CLCA2_MOUSE
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 03-AUG-2022, entry version 140.
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. [Q8BG22-2]
DR AlphaFoldDB; Q8BG22; -.
DR SMR; Q8BG22; -.
DR STRING; 10090.ENSMUSP00000036029; -.
DR GlyGen; Q8BG22; 10 sites.
DR PhosphoSitePlus; Q8BG22; -.
DR MaxQB; Q8BG22; -.
DR PaxDb; Q8BG22; -.
DR PRIDE; Q8BG22; -.
DR ProteomicsDB; 285471; -. [Q8BG22-1]
DR ProteomicsDB; 285472; -. [Q8BG22-2]
DR Antibodypedia; 33584; 91 antibodies from 21 providers.
DR DNASU; 229933; -.
DR Ensembl; ENSMUST00000040465; ENSMUSP00000036029; ENSMUSG00000036960. [Q8BG22-1]
DR Ensembl; ENSMUST00000198993; ENSMUSP00000143161; ENSMUSG00000036960. [Q8BG22-2]
DR GeneID; 229933; -.
DR KEGG; mmu:229933; -.
DR UCSC; uc008rqg.1; mouse. [Q8BG22-1]
DR CTD; 9635; -.
DR MGI; MGI:2139758; Clca2.
DR VEuPathDB; HostDB:ENSMUSG00000036960; -.
DR eggNOG; ENOG502RIMV; Eukaryota.
DR GeneTree; ENSGT00940000161548; -.
DR InParanoid; Q8BG22; -.
DR OMA; TREIFTF; -.
DR OrthoDB; 685640at2759; -.
DR PhylomeDB; Q8BG22; -.
DR TreeFam; TF328396; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR BioGRID-ORCS; 229933; 2 hits in 74 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 61 other tissues.
DR Genevisible; Q8BG22; MM.
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:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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 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 Gene3D; 3.40.50.410; -; 1.
DR InterPro; IPR004727; CLCA_chordata.
DR InterPro; IPR013642; CLCA_N.
DR InterPro; IPR002035; VWF_A.
DR InterPro; IPR036465; vWFA_dom_sf.
DR Pfam; PF08434; CLCA; 1.
DR Pfam; PF13519; VWA_2; 1.
DR SMART; SM00327; VWA; 1.
DR SUPFAM; SSF53300; SSF53300; 1.
DR TIGRFAMs; TIGR00868; hCaCC; 1.
DR PROSITE; PS50234; VWFA; 1.
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
