; AJ272502; CAC81354.1; -; mRNA.
DR EMBL; AL160175; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007753; AAH07753.1; -; mRNA.
DR EMBL; BC069627; AAH69627.1; -; mRNA.
DR EMBL; BC092413; AAH92413.1; -; mRNA.
DR EMBL; BC127622; AAI27623.1; -; mRNA.
DR CCDS; CCDS13191.1; -.
DR RefSeq; NP_149109.1; NM_033118.3.
DR PDB; 2LV6; Other; -; B=566-591.
DR PDB; 3KF9; X-ray; 2.60 A; B/D=566-587.
DR PDBsum; 2LV6; -.
DR PDBsum; 3KF9; -.
DR AlphaFoldDB; Q9H1R3; -.
DR BMRB; Q9H1R3; -.
DR SMR; Q9H1R3; -.
DR BioGRID; 124494; 84.
DR IntAct; Q9H1R3; 89.
DR MINT; Q9H1R3; -.
DR STRING; 9606.ENSP00000365162; -.
DR BindingDB; Q9H1R3; -.
DR ChEMBL; CHEMBL2777; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB04825; Prenylamine.
DR DrugCentral; Q9H1R3; -.
DR GuidetoPHARMACOLOGY; 1553; -.
DR iPTMnet; Q9H1R3; -.
DR PhosphoSitePlus; Q9H1R3; -.
DR BioMuta; MYLK2; -.
DR DMDM; 24211884; -.
DR EPD; Q9H1R3; -.
DR jPOST; Q9H1R3; -.
DR MassIVE; Q9H1R3; -.
DR MaxQB; Q9H1R3; -.
DR PaxDb; Q9H1R3; -.
DR PeptideAtlas; Q9H1R3; -.
DR PRIDE; Q9H1R3; -.
DR ProteomicsDB; 80445; -.
DR Antibodypedia; 25246; 154 antibodies from 26 providers.
DR DNASU; 85366; -.
DR Ensembl; ENST00000375985.5; ENSP00000365152.4; ENSG00000101306.11.
DR Ensembl; ENST00000375994.6; ENSP00000365162.2; ENSG00000101306.11.
DR GeneID; 85366; -.
DR KEGG; hsa:85366; -.
DR MANE-Select; ENST00000375985.5; ENSP00000365152.4; NM_033118.4; NP_149109.1.
DR UCSC; uc002wwq.3; human.
DR CTD; 85366; -.
DR DisGeNET; 85366; -.
DR GeneCards; MYLK2; -.
DR HGNC; HGNC:16243; MYLK2.
DR HPA; ENSG00000101306; Tissue enriched (skeletal).
DR MalaCards; MYLK2; -.
DR MIM; 192600; phenotype.
DR MIM; 606566; gene.
DR neXtProt; NX_Q9H1R3; -.
DR OpenTargets; ENSG00000101306; -.
DR Orphanet; 155; NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy.
DR PharmGKB; PA31389; -.
DR VEuPathDB; HostDB:ENSG00000101306; -.
DR eggNOG; KOG0032; Eukaryota.
DR GeneTree; ENSGT00940000161489; -.
DR HOGENOM; CLU_000288_90_1_1; -.
DR InParanoid; Q9H1R3; -.
DR OMA; PPDPKKD; -.
DR OrthoDB; 218222at2759; -.
DR PhylomeDB; Q9H1R3; -.
DR TreeFam; TF314166; -.
DR BRENDA; 2.7.11.18; 2681.
DR PathwayCommons; Q9H1R3; -.
DR SignaLink; Q9H1R3; -.
DR SIGNOR; Q9H1R3; -.
DR BioGRID-ORCS; 85366; 15 hits in 1102 CRISPR screens.
DR EvolutionaryTrace; Q9H1R3; -.
DR GeneWiki; MYLK2; -.
DR GenomeRNAi; 85366; -.
DR Pharos; Q9H1R3; Tchem.
DR PRO; PR:Q9H1R3; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9H1R3; protein.
DR Bgee; ENSG00000101306; Expressed in hindlimb stylopod muscle and 120 other tissues.
DR Genevisible; Q9H1R3; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0030017; C:sarcomere; IC:BHF-UCL.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; ISS:BHF-UCL.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; ISS:BHF-UCL.
DR GO; GO:0032027; F:myosin light chain binding; IBA:GO_Central.
DR GO; GO:0004687; F:myosin light chain kinase activity; IDA:BHF-UCL.
DR GO; GO:0060048; P:cardiac muscle contraction; IC:BHF-UCL.
DR GO; GO:0055008; P:cardiac muscle tissue morphogenesis; IMP:BHF-UCL.
DR GO; GO:0007274; P:neuromuscular synaptic transmission; IEA:Ensembl.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0032971; P:regulation of muscle filament sliding; IDA:BHF-UCL.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IDA:UniProtKB.
DR GO; GO:0014816; P:skeletal muscle satellite cell differentiation; IEA:Ensembl.
DR GO; GO:0006941; P:striated muscle contraction; IDA:BHF-UCL.
DR CDD; cd14190; STKc_MLCK2; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR042717; MLCK2_STKc.
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 3D-structure; Acetylation; ATP-binding; Calmodulin-binding; Cardiomyopathy;
KW Cytoplasm; Disease variant; Kinase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P07313"
FT CHAIN 2..596
FT /note="Myosin light chain kinase 2, skeletal/cardiac
FT muscle"
FT /id="PRO_0000086408"
FT DOMAIN 285..540
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..224
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 574..586
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 39..59
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 188..204
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 406
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 291..299
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 314
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P07313"
FT MOD_RES 143
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCR8"
FT MOD_RES 149
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCR8"
FT MOD_RES 151
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCR8"
FT MOD_RES 445
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P20689"
FT VARIANT 87
FT /note="A -> V (in CMH; dbSNP:rs121908107)"
FT /evidence="ECO:0000269|PubMed:11733062"
FT /id="VAR_014197"
FT VARIANT 95
FT /note="A -> E (in CMH; dbSNP:rs121908108)"
FT /evidence="ECO:0000269|PubMed:11733062"
FT /id="VAR_014198"
FT VARIANT 117
FT /note="A -> V (in a lung neuroendocrine carcinoma sample;
FT somatic mutation; dbSNP:rs1229709568)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040860"
FT VARIANT 142
FT /note="G -> V (in dbSNP:rs56385445)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040861"
FT VARIANT 144
FT /note="P -> A (in dbSNP:rs34396614)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040862"
FT VARIANT 324
FT /note="K -> N (in dbSNP:rs34146416)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040863"
FT CONFLICT 355..361
FT /note="IVLFMEY -> GGVCAHS (in Ref. 4; AAH07753)"
FT /evidence="ECO:0000305"
FT HELIX 567..586
FT /evidence="ECO:0007829|PDB:3KF9"
SQ SEQUENCE 596 AA; 64685 MW; 671A2B5DE9453ADE CRC64;
MATENGAVEL GIQNPSTDKA PKGPTGERPL AAGKDPGPPD PKKAPDPPTL KKDAKAPASE
KGDGTLAQPS TSSQGPKGEG DRGGGPAEGS AGPPAALPQQ TATPETSVKK PKAEQGASGS
QDPGKPRVGK KAAEGQAAAR RGSPAFLHSP SCPAIISSSE KLLAKKPPSE ASELTFEGVP
MTHSPTDPRP AKAEEGKNIL AESQKEVGEK TPGQAGQAKM QGDTSRGIEF QAVPSEKSEV
GQALCLTARE EDCFQILDDC PPPPAPFPHR MVELRTGNVS SEFSMNSKEA LGGGKFGAVC
TCMEKATGLK LAAKVIKKQT PKDKEMVLLE IEVMNQLNHR NLIQLYAAIE TPHEIVLFME
YIEGGELFER IVDEDYHLTE VDTMVFVRQI CDGILFMHKM RVLHLDLKPE NILCVNTTGH
LVKIIDFGLA RRYNPNEKLK VNFGTPEFLS PEVVNYDQIS DKTDMWSMGV ITYMLLSGLS
PFLGDDDTET LNNVLSGNWY FDEETFEAVS DEAKDFVSNL IVKDQRARMN AAQCLAHPWL
NNLAEKAKRC NRRLKSQILL KKYLMKRRWK KNFIAVSAAN RFKKISSSGA LMALGV
