ID MLRV_HUMAN Reviewed; 166 AA. AC P10916; Q16123; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 02-NOV-2016, entry version 171. DE RecName: Full=Myosin regulatory light chain 2, ventricular/cardiac muscle isoform {ECO:0000305}; DE Short=MLC-2 {ECO:0000250|UniProtKB:P08733}; DE Short=MLC-2v; DE AltName: Full=Cardiac myosin light chain 2 {ECO:0000303|Ref.3}; DE AltName: Full=Myosin light chain 2, slow skeletal/ventricular muscle isoform {ECO:0000250|UniProtKB:Q7M2V4}; DE Short=MLC-2s/v {ECO:0000250|UniProtKB:Q7M2V4}; DE AltName: Full=Ventricular myosin light chain 2 {ECO:0000303|PubMed:2704627}; GN Name=MYL2 {ECO:0000312|HGNC:HGNC:7583}; GN Synonyms=MLC2 {ECO:0000303|PubMed:8287067}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Heart; RX PubMed=2704627; DOI=10.1093/nar/17.6.2360; RA Libera L.D., Hoffmann E., Floroff M., Jackowski G.; RT "Isolation and nucleotide sequence of the cDNA encoding human RT ventricular myosin light chain 2."; RL Nucleic Acids Res. 17:2360-2360(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Muscle; RA Wu Q.L.; RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Margossian S.S., Umeda P.K., Sciaky D., Anderson P.A.W.; RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8287067; RA Wadgaonkar R., Shafiq S., Rajmanickam C., Siddiqui M.A.; RT "Interaction of a conserved peptide domain in recombinant human RT ventricular myosin light chain-2 with myosin heavy chain."; RL Cell. Mol. Biol. Res. 39:13-26(1993). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Prostate, and 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PROTEIN SEQUENCE OF 138-144. 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 RT database of human heart."; RL Electrophoresis 16:1160-1169(1995). RN [7] RP INTERACTION WITH MYOC. RX PubMed=11773029; RA Wentz-Hunter K., Ueda J., Yue B.Y.; RT "Protein interactions with myocilin."; RL Invest. Ophthalmol. Vis. Sci. 43:176-182(2002). RN [8] RP PHOSPHORYLATION AT SER-15 BY DAPK3, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=20038585; DOI=10.1074/jbc.C109.076489; RA Chang A.N., Chen G., Gerard R.D., Kamm K.E., Stull J.T.; RT "Cardiac myosin is a substrate for zipper-interacting protein kinase RT (ZIPK)."; RL J. Biol. Chem. 285:5122-5126(2010). RN [9] RP PHOSPHORYLATION AT SER-15, DEAMIDATION AT ASN-14, AND IDENTIFICATION RP BY MASS SPECTROMETRY. RX PubMed=20445002; DOI=10.1074/mcp.M110.000075; RA Scruggs S.B., Reisdorph R., Armstrong M.L., Warren C.M., Reisdorph N., RA Solaro R.J., Buttrick P.M.; RT "A novel, in-solution separation of endogenous cardiac sarcomeric RT proteins and identification of distinct charged variants of regulatory RT light chain."; RL Mol. Cell. Proteomics 9:1804-1818(2010). RN [10] RP VARIANTS CMH10 THR-13; LYS-22 AND ALA-95. RX PubMed=8673105; DOI=10.1038/ng0596-63; RA Poetter K., Jiang H., Hassanzadeh S., Master S.R., Chang A., RA Dalakas M.C., Rayment I., Sellers J.R., Fananapazir L., Epstein N.D.; RT "Mutations in either the essential or regulatory light chains of RT myosin are associated with a rare myopathy in human heart and skeletal RT muscle."; RL Nat. Genet. 13:63-69(1996). RN [11] RP VARIANTS CMH10 LEU-18 AND GLN-58. RX PubMed=9535554; DOI=10.1007/s001090050210; RA Flavigny J., Richard P., Isnard R., Carrier L., Charron P., Bonne G., RA Forissier J.F., Desnos M., Dubourg O., Komajda M., Schwartz K., RA Hainque B.; RT "Identification of two novel mutations in the ventricular regulatory RT myosin light chain gene (MYL2) associated with familial and classical RT forms of hypertrophic cardiomyopathy."; RL J. Mol. Med. 76:208-214(1998). RN [12] RP VARIANTS CMH10 THR-13; LEU-18; LYS-22; GLN-58 AND ALA-95, AND RP CHARACTERIZATION OF VARIANTS CMH10 THR-13; LEU-18; LYS-22; GLN-58 AND RP ALA-95. RX PubMed=11102452; DOI=10.1074/jbc.M009823200; RA Szczesna D., Ghosh D., Li Q., Gomes A.V., Guzman G., Arana C., Zhi G., RA Stull J.T., Potter J.D.; RT "Familial hypertrophic cardiomyopathy mutations in the regulatory RT light chains of myosin affect their structure, Ca2+ binding, and RT phosphorylation."; RL J. Biol. Chem. 276:7086-7092(2001). RN [13] RP VARIANTS CMH10 LYS-22 AND GLN-58. RX PubMed=12404107; DOI=10.1038/sj.ejhg.5200872; RA Kabaeva Z.T., Perrot A., Wolter B., Dietz R., Cardim N., Correia J.M., RA Schulte H.D., Aldashev A.A., Mirrakhimov M.M., Osterziel K.J.; RT "Systematic analysis of the regulatory and essential myosin light RT chain genes: genetic variants and mutations in hypertrophic RT cardiomyopathy."; RL Eur. J. Hum. Genet. 10:741-748(2002). RN [14] RP VARIANT CMH10 VAL-166. RX PubMed=12707239; DOI=10.1161/01.CIR.0000066323.15244.54; RA Richard P., Charron P., Carrier L., Ledeuil C., Cheav T., RA Pichereau C., Benaiche A., Isnard R., Dubourg O., Burban M., RA Gueffet J.-P., Millaire A., Desnos M., Schwartz K., Hainque B., RA Komajda M.; RT "Hypertrophic cardiomyopathy: distribution of disease genes, spectrum RT of mutations, and implications for a molecular diagnosis strategy."; RL Circulation 107:2227-2232(2003). RN [15] RP ERRATUM. RA Richard P., Charron P., Carrier L., Ledeuil C., Cheav T., RA Pichereau C., Benaiche A., Isnard R., Dubourg O., Burban M., RA Gueffet J.-P., Millaire A., Desnos M., Schwartz K., Hainque B., RA Komajda M.; RL Circulation 109:3258-3258(2004). RN [16] RP VARIANT CMH10 GLN-58. RX PubMed=12818575; DOI=10.1016/S0022-2828(03)00146-9; RA Moerner S., Richard P., Kazzam E., Hellman U., Hainque B., RA Schwartz K., Waldenstroem A.; RT "Identification of the genotypes causing hypertrophic cardiomyopathy RT in northern Sweden."; RL J. Mol. Cell. Cardiol. 35:841-849(2003). CC -!- FUNCTION: Contractile protein that plays a role in heart CC development and function (By similarity). Following CC phosphorylation, plays a role in cross-bridge cycling kinetics and CC cardiac muscle contraction by increasing myosin lever arm CC stiffness and promoting myosin head diffusion; as a consequence of CC the increase in maximum contraction force and calcium sensitivity CC of contraction force. These events altogether slow down myosin CC kinetics and prolong duty cycle resulting in accumulated myosins CC being cooperatively recruited to actin binding sites to sustain CC thin filament activation as a means to fine-tune myofilament CC calcium sensitivity to force (By similarity). During cardiogenesis CC plays an early role in cardiac contractility by promoting cardiac CC myofibril assembly (By similarity). {ECO:0000250|UniProtKB:P08733, CC ECO:0000250|UniProtKB:P51667}. CC -!- SUBUNIT: Myosin is a hexamer of 2 heavy chains and 4 light chains. CC Interacts with MYOC (PubMed:11773029). {ECO:0000250, CC ECO:0000269|PubMed:11773029}. CC -!- INTERACTION: CC P35125-3:USP6; NbExp=5; IntAct=EBI-725770, EBI-954590; CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, A band CC {ECO:0000250|UniProtKB:P08733}. CC -!- PTM: N-terminus is methylated by METTL11A/NTM1. CC {ECO:0000250|UniProtKB:P51667}. CC -!- PTM: Phosphorylated by MYLK3 and MYLK2; promotes cardiac muscle CC contraction and function (By similarity). Dephosphorylated by CC PPP1CB complexed to PPP1R12B (By similarity). The phosphorylated CC form in adult is expressed as gradients across the heart from CC endocardium (low phosphorylation) to epicardium (high CC phosphorylation); regulates cardiac torsion and workload CC distribution (By similarity). {ECO:0000250|UniProtKB:P08733, CC ECO:0000250|UniProtKB:P51667}. CC -!- DISEASE: Cardiomyopathy, familial hypertrophic 10 (CMH10) CC [MIM:608758]: A hereditary heart disorder characterized by CC ventricular hypertrophy, which is usually asymmetric and often CC involves the interventricular septum. The symptoms include CC dyspnea, syncope, collapse, palpitations, and chest pain. They can CC be readily provoked by exercise. The disorder has inter- and CC intrafamilial variability ranging from benign to malignant forms CC with high risk of cardiac failure and sudden cardiac death. CC Rarely, patients present a variant of familial hypertrophic CC cardiomyopathy, characterized by mid-left ventricular chamber CC thickening. {ECO:0000269|PubMed:11102452, CC ECO:0000269|PubMed:12404107, ECO:0000269|PubMed:12707239, CC ECO:0000269|PubMed:12818575, ECO:0000269|PubMed:8673105, CC ECO:0000269|PubMed:9535554}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- MISCELLANEOUS: This chain binds calcium. CC -!- SIMILARITY: Contains 3 EF-hand domains. {ECO:0000255|PROSITE- CC ProRule:PRU00448}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X14332; CAA32510.1; -; mRNA. DR EMBL; M22815; AAA91832.1; -; mRNA. DR EMBL; AF020768; AAB91993.1; -; mRNA. DR EMBL; S69022; AAB29658.2; -; mRNA. DR EMBL; BC015821; AAH15821.1; -; mRNA. DR EMBL; BC031006; AAH31006.1; -; mRNA. DR EMBL; BC031008; AAH31008.1; -; mRNA. DR CCDS; CCDS31901.1; -. DR RefSeq; NP_000423.2; NM_000432.3. DR UniGene; Hs.75535; -. DR ProteinModelPortal; P10916; -. DR SMR; P10916; -. DR BioGrid; 110717; 11. DR IntAct; P10916; 5. DR MINT; MINT-1430124; -. DR STRING; 9606.ENSP00000228841; -. DR iPTMnet; P10916; -. DR PhosphoSitePlus; P10916; -. DR BioMuta; MYL2; -. DR DMDM; 6166556; -. DR UCD-2DPAGE; P10916; -. DR PaxDb; P10916; -. DR PeptideAtlas; P10916; -. DR PRIDE; P10916; -. DR DNASU; 4633; -. DR Ensembl; ENST00000228841; ENSP00000228841; ENSG00000111245. DR GeneID; 4633; -. DR KEGG; hsa:4633; -. DR CTD; 4633; -. DR DisGeNET; 4633; -. DR GeneCards; MYL2; -. DR GeneReviews; MYL2; -. DR HGNC; HGNC:7583; MYL2. DR HPA; HPA019763; -. DR HPA; HPA039262; -. DR MalaCards; MYL2; -. DR MIM; 160781; gene. DR MIM; 608758; phenotype. DR neXtProt; NX_P10916; -. DR OpenTargets; ENSG00000111245; -. DR Orphanet; 2020; Congenital fiber-type disproportion myopathy. DR Orphanet; 155; Familial isolated hypertrophic cardiomyopathy. DR PharmGKB; PA31380; -. DR eggNOG; KOG0031; Eukaryota. DR eggNOG; COG5126; LUCA. DR GeneTree; ENSGT00760000119196; -. DR HOGENOM; HOG000233018; -. DR HOVERGEN; HBG012180; -. DR InParanoid; P10916; -. DR KO; K10351; -. DR OMA; KDYVTEM; -. DR OrthoDB; EOG091G0QF6; -. DR PhylomeDB; P10916; -. DR TreeFam; TF314218; -. DR BioCyc; ZFISH:ENSG00000111245-MONOMER; -. DR Reactome; R-HSA-390522; Striated Muscle Contraction. DR SIGNOR; P10916; -. DR ChiTaRS; MYL2; human. DR GeneWiki; MYL2; -. DR GenomeRNAi; 4633; -. DR PRO; PR:P10916; -. DR Proteomes; UP000005640; Chromosome 12. DR Bgee; ENSG00000111245; -. DR CleanEx; HS_MYL2; -. DR ExpressionAtlas; P10916; baseline and differential. DR Genevisible; P10916; HS. DR GO; GO:0031672; C:A band; IEA:UniProtKB-SubCell. DR GO; GO:0005856; C:cytoskeleton; IDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030016; C:myofibril; NAS:BHF-UCL. DR GO; GO:0016459; C:myosin complex; TAS:BHF-UCL. 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; IDA:MGI. DR GO; GO:0032036; F:myosin heavy chain binding; NAS:BHF-UCL. DR GO; GO:0008307; F:structural constituent of muscle; NAS:BHF-UCL. DR GO; GO:0060048; P:cardiac muscle contraction; IEA:Ensembl. DR GO; GO:0055003; P:cardiac myofibril assembly; ISS:BHF-UCL. DR GO; GO:0060047; P:heart contraction; ISS:BHF-UCL. DR GO; GO:0007507; P:heart development; ISS:UniProtKB. DR GO; GO:0042694; P:muscle cell fate specification; IEA:Ensembl. DR GO; GO:0048747; P:muscle fiber development; IEA:Ensembl. DR GO; GO:0030049; P:muscle filament sliding; TAS:Reactome. DR GO; GO:0030308; P:negative regulation of cell growth; IMP:BHF-UCL. DR GO; GO:0098735; P:positive regulation of the force of heart contraction; ISS:UniProtKB. DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl. DR GO; GO:0006942; P:regulation of striated muscle contraction; TAS:ProtInc. DR GO; GO:0002026; P:regulation of the force of heart contraction; ISS:UniProtKB. DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP:BHF-UCL. DR Gene3D; 1.10.238.10; -; 2. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR018247; EF_Hand_1_Ca_BS. DR InterPro; IPR002048; EF_hand_dom. DR Pfam; PF13405; EF-hand_6; 1. DR SMART; SM00054; EFh; 3. DR SUPFAM; SSF47473; SSF47473; 1. DR PROSITE; PS00018; EF_HAND_1; 1. DR PROSITE; PS50222; EF_HAND_2; 3. PE 1: Evidence at protein level; KW Calcium; Cardiomyopathy; Complete proteome; Cytoplasm; KW Direct protein sequencing; Disease mutation; Metal-binding; KW Methylation; Motor protein; Muscle protein; Myosin; Phosphoprotein; KW Polymorphism; Reference proteome; Repeat. FT INIT_MET 1 1 Removed. {ECO:0000250|UniProtKB:P51667}. FT CHAIN 2 166 Myosin regulatory light chain 2, FT ventricular/cardiac muscle isoform. FT /FTId=PRO_0000198727. FT DOMAIN 24 59 EF-hand 1. {ECO:0000255|PROSITE- FT ProRule:PRU00448}. FT DOMAIN 94 129 EF-hand 2. {ECO:0000255|PROSITE- FT ProRule:PRU00448}. FT DOMAIN 130 165 EF-hand 3. {ECO:0000255|PROSITE- FT ProRule:PRU00448}. FT CA_BIND 37 48 FT MOD_RES 2 2 N,N,N-trimethylalanine. FT {ECO:0000250|UniProtKB:P51667}. FT MOD_RES 14 14 Deamidated asparagine. FT {ECO:0000269|PubMed:20445002}. FT MOD_RES 15 15 Phosphoserine; by ZIPK/DAPK3. FT {ECO:0000269|PubMed:20038585, FT ECO:0000269|PubMed:20445002}. FT MOD_RES 19 19 Phosphoserine. FT {ECO:0000250|UniProtKB:P51667}. FT MOD_RES 52 52 Phosphothreonine. FT {ECO:0000250|UniProtKB:P08733}. FT VARIANT 13 13 A -> T (in CMH10; with mid-left FT ventricular chamber thickening; decrease FT calcium binding affinity; large increase FT in its calcium binding affinity upon FT phosphorylation; dbSNP:rs104894363). FT {ECO:0000269|PubMed:11102452, FT ECO:0000269|PubMed:8673105}. FT /FTId=VAR_004601. FT VARIANT 18 18 F -> L (in CMH10; decrease calcium FT binding affinity; dbSNP:rs28932774). FT {ECO:0000269|PubMed:11102452, FT ECO:0000269|PubMed:9535554}. FT /FTId=VAR_004602. FT VARIANT 22 22 E -> K (in CMH10; some patients present FT with mid-left ventricular chamber FT thickening; significantly decrease FT calcium binding affinity; loss of FT phosphorylation; dbSNP:rs104894368). FT {ECO:0000269|PubMed:11102452, FT ECO:0000269|PubMed:12404107, FT ECO:0000269|PubMed:8673105}. FT /FTId=VAR_004603. FT VARIANT 57 57 G -> R (in dbSNP:rs2428140). FT /FTId=VAR_029449. FT VARIANT 58 58 R -> Q (in CMH10; impairs calcium FT binding; bind calcium upon FT phosphorylation; dbSNP:rs28933099). FT {ECO:0000269|PubMed:11102452, FT ECO:0000269|PubMed:12404107, FT ECO:0000269|PubMed:12818575, FT ECO:0000269|PubMed:9535554}. FT /FTId=VAR_004604. FT VARIANT 95 95 P -> A (in CMH10; with mid-left FT ventricular chamber thickening; decrease FT calcium binding affinity; FT dbSNP:rs121913658). FT {ECO:0000269|PubMed:11102452, FT ECO:0000269|PubMed:8673105}. FT /FTId=VAR_004605. FT VARIANT 166 166 D -> V (in CMH10; dbSNP:rs199474815). FT {ECO:0000269|PubMed:12707239}. FT /FTId=VAR_019844. SQ SEQUENCE 166 AA; 18789 MW; EA0BEF886AA3FAF5 CRC64; MAPKKAKKRA GGANSNVFSM FEQTQIQEFK EAFTIMDQNR DGFIDKNDLR DTFAALGRVN VKNEEIDEMI KEAPGPINFT VFLTMFGEKL KGADPEETIL NAFKVFDPEG KGVLKADYVR EMLTTQAERF SKEEVDQMFA AFPPDVTGNL DYKNLVHIIT HGEEKD //