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Protein

Myosin regulatory light chain 2, ventricular/cardiac muscle isoform

Gene

Myl2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Contractile protein that plays a role in heart development and function (PubMed:10409661). Following phosphorylation, plays a role in cross-bridge cycling kinetics and cardiac muscle contraction by increasing myosin lever arm stiffness and promoting myosin head diffusion; as a consequence of the increase in maximum contraction force and calcium sensitivity of contraction force. These events altogether slow down myosin kinetics and prolong duty cycle resulting in accumulated myosins being cooperatively recruited to actin binding sites to sustain thin filament activation as a means to fine-tune myofilament calcium sensitivity to force (By similarity) (PubMed:22426213, PubMed:16908724, PubMed:10409661). During cardiogenesis plays an early role in cardiac contractility by promoting cardiac myofibril assembly (PubMed:9422794).By similarity4 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi37 – 4812Add
BLAST

GO - Molecular functioni

GO - Biological processi

  • cardiac muscle contraction Source: MGI
  • cardiac myofibril assembly Source: MGI
  • heart contraction Source: UniProtKB
  • heart development Source: UniProtKB
  • heart morphogenesis Source: MGI
  • muscle cell fate specification Source: MGI
  • muscle fiber development Source: MGI
  • negative regulation of cell growth Source: MGI
  • positive regulation of the force of heart contraction Source: UniProtKB
  • post-embryonic development Source: MGI
  • ventricular cardiac muscle tissue morphogenesis Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Motor protein, Muscle protein, Myosin

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-390522. Striated Muscle Contraction.

Names & Taxonomyi

Protein namesi
Recommended name:
Myosin regulatory light chain 2, ventricular/cardiac muscle isoformCurated
Short name:
MLC-21 Publication
Short name:
MLC-2v
Alternative name(s):
Myosin light chain 2, slow skeletal/ventricular muscle isoformBy similarity
Short name:
MLC-2s/vBy similarity
Gene namesi
Name:Myl2Imported
Synonyms:MylpcImported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:97272. Myl2.

Subcellular locationi

  • CytoplasmmyofibrilsarcomereA band By similarity

GO - Cellular componenti

  • A band Source: UniProtKB-SubCell
  • cytoskeleton Source: MGI
  • myofibril Source: MGI
  • myosin complex Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Myl2 homozygous die at E12.5, which is associated with ultrastructural defects in ventricular sarcomere assembly, that included disruptions and disorganization of the normal parallel alignment of the thick and thin filaments, narrower fiber widths and larger distances between Z disks and misalignment of Z-band between sarcomeres.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi14 – 141S → A: Loss of cardiac myofibril assembly; when associated with A-15 and A-19. Loss of phosphorylation; when associated with A-15 and A-19. Loss of calcium sensitivity of force development; when associated with A-15 and A-19. Phosphorylation at Ser-19; when associated with A-15. Significant decrease in phosphorylation by MLCK; when associated with A-15. Adult lethality associated with early defects in cardiac twitch relaxation and torsion leading to dilated cardiomyopathy, heart failure and premature death; when associated with A-15.Significant acceleration of twitch relaxation in absence of changes in calcium transients; when associated with A-15. Absence of transmural phosphorylation gradient leading to alteration of torsion; when associated with A-14. 2 Publications
Mutagenesisi15 – 151S → A: Loss of cardiac myofibril assembly; when associated with A-14 and A-19. Loss of phosphorylation; when associated with A-14 and A-19. Loss of calcium sensitivity of force development; when associated with A-14 and A-19. Increase of phosphorylation. Phosphorylation at Ser-14 and at Ser-19. Phosphorylation at Ser-19; when associated with A-14. Significant decrease in phosphorylation by MLCK; when associated with A-14. Adult lethality associated with early defects in cardiac twitch relaxation and torsion leading to dilated cardiomyopathy, heart failure and premature death; when associated with A-14. Significant acceleration of twitch relaxation in absence of changes in calcium transients; when associated with A-14. Absence of transmural phosphorylation gradient leading to alteration of torsion; when associated with A-14. 2 Publications
Mutagenesisi19 – 191S → A: Loss of cardiac myofibril assembly; when associated with A-14 and A-15. Loss of phosphorylation; when associated with A-14 and A-15. Loss of calcium sensitivity of force development; when associated with A-14 and A-15. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved1 Publication
Chaini2 – 166165Myosin regulatory light chain 2, ventricular/cardiac muscle isoformPRO_0000198728Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N,N,N-trimethylalanine1 Publication
Modified residuei14 – 141Phosphoserine; by MLCKCombined sources2 Publications
Modified residuei15 – 151Phosphoserine; by MLCKCombined sources2 Publications
Modified residuei19 – 191PhosphoserineCombined sources1 Publication
Modified residuei52 – 521PhosphothreonineBy similarity

Post-translational modificationi

N-terminus is methylated by METTL11A/NTM1.1 Publication
Phosphorylated by MYLK3 and MYLK2; promotes cardiac muscle contraction and function. Dephosphorylated by PPP1CB complexed to PPP1R12B (By similarity). The phosphorylated form in adult is expressed as gradients across the heart from endocardium (low phosphorylation) to epicardium (high phosphorylation); regulates cardiac torsion and workload distribution (PubMed:22426213).By similarity2 Publications

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

MaxQBiP51667.
PaxDbiP51667.
PeptideAtlasiP51667.
PRIDEiP51667.
TopDownProteomicsiP51667.

PTM databases

iPTMnetiP51667.
PhosphoSiteiP51667.

Expressioni

Tissue specificityi

Abundantly expressed in both cardiac and slow skeletal muscle (PubMed:1379240). In the adult heart, the phosphorylated form is highly expressed in epicardium and weakly in endocardium (PubMed:22426213).2 Publications

Developmental stagei

At 8 dpc highly expressed in the ventricular portion of the heart tube, with no detectable expression in the atrial or sinus venosus regions; also expressed in the proximal outflow tract of the heart tube at minimally detectable levels. At 9-10 dpc expression is well established in the proximal outflow tract region adjacent to the ventricular segment. At 11 dpc, expression becomes restricted to the ventricular region.1 Publication

Gene expression databases

BgeeiENSMUSG00000013936.
ExpressionAtlasiP51667. baseline and differential.
GenevisibleiP51667. MM.

Interactioni

Subunit structurei

Myosin is a hexamer of 2 heavy chains and 4 light chains (By similarity). Interacts with MYOC (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiP51667. 3 interactions.
MINTiMINT-4130491.
STRINGi10090.ENSMUSP00000014080.

Structurei

3D structure databases

ProteinModelPortaliP51667.
SMRiP51667. Positions 16-165.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini24 – 5936EF-hand 1PROSITE-ProRule annotationAdd
BLAST
Domaini94 – 12936EF-hand 2PROSITE-ProRule annotationAdd
BLAST
Domaini130 – 16536EF-hand 3PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 3 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0031. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00760000119196.
HOGENOMiHOG000233018.
HOVERGENiHBG012180.
InParanoidiP51667.
KOiK10351.
OMAiKDYVTEM.
PhylomeDBiP51667.
TreeFamiTF314218.

Family and domain databases

Gene3Di1.10.238.10. 2 hits.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]
PfamiPF13405. EF-hand_6. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 3 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P51667-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPKKAKKRI EGGSSNVFSM FEQTQIQEFK EAFTIMDQNR DGFIDKNDLR
60 70 80 90 100
DTFAALGRVN VKNEEIDEMI KEAPGPINFT VFLTMFGEKL KGADPEETIL
110 120 130 140 150
NAFKVFDPEG KGSLKADYVR EMLTTQAERF SKEEIDQMFA AFPPDVTGNL
160
DYKNLVHIIT HGEEKD
Length:166
Mass (Da):18,864
Last modified:April 3, 2007 - v3
Checksum:iEA25C1FAA18E2EA8
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti4 – 52KK → LF in AAA39796 (PubMed:1379240).Curated
Sequence conflicti14 – 141S → T in AAA39796 (PubMed:1379240).Curated
Sequence conflicti128 – 1281E → G in AAH61144 (PubMed:15489334).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M91602 mRNA. Translation: AAA39796.1.
AK002367 mRNA. Translation: BAB22045.1.
AK146674 mRNA. Translation: BAE27350.1.
BC061144 mRNA. Translation: AAH61144.1.
CCDSiCCDS39252.1.
PIRiA42858.
RefSeqiNP_034991.3. NM_010861.3.
UniGeneiMm.1529.

Genome annotation databases

EnsembliENSMUST00000014080; ENSMUSP00000014080; ENSMUSG00000013936.
ENSMUST00000111751; ENSMUSP00000107380; ENSMUSG00000013936.
GeneIDi17906.
KEGGimmu:17906.
UCSCiuc008zkp.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M91602 mRNA. Translation: AAA39796.1.
AK002367 mRNA. Translation: BAB22045.1.
AK146674 mRNA. Translation: BAE27350.1.
BC061144 mRNA. Translation: AAH61144.1.
CCDSiCCDS39252.1.
PIRiA42858.
RefSeqiNP_034991.3. NM_010861.3.
UniGeneiMm.1529.

3D structure databases

ProteinModelPortaliP51667.
SMRiP51667. Positions 16-165.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP51667. 3 interactions.
MINTiMINT-4130491.
STRINGi10090.ENSMUSP00000014080.

PTM databases

iPTMnetiP51667.
PhosphoSiteiP51667.

Proteomic databases

MaxQBiP51667.
PaxDbiP51667.
PeptideAtlasiP51667.
PRIDEiP51667.
TopDownProteomicsiP51667.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000014080; ENSMUSP00000014080; ENSMUSG00000013936.
ENSMUST00000111751; ENSMUSP00000107380; ENSMUSG00000013936.
GeneIDi17906.
KEGGimmu:17906.
UCSCiuc008zkp.1. mouse.

Organism-specific databases

CTDi4633.
MGIiMGI:97272. Myl2.

Phylogenomic databases

eggNOGiKOG0031. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00760000119196.
HOGENOMiHOG000233018.
HOVERGENiHBG012180.
InParanoidiP51667.
KOiK10351.
OMAiKDYVTEM.
PhylomeDBiP51667.
TreeFamiTF314218.

Enzyme and pathway databases

ReactomeiR-MMU-390522. Striated Muscle Contraction.

Miscellaneous databases

PROiP51667.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000013936.
ExpressionAtlasiP51667. baseline and differential.
GenevisibleiP51667. MM.

Family and domain databases

Gene3Di1.10.238.10. 2 hits.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]
PfamiPF13405. EF-hand_6. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 3 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMLRV_MOUSE
AccessioniPrimary (citable) accession number: P51667
Secondary accession number(s): Q6P8P4, Q9QVP3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: April 3, 2007
Last modified: September 7, 2016
This is version 135 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

This chain binds calcium.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.