ID   CLCA2_MOUSE             Reviewed;         942 AA.
AC   Q8BG22; Q8BZF7;
DT   20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   27-MAR-2024, entry version 149.
DE   RecName: Full=Calcium-activated chloride channel regulator 2;
DE            EC=3.4.-.- {ECO:0000250|UniProtKB:A8K7I4};
DE   AltName: Full=Calcium-activated chloride channel family member 5;
DE            Short=mCLCA5;
DE   Flags: Precursor;
GN   Name=Clca2; Synonyms=Clca5;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP   INDUCTION.
RC   STRAIN=BALB/cJ;
RX   PubMed=15292178; DOI=10.1074/jbc.m408334200;
RA   Beckley J.R., Pauli B.U., Elble R.C.;
RT   "Re-expression of detachment-inducible chloride channel mCLCA5 suppresses
RT   growth of metastatic breast cancer cells.";
RL   J. Biol. Chem. 279:41634-41641(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP   TISSUE SPECIFICITY.
RC   TISSUE=Eye;
RX   PubMed=15284223; DOI=10.1074/jbc.m408354200;
RA   Evans S.R., Thoreson W.B., Beck C.L.;
RT   "Molecular and functional analyses of two new calcium-activated chloride
RT   channel family members from mouse eye and intestine.";
RL   J. Biol. Chem. 279:41792-41800(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   STRAIN=C57BL/6J; TISSUE=Head, and Skin;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   STRAIN=129; TISSUE=Mammary tumor;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
CC   -!- FUNCTION: Plays a role in modulating chloride current across the plasma
CC       membrane in a calcium-dependent manner, and cell adhesion. Involved in
CC       basal cell adhesion and/or stratification of squamous epithelia. May
CC       act as a tumor suppressor in breast and colorectal cancer. Plays a key
CC       role for cell adhesion in the beginning stages of lung metastasis via
CC       the binding to ITGB4. {ECO:0000269|PubMed:15284223,
CC       ECO:0000269|PubMed:15292178}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15284223};
CC       Single-pass type I membrane protein {ECO:0000269|PubMed:15284223}.
CC       Basal cell membrane {ECO:0000269|PubMed:15284223}; Single-pass type I
CC       membrane protein {ECO:0000269|PubMed:15284223}. Cell junction
CC       {ECO:0000269|PubMed:15284223}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q8BG22-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8BG22-2; Sequence=VSP_033515;
CC   -!- TISSUE SPECIFICITY: Highly expressed in eye, spleen, lung, kidney,
CC       uterus, and endothelial cells. Weakly expressed in heart and throughout
CC       the gastrointestinal tract. Highly expressed in mammary cell lines. Its
CC       expression in immortalized cell line HC11 correlates with slow or
CC       arrested growth. Re-expression in mammary tumor cells reduces colony
CC       survival. {ECO:0000269|PubMed:15284223, ECO:0000269|PubMed:15292178}.
CC   -!- INDUCTION: By 30-fold when cells are deprived of growth factors or
CC       anchorage in mammary epithelial cell. Down-regulated in metastatic
CC       mammary tumor cell lines. {ECO:0000269|PubMed:15292178}.
CC   -!- DOMAIN: The metalloprotease region is responsible for autoproteolytic
CC       processing. It can also cross-cleave other CLCA substrates.
CC       {ECO:0000250|UniProtKB:A8K7I4}.
CC   -!- PTM: The translation product is autoproteolytically cleaved by the
CC       metalloprotease domain in the endoplasmic reticulum into a N-terminal
CC       and a C-terminal products that remain physically associated with each
CC       other. The cleavage is necessary for calcium-activated chloride channel
CC       (CaCC) activation activity. {ECO:0000250|UniProtKB:A8K7I4}.
CC   -!- PTM: N-glycosylated. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the CLCR family. {ECO:0000305}.
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DR   EMBL; AY161007; AAO18366.1; -; mRNA.
DR   EMBL; AK028704; BAC26076.1; -; mRNA.
DR   EMBL; AK035512; BAC29086.1; -; mRNA.
DR   EMBL; AK048276; BAC33291.1; -; mRNA.
DR   EMBL; BC096379; AAH96379.1; -; mRNA.
DR   CCDS; CCDS17890.1; -. [Q8BG22-1]
DR   RefSeq; NP_848812.1; NM_178697.5. [Q8BG22-1]
DR   RefSeq; XP_006501498.1; XM_006501435.1.
DR   AlphaFoldDB; Q8BG22; -.
DR   SMR; Q8BG22; -.
DR   STRING; 10090.ENSMUSP00000036029; -.
DR   GlyCosmos; Q8BG22; 10 sites, No reported glycans.
DR   GlyGen; Q8BG22; 10 sites.
DR   PhosphoSitePlus; Q8BG22; -.
DR   MaxQB; Q8BG22; -.
DR   PaxDb; 10090-ENSMUSP00000036029; -.
DR   ProteomicsDB; 285471; -. [Q8BG22-1]
DR   ProteomicsDB; 285472; -. [Q8BG22-2]
DR   Antibodypedia; 33584; 96 antibodies from 21 providers.
DR   DNASU; 229933; -.
DR   Ensembl; ENSMUST00000040465.11; ENSMUSP00000036029.7; ENSMUSG00000036960.11. [Q8BG22-1]
DR   Ensembl; ENSMUST00000198993.2; ENSMUSP00000143161.2; ENSMUSG00000036960.11. [Q8BG22-2]
DR   GeneID; 229933; -.
DR   KEGG; mmu:229933; -.
DR   UCSC; uc008rqg.1; mouse. [Q8BG22-1]
DR   AGR; MGI:2139758; -.
DR   CTD; 9635; -.
DR   MGI; MGI:2139758; Clca2.
DR   VEuPathDB; HostDB:ENSMUSG00000036960; -.
DR   eggNOG; ENOG502RIMV; Eukaryota.
DR   GeneTree; ENSGT00940000161548; -.
DR   InParanoid; Q8BG22; -.
DR   OMA; GPICNLK; -.
DR   OrthoDB; 5479609at2759; -.
DR   PhylomeDB; Q8BG22; -.
DR   TreeFam; TF328396; -.
DR   Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR   BioGRID-ORCS; 229933; 2 hits in 79 CRISPR screens.
DR   PRO; PR:Q8BG22; -.
DR   Proteomes; UP000000589; Chromosome 3.
DR   RNAct; Q8BG22; Protein.
DR   Bgee; ENSMUSG00000036960; Expressed in skin of external ear and 62 other cell types or tissues.
DR   GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR   GO; GO:0009925; C:basal plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0030054; C:cell junction; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0005254; F:chloride channel activity; IDA:MGI.
DR   GO; GO:0005229; F:intracellular calcium activated chloride channel activity; IBA:GO_Central.
DR   GO; GO:0015276; F:ligand-gated monoatomic ion channel activity; IDA:MGI.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR   GO; GO:0006821; P:chloride transport; IMP:MGI.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd00198; vWFA; 1.
DR   Gene3D; 3.40.50.410; von Willebrand factor, type A domain; 1.
DR   InterPro; IPR004727; CLCA_chordata.
DR   InterPro; IPR013642; CLCA_N.
DR   InterPro; IPR002035; VWF_A.
DR   InterPro; IPR036465; vWFA_dom_sf.
DR   NCBIfam; TIGR00868; hCaCC; 1.
DR   PANTHER; PTHR10579; CALCIUM-ACTIVATED CHLORIDE CHANNEL REGULATOR; 1.
DR   PANTHER; PTHR10579:SF66; CALCIUM-ACTIVATED CHLORIDE CHANNEL REGULATOR 2; 1.
DR   Pfam; PF08434; CLCA; 1.
DR   Pfam; PF13519; VWA_2; 1.
DR   SMART; SM00327; VWA; 1.
DR   SUPFAM; SSF53300; vWA-like; 1.
DR   PROSITE; PS50234; VWFA; 1.
DR   Genevisible; Q8BG22; MM.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Autocatalytic cleavage; Calcium; Cell adhesion;
KW   Cell junction; Cell membrane; Chloride; Glycoprotein; Hydrolase;
KW   Ion transport; Membrane; Metal-binding; Metalloprotease; Protease;
KW   Reference proteome; Signal; Transmembrane; Transmembrane helix; Transport;
KW   Zinc.
FT   SIGNAL          1..32
FT                   /evidence="ECO:0000255"
FT   CHAIN           33..942
FT                   /note="Calcium-activated chloride channel regulator 2"
FT                   /id="PRO_0000333696"
FT   TOPO_DOM        33..905
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        906..926
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        927..942
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          311..483
FT                   /note="VWFA"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT   REGION          54..205
FT                   /note="Metalloprotease domain"
FT                   /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT   ACT_SITE        165
FT                   /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT   BINDING         164
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT   BINDING         168
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT   BINDING         175
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT   SITE            708..709
FT                   /note="Cleavage; by autolysis"
FT                   /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT   CARBOHYD        74
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        97
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        231
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        235
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        254
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        286
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        522
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        580
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        637
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        821
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         675..942
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_033515"
SQ   SEQUENCE   942 AA;  103626 MW;  D0511E33CF317E4F CRC64;
     MTHRDSTGPV IGLKLVTLLF TLSPELLFLG AGLKLKENGY DGLLVAINPR VPEDLKLITN
     IKEMITEASF YLFNATKRRV FFRNVQILVP ATWTDHNYSR VRQESYDKAN VIVAEQSEEH
     GDDPYTLQHR GCGQEGRYIH FTPSFLLNDE LAAGYGARGR VFVHEWAHLR WGVFDEYNND
     KPFYVNGRNE IQVTRCSSDI TGVFVCEKGL CPHEDCIISK IFREGCTFLY NSTQNATGSI
     MFMPSLPSVV EFCNESTHNQ EAPNLQNQVC SLRSTWDVIT ASSDLNHSLP VHGVGLPAPP
     TFSLLQAGDR VVCLVIDVSR KMAEGDRLLR LQQAAELYLM QVVEAHTFVG IVTFDSKGEI
     RASLQQIYSD DDRKLLVSYL PTAVSTDAET NICAGVKKGF EVVEERNGRA DGSVLILVTS
     GADEHIANCL LTSMNSGSTI HSMALGSSAA RKVGELSRLT GGLKFFIPDK FTSNGMTEAF
     VRISSGTGDI FQQSLQVESV CETVQPQHQL ADTMTVDSAV GNDTLFLVTW QTGGPPEIAL
     LDPSGRKYNT GDFIINLAFR TASLKIPGTA KHGHWTYTLN NTHHSPQALK VTVASRASSL
     AMSPATLEAF VERDSTYFPQ PVIIYANVRK GLHPILNATV VATVEPEAGD PVVLQLLDGG
     AGADVIRNDG IYSRYFSSFA VSGSYSLTVH VRHSPSTSTL ALPVPGNHAM YVPGYITNDN
     IQMNAPKNLG HRPVKERWGF SRVSSGGSFS VLGVPDGPHP DMFPPCKITD LEAMKVEDDV
     VLSWTAPGED FDQGQTTSYE IRMSRSLWNI RDDFDNAILV NSSELVPQHA GTRETFTFSP
     KLVTHELDHE LAEDAQEPYI VYVALRAMDR SSLRSAVSNI ALVSMSLPPN SSPVVSRDDL
     ILKGVLTTVG LIAILCLIMV VAHCIFNRKK RPSRKENETK FL
//