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Protein

Calcium load-activated calcium channel

Gene

TMCO1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Calcium-selective channel required to prevent calcium stores from overfilling, thereby playing a key role in calcium homeostasis (PubMed:27212239). In response to endoplasmic reticulum overloading, assembles into a homotetramer, forming a functional calcium-selective channel, regulating the calcium content in endoplasmic reticulum store (PubMed:27212239).1 Publication

GO - Molecular functioni

  • calcium channel activity Source: UniProtKB

GO - Biological processi

  • calcium ion transmembrane transport Source: UniProtKB
  • endoplasmic reticulum calcium ion homeostasis Source: UniProtKB
  • ER overload response Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Calcium channel, Ion channel

Keywords - Biological processi

Calcium transport, Ion transport, Transport

Keywords - Ligandi

Calcium

Protein family/group databases

TCDBi1.A.106.1.1. the calcium load-activated calcium channel (clac) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium load-activated calcium channel1 Publication
Short name:
CLAC channel1 Publication
Alternative name(s):
Transmembrane and coiled-coil domain-containing protein 1Curated
Transmembrane and coiled-coil domains protein 4Curated
Xenogeneic cross-immune protein PCIA31 Publication
Gene namesi
Name:TMCO1Imported
Synonyms:TMCC4Imported
ORF Names:PNAS-101 Publication, PNAS-1361 Publication, UNQ151/PRO1771 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:18188. TMCO1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 9Cytoplasmic1 Publication9
Transmembranei10 – 30HelicalSequence analysisAdd BLAST21
Topological domaini31 – 90Lumenal1 PublicationAdd BLAST60
Transmembranei91 – 111HelicalSequence analysisAdd BLAST21
Topological domaini112 – 137Cytoplasmic1 PublicationAdd BLAST26
Intramembranei138 – 154Pore-forming1 PublicationAdd BLAST17
Topological domaini155 – 188Cytoplasmic1 PublicationAdd BLAST34

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

Craniofacial dysmorphism, skeletal anomalies and mental retardation syndrome (CFSMR)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by craniofacial and skeletal anomalies, associated with mental retardation. Typical craniofacial dysmorphism include brachycephaly, highly arched bushy eyebrows, synophrys, long eyelashes, low-set ears, microdontism of primary teeth, and generalized gingival hyperplasia, whereas Sprengel deformity of scapula, fusion of spine, rib abnormities, pectus excavatum, and pes planus represent skeletal anomalies.
See also OMIM:213980
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07665247 – 188Missing in CFSMR. 1 PublicationAdd BLAST142
Natural variantiVAR_07665387 – 188Missing in CFSMR. 2 PublicationsAdd BLAST102
Glaucoma, primary open angle (POAG)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA complex and genetically heterogeneous ocular disorder characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. In some cases, POAG shows digenic inheritance involving mutations in CYP1B1 and MYOC genes.
See also OMIM:137760

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi140D → A: Abolishes the calcium channel activity. 1 Publication1
Mutagenesisi140D → E: Retains some of the calcium channel activity. 1 Publication1

Keywords - Diseasei

Disease mutation, Glaucoma, Mental retardation

Organism-specific databases

DisGeNETi54499.
MalaCardsiTMCO1.
MIMi137760. phenotype.
213980. phenotype.
OpenTargetsiENSG00000143183.
Orphaneti1394. Cerebro-facio-thoracic dysplasia.
PharmGKBiPA142670792.

Polymorphism and mutation databases

BioMutaiTMCO1.
DMDMi74753399.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002440761 – 188Calcium load-activated calcium channelAdd BLAST188

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei60PhosphoserineCombined sources1
Modified residuei188PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9UM00.
PaxDbiQ9UM00.
PeptideAtlasiQ9UM00.
PRIDEiQ9UM00.
TopDownProteomicsiQ9UM00-1. [Q9UM00-1]

PTM databases

iPTMnetiQ9UM00.
PhosphoSitePlusiQ9UM00.
SwissPalmiQ9UM00.

Expressioni

Tissue specificityi

Widely expressed in adult and fetal tissues, with higher levels in thymus, prostate, testis and small intestine and lower levels in brain, placenta, lung and kidney (PubMed:10393320, PubMed:20018682). Present in most tissues in the eye, including the trabecular meshwork and retina (at protein level) (PubMed:22714896).3 Publications

Gene expression databases

BgeeiENSG00000143183.
CleanExiHS_TMCO1.
ExpressionAtlasiQ9UM00. baseline and differential.
GenevisibleiQ9UM00. HS.

Organism-specific databases

HPAiHPA054768.

Interactioni

Subunit structurei

Homodimer and homotetramer (PubMed:27212239). Homodimer under resting conditions; forms homotetramers following and endoplasmic reticulum calcium overload (PubMed:27212239).1 Publication

Protein-protein interaction databases

BioGridi119995. 42 interactors.
IntActiQ9UM00. 20 interactors.
STRINGi9606.ENSP00000375975.

Structurei

3D structure databases

ProteinModelPortaliQ9UM00.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili32 – 89Sequence analysisAdd BLAST58

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi180 – 183Poly-Pro4

Sequence similaritiesi

Belongs to the TMCO1 family.Curated

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3312. Eukaryota.
ENOG410XR8B. LUCA.
GeneTreeiENSGT00390000002659.
HOGENOMiHOG000240371.
HOVERGENiHBG054437.
InParanoidiQ9UM00.
PhylomeDBiQ9UM00.
TreeFamiTF315045.

Family and domain databases

InterProiIPR002809. EMC3/TMCO1.
IPR008559. TMCO1.
[Graphical view]
PANTHERiPTHR20917. PTHR20917. 1 hit.
PfamiPF01956. DUF106. 1 hit.
[Graphical view]
PIRSFiPIRSF023322. DUF841_euk. 1 hit.
SMARTiSM01415. DUF106. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UM00-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSTMFADTLL IVFISVCTAL LAEGITWVLV YRTDKYKRLK AEVEKQSKKL
60 70 80 90 100
EKKKETITES AGRQQKKKIE RQEEKLKNNN RDLSMVRMKS MFAIGFCFTA
110 120 130 140 150
LMGMFNSIFD GRVVAKLPFT PLSYIQGLSH RNLLGDDTTD CSFIFLYILC
160 170 180
TMSIRQNIQK ILGLAPSRAA TKQAGGFLGP PPPSGKFS
Length:188
Mass (Da):21,175
Last modified:May 1, 2000 - v1
Checksum:iFB77BFC4F0629EB1
GO
Isoform 2 (identifier: Q9UM00-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     64-82: Missing.

Note: No experimental confirmation available.
Show »
Length:169
Mass (Da):18,766
Checksum:i263365EFFEE1C17B
GO

Sequence cautioni

The sequence AAC25388 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAK07514 differs from that shown. Reason: Frameshift at several positions.Curated
The sequence AAK07549 differs from that shown. Reason: Frameshift at several positions.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti129S → P in AAK07514 (Ref. 4) Curated1
Sequence conflicti129S → P in AAK07549 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07665247 – 188Missing in CFSMR. 1 PublicationAdd BLAST142
Natural variantiVAR_07665387 – 188Missing in CFSMR. 2 PublicationsAdd BLAST102

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01950564 – 82Missing in isoform 2. 1 PublicationAdd BLAST19

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020980 mRNA. Translation: BAA86974.1.
AY763589 mRNA. Translation: AAV34755.1.
AF070626 mRNA. Translation: AAC25388.1. Different initiation.
AF274935 mRNA. Translation: AAK07514.1. Frameshift.
AF277194 mRNA. Translation: AAK07549.1. Frameshift.
AY359027 mRNA. Translation: AAQ89386.1.
AK316610 mRNA. Translation: BAG38197.1.
AL451074 Genomic DNA. Translation: CAH74064.1.
BC000104 mRNA. Translation: AAH00104.1.
RefSeqiNP_061899.2. NM_019026.4.
UniGeneiHs.31498.

Genome annotation databases

EnsembliENST00000392129; ENSP00000375975; ENSG00000143183. [Q9UM00-1]
GeneIDi54499.
KEGGihsa:54499.
UCSCiuc057mzb.1. human. [Q9UM00-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020980 mRNA. Translation: BAA86974.1.
AY763589 mRNA. Translation: AAV34755.1.
AF070626 mRNA. Translation: AAC25388.1. Different initiation.
AF274935 mRNA. Translation: AAK07514.1. Frameshift.
AF277194 mRNA. Translation: AAK07549.1. Frameshift.
AY359027 mRNA. Translation: AAQ89386.1.
AK316610 mRNA. Translation: BAG38197.1.
AL451074 Genomic DNA. Translation: CAH74064.1.
BC000104 mRNA. Translation: AAH00104.1.
RefSeqiNP_061899.2. NM_019026.4.
UniGeneiHs.31498.

3D structure databases

ProteinModelPortaliQ9UM00.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119995. 42 interactors.
IntActiQ9UM00. 20 interactors.
STRINGi9606.ENSP00000375975.

Protein family/group databases

TCDBi1.A.106.1.1. the calcium load-activated calcium channel (clac) family.

PTM databases

iPTMnetiQ9UM00.
PhosphoSitePlusiQ9UM00.
SwissPalmiQ9UM00.

Polymorphism and mutation databases

BioMutaiTMCO1.
DMDMi74753399.

Proteomic databases

EPDiQ9UM00.
PaxDbiQ9UM00.
PeptideAtlasiQ9UM00.
PRIDEiQ9UM00.
TopDownProteomicsiQ9UM00-1. [Q9UM00-1]

Protocols and materials databases

DNASUi54499.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000392129; ENSP00000375975; ENSG00000143183. [Q9UM00-1]
GeneIDi54499.
KEGGihsa:54499.
UCSCiuc057mzb.1. human. [Q9UM00-1]

Organism-specific databases

CTDi54499.
DisGeNETi54499.
GeneCardsiTMCO1.
HGNCiHGNC:18188. TMCO1.
HPAiHPA054768.
MalaCardsiTMCO1.
MIMi137760. phenotype.
213980. phenotype.
614123. gene.
neXtProtiNX_Q9UM00.
OpenTargetsiENSG00000143183.
Orphaneti1394. Cerebro-facio-thoracic dysplasia.
PharmGKBiPA142670792.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3312. Eukaryota.
ENOG410XR8B. LUCA.
GeneTreeiENSGT00390000002659.
HOGENOMiHOG000240371.
HOVERGENiHBG054437.
InParanoidiQ9UM00.
PhylomeDBiQ9UM00.
TreeFamiTF315045.

Miscellaneous databases

ChiTaRSiTMCO1. human.
GeneWikiiTMCO1.
GenomeRNAii54499.
PROiQ9UM00.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000143183.
CleanExiHS_TMCO1.
ExpressionAtlasiQ9UM00. baseline and differential.
GenevisibleiQ9UM00. HS.

Family and domain databases

InterProiIPR002809. EMC3/TMCO1.
IPR008559. TMCO1.
[Graphical view]
PANTHERiPTHR20917. PTHR20917. 1 hit.
PfamiPF01956. DUF106. 1 hit.
[Graphical view]
PIRSFiPIRSF023322. DUF841_euk. 1 hit.
SMARTiSM01415. DUF106. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTMCO1_HUMAN
AccessioniPrimary (citable) accession number: Q9UM00
Secondary accession number(s): B2REA0
, O75545, Q9BZS3, Q9BZU8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 27, 2006
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 134 of the entry and version 1 of the sequence. [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, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. 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.