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Protein

Myosin regulatory light chain 2, ventricular/cardiac muscle isoform

Gene

MYL2

Organism
Homo sapiens (Human)
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 (By similarity). 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). During cardiogenesis plays an early role in cardiac contractility by promoting cardiac myofibril assembly (By similarity).By similarity

Miscellaneous

This chain binds calcium.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi37 – 48Add BLAST12

GO - Molecular functioni

  • actin monomer binding Source: BHF-UCL
  • calcium ion binding Source: MGI
  • myosin heavy chain binding Source: BHF-UCL
  • structural constituent of muscle Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionMotor protein, Muscle protein, Myosin
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-390522. Striated Muscle Contraction.
SIGNORiP10916.

Names & Taxonomyi

Protein namesi
Recommended name:
Myosin regulatory light chain 2, ventricular/cardiac muscle isoformCurated
Short name:
MLC-2By similarity
Short name:
MLC-2v
Alternative name(s):
Cardiac myosin light chain 21 Publication
Myosin light chain 2, slow skeletal/ventricular muscle isoformBy similarity
Short name:
MLC-2s/vBy similarity
Ventricular myosin light chain 21 Publication
Gene namesi
Name:MYL2Imported
Synonyms:MLC21 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:7583. MYL2.

Subcellular locationi

  • CytoplasmmyofibrilsarcomereA band By similarity

GO - Cellular componenti

  • A band Source: UniProtKB-SubCell
  • cardiac myofibril Source: CAFA
  • cytoskeleton Source: BHF-UCL
  • cytosol Source: Reactome
  • myofibril Source: BHF-UCL
  • myosin complex Source: BHF-UCL
  • sarcomere Source: BHF-UCL

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Cardiomyopathy, familial hypertrophic 10 (CMH10)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. Rarely, patients present a variant of familial hypertrophic cardiomyopathy, characterized by mid-left ventricular chamber thickening.
See also OMIM:608758
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00460113A → T in CMH10; with mid-left ventricular chamber thickening; decrease calcium binding affinity; large increase in its calcium binding affinity upon phosphorylation. 2 PublicationsCorresponds to variant dbSNP:rs104894363Ensembl.1
Natural variantiVAR_00460218F → L in CMH10; decrease calcium binding affinity. 2 PublicationsCorresponds to variant dbSNP:rs28932774Ensembl.1
Natural variantiVAR_00460322E → K in CMH10; some patients present with mid-left ventricular chamber thickening; significantly decrease calcium binding affinity; loss of phosphorylation. 3 PublicationsCorresponds to variant dbSNP:rs104894368Ensembl.1
Natural variantiVAR_00460458R → Q in CMH10; impairs calcium binding; bind calcium upon phosphorylation. 4 PublicationsCorresponds to variant dbSNP:rs28933099Ensembl.1
Natural variantiVAR_00460595P → A in CMH10; with mid-left ventricular chamber thickening; decrease calcium binding affinity. 2 PublicationsCorresponds to variant dbSNP:rs121913658Ensembl.1
Natural variantiVAR_019844166D → V in CMH10. 1 PublicationCorresponds to variant dbSNP:rs199474815Ensembl.1

Keywords - Diseasei

Cardiomyopathy, Disease mutation

Organism-specific databases

DisGeNETi4633.
MalaCardsiMYL2.
MIMi608758. phenotype.
OpenTargetsiENSG00000111245.
Orphaneti2020. Congenital fiber-type disproportion myopathy.
155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBiPA31380.

Polymorphism and mutation databases

BioMutaiMYL2.
DMDMi6166556.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001987272 – 166Myosin regulatory light chain 2, ventricular/cardiac muscle isoformAdd BLAST165

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N,N,N-trimethylalanineBy similarity1
Modified residuei14Deamidated asparagine1 Publication1
Modified residuei15Phosphoserine; by ZIPK/DAPK32 Publications1
Modified residuei19PhosphoserineBy similarity1
Modified residuei52PhosphothreonineBy similarity1

Post-translational modificationi

N-terminus is methylated by METTL11A/NTM1.By similarity
Phosphorylated by MYLK3 and MYLK2; promotes cardiac muscle contraction and function (By similarity). 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 (By similarity).By similarity

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

PaxDbiP10916.
PeptideAtlasiP10916.
PRIDEiP10916.

2D gel databases

UCD-2DPAGEiP10916.

PTM databases

iPTMnetiP10916.
PhosphoSitePlusiP10916.

Expressioni

Gene expression databases

BgeeiENSG00000111245.
CleanExiHS_MYL2.
ExpressionAtlasiP10916. baseline and differential.
GenevisibleiP10916. HS.

Organism-specific databases

HPAiHPA019763.
HPA039262.

Interactioni

Subunit structurei

Myosin is a hexamer of 2 heavy chains and 4 light chains. Interacts with MYOC (PubMed:11773029).By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • actin monomer binding Source: BHF-UCL
  • myosin heavy chain binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi110717. 11 interactors.
IntActiP10916. 6 interactors.
MINTiMINT-1430124.
STRINGi9606.ENSP00000228841.

Structurei

3D structure databases

ProteinModelPortaliP10916.
SMRiP10916.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 59EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini94 – 129EF-hand 2PROSITE-ProRule annotationAdd BLAST36
Domaini130 – 165EF-hand 3PROSITE-ProRule annotationAdd BLAST36

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0031. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00760000119196.
HOGENOMiHOG000233018.
HOVERGENiHBG012180.
InParanoidiP10916.
KOiK10351.
OMAiIVTHRAE.
OrthoDBiEOG091G0QF6.
PhylomeDBiP10916.
TreeFamiTF314218.

Family and domain databases

CDDicd00051. EFh. 1 hit.
InterProiView protein in InterPro
IPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
PfamiView protein in Pfam
PF13405. EF-hand_6. 1 hit.
SMARTiView protein in SMART
SM00054. EFh. 3 hits.
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiView protein in PROSITE
PS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 3 hits.

Sequencei

Sequence statusi: Complete.

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

P10916-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPKKAKKRA GGANSNVFSM FEQTQIQEFK EAFTIMDQNR DGFIDKNDLR
60 70 80 90 100
DTFAALGRVN VKNEEIDEMI KEAPGPINFT VFLTMFGEKL KGADPEETIL
110 120 130 140 150
NAFKVFDPEG KGVLKADYVR EMLTTQAERF SKEEVDQMFA AFPPDVTGNL
160
DYKNLVHIIT HGEEKD
Length:166
Mass (Da):18,789
Last modified:January 23, 2007 - v3
Checksum:iEA0BEF886AA3FAF5
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00460113A → T in CMH10; with mid-left ventricular chamber thickening; decrease calcium binding affinity; large increase in its calcium binding affinity upon phosphorylation. 2 PublicationsCorresponds to variant dbSNP:rs104894363Ensembl.1
Natural variantiVAR_00460218F → L in CMH10; decrease calcium binding affinity. 2 PublicationsCorresponds to variant dbSNP:rs28932774Ensembl.1
Natural variantiVAR_00460322E → K in CMH10; some patients present with mid-left ventricular chamber thickening; significantly decrease calcium binding affinity; loss of phosphorylation. 3 PublicationsCorresponds to variant dbSNP:rs104894368Ensembl.1
Natural variantiVAR_02944957G → R. Corresponds to variant dbSNP:rs2428140Ensembl.1
Natural variantiVAR_00460458R → Q in CMH10; impairs calcium binding; bind calcium upon phosphorylation. 4 PublicationsCorresponds to variant dbSNP:rs28933099Ensembl.1
Natural variantiVAR_00460595P → A in CMH10; with mid-left ventricular chamber thickening; decrease calcium binding affinity. 2 PublicationsCorresponds to variant dbSNP:rs121913658Ensembl.1
Natural variantiVAR_019844166D → V in CMH10. 1 PublicationCorresponds to variant dbSNP:rs199474815Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14332 mRNA. Translation: CAA32510.1.
M22815 mRNA. Translation: AAA91832.1.
AF020768 mRNA. Translation: AAB91993.1.
S69022 mRNA. Translation: AAB29658.2.
BC015821 mRNA. Translation: AAH15821.1.
BC031006 mRNA. Translation: AAH31006.1.
BC031008 mRNA. Translation: AAH31008.1.
CCDSiCCDS31901.1.
RefSeqiNP_000423.2. NM_000432.3.
UniGeneiHs.75535.

Genome annotation databases

EnsembliENST00000228841; ENSP00000228841; ENSG00000111245.
GeneIDi4633.
KEGGihsa:4633.

Keywords - Coding sequence diversityi

Polymorphism

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.

Entry informationi

Entry nameiMLRV_HUMAN
AccessioniPrimary (citable) accession number: P10916
Secondary accession number(s): Q16123
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: January 23, 2007
Last modified: June 7, 2017
This is version 176 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot