Q921L3 · TMCO1_MOUSE
- ProteinCalcium load-activated calcium channel
- GeneTmco1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids188 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Endoplasmic reticulum (ER) calcium-selective channel preventing intracellular Ca2+ stores from overfilling and maintaining calcium homeostasis in the ER. In response to endoplasmic reticulum (ER) Ca2+ overloading, assembles into a homotetramer, forming a functional calcium-selective channel facilitating Ca2+ release (PubMed:27212239, PubMed:29467381, PubMed:30962442).
Mediates ER Ca2+ homeostasis in osteoblasts and plays a key role in bone formation, via the CaMKII-HDAC4-RUNX2 signaling axis (PubMed:30962442).
Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes (By similarity).
The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions (By similarity).
Within the MPT complex, the GEL subcomplex may mediate insertion of transmembrane regions into the membrane (By similarity).
Mediates ER Ca2+ homeostasis in osteoblasts and plays a key role in bone formation, via the CaMKII-HDAC4-RUNX2 signaling axis (PubMed:30962442).
Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes (By similarity).
The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions (By similarity).
Within the MPT complex, the GEL subcomplex may mediate insertion of transmembrane regions into the membrane (By similarity).
Catalytic activity
- Ca2+(in) = Ca2+(out)
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | Golgi membrane | |
Cellular Component | mitochondrial membrane | |
Cellular Component | multi-pass translocon complex | |
Molecular Function | calcium channel activity | |
Molecular Function | ribosome binding | |
Biological Process | calcium ion transmembrane transport | |
Biological Process | endoplasmic reticulum calcium ion homeostasis | |
Biological Process | ER overload response | |
Biological Process | multi-pass transmembrane protein insertion into ER membrane | |
Biological Process | ossification |
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameCalcium load-activated calcium channel
- Short namesCLAC channel
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ921L3
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Golgi apparatus membrane ; Multi-pass membrane protein
Mitochondrion membrane ; Multi-pass membrane protein
Note: The first transmembrane region is required for localization to the endoplasmic reticulum.
Features
Showing features for topological domain, transmembrane, intramembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-4 | Lumenal | ||||
Sequence: MSTM | ||||||
Transmembrane | 5-32 | Helical | ||||
Sequence: FADTLLIVFISVCTALLAEGITWVLVYR | ||||||
Topological domain | 33-86 | Cytoplasmic | ||||
Sequence: TDKYKRLKAEVEKQSKKLEKKKETITESAGRQQKKKIERQEEKLKNNNRDLSMV | ||||||
Transmembrane | 87-106 | Helical | ||||
Sequence: RMKSMFAIGFCFTALMGMFN | ||||||
Topological domain | 107-120 | Lumenal | ||||
Sequence: SIFDGRVVAKLPFT | ||||||
Intramembrane | 121-130 | |||||
Sequence: PLSYIQGLSH | ||||||
Topological domain | 131-140 | Lumenal | ||||
Sequence: RNLLGDDTTD | ||||||
Transmembrane | 141-162 | Helical | ||||
Sequence: CSFIFLYILCTMSIRQNIQKIL | ||||||
Topological domain | 163-188 | Cytoplasmic | ||||
Sequence: GLAPSRAATKQAGGFLGPPPPSGKFS |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mice are born at a much lower rate than predicted by the Mendelian ratio. Surviving mice show a reduced body size, low survival rate and delayed osteogenesis. Adult mice display craniofacial dysmorphism such as open cranial sutures, flattened faces with shorten nasal bones and skull anomalies. Moreover, magnetic resonance imaging (MRI) of brain shows significantly enlarged brain ventricles. Adult mice show defects in spatial recognition memory in a Y-maze task assay and a significant deficiency in motor coordination in rotarod assessments. Defects are probably due to calcium overload, calcium imaging results revealing a significant overload of endoplasmic reticulum calcium in osteoblasts (PubMed:27212239, PubMed:29467381).
Additionally female Tmco1-/- mice show impaired follicle development, subfertility, and premature ovarian failure (PubMed:29467381).
Additionally female Tmco1-/- mice show impaired follicle development, subfertility, and premature ovarian failure (PubMed:29467381).
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000244077 | 1-188 | Calcium load-activated calcium channel | |||
Sequence: MSTMFADTLLIVFISVCTALLAEGITWVLVYRTDKYKRLKAEVEKQSKKLEKKKETITESAGRQQKKKIERQEEKLKNNNRDLSMVRMKSMFAIGFCFTALMGMFNSIFDGRVVAKLPFTPLSYIQGLSHRNLLGDDTTDCSFIFLYILCTMSIRQNIQKILGLAPSRAATKQAGGFLGPPPPSGKFS | ||||||
Modified residue | 60 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 188 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Homodimer and homotetramer. Homodimer under resting conditions; forms homotetramers following ER calcium overload. Component of the GET- and EMC-like (GEL) complex, composed of RAB5IF/OPTI and TMCO1. The GEL complex is part of the multi-pass translocon (MPT) complex, composed of three subcomplexes, the GEL complex (composed of RAB5IF/OPTI and TMCO1), the BOS complex (composed of NCLN/Nicalin, NOMO1 and TMEM147) and the PAT complex (composed of WDR83OS/Asterix and CCDC47). The MPT complex associates with the SEC61 complex.
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for coiled coil.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Coiled coil | 32-89 | |||||
Sequence: RTDKYKRLKAEVEKQSKKLEKKKETITESAGRQQKKKIERQEEKLKNNNRDLSMVRMK |
Sequence similarities
Belongs to the TMCO1 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length188
- Mass (Da)21,175
- Last updated2001-12-01 v1
- ChecksumFB77BFC4F0629EB1
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0A6YVS2 | A0A0A6YVS2_MOUSE | Tmco1 | 200 | ||
A0A0A6YW31 | A0A0A6YW31_MOUSE | Tmco1 | 127 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK037709 EMBL· GenBank· DDBJ | BAC29856.1 EMBL· GenBank· DDBJ | mRNA | ||
AK162344 EMBL· GenBank· DDBJ | BAE36865.1 EMBL· GenBank· DDBJ | mRNA | ||
BC011457 EMBL· GenBank· DDBJ | AAH11457.1 EMBL· GenBank· DDBJ | mRNA | ||
BC019761 EMBL· GenBank· DDBJ | AAH19761.1 EMBL· GenBank· DDBJ | mRNA | ||
BC020098 EMBL· GenBank· DDBJ | AAH20098.1 EMBL· GenBank· DDBJ | mRNA |