Q921L3 · TMCO1_MOUSE

  • Protein
    Calcium load-activated calcium channel
  • Gene
    Tmco1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Catalytic activity

GO annotations

AspectTerm
Cellular Componentendoplasmic reticulum membrane
Cellular ComponentGolgi membrane
Cellular Componentmitochondrial membrane
Cellular Componentmulti-pass translocon complex
Molecular Functioncalcium channel activity
Molecular Functionribosome binding
Biological Processcalcium ion transmembrane transport
Biological Processendoplasmic reticulum calcium ion homeostasis
Biological ProcessER overload response
Biological Processmulti-pass transmembrane protein insertion into ER membrane
Biological Processossification

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Calcium load-activated calcium channel
  • Short names
    CLAC channel
  • Alternative names
    • GEL complex subunit TMCO1
    • Transmembrane and coiled-coil domain-containing protein 1

Gene names

    • Name
      Tmco1

Organism names

  • Taxonomic identifier
  • Strains
    • C57BL/6J
    • Czech II
    • FVB/N
    • FVB/N-3
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q921L3
  • Secondary accessions
    • Q3TS11

Proteomes

Organism-specific databases

Subcellular Location

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.

TypeIDPosition(s)Description
Topological domain1-4Lumenal
Transmembrane5-32Helical
Topological domain33-86Cytoplasmic
Transmembrane87-106Helical
Topological domain107-120Lumenal
Intramembrane121-130
Topological domain131-140Lumenal
Transmembrane141-162Helical
Topological domain163-188Cytoplasmic

Keywords

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).

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00002440771-188Calcium load-activated calcium channel
Modified residue60Phosphoserine
Modified residue188Phosphoserine

Keywords

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.

TypeIDPosition(s)Description
Coiled coil32-89

Sequence similarities

Belongs to the TMCO1 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    188
  • Mass (Da)
    21,175
  • Last updated
    2001-12-01 v1
  • Checksum
    FB77BFC4F0629EB1
MSTMFADTLLIVFISVCTALLAEGITWVLVYRTDKYKRLKAEVEKQSKKLEKKKETITESAGRQQKKKIERQEEKLKNNNRDLSMVRMKSMFAIGFCFTALMGMFNSIFDGRVVAKLPFTPLSYIQGLSHRNLLGDDTTDCSFIFLYILCTMSIRQNIQKILGLAPSRAATKQAGGFLGPPPPSGKFS

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A0A6YVS2A0A0A6YVS2_MOUSETmco1200
A0A0A6YW31A0A0A6YW31_MOUSETmco1127

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

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