MLRV_RAT
ID MLRV_RAT Reviewed; 166 AA.
AC P08733; A0JMZ7;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Myosin regulatory light chain 2, ventricular/cardiac muscle isoform {ECO:0000305};
DE Short=MLC-2 {ECO:0000305};
DE Short=MLC-2v;
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};
GN Name=Myl2 {ECO:0000312|RGD:1564245};
GN Synonyms=Mlc2 {ECO:0000312|RGD:1564245};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=3005270; DOI=10.1016/s0021-9258(17)35867-2;
RA Kumar C.C., Cribbs L., Delaney P., Chien K.R., Siddiqui M.A.Q.;
RT "Heart myosin light chain 2 gene. Nucleotide sequence of full length cDNA
RT and expression in normal and hypertensive rat.";
RL J. Biol. Chem. 261:2866-2872(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RX PubMed=3380697; DOI=10.1093/nar/16.10.4722;
RA Henderson S.A., You-Cheng X., Sen A., Chien K.R.;
RT "Nucleotide sequence of full length cDNAs encoding rat cardiac myosin light
RT chain-2.";
RL Nucleic Acids Res. 16:4722-4722(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Heart;
RX PubMed=2808370; DOI=10.1016/s0021-9258(19)84688-4;
RA Henderson S.A., Spencer M., Sen A., Kumar C., Siddiqui M.A.Q., Chien K.R.;
RT "Structure, organization, and expression of the rat cardiac myosin light
RT chain-2 gene. Identification of a 250-base pair fragment which confers
RT cardiac-specific expression.";
RL J. Biol. Chem. 264:18142-18148(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 TISSUE SPECIFICITY.
RX PubMed=1379240; DOI=10.1016/s0021-9258(19)49616-6;
RA Lee K.J., Ross R.S., Rockman H.A., Harris A.N., O'Brien T.X., Bilsen M.,
RA Shubeita H.E., Kandolf R., Brem G., Price J., Evans S.M., Zhu H.,
RA Franz W.M., Chien K.R.;
RT "Myosin light chain-2 luciferase transgenic mice reveal distinct regulatory
RT programs for cardiac and skeletal muscle-specific expression of a single
RT contractile protein gene.";
RL J. Biol. Chem. 267:15875-15885(1992).
RN [6]
RP FUNCTION.
RX PubMed=15331360; DOI=10.1152/ajpheart.01067.2003;
RA Olsson M.C., Patel J.R., Fitzsimons D.P., Walker J.W., Moss R.L.;
RT "Basal myosin light chain phosphorylation is a determinant of Ca2+
RT sensitivity of force and activation dependence of the kinetics of
RT myocardial force development.";
RL Am. J. Physiol. 287:H2712-H2718(2004).
RN [7]
RP DEPHOSPHORYLATION BY PPP1R12B-PPP1CB COMPLEX.
RX PubMed=16431080; DOI=10.1016/j.cellsig.2005.11.001;
RA Okamoto R., Kato T., Mizoguchi A., Takahashi N., Nakakuki T., Mizutani H.,
RA Isaka N., Imanaka-Yoshida K., Kaibuchi K., Lu Z., Mabuchi K., Tao T.,
RA Hartshorne D.J., Nakano T., Ito M.;
RT "Characterization and function of MYPT2, a target subunit of myosin
RT phosphatase in heart.";
RL Cell. Signal. 18:1408-1416(2006).
RN [8]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION BY MYLK3.
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-52, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Contractile protein that plays a role in heart development
CC and function (By similarity). Following phosphorylation, plays a role
CC in cross-bridge cycling kinetics and cardiac muscle contraction by
CC increasing myosin lever arm stiffness and promoting myosin head
CC diffusion; as a consequence of the increase in maximum contraction
CC force and calcium sensitivity of contraction force. These events
CC altogether slow down myosin kinetics and prolong duty cycle resulting
CC in accumulated myosins being cooperatively recruited to actin binding
CC sites to sustain thin filament activation as a means to fine-tune
CC myofilament calcium sensitivity to force (PubMed:15331360). During
CC cardiogenesis plays an early role in cardiac contractility by promoting
CC cardiac myofibril assembly (By similarity).
CC {ECO:0000250|UniProtKB:P51667, ECO:0000269|PubMed:15331360}.
CC -!- SUBUNIT: Myosin is a hexamer of 2 heavy chains and 4 light chains (By
CC similarity). Interacts with MYOC (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P10916}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, A band
CC {ECO:0000269|PubMed:17885681}.
CC -!- TISSUE SPECIFICITY: Abundantly expressed in both cardiac and slow
CC skeletal muscle (soleus), with no detectable expression in fast
CC skeletal muscle (vastus lateralis) or non-muscle tissue.
CC {ECO:0000269|PubMed:1379240}.
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) (PubMed:17885681).
CC Dephosphorylated by PPP1CB complexed to PPP1R12B (PubMed:16431080). The
CC phosphorylated form in adult is expressed as gradients across the heart
CC from endocardium (low phosphorylation) to epicardium (high
CC phosphorylation); regulates cardiac torsion and workload distribution
CC (By similarity). {ECO:0000250|UniProtKB:P51667,
CC ECO:0000269|PubMed:16431080, ECO:0000269|PubMed:17885681}.
CC -!- MISCELLANEOUS: This chain binds calcium.
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DR EMBL; M11851; AAA41621.1; -; mRNA.
DR EMBL; X07314; CAA30277.1; -; mRNA.
DR EMBL; M30304; AAA41624.1; -; Genomic_DNA.
DR EMBL; M30298; AAA41624.1; JOINED; Genomic_DNA.
DR EMBL; M30299; AAA41624.1; JOINED; Genomic_DNA.
DR EMBL; M30300; AAA41624.1; JOINED; Genomic_DNA.
DR EMBL; M30301; AAA41624.1; JOINED; Genomic_DNA.
DR EMBL; M30302; AAA41624.1; JOINED; Genomic_DNA.
DR EMBL; M30303; AAA41624.1; JOINED; Genomic_DNA.
DR EMBL; BC126064; AAI26065.1; -; mRNA.
DR PIR; S00752; MORT2C.
DR RefSeq; NP_001030329.2; NM_001035252.2.
DR AlphaFoldDB; P08733; -.
DR SMR; P08733; -.
DR BioGRID; 264496; 1.
DR iPTMnet; P08733; -.
DR PhosphoSitePlus; P08733; -.
DR PaxDb; P08733; -.
DR PRIDE; P08733; -.
DR Ensembl; ENSRNOT00000050368; ENSRNOP00000039707; ENSRNOG00000030848.
DR GeneID; 363925; -.
DR KEGG; rno:363925; -.
DR UCSC; RGD:1564245; rat.
DR CTD; 4633; -.
DR RGD; 1564245; Myl2.
DR eggNOG; KOG0031; Eukaryota.
DR GeneTree; ENSGT00940000155578; -.
DR InParanoid; P08733; -.
DR OrthoDB; 1435392at2759; -.
DR PhylomeDB; P08733; -.
DR Reactome; R-RNO-390522; Striated Muscle Contraction.
DR PRO; PR:P08733; -.
DR Proteomes; UP000002494; Chromosome 12.
DR GO; GO:0031672; C:A band; IEA:UniProtKB-SubCell.
DR GO; GO:0097512; C:cardiac myofibril; ISO:RGD.
DR GO; GO:0043292; C:contractile fiber; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; ISO:RGD.
DR GO; GO:0030016; C:myofibril; IDA:RGD.
DR GO; GO:0016459; C:myosin complex; IEA:UniProtKB-KW.
DR GO; GO:0003785; F:actin monomer binding; ISO:RGD.
DR GO; GO:0005509; F:calcium ion binding; ISO:RGD.
DR GO; GO:0008307; F:structural constituent of muscle; ISS:UniProtKB.
DR GO; GO:0060048; P:cardiac muscle contraction; IDA:RGD.
DR GO; GO:0055003; P:cardiac myofibril assembly; ISO:RGD.
DR GO; GO:0061049; P:cell growth involved in cardiac muscle cell development; IEP:RGD.
DR GO; GO:0060047; P:heart contraction; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR GO; GO:0003007; P:heart morphogenesis; ISO:RGD.
DR GO; GO:0055001; P:muscle cell development; ISO:RGD.
DR GO; GO:0042694; P:muscle cell fate specification; ISO:RGD.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:RGD.
DR GO; GO:0098735; P:positive regulation of the force of heart contraction; ISS:UniProtKB.
DR GO; GO:0009791; P:post-embryonic development; ISO:RGD.
DR GO; GO:0002026; P:regulation of the force of heart contraction; IDA:UniProtKB.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISO:RGD.
DR CDD; cd00051; EFh; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR Pfam; PF00036; EF-hand_1; 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; Cytoplasm; Metal-binding; Methylation; Motor protein;
KW Muscle protein; Myosin; Phosphoprotein; Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q3SZE5"
FT CHAIN 2..166
FT /note="Myosin regulatory light chain 2, ventricular/cardiac
FT muscle isoform"
FT /id="PRO_0000198729"
FT DOMAIN 24..59
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 94..129
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 130..165
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 37
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 39
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 41
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 48
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 2
FT /note="N,N,N-trimethylserine"
FT /evidence="ECO:0000250|UniProtKB:Q3SZE5"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51667"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10916"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51667"
FT MOD_RES 52
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CONFLICT 41
FT /note="D -> A (in Ref. 1; AAA41621)"
FT /evidence="ECO:0000305"
FT CONFLICT 87
FT /note="G -> R (in Ref. 1; AAA41621)"
FT /evidence="ECO:0000305"
FT CONFLICT 94
FT /note="D -> G (in Ref. 1; AAA41621)"
FT /evidence="ECO:0000305"
FT CONFLICT 99
FT /note="I -> L (in Ref. 1; AAA41621)"
FT /evidence="ECO:0000305"
FT CONFLICT 107..120
FT /note="DPEGKGSLKADYVR -> APRRRITGADCVQ (in Ref. 1;
FT AAA41621)"
FT /evidence="ECO:0000305"
FT CONFLICT 135
FT /note="I -> T (in Ref. 1; AAA41621)"
FT /evidence="ECO:0000305"
FT CONFLICT 145
FT /note="D -> N (in Ref. 1; AAA41621)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 166 AA; 18880 MW; 512FD14B06825275 CRC64;
MSPKKAKKRL EGGSSNVFSM FEQTQIQEFK EAFTIMDQNR DGFIDKNDLR DTFAALGRVN
VKNEEIDEMI KEAPGPINFT VFLTMFGEKL KGADPEETIL NAFKVFDPEG KGSLKADYVR
EMLTTQAERF SKEEIDQMFA AFPPDVTGNL DYKNLVHIIT HGEEKD
