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Protein

Calcium-activated chloride channel regulator 2

Gene

CLCA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 bindingi164Zinc; catalyticBy similarity1
Active sitei165By similarity1
Metal bindingi168Zinc; catalyticBy similarity1
Metal bindingi175Zinc; catalyticBy similarity1

GO - Molecular functioni

  • chloride channel activity Source: ProtInc
  • intracellular calcium activated chloride channel activity Source: GO_Central
  • ligand-gated ion channel activity Source: Ensembl
  • metal ion binding Source: UniProtKB-KW
  • metalloendopeptidase activity Source: Reactome

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
Biological processCell adhesion, Ion transport, Transport
LigandCalcium, 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

EuPathDBiHostDB:ENSG00000137975.7
HGNCiHGNC:2016 CLCA2
MIMi604003 gene
neXtProtiNX_Q9UQC9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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

Chemistry databases

ChEMBLiCHEMBL2364708

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...) asparagineSequence analysis1
Glycosylationi150N-linked (GlcNAc...) asparagine1
Glycosylationi231N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi522N-linked (GlcNAc...) asparagine1
Glycosylationi822N-linked (GlcNAc...) asparagine1

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

EPDiQ9UQC9
PaxDbiQ9UQC9
PeptideAtlasiQ9UQC9
PRIDEiQ9UQC9
ProteomicsDBi85543

PTM databases

GlyConnecti1057
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 Expressed in 118 organ(s), highest expression level in gingival epithelium
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
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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di3.40.50.410, 1 hit
InterProiView protein in InterPro
IPR004727 CLCA_chordata
IPR013642 CLCA_N
IPR002035 VWF_A
IPR036465 vWFA_dom_sf
PfamiView protein in Pfam
PF08434 CLCA, 1 hit
SMARTiView protein in SMART
SM00327 VWA, 1 hit
SUPFAMiSSF53300 SSF53300, 1 hit
TIGRFAMsiTIGR00868 hCaCC, 1 hit
PROSITEiView protein in PROSITE
PS50234 VWFA, 1 hit

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 dbSNP:rs11580625Ensembl.1
Natural variantiVAR_043148306Q → E. Corresponds to variant dbSNP:rs17409304Ensembl.1
Natural variantiVAR_054058534G → D. Corresponds to variant dbSNP:rs1413426Ensembl.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

Similar proteinsi

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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114994, 3 interactors
IntActiQ9UQC9, 1 interactor
STRINGi9606.ENSP00000359596

Chemistry databases

ChEMBLiCHEMBL2364708

Protein family/group databases

MEROPSiM87.003

PTM databases

GlyConnecti1057
iPTMnetiQ9UQC9
PhosphoSitePlusiQ9UQC9

Polymorphism and mutation databases

BioMutaiCLCA2
DMDMi189082520

Proteomic databases

EPDiQ9UQC9
PaxDbiQ9UQC9
PeptideAtlasiQ9UQC9
PRIDEiQ9UQC9
ProteomicsDBi85543

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi9635
DisGeNETi9635
EuPathDBiHostDB:ENSG00000137975.7
GeneCardsiCLCA2
HGNCiHGNC:2016 CLCA2
HPAiHPA047192
MIMi604003 gene
neXtProtiNX_Q9UQC9
OpenTargetsiENSG00000137975
PharmGKBiPA26543
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-HSA-2672351 Stimuli-sensing channels

Miscellaneous databases

ChiTaRSiCLCA2 human
GeneWikiiCLCA2
GenomeRNAii9635
PROiPR:Q9UQC9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137975 Expressed in 118 organ(s), highest expression level in gingival epithelium
CleanExiHS_CLCA2
GenevisibleiQ9UQC9 HS

Family and domain databases

Gene3Di3.40.50.410, 1 hit
InterProiView protein in InterPro
IPR004727 CLCA_chordata
IPR013642 CLCA_N
IPR002035 VWF_A
IPR036465 vWFA_dom_sf
PfamiView protein in Pfam
PF08434 CLCA, 1 hit
SMARTiView protein in SMART
SM00327 VWA, 1 hit
SUPFAMiSSF53300 SSF53300, 1 hit
TIGRFAMsiTIGR00868 hCaCC, 1 hit
PROSITEiView protein in PROSITE
PS50234 VWFA, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCLCA2_HUMAN
AccessioniPrimary (citable) accession number: Q9UQC9
Secondary accession number(s): A8K2T3, Q9Y6N2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: May 20, 2008
Last modified: November 7, 2018
This is version 134 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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