CA3A1_MOUSE
ID CA3A1_MOUSE Reviewed; 902 AA.
AC Q9QX15; B7ZN73; O88860; Q3UQR1; Q8C324; Q8CCM1;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Calcium-activated chloride channel regulator 3A-1 {ECO:0000305};
DE EC=3.4.-.- {ECO:0000305|PubMed:9822685};
DE Flags: Precursor;
GN Name=Clca3a1 {ECO:0000312|MGI:MGI:1316732};
GN Synonyms=Clca1 {ECO:0000303|PubMed:9822685};
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] {ECO:0000312|EMBL:AAC79982.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, GLYCOSYLATION,
RP AND PROTEOLYTIC CLEAVAGE.
RC TISSUE=Lung {ECO:0000312|EMBL:AAC79982.1};
RX PubMed=9822685; DOI=10.1074/jbc.273.48.32096;
RA Gandhi R., Elble R.C., Gruber A.D., Schreur K.D., Ji H.L., Fuller C.M.,
RA Pauli B.U.;
RT "Molecular and functional characterization of a calcium-sensitive chloride
RT channel from mouse lung.";
RL J. Biol. Chem. 273:32096-32101(1998).
RN [2] {ECO:0000312|EMBL:AAC35003.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10072771; DOI=10.1016/s0378-1119(98)00620-9;
RA Romio L., Musante L., Cinti R., Seri M., Moran O., Zegarra-Moran O.,
RA Galietta L.J.V.;
RT "Characterization of a murine gene homologous to the bovine CaCC chloride
RT channel.";
RL Gene 228:181-188(1999).
RN [3] {ECO:0000312|EMBL:BAC27903.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC27903.1};
RC TISSUE=Heart {ECO:0000312|EMBL:BAE24978.1},
RC Lung {ECO:0000312|EMBL:BAC39823.1},
RC Olfactory bulb {ECO:0000312|EMBL:BAC27903.1}, and
RC Testis {ECO:0000312|EMBL:BAE36582.1};
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] {ECO:0000312|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5] {ECO:0000312|EMBL:AAI32343.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Plays a role in modulating chloride current across the plasma
CC membrane in a calcium-dependent manner. {ECO:0000269|PubMed:10072771,
CC ECO:0000269|PubMed:9822685}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Peripheral membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Highly expressed in skin and spleen, and at lower
CC levels in kidney and liver (PubMed:9822685, PubMed:10072771). Also
CC detected in lung and brain (PubMed:9822685). Not detected in lung or
CC brain (PubMed:10072771). In lung, localizes to respiratory epithelia of
CC the bronchi and trachea and the submucosal glands (PubMed:9822685).
CC {ECO:0000269|PubMed:10072771, ECO:0000269|PubMed:9822685}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:9822685}.
CC -!- PTM: The 130-kDa product is autoproteolytically processed by the
CC metalloprotease domain and yields two subunits, a 90-kDa protein and a
CC group of 32- to 38-kDa proteins (PubMed:9822685). The cleavage is
CC necessary for calcium-activated chloride channel (CaCC) activation
CC activity (By similarity). {ECO:0000250|UniProtKB:A8K7I4,
CC ECO:0000269|PubMed:9822685}.
CC -!- SIMILARITY: Belongs to the CLCR family. {ECO:0000305}.
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DR EMBL; AF047838; AAC79982.1; -; mRNA.
DR EMBL; AF052746; AAC35003.1; -; mRNA.
DR EMBL; AK032511; BAC27903.1; -; mRNA.
DR EMBL; AK087213; BAC39823.1; -; mRNA.
DR EMBL; AK142211; BAE24978.1; -; mRNA.
DR EMBL; AK161805; BAE36582.1; -; mRNA.
DR EMBL; AC134404; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC137128; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC132342; AAI32343.1; -; mRNA.
DR EMBL; BC145057; AAI45058.1; -; mRNA.
DR CCDS; CCDS17886.1; -.
DR RefSeq; NP_034029.2; NM_009899.4.
DR AlphaFoldDB; Q9QX15; -.
DR SMR; Q9QX15; -.
DR STRING; 10090.ENSMUSP00000054526; -.
DR MEROPS; M87.006; -.
DR GlyGen; Q9QX15; 8 sites.
DR PhosphoSitePlus; Q9QX15; -.
DR MaxQB; Q9QX15; -.
DR PaxDb; Q9QX15; -.
DR PRIDE; Q9QX15; -.
DR ProteomicsDB; 265482; -.
DR DNASU; 12722; -.
DR Ensembl; ENSMUST00000059091; ENSMUSP00000054526; ENSMUSG00000056025.
DR GeneID; 12722; -.
DR KEGG; mmu:12722; -.
DR UCSC; uc008rpx.2; mouse.
DR CTD; 12722; -.
DR MGI; MGI:1316732; Clca3a1.
DR VEuPathDB; HostDB:ENSMUSG00000056025; -.
DR eggNOG; ENOG502QRRD; Eukaryota.
DR GeneTree; ENSGT00940000157555; -.
DR HOGENOM; CLU_005812_0_1_1; -.
DR OMA; NSEAPNM; -.
DR OrthoDB; 685640at2759; -.
DR PhylomeDB; Q9QX15; -.
DR TreeFam; TF328396; -.
DR BioGRID-ORCS; 12722; 0 hits in 33 CRISPR screens.
DR ChiTaRS; Clca3a1; mouse.
DR PRO; PR:Q9QX15; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9QX15; protein.
DR Bgee; ENSMUSG00000056025; Expressed in endothelial cell of lymphatic vessel and 150 other tissues.
DR ExpressionAtlas; Q9QX15; baseline and differential.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:MGI.
DR GO; GO:0005229; F:intracellular calcium activated chloride 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:0006821; P:chloride transport; IDA: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; PF00092; VWA; 1.
DR SMART; SM00327; VWA; 1.
DR SUPFAM; SSF53300; SSF53300; 1.
DR TIGRFAMs; TIGR00868; hCaCC; 1.
DR PROSITE; PS50234; VWFA; 1.
PE 1: Evidence at protein level;
KW Autocatalytic cleavage; Calcium; Cell membrane; Chloride; Glycoprotein;
KW Hydrolase; Ion transport; Membrane; Metal-binding; Metalloprotease;
KW Protease; Reference proteome; Signal; Transport; Zinc.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..902
FT /note="Calcium-activated chloride channel regulator 3A-1"
FT /id="PRO_5010510991"
FT DOMAIN 308..476
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT REGION 45..199
FT /note="Metalloprotease domain"
FT /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT ACT_SITE 156
FT /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT BINDING 155
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT BINDING 159
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT BINDING 166
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT SITE 698..699
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 504
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 515
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 630
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 687
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 697
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 809
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 814
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CONFLICT 88
FT /note="P -> S (in Ref. 5; AAI45058)"
FT /evidence="ECO:0000305"
FT CONFLICT 116
FT /note="P -> T (in Ref. 3; BAC27903)"
FT /evidence="ECO:0000305"
FT CONFLICT 303
FT /note="K -> E (in Ref. 3; BAE24978)"
FT /evidence="ECO:0000305"
FT CONFLICT 674
FT /note="G -> S (in Ref. 2; AAC35003)"
FT /evidence="ECO:0000305"
FT CONFLICT 685..688
FT /note="QRNK -> PRNQ (in Ref. 3; BAC39823)"
FT /evidence="ECO:0000305"
FT CONFLICT 721
FT /note="Q -> P (in Ref. 3; BAC39823)"
FT /evidence="ECO:0000305"
FT CONFLICT 786
FT /note="N -> H (in Ref. 3; BAC39823)"
FT /evidence="ECO:0000305"
FT CONFLICT 882
FT /note="Missing (in Ref. 2; AAC35003)"
FT /evidence="ECO:0000305"
FT CONFLICT 887
FT /note="S -> C (in Ref. 2; AAC35003)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 902 AA; 100108 MW; D9A915E698EA2D85 CRC64;
MVPGLQVLLF LTLHLLQNTE SSMVHLNSNG YEGVVIAINP SVPEDERLIP SIKEMVTQAS
TYLFEASQGR VYFRNISILV PMTWKSKPEY LMPKRESYDK ADVIVADPHL QHGDDPYTLQ
YGQCGDRGQY IHFTPNFLLT DNLRIYGPRG RVFVHEWAHL RWGVFDEYNV DQPFYMSRKN
TIEATRCSTR ITGTNVVHNC ERGNCVTRAC RRDSKTRLYE PKCTFIPDKI QTAGASIMFM
QNLNSVVEFC TEKNHNAEAP NLQNKMCNRR STWDVIKTSA DFQNAPPMRG TEAPPPPTFS
LLKSRRRVVC LVLDKSGSMD KEDRLIRMNQ AAELYLTQIV EKESMVGLVT FDSAAHIQNY
LIKITSSSDY QKITANLPQQ ASGGTSICHG LQAGFQAITS SDQSTSGSEI VLLTDGEDNG
IRSCFEAVSR SGAIIHTIAL GPSAARELET LSDMTGGLRF YANKDLNSLI DAFSRISSTS
GSVSQQALQL ESKAFDVRAG AWINGTVPLD STVGNDTFFV ITWMVKKPEI ILQDPKGKKY
TTSDFQDDKL NIRSARLQIP GTAETGTWTY SITGTKSQLI TMTVTTRARS PTMEPLLATA
HMSQSTAQYP SRMIVYARVS QGFLPVLGAN VTALIEAEHG HQVTLELWDN GAGADTVKND
GIYTRYFTDY HGNGRYSLKV RVQAQRNKTR LSLRQKNKSL YIPGYVENGK IVLNPPRPDV
QEEAIEATVE DFNRVTSGGS FTVSGAPPDG DHARVFPPSK VTDLEAEFIG DYIHLTWTAP
GKVLDNGRAH RYIIRMSQHP LDLQEDFNNA TLVNASSLIP KEAGSKETFK FKPETFKIAN
GIQLYIAIQA DNEASLTSEV SNIAQAVKLT SLEDSISALG DDISAISMTI WGLTVIFNSI
LN
