MYL3_HUMAN
ID MYL3_HUMAN Reviewed; 195 AA.
AC P08590; B2R534; Q9NRS8;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Myosin light chain 3 {ECO:0000305};
DE AltName: Full=Cardiac myosin light chain 1 {ECO:0000303|Ref.5};
DE Short=CMLC1 {ECO:0000303|Ref.5};
DE AltName: Full=Myosin light chain 1, slow-twitch muscle B/ventricular isoform {ECO:0000305};
DE Short=MLC1SB;
DE AltName: Full=Ventricular myosin alkali light chain {ECO:0000303|PubMed:3417683};
DE AltName: Full=Ventricular myosin light chain 1 {ECO:0000303|PubMed:3357795};
DE Short=VLCl {ECO:0000303|PubMed:3357795};
DE AltName: Full=Ventricular/slow twitch myosin alkali light chain {ECO:0000303|PubMed:2789520};
DE Short=MLC-lV/sb {ECO:0000303|PubMed:2789520};
GN Name=MYL3 {ECO:0000312|HGNC:HGNC:7584};
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].
RX PubMed=3417683; DOI=10.1016/s0021-9258(18)68333-4;
RA Kurabayashi M., Komuro I., Tsuchimochi H., Takaku F., Yazaki Y.;
RT "Molecular cloning and characterization of human atrial and ventricular
RT myosin alkali light chain cDNA clones.";
RL J. Biol. Chem. 263:13930-13936(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3357795; DOI=10.1093/nar/16.5.2353;
RA Hoffmann E., Shi Q.W., Floroff M., Mickle D.A.G., Wu T.-W., Olley P.M.,
RA Jackowski G.;
RT "Molecular cloning and complete nucleotide sequence of a human ventricular
RT myosin light chain 1.";
RL Nucleic Acids Res. 16:2353-2353(1988).
RN [3]
RP SEQUENCE REVISION.
RA Jackowski G.;
RL Submitted (MAY-1988) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2789520; DOI=10.1016/s0021-9258(18)94153-0;
RA Fodor W.L., Darras B., Seharaseyon J., Falkenthal S., Francke U.,
RA Vanin E.F.;
RT "Human ventricular/slow twitch myosin alkali light chain gene
RT characterization, sequence, and chromosomal location.";
RL J. Biol. Chem. 264:2143-2149(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Huang R., Peng B., Zhou G., Gong Z.;
RT "The sequence of human cardiac myosin light chain I (CMLC-1) from a Chinese
RT patient and the preparation of monoclonal antibody to CHCMLC1.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skeletal muscle;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skeletal 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 [9]
RP PROTEIN SEQUENCE OF 20-27; 34-40; 95-100; 124-129; 139-142 AND 155-171.
RC TISSUE=Heart;
RX PubMed=7498159; DOI=10.1002/elps.11501601192;
RA Kovalyov L.I., Shishkin S.S., Efimochkin A.S., Kovalyova M.A.,
RA Ershova E.S., Egorov T.A., Musalyamov A.K.;
RT "The major protein expression profile and two-dimensional protein database
RT of human heart.";
RL Electrophoresis 16:1160-1169(1995).
RN [10]
RP METHYLATION AT ALA-2.
RX PubMed=3979397; DOI=10.1111/j.1432-1033.1985.tb08809.x;
RA Henry G.D., Trayer I.P., Brewer S., Levine B.A.;
RT "The widespread distribution of alpha-N-trimethylalanine as the N-terminal
RT amino acid of light chains from vertebrate striated muscle myosins.";
RL Eur. J. Biochem. 148:75-82(1985).
RN [11]
RP VARIANTS CMH8 VAL-149 AND HIS-154.
RX PubMed=8673105; DOI=10.1038/ng0596-63;
RA Poetter K., Jiang H., Hassanzadeh S., Master S.R., Chang A., Dalakas M.C.,
RA Rayment I., Sellers J.R., Fananapazir L., Epstein N.D.;
RT "Mutations in either the essential or regulatory light chains of myosin are
RT associated with a rare myopathy in human heart and skeletal muscle.";
RL Nat. Genet. 13:63-69(1996).
RN [12]
RP VARIANT CMH8 LYS-143.
RX PubMed=12021217; DOI=10.1161/01.cir.0000018444.47798.94;
RA Olson T.M., Karst M.L., Whitby F.G., Driscoll D.J.;
RT "Myosin light chain mutation causes autosomal recessive cardiomyopathy with
RT mid-cavitary hypertrophy and restrictive physiology.";
RL Circulation 105:2337-2340(2002).
RN [13]
RP VARIANT CMH8 GLY-56.
RX PubMed=12707239; DOI=10.1161/01.cir.0000066323.15244.54;
RA Richard P., Charron P., Carrier L., Ledeuil C., Cheav T., Pichereau C.,
RA Benaiche A., Isnard R., Dubourg O., Burban M., Gueffet J.-P., Millaire A.,
RA Desnos M., Schwartz K., Hainque B., Komajda M.;
RT "Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of
RT mutations, and implications for a molecular diagnosis strategy.";
RL Circulation 107:2227-2232(2003).
RN [14]
RP ERRATUM OF PUBMED:12707239.
RA Richard P., Charron P., Carrier L., Ledeuil C., Cheav T., Pichereau C.,
RA Benaiche A., Isnard R., Dubourg O., Burban M., Gueffet J.-P., Millaire A.,
RA Desnos M., Schwartz K., Hainque B., Komajda M.;
RL Circulation 109:3258-3258(2004).
RN [15]
RP VARIANT CMH8 GLY-177.
RX PubMed=23594557; DOI=10.1159/000347138;
RA Jay A., Chikarmane R., Poulik J., Misra V.K.;
RT "Infantile hypertrophic cardiomyopathy associated with a novel MYL3
RT mutation.";
RL Cardiology 124:248-251(2013).
CC -!- FUNCTION: Regulatory light chain of myosin. Does not bind calcium.
CC -!- SUBUNIT: Myosin is a hexamer of 2 heavy chains and 4 light chains.
CC -!- PTM: The N-terminus is blocked.
CC -!- PTM: N-terminus is methylated by METTL11A/NTM1. {ECO:0000250}.
CC -!- DISEASE: Cardiomyopathy, familial hypertrophic 8 (CMH8) [MIM:608751]: 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. Rarely, patients present a variant of familial hypertrophic
CC cardiomyopathy, characterized by mid-left ventricular chamber
CC thickening. {ECO:0000269|PubMed:12021217, ECO:0000269|PubMed:12707239,
CC ECO:0000269|PubMed:23594557, ECO:0000269|PubMed:8673105}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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DR EMBL; M24122; AAA59895.1; -; mRNA.
DR EMBL; X07373; CAA30292.1; -; mRNA.
DR EMBL; M24247; AAA59851.1; -; Genomic_DNA.
DR EMBL; M24242; AAA59851.1; JOINED; Genomic_DNA.
DR EMBL; M24243; AAA59851.1; JOINED; Genomic_DNA.
DR EMBL; M24244; AAA59851.1; JOINED; Genomic_DNA.
DR EMBL; M24245; AAA59851.1; JOINED; Genomic_DNA.
DR EMBL; M24246; AAA59851.1; JOINED; Genomic_DNA.
DR EMBL; AF174483; AAF91089.1; -; mRNA.
DR EMBL; AK312044; BAG34981.1; -; mRNA.
DR EMBL; CH471055; EAW64791.1; -; Genomic_DNA.
DR EMBL; BC009790; AAH09790.1; -; mRNA.
DR CCDS; CCDS2746.1; -.
DR PIR; B30881; MOHU3V.
DR RefSeq; NP_000249.1; NM_000258.2.
DR PDB; 5TBY; EM; 20.00 A; C/D=1-195.
DR PDBsum; 5TBY; -.
DR AlphaFoldDB; P08590; -.
DR SMR; P08590; -.
DR BioGRID; 110718; 20.
DR IntAct; P08590; 11.
DR MINT; P08590; -.
DR STRING; 9606.ENSP00000379210; -.
DR ChEMBL; CHEMBL3831286; -.
DR GlyGen; P08590; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P08590; -.
DR PhosphoSitePlus; P08590; -.
DR BioMuta; MYL3; -.
DR DMDM; 127149; -.
DR UCD-2DPAGE; P08590; -.
DR EPD; P08590; -.
DR jPOST; P08590; -.
DR MassIVE; P08590; -.
DR MaxQB; P08590; -.
DR PaxDb; P08590; -.
DR PeptideAtlas; P08590; -.
DR PRIDE; P08590; -.
DR ProteomicsDB; 52134; -.
DR Antibodypedia; 12839; 390 antibodies from 35 providers.
DR CPTC; P08590; 1 antibody.
DR DNASU; 4634; -.
DR Ensembl; ENST00000292327.6; ENSP00000292327.4; ENSG00000160808.11.
DR Ensembl; ENST00000395869.5; ENSP00000379210.1; ENSG00000160808.11.
DR Ensembl; ENST00000653454.1; ENSP00000499624.1; ENSG00000160808.11.
DR Ensembl; ENST00000654597.1; ENSP00000499406.1; ENSG00000160808.11.
DR Ensembl; ENST00000662933.1; ENSP00000499577.1; ENSG00000160808.11.
DR GeneID; 4634; -.
DR KEGG; hsa:4634; -.
DR MANE-Select; ENST00000292327.6; ENSP00000292327.4; NM_000258.3; NP_000249.1.
DR UCSC; uc003cql.2; human.
DR CTD; 4634; -.
DR DisGeNET; 4634; -.
DR GeneCards; MYL3; -.
DR GeneReviews; MYL3; -.
DR HGNC; HGNC:7584; MYL3.
DR HPA; ENSG00000160808; Group enriched (heart muscle, skeletal muscle, tongue).
DR MalaCards; MYL3; -.
DR MIM; 160790; gene.
DR MIM; 608751; phenotype.
DR neXtProt; NX_P08590; -.
DR OpenTargets; ENSG00000160808; -.
DR Orphanet; 155; NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy.
DR PharmGKB; PA31381; -.
DR VEuPathDB; HostDB:ENSG00000160808; -.
DR eggNOG; KOG0030; Eukaryota.
DR GeneTree; ENSGT01030000234570; -.
DR HOGENOM; CLU_061288_13_0_1; -.
DR InParanoid; P08590; -.
DR OMA; YDRTPKC; -.
DR OrthoDB; 1470794at2759; -.
DR PhylomeDB; P08590; -.
DR TreeFam; TF351553; -.
DR PathwayCommons; P08590; -.
DR Reactome; R-HSA-390522; Striated Muscle Contraction.
DR SignaLink; P08590; -.
DR BioGRID-ORCS; 4634; 15 hits in 1063 CRISPR screens.
DR ChiTaRS; MYL3; human.
DR GeneWiki; MYL3; -.
DR GenomeRNAi; 4634; -.
DR Pharos; P08590; Tbio.
DR PRO; PR:P08590; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P08590; protein.
DR Bgee; ENSG00000160808; Expressed in apex of heart and 123 other tissues.
DR ExpressionAtlas; P08590; baseline and differential.
DR Genevisible; P08590; HS.
DR GO; GO:0031672; C:A band; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031674; C:I band; IDA:BHF-UCL.
DR GO; GO:0005859; C:muscle myosin complex; TAS:ProtInc.
DR GO; GO:0016460; C:myosin II complex; IBA:GO_Central.
DR GO; GO:0030017; C:sarcomere; TAS:BHF-UCL.
DR GO; GO:0003785; F:actin monomer binding; IDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0032038; F:myosin II heavy chain binding; NAS:BHF-UCL.
DR GO; GO:0008307; F:structural constituent of muscle; TAS:ProtInc.
DR GO; GO:0060048; P:cardiac muscle contraction; IMP:BHF-UCL.
DR GO; GO:0032781; P:positive regulation of ATP-dependent activity; ISS:BHF-UCL.
DR GO; GO:0006942; P:regulation of striated muscle contraction; IMP:BHF-UCL.
DR GO; GO:0002026; P:regulation of the force of heart contraction; IMP:BHF-UCL.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP:BHF-UCL.
DR CDD; cd00051; EFh; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR002048; EF_hand_dom.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS50222; EF_HAND_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Cardiomyopathy; Direct protein sequencing; Disease variant;
KW Methylation; Motor protein; Muscle protein; Myosin; Phosphoprotein;
KW Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P09542"
FT CHAIN 2..195
FT /note="Myosin light chain 3"
FT /id="PRO_0000198696"
FT DOMAIN 49..86
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 128..163
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 163..195
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..16
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N,N,N-trimethylalanine"
FT /evidence="ECO:0000305|PubMed:3979397"
FT MOD_RES 88
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P16409"
FT MOD_RES 127
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P09542"
FT MOD_RES 129
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P16409"
FT MOD_RES 130
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P16409"
FT MOD_RES 179
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09542"
FT VARIANT 56
FT /note="E -> G (in CMH8; dbSNP:rs199474702)"
FT /evidence="ECO:0000269|PubMed:12707239"
FT /id="VAR_019842"
FT VARIANT 143
FT /note="E -> K (in CMH8; autosomal recessive;
FT dbSNP:rs104893750)"
FT /evidence="ECO:0000269|PubMed:12021217"
FT /id="VAR_019843"
FT VARIANT 149
FT /note="M -> V (in CMH8; with mid-left ventricular chamber
FT thickening; dbSNP:rs104893748)"
FT /evidence="ECO:0000269|PubMed:8673105"
FT /id="VAR_004599"
FT VARIANT 154
FT /note="R -> H (in CMH8; with mid-left ventricular chamber
FT thickening; dbSNP:rs104893749)"
FT /evidence="ECO:0000269|PubMed:8673105"
FT /id="VAR_004600"
FT VARIANT 177
FT /note="E -> G (in CMH8; dbSNP:rs193922391)"
FT /evidence="ECO:0000269|PubMed:23594557"
FT /id="VAR_073726"
FT CONFLICT 171
FT /note="K -> R (in Ref. 5; AAF91089)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 195 AA; 21932 MW; 306CF328841729DD CRC64;
MAPKKPEPKK DDAKAAPKAA PAPAPPPEPE RPKEVEFDAS KIKIEFTPEQ IEEFKEAFML
FDRTPKCEMK ITYGQCGDVL RALGQNPTQA EVLRVLGKPR QEELNTKMMD FETFLPMLQH
ISKNKDTGTY EDFVEGLRVF DKEGNGTVMG AELRHVLATL GERLTEDEVE KLMAGQEDSN
GCINYEAFVK HIMSS
