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Q9UQC9

- CLCA2_HUMAN

UniProt

Q9UQC9 - CLCA2_HUMAN

Protein

Calcium-activated chloride channel regulator 2

Gene

CLCA2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 95 (01 Oct 2014)
      Sequence version 2 (20 May 2008)
      Previous versions | rss
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    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

    GO - Molecular functioni

    1. chloride channel activity Source: ProtInc
    2. ligand-gated ion channel activity Source: Ensembl

    GO - Biological processi

    1. cell adhesion Source: UniProtKB-KW
    2. chloride transmembrane transport Source: GOC
    3. transport Source: ProtInc

    Keywords - Biological processi

    Cell adhesion, Ion transport, Transport

    Keywords - Ligandi

    Calcium, Chloride

    Protein family/group databases

    MEROPSiM87.003.

    Names & Taxonomyi

    Protein namesi
    Recommended 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
    Cleaved into the following 2 chains:
    Gene namesi
    Name:CLCA2
    Synonyms:CACC3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:2016. CLCA2.

    Subcellular locationi

    Chain 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.

    GO - Cellular componenti

    1. basal plasma membrane Source: UniProtKB-SubCell
    2. cell junction Source: UniProtKB-SubCell
    3. extracellular region Source: UniProtKB-SubCell
    4. integral component of plasma membrane Source: ProtInc

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Membrane, Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi150 – 1501N → Q: Reduction in size by around 2 kDa. 1 Publication
    Mutagenesisi292 – 2921N → Q: No change in size. 1 Publication
    Mutagenesisi522 – 5221N → Q: Reduction in size by around 2 kDa. 1 Publication
    Mutagenesisi637 – 6371N → Q: No change in size. 1 Publication
    Mutagenesisi822 – 8221N → Q: Reduction in size by around 2 kDa. 1 Publication
    Mutagenesisi938 – 9381N → Q: No change in size. 1 Publication

    Organism-specific databases

    PharmGKBiPA26543.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini? – 943Calcium-activated chloride channel regulator 2, 35 kDa formPRO_0000344502
    Signal peptidei1 – 3131Sequence AnalysisAdd
    BLAST
    Chaini32 – 943912Calcium-activated chloride channel regulator 2PRO_0000333694Add
    BLAST
    Chaini33 – ?Calcium-activated chloride channel regulator 2, 109 kDa formPRO_0000333695

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi74 – 741N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi150 – 1501N-linked (GlcNAc...)
    Glycosylationi231 – 2311N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi522 – 5221N-linked (GlcNAc...)
    Glycosylationi822 – 8221N-linked (GlcNAc...)

    Post-translational modificationi

    The 141 kDa mature form is shedded, producing a 109 kDa form and a 35 kDa form.
    N-glycosylated.2 Publications

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    PaxDbiQ9UQC9.
    PRIDEiQ9UQC9.

    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

    BgeeiQ9UQC9.
    CleanExiHS_CLCA2.
    GenevestigatoriQ9UQC9.

    Organism-specific databases

    HPAiHPA047192.

    Interactioni

    Protein-protein interaction databases

    BioGridi114994. 1 interaction.
    IntActiQ9UQC9. 1 interaction.
    STRINGi9606.ENSP00000359596.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9UQC9.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini32 – 901870ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini923 – 94321CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei902 – 92221HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini311 – 483173VWFAPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

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

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG42884.
    HOGENOMiHOG000015107.
    HOVERGENiHBG005560.
    InParanoidiQ9UQC9.
    KOiK05028.
    OMAiEKGPCPQ.
    OrthoDBiEOG78WKR1.
    PhylomeDBiQ9UQC9.
    TreeFamiTF328396.

    Family and domain databases

    Gene3Di3.40.50.410. 1 hit.
    InterProiIPR004727. CaCC_prot.
    IPR013642. Cl_channel_Ca.
    IPR015394. DUF1973.
    IPR002035. VWF_A.
    [Graphical view]
    PfamiPF08434. CLCA_N. 1 hit.
    PF09315. DUF1973. 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

    MTQRSIAGPI CNLKFVTLLV ALSSELPFLG AGVQLQDNGY NGLLIAINPQ    50
    VPENQNLISN IKEMITEASF YLFNATKRRV FFRNIKILIP ATWKANNNSK 100
    IKQESYEKAN VIVTDWYGAH GDDPYTLQYR GCGKEGKYIH FTPNFLLNDN 150
    LTAGYGSRGR VFVHEWAHLR WGVFDEYNND KPFYINGQNQ IKVTRCSSDI 200
    TGIFVCEKGP CPQENCIISK LFKEGCTFIY NSTQNATASI MFMQSLSSVV 250
    EFCNASTHNQ EAPNLQNQMC SLRSAWDVIT DSADFHHSFP MNGTELPPPP 300
    TFSLVQAGDK VVCLVLDVSS KMAEADRLLQ LQQAAEFYLM QIVEIHTFVG 350
    IASFDSKGEI RAQLHQINSN DDRKLLVSYL PTTVSAKTDI SICSGLKKGF 400
    EVVEKLNGKA YGSVMILVTS GDDKLLGNCL PTVLSSGSTI HSIALGSSAA 450
    PNLEELSRLT GGLKFFVPDI SNSNSMIDAF SRISSGTGDI FQQHIQLEST 500
    GENVKPHHQL KNTVTVDNTV GNDTMFLVTW QASGPPEIIL FDPDGRKYYT 550
    NNFITNLTFR TASLWIPGTA KPGHWTYTLN NTHHSLQALK VTVTSRASNS 600
    AVPPATVEAF VERDSLHFPH PVMIYANVKQ GFYPILNATV TATVEPETGD 650
    PVTLRLLDDG AGADVIKNDG IYSRYFFSFA ANGRYSLKVH VNHSPSISTP 700
    AHSIPGSHAM YVPGYTANGN IQMNAPRKSV GRNEEERKWG FSRVSSGGSF 750
    SVLGVPAGPH PDVFPPCKII DLEAVKVEEE LTLSWTAPGE DFDQGQATSY 800
    EIRMSKSLQN IQDDFNNAIL VNTSKRNPQQ AGIREIFTFS PQISTNGPEH 850
    QPNGETHESH RIYVAIRAMD RNSLQSAVSN IAQAPLFIPP NSDPVPARDY 900
    LILKGVLTAM GLIGIICLII VVTHHTLSRK KRADKKENGT KLL 943
    Length:943
    Mass (Da):103,941
    Last modified:May 20, 2008 - v2
    Checksum:i0E09A09090D2529B
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti178 – 1781N → I in BAA77810. (PubMed:11262615)Curated
    Sequence conflicti830 – 8301Q → R in BAF83037. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti80 – 801V → I.
    Corresponds to variant rs11580625 [ dbSNP | Ensembl ].
    VAR_054057
    Natural varianti306 – 3061Q → E.
    Corresponds to variant rs17409304 [ dbSNP | Ensembl ].
    VAR_043148
    Natural varianti534 – 5341G → D.
    Corresponds to variant rs1413426 [ dbSNP | Ensembl ].
    VAR_054058
    Natural varianti754 – 7541G → E in a breast cancer sample; somatic mutation. 1 Publication
    VAR_043149

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_006536.5.
    UniGeneiHs.241551.

    Genome annotation databases

    EnsembliENST00000370565; ENSP00000359596; ENSG00000137975.
    GeneIDi9635.
    KEGGihsa:9635.
    UCSCiuc001dlr.4. human.

    Polymorphism databases

    DMDMi189082520.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS708.1.
    RefSeqi NP_006527.1. NM_006536.5.
    UniGenei Hs.241551.

    3D structure databases

    ProteinModelPortali Q9UQC9.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114994. 1 interaction.
    IntActi Q9UQC9. 1 interaction.
    STRINGi 9606.ENSP00000359596.

    Chemistry

    ChEMBLi CHEMBL2364708.

    Protein family/group databases

    MEROPSi M87.003.

    Polymorphism databases

    DMDMi 189082520.

    Proteomic databases

    PaxDbi Q9UQC9.
    PRIDEi Q9UQC9.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000370565 ; ENSP00000359596 ; ENSG00000137975 .
    GeneIDi 9635.
    KEGGi hsa:9635.
    UCSCi uc001dlr.4. human.

    Organism-specific databases

    CTDi 9635.
    GeneCardsi GC01P086889.
    HGNCi HGNC:2016. CLCA2.
    HPAi HPA047192.
    MIMi 604003. gene.
    neXtProti NX_Q9UQC9.
    PharmGKBi PA26543.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG42884.
    HOGENOMi HOG000015107.
    HOVERGENi HBG005560.
    InParanoidi Q9UQC9.
    KOi K05028.
    OMAi EKGPCPQ.
    OrthoDBi EOG78WKR1.
    PhylomeDBi Q9UQC9.
    TreeFami TF328396.

    Miscellaneous databases

    ChiTaRSi CLCA2. human.
    GeneWikii CLCA2.
    GenomeRNAii 9635.
    NextBioi 36163.
    PROi Q9UQC9.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9UQC9.
    CleanExi HS_CLCA2.
    Genevestigatori Q9UQC9.

    Family and domain databases

    Gene3Di 3.40.50.410. 1 hit.
    InterProi IPR004727. CaCC_prot.
    IPR013642. Cl_channel_Ca.
    IPR015394. DUF1973.
    IPR002035. VWF_A.
    [Graphical view ]
    Pfami PF08434. CLCA_N. 1 hit.
    PF09315. DUF1973. 1 hit.
    [Graphical view ]
    SMARTi SM00327. VWA. 1 hit.
    [Graphical view ]
    SUPFAMi SSF53300. SSF53300. 1 hit.
    TIGRFAMsi TIGR00868. hCaCC. 1 hit.
    PROSITEi PS50234. VWFA. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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. 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. Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-754.

    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: October 1, 2014
    This is version 95 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

    External Data

    Dasty 3