CLA4A_MOUSE
ID CLA4A_MOUSE Reviewed; 924 AA.
AC Q6Q473; Q6Q472;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 2.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Calcium-activated chloride channel regulator 4A {ECO:0000312|MGI:MGI:2139744};
DE EC=3.4.-.- {ECO:0000250|UniProtKB:A8K7I4};
DE AltName: Full=Calcium-activated chloride channel regulator 6;
DE Short=mClca6;
DE Contains:
DE RecName: Full=Calcium-activated chloride channel regulator 4A, 110 kDa form {ECO:0000305};
DE Contains:
DE RecName: Full=Calcium-activated chloride channel regulator 4A, 30 kDa form {ECO:0000305};
DE Flags: Precursor;
GN Name=Clca4a {ECO:0000312|MGI:MGI:2139744};
GN Synonyms=Clca6 {ECO:0000312|MGI:MGI:2139744};
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] (ISOFORMS 1 AND 2), FUNCTION, TISSUE
RP SPECIFICITY, SUBCELLULAR LOCATION, GLYCOSYLATION, AND PROCESSING.
RC STRAIN=C57BL/6 x SJL/J; TISSUE=Intestine;
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 [2]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, GLYCOSYLATION,
RP SYNTHESIS OF 85-98; 106-119; 803-817 AND 870-882, AND PROCESSING.
RX PubMed=18285349; DOI=10.1369/jhc.2008.950592;
RA Bothe M.K., Braun J., Mundhenk L., Gruber A.D.;
RT "Murine mCLCA6 is an integral apical membrane protein of non-goblet cell
RT enterocytes and co-localizes with the cystic fibrosis transmembrane
RT conductance regulator.";
RL J. Histochem. Cytochem. 56:495-509(2008).
CC -!- FUNCTION: May be involved in mediating calcium-activated chloride
CC conductance. {ECO:0000269|PubMed:15284223,
CC ECO:0000269|PubMed:18285349}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass membrane protein.
CC Apical cell membrane. Secreted. Note=The C-terminus 30 kDa form is
CC anchored to the membrane. The N-terminus 110 kDa form is released from
CC the membrane triggered by an unknown stimulus. Associated with the
CC microvilli of non-goblet cell enterocytes in the small and large
CC intestine. Colocalizes with CFTR.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6Q473-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6Q473-2; Sequence=VSP_034942, VSP_034943;
CC -!- TISSUE SPECIFICITY: Expressed in the non-goblet intestinal cells. High
CC levels in intestine and stomach, and lower levels in eye, liver and
CC spleen. Increasing expression from the duodenum to the ilium, and
CC decreasing expression to the colon. Isoform 2 is expressed in intestine
CC and stomach but at lower levels than isoform 1.
CC {ECO:0000269|PubMed:15284223, ECO:0000269|PubMed:18285349}.
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: N-Glycosylated. {ECO:0000269|PubMed:15284223,
CC ECO:0000269|PubMed:18285349}.
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 -!- SIMILARITY: Belongs to the CLCR family. {ECO:0000305}.
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DR EMBL; AY560902; AAS86332.2; -; mRNA.
DR EMBL; AY560903; AAS86333.2; -; mRNA.
DR AlphaFoldDB; Q6Q473; -.
DR SMR; Q6Q473; -.
DR STRING; 10090.ENSMUSP00000029923; -.
DR MEROPS; M87.004; -.
DR GlyGen; Q6Q473; 12 sites.
DR iPTMnet; Q6Q473; -.
DR PhosphoSitePlus; Q6Q473; -.
DR MaxQB; Q6Q473; -.
DR PaxDb; Q6Q473; -.
DR PRIDE; Q6Q473; -.
DR ProteomicsDB; 285462; -. [Q6Q473-1]
DR ProteomicsDB; 285463; -. [Q6Q473-2]
DR MGI; MGI:2139744; Clca4a.
DR eggNOG; ENOG502QRRD; Eukaryota.
DR InParanoid; Q6Q473; -.
DR PhylomeDB; Q6Q473; -.
DR PRO; PR:Q6Q473; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q6Q473; protein.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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; IMP: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; IMP:MGI.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.40.50.410; -; 1.
DR InterPro; IPR004727; CLCA_chordata.
DR InterPro; IPR013642; CLCA_N.
DR InterPro; IPR013783; Ig-like_fold.
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 Alternative splicing; Autocatalytic cleavage; Cell membrane; Chloride;
KW Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Protease; Reference proteome; Secreted; Signal; Transmembrane;
KW Transmembrane helix; Transport; Zinc.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..924
FT /note="Calcium-activated chloride channel regulator 4A"
FT /evidence="ECO:0000305"
FT /id="PRO_0000345392"
FT CHAIN 23..?
FT /note="Calcium-activated chloride channel regulator 4A, 110
FT kDa form"
FT /evidence="ECO:0000305"
FT /id="PRO_0000345393"
FT CHAIN ?..924
FT /note="Calcium-activated chloride channel regulator 4A, 30
FT kDa form"
FT /evidence="ECO:0000305"
FT /id="PRO_0000345394"
FT TRANSMEM 884..904
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 307..477
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT REGION 46..200
FT /note="Metalloprotease domain"
FT /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT ACT_SITE 157
FT /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT BINDING 156
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT BINDING 160
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT BINDING 167
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 76
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 214
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 284
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 341
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 449
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 499
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 505
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 543
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 589
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 730
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 833
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 838
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 397..430
FT /note="FKNGEYQTDGTEILLLSDGEDSTAKDCIDEVKDS -> ETISLLQMKPRTMD
FT SLMLSGPWLQKMLISPRSHF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15284223"
FT /id="VSP_034942"
FT VAR_SEQ 431..511
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15284223"
FT /id="VSP_034943"
SQ SEQUENCE 924 AA; 101872 MW; D1E45A374F1FD897 CRC64;
MAFSRGPVFL LLLLYLLWGS DTSLIRLNEN GYEDIIIAID PAVPEDTTII EHIKGMVTKA
STYLFEATEK RFFFKNVSIL IPESWKDSPQ YRRPKQESYK HADIKVAPPT VEGRDEPYTR
QFTQCEEKAE YIHFTPDFVL GRKQDEYGDS GKVLVHEWAH LRWGVFDEYN EDQPFYSASS
KKIEATRCST GITGTNRVYA CQGGSCAMRR CRTNSTTKLY EKDCQFFPDK VQSEKASIMF
MQSIDSVTEF CKKENHNREA PTLHNKKCNY RSTWEVISTS EDFNSSTPME TSPSPPFFSL
LRISERIMCL VLDVSGSMTS YDRLNRMNQA AKYFLSQIIE NRSWVGMVHF SSQATIVHEL
IQINSDIERN QLLQTLPTSA NGGTSICSGI KAAFQVFKNG EYQTDGTEIL LLSDGEDSTA
KDCIDEVKDS GSIVHFIALG PLADLAVTNM SILTGGNHKL ATDEAQNNGL IDAFGALASE
NADITQKSLQ LESKGAILNN SLWLNDTVVI DSTLGRDTFF LVTWSKQAPA IYLRDPKGTQ
TTNFTMDSAS KMAYLSIPGT AQVGVWTYNL EAKENSEILT ITVTSRAANS SVPPITVNAK
VNTDTNTFPS PMIVYAEVLQ GYTPIIGARV TATIESNSGK TEELVLLDNG AGADAFKDDG
VYSRFFTAYS VNGRYSLKVR ADGGRNSARR SLRHPSSRAA YIPGWVVDGE IQGNPPRPET
TEATQPVLEN FSRTASGGAF VVSNVPSGPL PDLYPPNQIT DLQATLDGEE ISLTWTAPGD
DYDVGRVQQY IIRTSKNIIE LRDNFNNSPR VDTTNLTPKE ANSEETFAFK PENITEENAT
YIFIAIESVD KSSLSSGPSN IAQVALFTPQ AEPDPDESPS SSGVSVATIV LSVLGALVLV
CIIVGTTICI LKNKRSSSAA ITKF
