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Protein

Calcium homeostasis modulator protein 1

Gene

CALHM1

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

Functioni

Pore-forming subunit of a voltage-gated ion channel required for sensory perception of sweet, bitter and umami tastes. Specifically present in type II taste bud cells, where it plays a central role in sweet, bitter and umami taste perception by inducing ATP release from the cell, ATP acting as a neurotransmitter to activate afferent neural gustatory pathways. Acts both as a voltage-gated and calcium-activated ion channel: mediates neuronal excitability in response to changes in extracellular Ca2+ concentration. Has poor ion selectivity and forms a wide pore (around 14 Angstroms) that mediates permeation of Ca2+, Na+ and K+, as well as permeation of monovalent anions. Acts as an activator of the ERK1 and ERK2 cascade. Triggers endoplasmic reticulum stress by reducing the calcium content of the endoplasmic reticulum. May indirectly control amyloid precursor protein (APP) proteolysis and aggregated amyloid-beta (Abeta) peptides levels in a Ca2+ dependent manner.5 Publications

Enzyme regulationi

Inhibited by Gd3+, Ruthenium Red, and Zn2+ and partially inhibited by 2-aminoethoxydiphenyl borate.1 Publication

GO - Molecular functioni

  • calcium activated cation channel activity Source: UniProtKB
  • voltage-gated calcium channel activity Source: Ensembl
  • voltage-gated ion channel activity Source: UniProtKB

GO - Biological processi

  • ATP transport Source: UniProtKB
  • cation transport Source: UniProtKB
  • protein homooligomerization Source: UniProtKB
  • regulation of ion transmembrane transport Source: UniProtKB
  • sensory perception of bitter taste Source: UniProtKB
  • sensory perception of sweet taste Source: UniProtKB
  • sensory perception of umami taste Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Calcium channel, Ion channel

Keywords - Biological processi

Calcium transport, Ion transport, Transport

Keywords - Ligandi

Calcium

Enzyme and pathway databases

BioCyciZFISH:G66-32619-MONOMER.

Protein family/group databases

TCDBi1.A.84.1.1. the calcium homeostasis modulator ca(2+) channel (calhm-c) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium homeostasis modulator protein 1
Alternative name(s):
Protein FAM26C
Gene namesi
Name:CALHM1
Synonyms:FAM26C
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:23494. CALHM1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 17CytoplasmicSequence analysisAdd BLAST17
Transmembranei18 – 38HelicalSequence analysisAdd BLAST21
Topological domaini39 – 50ExtracellularSequence analysisAdd BLAST12
Transmembranei51 – 71HelicalSequence analysisAdd BLAST21
Topological domaini72 – 108CytoplasmicSequence analysisAdd BLAST37
Transmembranei109 – 129HelicalSequence analysisAdd BLAST21
Topological domaini130 – 181ExtracellularSequence analysisAdd BLAST52
Transmembranei182 – 202HelicalSequence analysisAdd BLAST21
Topological domaini203 – 346CytoplasmicSequence analysisAdd BLAST144

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi72N → G: Significant inhibition on the control of cytosolic Ca(2+) levels. Does not affect ion channel activity. 2 Publications1
Mutagenesisi74N → A: Has no effect on glycosylation. 1 Publication1
Mutagenesisi114W → A: Impairs ability to activate the ERK1 and ERK2 cascade. 1 Publication1
Mutagenesisi121D → C: Impaired ion channel activity in response to change in extracellular Ca(2+) concentration. 1 Publication1
Mutagenesisi121D → E: No effect. 1 Publication1
Mutagenesisi140N → A: Prevents glycosylation and impairs ability to activate the ERK1 and ERK2 cascade. 2 Publications1
Mutagenesisi163E → A: No effect. 1 Publication1
Mutagenesisi166D → R: No effect. 1 Publication1

Organism-specific databases

DisGeNETi255022.
OpenTargetsiENSG00000185933.
PharmGKBiPA162380954.

Polymorphism and mutation databases

BioMutaiCALHM1.
DMDMi68565595.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001867231 – 346Calcium homeostasis modulator protein 1Add BLAST346

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi140N-linked (GlcNAc...)1 Publication1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei74Not glycosylated1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8IU99.
PeptideAtlasiQ8IU99.
PRIDEiQ8IU99.

PTM databases

PhosphoSitePlusiQ8IU99.

Expressioni

Tissue specificityi

Predominantly expressed in adult brain. Detected also in retinoic acid-differentiated SH-SY5Y cells. Specifically expressed in circumvallate taste bud cells.2 Publications

Gene expression databases

BgeeiENSG00000185933.
CleanExiHS_CALHM1.
GenevisibleiQ8IU99. HS.

Organism-specific databases

HPAiHPA018317.

Interactioni

Subunit structurei

Homohexamer.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-1790341,EBI-1790341

Protein-protein interaction databases

STRINGi9606.ENSP00000329926.

Structurei

3D structure databases

ProteinModelPortaliQ8IU99.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the FAM26 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IG7G. Eukaryota.
ENOG410YNIM. LUCA.
GeneTreeiENSGT00530000062796.
HOGENOMiHOG000111295.
HOVERGENiHBG096020.
InParanoidiQ8IU99.
KOiK19738.
OMAiMNNNVSM.
OrthoDBiEOG091G09L8.
PhylomeDBiQ8IU99.
TreeFamiTF329085.

Family and domain databases

InterProiIPR029568. CALHM1.
IPR029569. FAM26.
[Graphical view]
PANTHERiPTHR32261. PTHR32261. 2 hits.
PTHR32261:SF2. PTHR32261:SF2. 2 hits.
PfamiPF14798. Ca_hom_mod. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8IU99-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMDKFRMIFQ FLQSNQESFM NGICGIMALA SAQMYSAFDF NCPCLPGYNA
60 70 80 90 100
AYSAGILLAP PLVLFLLGLV MNNNVSMLAE EWKRPLGRRA KDPAVLRYMF
110 120 130 140 150
CSMAQRALIA PVVWVAVTLL DGKCFLCAFC TAVPVSALGN GSLAPGLPAP
160 170 180 190 200
ELARLLARVP CPEIYDGDWL LAREVAVRYL RCISQALGWS FVLLTTLLAF
210 220 230 240 250
VVRSVRPCFT QAAFLKSKYW SHYIDIERKL FDETCTEHAK AFAKVCIQQF
260 270 280 290 300
FEAMNHDLEL GHTHGTLATA PASAAAPTTP DGAEEEREKL RGITDQGTMN
310 320 330 340
RLLTSWHKCK PPLRLGQEEP PLMGNGWAGG GPRPPRKEVA TYFSKV
Length:346
Mass (Da):38,264
Last modified:July 5, 2005 - v2
Checksum:i13A1FBA6592A9EC1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti264H → N in AAH36193 (PubMed:15489334).Curated1
Sequence conflicti264H → N in AAH36208 (PubMed:15489334).Curated1

Polymorphismi

Leu-86 causes a dysregulation of Ca2+ homeostasis and amyloid precursor protein (APP) metabolism and has been suggested to be a risk factor for the development of Alzheimer disease (PubMed:18585350, PubMed:20061624, PubMed:20164592). However, this association with Alzheimer disease could not be confirmed in a number of studies performed in different populations (PubMed:19472444, PubMed:19070563, PubMed:19191331, PubMed:19191332, PubMed:19545933, PubMed:19655363, PubMed:21378601). According to a meta-analysis study, Leu-86 is likely not a genetic determinant of Alzheimer disease but may modulate age of onset by interacting with the effect of the APOE*4 allele of the APOE gene (PubMed:20847397).11 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02309586L → P.12 PublicationsCorresponds to variant rs2986017dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL139339 Genomic DNA. Translation: CAH71484.1.
BC036193 mRNA. Translation: AAH36193.1.
BC036208 mRNA. Translation: AAH36208.1.
CCDSiCCDS7550.1.
RefSeqiNP_001001412.3. NM_001001412.3.
UniGeneiHs.680365.

Genome annotation databases

EnsembliENST00000329905; ENSP00000329926; ENSG00000185933.
GeneIDi255022.
KEGGihsa:255022.
UCSCiuc001kxe.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL139339 Genomic DNA. Translation: CAH71484.1.
BC036193 mRNA. Translation: AAH36193.1.
BC036208 mRNA. Translation: AAH36208.1.
CCDSiCCDS7550.1.
RefSeqiNP_001001412.3. NM_001001412.3.
UniGeneiHs.680365.

3D structure databases

ProteinModelPortaliQ8IU99.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000329926.

Protein family/group databases

TCDBi1.A.84.1.1. the calcium homeostasis modulator ca(2+) channel (calhm-c) family.

PTM databases

PhosphoSitePlusiQ8IU99.

Polymorphism and mutation databases

BioMutaiCALHM1.
DMDMi68565595.

Proteomic databases

PaxDbiQ8IU99.
PeptideAtlasiQ8IU99.
PRIDEiQ8IU99.

Protocols and materials databases

DNASUi255022.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000329905; ENSP00000329926; ENSG00000185933.
GeneIDi255022.
KEGGihsa:255022.
UCSCiuc001kxe.3. human.

Organism-specific databases

CTDi255022.
DisGeNETi255022.
GeneCardsiCALHM1.
H-InvDBHIX0201512.
HGNCiHGNC:23494. CALHM1.
HPAiHPA018317.
MIMi612234. gene.
neXtProtiNX_Q8IU99.
OpenTargetsiENSG00000185933.
PharmGKBiPA162380954.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IG7G. Eukaryota.
ENOG410YNIM. LUCA.
GeneTreeiENSGT00530000062796.
HOGENOMiHOG000111295.
HOVERGENiHBG096020.
InParanoidiQ8IU99.
KOiK19738.
OMAiMNNNVSM.
OrthoDBiEOG091G09L8.
PhylomeDBiQ8IU99.
TreeFamiTF329085.

Enzyme and pathway databases

BioCyciZFISH:G66-32619-MONOMER.

Miscellaneous databases

GenomeRNAii255022.
PROiQ8IU99.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185933.
CleanExiHS_CALHM1.
GenevisibleiQ8IU99. HS.

Family and domain databases

InterProiIPR029568. CALHM1.
IPR029569. FAM26.
[Graphical view]
PANTHERiPTHR32261. PTHR32261. 2 hits.
PTHR32261:SF2. PTHR32261:SF2. 2 hits.
PfamiPF14798. Ca_hom_mod. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCAHM1_HUMAN
AccessioniPrimary (citable) accession number: Q8IU99
Secondary accession number(s): Q5W091
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: July 5, 2005
Last modified: November 2, 2016
This is version 110 of the entry and version 2 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 10
    Human chromosome 10: 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
  5. 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.