P10916 · MLRV_HUMAN
- ProteinMyosin regulatory light chain 2, ventricular/cardiac muscle isoform
- GeneMYL2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids166 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Contractile protein that plays a role in heart development and function (PubMed:23365102, PubMed:32453731).
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).
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).
Miscellaneous
This chain binds calcium.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | A band | |
Cellular Component | cardiac myofibril | |
Cellular Component | cytoplasm | |
Cellular Component | cytoskeleton | |
Cellular Component | cytosol | |
Cellular Component | myofibril | |
Cellular Component | myosin complex | |
Cellular Component | sarcomere | |
Molecular Function | actin monomer binding | |
Molecular Function | calcium ion binding | |
Molecular Function | myosin heavy chain binding | |
Molecular Function | structural constituent of muscle | |
Biological Process | cardiac muscle contraction | |
Biological Process | cardiac myofibril assembly | |
Biological Process | heart contraction | |
Biological Process | heart development | |
Biological Process | muscle cell fate specification | |
Biological Process | negative regulation of cell growth | |
Biological Process | positive regulation of the force of heart contraction | |
Biological Process | regulation of striated muscle contraction | |
Biological Process | regulation of the force of heart contraction | |
Biological Process | ventricular cardiac muscle tissue morphogenesis |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMyosin regulatory light chain 2, ventricular/cardiac muscle isoform
- Short namesMLC-2 ; MLC-2v
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP10916
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Cardiomyopathy, familial hypertrophic, 10 (CMH10)
- Note
- 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 alsoMIM:608758
Natural variants in CMH10
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_004601 | 13 | A>T | in CMH10; with mid-left ventricular chamber thickening; decrease calcium binding affinity; large increase in its calcium binding affinity upon phosphorylation; dbSNP:rs104894363 | |
VAR_004602 | 18 | F>L | in CMH10; decrease calcium binding affinity; dbSNP:rs104894370 | |
VAR_004603 | 22 | E>K | in CMH10; some patients present with mid-left ventricular chamber thickening; significantly decrease calcium binding affinity; loss of phosphorylation; dbSNP:rs104894368 | |
VAR_004604 | 58 | R>Q | in CMH10; impairs calcium binding; bind calcium upon phosphorylation; dbSNP:rs104894369 | |
VAR_004605 | 95 | P>A | in CMH10; with mid-left ventricular chamber thickening; decrease calcium binding affinity; dbSNP:rs121913658 | |
VAR_019844 | 166 | D>V | in CMH10; dbSNP:rs199474815 |
Myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy (MFM12)
- Note
- DescriptionA form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM12 is an autosomal recessive, severe form characterized by progressive myopathy with onset shortly after birth, tremor or clonus at birth, and cardiomyopathy usually leading to death by 6 months of age. Skeletal and cardiac muscle tissues show fiber-type disproportion with small type I and normal sized type II fibers, and myofibrillar disorganization.
- See alsoMIM:619424
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_004601 | 13 | in CMH10; with mid-left ventricular chamber thickening; decrease calcium binding affinity; large increase in its calcium binding affinity upon phosphorylation; dbSNP:rs104894363 | |||
Sequence: A → T | ||||||
Natural variant | VAR_004602 | 18 | in CMH10; decrease calcium binding affinity; dbSNP:rs104894370 | |||
Sequence: F → L | ||||||
Natural variant | VAR_004603 | 22 | in CMH10; some patients present with mid-left ventricular chamber thickening; significantly decrease calcium binding affinity; loss of phosphorylation; dbSNP:rs104894368 | |||
Sequence: E → K | ||||||
Natural variant | VAR_029449 | 57 | in dbSNP:rs2428140 | |||
Sequence: G → R | ||||||
Natural variant | VAR_004604 | 58 | in CMH10; impairs calcium binding; bind calcium upon phosphorylation; dbSNP:rs104894369 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_004605 | 95 | in CMH10; with mid-left ventricular chamber thickening; decrease calcium binding affinity; dbSNP:rs121913658 | |||
Sequence: P → A | ||||||
Natural variant | VAR_019844 | 166 | in CMH10; dbSNP:rs199474815 | |||
Sequence: D → V |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 317 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N,N,N-trimethylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000198727 | 2-166 | UniProt | Myosin regulatory light chain 2, ventricular/cardiac muscle isoform | |||
Sequence: APKKAKKRAGGANSNVFSMFEQTQIQEFKEAFTIMDQNRDGFIDKNDLRDTFAALGRVNVKNEEIDEMIKEAPGPINFTVFLTMFGEKLKGADPEETILNAFKVFDPEGKGVLKADYVREMLTTQAERFSKEEVDQMFAAFPPDVTGNLDYKNLVHIITHGEEKD | |||||||
Modified residue | 14 | UniProt | Deamidated asparagine | ||||
Sequence: N | |||||||
Modified residue | 15 | UniProt | Phosphoserine; by ZIPK/DAPK3 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 15 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 19 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 19 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 52 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 125 | PRIDE | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
N-terminus is methylated by METTL11A/NTM1.
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).
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).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in type I muscle fibers.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Myosin is a hexamer of 2 heavy chains and 4 light chains. Interacts with MYOC (PubMed:11773029).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P10916 | IRX6 P78412 | 3 | EBI-725770, EBI-12100506 | |
BINARY | P10916 | MYOC Q99972 | 7 | EBI-725770, EBI-11692272 | |
BINARY | P10916 | PSORS1C2 Q9UIG4 | 3 | EBI-725770, EBI-11974061 | |
BINARY | P10916 | USP6 P35125-3 | 5 | EBI-725770, EBI-954590 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 24-59 | EF-hand 1 | ||||
Sequence: TQIQEFKEAFTIMDQNRDGFIDKNDLRDTFAALGRV | ||||||
Domain | 94-129 | EF-hand 2 | ||||
Sequence: DPEETILNAFKVFDPEGKGVLKADYVREMLTTQAER | ||||||
Domain | 130-165 | EF-hand 3 | ||||
Sequence: FSKEEVDQMFAAFPPDVTGNLDYKNLVHIITHGEEK |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length166
- Mass (Da)18,789
- Last updated2007-01-23 v3
- ChecksumEA0BEF886AA3FAF5
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0AAQ5BH12 | A0AAQ5BH12_HUMAN | MYL2 | 131 | ||
G3V1V8 | G3V1V8_HUMAN | MYL2 | 152 | ||
A0A590UJU8 | A0A590UJU8_HUMAN | MYL2 | 147 | ||
A0A590UK07 | A0A590UK07_HUMAN | MYL2 | 82 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X14332 EMBL· GenBank· DDBJ | CAA32510.1 EMBL· GenBank· DDBJ | mRNA | ||
M22815 EMBL· GenBank· DDBJ | AAA91832.1 EMBL· GenBank· DDBJ | mRNA | ||
AF020768 EMBL· GenBank· DDBJ | AAB91993.1 EMBL· GenBank· DDBJ | mRNA | ||
S69022 EMBL· GenBank· DDBJ | AAB29658.2 EMBL· GenBank· DDBJ | mRNA | ||
BC015821 EMBL· GenBank· DDBJ | AAH15821.1 EMBL· GenBank· DDBJ | mRNA | ||
BC031006 EMBL· GenBank· DDBJ | AAH31006.1 EMBL· GenBank· DDBJ | mRNA | ||
BC031008 EMBL· GenBank· DDBJ | AAH31008.1 EMBL· GenBank· DDBJ | mRNA |