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Q9UQC9 (CLCA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calcium-activated chloride channel regulator 2
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
Gene names
Name:CLCA2
Synonyms:CACC3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length943 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.8 Ref.9 Ref.11 Ref.12

Subcellular location

Cell membrane; Single-pass type I membrane protein. Basal cell membrane; Single-pass type I membrane protein. Cell junction Ref.1 Ref.10 Ref.11 Ref.13.

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. Ref.1 Ref.10 Ref.11 Ref.13

Tissue specificity

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. Ref.1 Ref.2 Ref.3 Ref.7 Ref.9 Ref.10 Ref.11 Ref.12

Induction

Significantly down-regulated in breast and colorectal cancer. Ref.7 Ref.8

Post-translational modification

The 141 kDa mature form is shedded, producing a 109 kDa form and a 35 kDa form.

N-glycosylated. Ref.1 Ref.13

Sequence similarities

Belongs to the CLCR family.

Contains 1 VWFA domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131 Potential
Chain32 – 943912Calcium-activated chloride channel regulator 2
PRO_0000333694
Chain33 – ?Calcium-activated chloride channel regulator 2, 109 kDa formPRO_0000333695
Chain? – 943Calcium-activated chloride channel regulator 2, 35 kDa formPRO_0000344502

Regions

Topological domain32 – 901870Extracellular Potential
Transmembrane902 – 92221Helical; Potential
Topological domain923 – 94321Cytoplasmic Potential
Domain311 – 483173VWFA

Amino acid modifications

Glycosylation741N-linked (GlcNAc...) Potential
Glycosylation1501N-linked (GlcNAc...)
Glycosylation2311N-linked (GlcNAc...) Potential
Glycosylation5221N-linked (GlcNAc...)
Glycosylation8221N-linked (GlcNAc...)

Natural variations

Natural variant801V → I.
Corresponds to variant rs11580625 [ dbSNP | Ensembl ].
VAR_054057
Natural variant3061Q → E.
Corresponds to variant rs17409304 [ dbSNP | Ensembl ].
VAR_043148
Natural variant5341G → D.
Corresponds to variant rs1413426 [ dbSNP | Ensembl ].
VAR_054058
Natural variant7541G → E in a breast cancer sample; somatic mutation. Ref.14
VAR_043149

Experimental info

Mutagenesis1501N → Q: Reduction in size by around 2 kDa. Ref.1
Mutagenesis2921N → Q: No change in size. Ref.1
Mutagenesis5221N → Q: Reduction in size by around 2 kDa. Ref.1
Mutagenesis6371N → Q: No change in size. Ref.1
Mutagenesis8221N → Q: Reduction in size by around 2 kDa. Ref.1
Mutagenesis9381N → Q: No change in size. Ref.1
Sequence conflict1781N → I in BAA77810. Ref.3
Sequence conflict8301Q → R in BAF83037. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Q9UQC9 [UniParc].

Last modified May 20, 2008. Version 2.
Checksum: 0E09A09090D2529B

FASTA943103,941
        10         20         30         40         50         60 
MTQRSIAGPI CNLKFVTLLV ALSSELPFLG AGVQLQDNGY NGLLIAINPQ VPENQNLISN 

        70         80         90        100        110        120 
IKEMITEASF YLFNATKRRV FFRNIKILIP ATWKANNNSK IKQESYEKAN VIVTDWYGAH 

       130        140        150        160        170        180 
GDDPYTLQYR GCGKEGKYIH FTPNFLLNDN LTAGYGSRGR VFVHEWAHLR WGVFDEYNND 

       190        200        210        220        230        240 
KPFYINGQNQ IKVTRCSSDI TGIFVCEKGP CPQENCIISK LFKEGCTFIY NSTQNATASI 

       250        260        270        280        290        300 
MFMQSLSSVV EFCNASTHNQ EAPNLQNQMC SLRSAWDVIT DSADFHHSFP MNGTELPPPP 

       310        320        330        340        350        360 
TFSLVQAGDK VVCLVLDVSS KMAEADRLLQ LQQAAEFYLM QIVEIHTFVG IASFDSKGEI 

       370        380        390        400        410        420 
RAQLHQINSN DDRKLLVSYL PTTVSAKTDI SICSGLKKGF EVVEKLNGKA YGSVMILVTS 

       430        440        450        460        470        480 
GDDKLLGNCL PTVLSSGSTI HSIALGSSAA PNLEELSRLT GGLKFFVPDI SNSNSMIDAF 

       490        500        510        520        530        540 
SRISSGTGDI FQQHIQLEST GENVKPHHQL KNTVTVDNTV GNDTMFLVTW QASGPPEIIL 

       550        560        570        580        590        600 
FDPDGRKYYT NNFITNLTFR TASLWIPGTA KPGHWTYTLN NTHHSLQALK VTVTSRASNS 

       610        620        630        640        650        660 
AVPPATVEAF VERDSLHFPH PVMIYANVKQ GFYPILNATV TATVEPETGD PVTLRLLDDG 

       670        680        690        700        710        720 
AGADVIKNDG IYSRYFFSFA ANGRYSLKVH VNHSPSISTP AHSIPGSHAM YVPGYTANGN 

       730        740        750        760        770        780 
IQMNAPRKSV GRNEEERKWG FSRVSSGGSF SVLGVPAGPH PDVFPPCKII DLEAVKVEEE 

       790        800        810        820        830        840 
LTLSWTAPGE DFDQGQATSY EIRMSKSLQN IQDDFNNAIL VNTSKRNPQQ AGIREIFTFS 

       850        860        870        880        890        900 
PQISTNGPEH QPNGETHESH RIYVAIRAMD RNSLQSAVSN IAQAPLFIPP NSDPVPARDY 

       910        920        930        940 
LILKGVLTAM GLIGIICLII VVTHHTLSRK KRADKKENGT KLL 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and transmembrane structure of hCLCA2 from human lung, trachea, and mammary gland."
Gruber A.D., Schreur K.D., Ji H.-L., Fuller C.M., Pauli B.U.
Am. J. Physiol. 276:C1261-C1270(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION, MUTAGENESIS OF ASN-150; ASN-292; ASN-522; ASN-637; ASN-822 AND ASN-938.
Tissue: Lung.
[2]"Identification of three novel members of the calcium-dependent chloride channel (CaCC) family predominantly expressed in the digestive tract and trachea."
Agnel M., Vermat T., Culouscou J.-M.
FEBS Lett. 455:295-301(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[3]"Isolation and characterization of a Ca(2+)-activated chloride channel from human corneal epithelium."
Itoh R., Kawamoto S., Miyamoto Y., Kinoshita S., Okubo K.
Curr. Eye Res. 21:918-925(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Corneal epithelium.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Tongue.
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[7]"Tumorigenicity of human breast cancer is associated with loss of the Ca2+-activated chloride channel CLCA2."
Gruber A.D., Pauli B.U.
Cancer Res. 59:5488-5491(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, TISSUE SPECIFICITY, FUNCTION.
[8]"Expression of the Ca2+-activated chloride channel genes CLCA1 and CLCA2 is downregulated in human colorectal cancer."
Bustin S.A., Li S.-R., Dorudi S.
DNA Cell Biol. 20:331-338(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, FUNCTION.
[9]"The breast cancer beta 4 integrin and endothelial human CLCA2 mediate lung metastasis."
Abdel-Ghany M., Cheng H.-C., Elble R.C., Pauli B.U.
J. Biol. Chem. 276:25438-25446(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, FUNCTION.
[10]"Calcium-activated chloride channel-2 in human epithelia."
Connon C.J., Yamasaki K., Kawasaki S., Quantock A.J., Koizumi N., Kinoshita S.
J. Histochem. Cytochem. 52:415-418(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[11]"The quantification of hCLCA2 and colocalisation with integrin beta4 in stratified human epithelia."
Connon C.J., Kawasaki S., Yamasaki K., Quantock A.J., Kinoshita S.
Acta Histochem. 106:421-425(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, FUNCTION, TISSUE SPECIFICITY.
[12]"Gene expression and immunolocalisation of a calcium-activated chloride channel during the stratification of cultivated and developing corneal epithelium."
Connon C.J., Kawasaki S., Liles M., Koizumi N., Yamasaki K., Nakamura T., Quantock A.J., Kinoshita S.
Cell Tissue Res. 323:177-182(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, FUNCTION.
[13]"The putative chloride channel hCLCA2 has a single C-terminal transmembrane segment."
Elble R.C., Walia V., Cheng H.-C., Connon C.J., Mundhenk L., Gruber A.D., Pauli B.U.
J. Biol. Chem. 281:29448-29454(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, SHEDDING, GLYCOSYLATION, TOPOLOGY.
[14]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-754.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_006527.1. NM_006536.5.
UniGeneHs.241551.

3D structure databases

ProteinModelPortalQ9UQC9.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114994. 1 interaction.
IntActQ9UQC9. 1 interaction.
STRING9606.ENSP00000359596.

Chemistry

ChEMBLCHEMBL2364708.

Protein family/group databases

MEROPSM87.003.

Polymorphism databases

DMDM189082520.

Proteomic databases

PaxDbQ9UQC9.
PRIDEQ9UQC9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000370565; ENSP00000359596; ENSG00000137975.
GeneID9635.
KEGGhsa:9635.
UCSCuc001dlr.4. human.

Organism-specific databases

CTD9635.
GeneCardsGC01P086889.
HGNCHGNC:2016. CLCA2.
HPAHPA047192.
MIM604003. gene.
neXtProtNX_Q9UQC9.
PharmGKBPA26543.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG42884.
HOGENOMHOG000015107.
HOVERGENHBG005560.
InParanoidQ9UQC9.
KOK05028.
OMAEKGPCPQ.
OrthoDBEOG78WKR1.
PhylomeDBQ9UQC9.
TreeFamTF328396.

Gene expression databases

BgeeQ9UQC9.
CleanExHS_CLCA2.
GenevestigatorQ9UQC9.

Family and domain databases

Gene3D3.40.50.410. 1 hit.
InterProIPR004727. CaCC_prot.
IPR013642. Cl_channel_Ca.
IPR015394. DUF1973.
IPR002035. VWF_A.
[Graphical view]
PfamPF08434. CLCA_N. 1 hit.
PF09315. DUF1973. 1 hit.
[Graphical view]
SMARTSM00327. VWA. 1 hit.
[Graphical view]
SUPFAMSSF53300. SSF53300. 1 hit.
TIGRFAMsTIGR00868. hCaCC. 1 hit.
PROSITEPS50234. VWFA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCLCA2. human.
GeneWikiCLCA2.
GenomeRNAi9635.
NextBio36163.
PROQ9UQC9.
SOURCESearch...

Entry information

Entry nameCLCA2_HUMAN
AccessionPrimary (citable) accession number: Q9UQC9
Secondary accession number(s): A8K2T3, Q9Y6N2
Entry history
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: May 20, 2008
Last modified: April 16, 2014
This is version 93 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM