Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Calcium-activated chloride channel regulator 2

Gene

CLCA2

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

Functioni

Plays a role in modulating chloride current across the plasma membrane in a calcium-dependent manner, and cell adhesion. Involved in basal cell adhesion and/or stratification of squamous epithelia. May act as a tumor suppressor in breast and colorectal cancer. Plays a key role for cell adhesion in the beginning stages of lung metastasis via the binding to ITGB4.5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi164ZincBy similarity1
Metal bindingi168ZincBy similarity1
Metal bindingi175ZincBy similarity1

GO - Molecular functioni

GO - Biological processi

  • cell adhesion Source: UniProtKB-KW
  • ion transmembrane transport Source: Reactome
  • transport Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Cell adhesion, Ion transport, Transport

Keywords - Ligandi

Calcium, Chloride, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-2672351. Stimuli-sensing channels.

Protein family/group databases

MEROPSiM87.003.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium-activated chloride channel regulator 2 (EC:3.4.-.-By similarity)
Alternative name(s):
Calcium-activated chloride channel family member 2
Short name:
hCLCA2
Calcium-activated chloride channel protein 3
Short name:
CaCC-3
Short name:
hCaCC-3
Cleaved into the following 2 chains:
Gene namesi
Name:CLCA2
Synonyms:CACC3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:2016. CLCA2.

Subcellular locationi

Calcium-activated chloride channel regulator 2, 109 kDa form :
  • Secreted

  • Note: Remains associated to the 35 kDa form until an unidentified event triggers the release.

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini32 – 901ExtracellularSequence analysisAdd BLAST870
Transmembranei902 – 922HelicalSequence analysisAdd BLAST21
Topological domaini923 – 943CytoplasmicSequence analysisAdd BLAST21

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi150N → Q: Reduction in size by around 2 kDa. 1 Publication1
Mutagenesisi292N → Q: No change in size. 1 Publication1
Mutagenesisi522N → Q: Reduction in size by around 2 kDa. 1 Publication1
Mutagenesisi637N → Q: No change in size. 1 Publication1
Mutagenesisi822N → Q: Reduction in size by around 2 kDa. 1 Publication1
Mutagenesisi938N → Q: No change in size. 1 Publication1

Organism-specific databases

DisGeNETi9635.
OpenTargetsiENSG00000137975.
PharmGKBiPA26543.

Polymorphism and mutation databases

BioMutaiCLCA2.
DMDMi189082520.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000344502? – 943Calcium-activated chloride channel regulator 2, 35 kDa form
Signal peptidei1 – 31Sequence analysisAdd BLAST31
ChainiPRO_000033369432 – 943Calcium-activated chloride channel regulator 2Add BLAST912
ChainiPRO_000033369533 – ?Calcium-activated chloride channel regulator 2, 109 kDa form

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi74N-linked (GlcNAc...)Sequence analysis1
Glycosylationi150N-linked (GlcNAc...)1
Glycosylationi231N-linked (GlcNAc...)Sequence analysis1
Glycosylationi522N-linked (GlcNAc...)1
Glycosylationi822N-linked (GlcNAc...)1

Post-translational modificationi

The 141 kDa mature form is autoproteolytically cleaved by the metalloprotease domain, producing a 109 kDa form and a 35 kDa form. The cleavage is necessary for calcium-activated chloride channel (CaCC) activation activity.By similarity
N-glycosylated.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei708 – 709Cleavage; by autolysisBy similarity2

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein

Proteomic databases

PaxDbiQ9UQC9.
PeptideAtlasiQ9UQC9.
PRIDEiQ9UQC9.

PTM databases

iPTMnetiQ9UQC9.
PhosphoSitePlusiQ9UQC9.

Expressioni

Tissue specificityi

Expressed in cornea, skin, vagina, esophagus, and larynx (at protein level). Expressed in trachea and mammary gland. Weakly expressed in testis and kidney. Highly expressed in corneal epithelium, colon and trachea. Moderately expressed in brain, urogenital organs, bladder, uterus and prostate. Highly expressed in tissues containing stratified epithelium including cornea, esophagus, larynx, skin and vagina than those tissues which contain only epithelial monolayers. Expressed in normal breast epithelium but not in breast cancer. Highly expressed during epithelial stratification. Expressed in endothelial cells of lung. Expressed selectively in endothelia of small pulmonary arteries, arterioles, and subpleural and interlobular venules.8 Publications

Inductioni

Significantly down-regulated in breast and colorectal cancer.2 Publications

Gene expression databases

BgeeiENSG00000137975.
CleanExiHS_CLCA2.
GenevisibleiQ9UQC9. HS.

Organism-specific databases

HPAiHPA047192.

Interactioni

Protein-protein interaction databases

BioGridi114994. 3 interactors.
IntActiQ9UQC9. 1 interactor.
STRINGi9606.ENSP00000359596.

Structurei

3D structure databases

ProteinModelPortaliQ9UQC9.
SMRiQ9UQC9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini311 – 483VWFAPROSITE-ProRule annotationAdd BLAST173

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni54 – 205Metalloprotease domainBy similarityAdd BLAST152

Domaini

The metalloprotease region is responsible for autoproteolytic processing. It can also cross-cleave other CLCA Substrates.By similarity

Sequence similaritiesi

Belongs to the CLCR family.Curated
Contains 1 VWFA domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IEPS. Eukaryota.
ENOG410XPSZ. LUCA.
GeneTreeiENSGT00390000004810.
HOGENOMiHOG000015107.
HOVERGENiHBG005560.
InParanoidiQ9UQC9.
KOiK05028.
OMAiTNGPEHQ.
OrthoDBiEOG091G09E6.
PhylomeDBiQ9UQC9.
TreeFamiTF328396.

Family and domain databases

Gene3Di3.40.50.410. 1 hit.
InterProiIPR013642. CLCA.
IPR004727. CLCA_chordata.
IPR002035. VWF_A.
[Graphical view]
PfamiPF08434. CLCA. 1 hit.
[Graphical view]
SMARTiSM00327. VWA. 1 hit.
[Graphical view]
SUPFAMiSSF53300. SSF53300. 1 hit.
TIGRFAMsiTIGR00868. hCaCC. 1 hit.
PROSITEiPS50234. VWFA. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9UQC9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTQRSIAGPI CNLKFVTLLV ALSSELPFLG AGVQLQDNGY NGLLIAINPQ
60 70 80 90 100
VPENQNLISN IKEMITEASF YLFNATKRRV FFRNIKILIP ATWKANNNSK
110 120 130 140 150
IKQESYEKAN VIVTDWYGAH GDDPYTLQYR GCGKEGKYIH FTPNFLLNDN
160 170 180 190 200
LTAGYGSRGR VFVHEWAHLR WGVFDEYNND KPFYINGQNQ IKVTRCSSDI
210 220 230 240 250
TGIFVCEKGP CPQENCIISK LFKEGCTFIY NSTQNATASI MFMQSLSSVV
260 270 280 290 300
EFCNASTHNQ EAPNLQNQMC SLRSAWDVIT DSADFHHSFP MNGTELPPPP
310 320 330 340 350
TFSLVQAGDK VVCLVLDVSS KMAEADRLLQ LQQAAEFYLM QIVEIHTFVG
360 370 380 390 400
IASFDSKGEI RAQLHQINSN DDRKLLVSYL PTTVSAKTDI SICSGLKKGF
410 420 430 440 450
EVVEKLNGKA YGSVMILVTS GDDKLLGNCL PTVLSSGSTI HSIALGSSAA
460 470 480 490 500
PNLEELSRLT GGLKFFVPDI SNSNSMIDAF SRISSGTGDI FQQHIQLEST
510 520 530 540 550
GENVKPHHQL KNTVTVDNTV GNDTMFLVTW QASGPPEIIL FDPDGRKYYT
560 570 580 590 600
NNFITNLTFR TASLWIPGTA KPGHWTYTLN NTHHSLQALK VTVTSRASNS
610 620 630 640 650
AVPPATVEAF VERDSLHFPH PVMIYANVKQ GFYPILNATV TATVEPETGD
660 670 680 690 700
PVTLRLLDDG AGADVIKNDG IYSRYFFSFA ANGRYSLKVH VNHSPSISTP
710 720 730 740 750
AHSIPGSHAM YVPGYTANGN IQMNAPRKSV GRNEEERKWG FSRVSSGGSF
760 770 780 790 800
SVLGVPAGPH PDVFPPCKII DLEAVKVEEE LTLSWTAPGE DFDQGQATSY
810 820 830 840 850
EIRMSKSLQN IQDDFNNAIL VNTSKRNPQQ AGIREIFTFS PQISTNGPEH
860 870 880 890 900
QPNGETHESH RIYVAIRAMD RNSLQSAVSN IAQAPLFIPP NSDPVPARDY
910 920 930 940
LILKGVLTAM GLIGIICLII VVTHHTLSRK KRADKKENGT KLL
Length:943
Mass (Da):103,941
Last modified:May 20, 2008 - v2
Checksum:i0E09A09090D2529B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti178N → I in BAA77810 (PubMed:11262615).Curated1
Sequence conflicti830Q → R in BAF83037 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05405780V → I.Corresponds to variant rs11580625dbSNPEnsembl.1
Natural variantiVAR_043148306Q → E.Corresponds to variant rs17409304dbSNPEnsembl.1
Natural variantiVAR_054058534G → D.Corresponds to variant rs1413426dbSNPEnsembl.1
Natural variantiVAR_043149754G → E in a breast cancer sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF043977 mRNA. Translation: AAD40367.1.
AF127980 mRNA. Translation: AAD48397.1.
AB026833 mRNA. Translation: BAA77810.1.
AK290348 mRNA. Translation: BAF83037.1.
CH471097 Genomic DNA. Translation: EAW73187.1.
BC041096 mRNA. Translation: AAH41096.1.
CCDSiCCDS708.1.
RefSeqiNP_006527.1. NM_006536.6.
UniGeneiHs.241551.

Genome annotation databases

EnsembliENST00000370565; ENSP00000359596; ENSG00000137975.
GeneIDi9635.
KEGGihsa:9635.
UCSCiuc001dlr.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF043977 mRNA. Translation: AAD40367.1.
AF127980 mRNA. Translation: AAD48397.1.
AB026833 mRNA. Translation: BAA77810.1.
AK290348 mRNA. Translation: BAF83037.1.
CH471097 Genomic DNA. Translation: EAW73187.1.
BC041096 mRNA. Translation: AAH41096.1.
CCDSiCCDS708.1.
RefSeqiNP_006527.1. NM_006536.6.
UniGeneiHs.241551.

3D structure databases

ProteinModelPortaliQ9UQC9.
SMRiQ9UQC9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114994. 3 interactors.
IntActiQ9UQC9. 1 interactor.
STRINGi9606.ENSP00000359596.

Protein family/group databases

MEROPSiM87.003.

PTM databases

iPTMnetiQ9UQC9.
PhosphoSitePlusiQ9UQC9.

Polymorphism and mutation databases

BioMutaiCLCA2.
DMDMi189082520.

Proteomic databases

PaxDbiQ9UQC9.
PeptideAtlasiQ9UQC9.
PRIDEiQ9UQC9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000370565; ENSP00000359596; ENSG00000137975.
GeneIDi9635.
KEGGihsa:9635.
UCSCiuc001dlr.5. human.

Organism-specific databases

CTDi9635.
DisGeNETi9635.
GeneCardsiCLCA2.
HGNCiHGNC:2016. CLCA2.
HPAiHPA047192.
MIMi604003. gene.
neXtProtiNX_Q9UQC9.
OpenTargetsiENSG00000137975.
PharmGKBiPA26543.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEPS. Eukaryota.
ENOG410XPSZ. LUCA.
GeneTreeiENSGT00390000004810.
HOGENOMiHOG000015107.
HOVERGENiHBG005560.
InParanoidiQ9UQC9.
KOiK05028.
OMAiTNGPEHQ.
OrthoDBiEOG091G09E6.
PhylomeDBiQ9UQC9.
TreeFamiTF328396.

Enzyme and pathway databases

ReactomeiR-HSA-2672351. Stimuli-sensing channels.

Miscellaneous databases

ChiTaRSiCLCA2. human.
GeneWikiiCLCA2.
GenomeRNAii9635.
PROiQ9UQC9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137975.
CleanExiHS_CLCA2.
GenevisibleiQ9UQC9. HS.

Family and domain databases

Gene3Di3.40.50.410. 1 hit.
InterProiIPR013642. CLCA.
IPR004727. CLCA_chordata.
IPR002035. VWF_A.
[Graphical view]
PfamiPF08434. CLCA. 1 hit.
[Graphical view]
SMARTiSM00327. VWA. 1 hit.
[Graphical view]
SUPFAMiSSF53300. SSF53300. 1 hit.
TIGRFAMsiTIGR00868. hCaCC. 1 hit.
PROSITEiPS50234. VWFA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCLCA2_HUMAN
AccessioniPrimary (citable) accession number: Q9UQC9
Secondary accession number(s): A8K2T3, Q9Y6N2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: May 20, 2008
Last modified: November 30, 2016
This is version 117 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 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. 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.