Q9D7Z6 (CLCA1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calcium-activated chloride channel regulator 1

Alternative name(s):
Calcium-activated chloride channel family member 3
Short name=mCLCA3
Protein gob-5

Gene names

Name:	Clca1
Synonyms:	Clca3, Gob5

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	913 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May be involved in mediating calcium-activated chloride conductance. May play critical roles in goblet cell metaplasia, mucus hypersecretion, cystic fibrosis and AHR. May be involved in the regulation of mucus production and/or secretion by goblet cells. Involved in the regulation of tissue inflammation in the innate immune response. May play a role as a tumor suppressor. Induces MUC5AC. Ref.2 Ref.5 Ref.10
Subcellular location	Secreted › extracellular space. Note: The 75 kDa N-terminal and a 35 kDa C-terminal products are fully secreted into extracellular environment as a soluble complex of two glycoproteins. Ref.6 Ref.8 Ref.11
Tissue specificity	Exclusively expressed in the digestive and respiratory tracts and in the uterus (at protein level). Expressed in small intestine, colon, stomach, and uterus and slightly expressed in trachea tissue. Exclusively expressed in the mucin granule membranes of gastrointestinal, respiratory, and uterine goblet cells and other mucin-producing cells. In the colon, expressed in the surface mucous cells. In the stomach highly expressed in the surface epithelium in the pylorus. Strongly expressed in the airway epithelium of lung tissues associated with airway hyperresponsiveness (AHR). Ref.1 Ref.5 Ref.6
Induction	By IL3, IL4 and IL9 in the lung. Increases in the bronchiolar epithelium of asbestos-induced fibrogenesis. Decreases in cystic fibrosis knockout mice. Ref.2 Ref.7 Ref.9
Post-translational modification	The 110 kDa translation product is cleaved in the endoplasmic reticulum into a 75 kDa N-terminal and a 35 kDa C-terminal products that remain physically associated with each other. Ref.6 Ref.11 Glycosylated. Ref.6 Ref.11
Disruption phenotype	Mice exhibit significantly increased bronchoalveolar lavage (BAL) inflammation consisted predominantly of neutrophils; have decreased goblet cell hyperplasia as well as decreased mucus production; have decreased airway hypersensitivity after cholinergic provocation with methacholine. Ref.10
Sequence similarities	Belongs to the CLCR family. Contains 1 VWFA domain.

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Secreted
Domain	Signal
Ligand	Calcium Chloride
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	calcium ion transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from direct assay Ref.6. Source: MGI secretory granule Inferred from direct assay Ref.6. Source: MGI
Molecular_function	chloride channel activity Inferred from sequence alignment Ref.1. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 913	892	Calcium-activated chloride channel regulator 1		PRO_0000333692
Regions
	Domain	307 – 476	170	VWFA
Amino acid modifications
	Glycosylation	504	1	N-linked (GlcNAc...) Potential
	Glycosylation	770	1	N-linked (GlcNAc...) Potential
	Glycosylation	804	1	N-linked (GlcNAc...) Potential
	Glycosylation	810	1	N-linked (GlcNAc...) Potential
	Glycosylation	836	1	N-linked (GlcNAc...) Potential
	Glycosylation	887	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	469	1	L → F in AAH28343. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q9D7Z6 [UniParc]. Last modified December 1, 2001. Version 2. Checksum: A7FA2F9E1089806D	FASTA	913	100,071
	10 20 30 40 50 60 MESLKSPVFL LILHLLEGVL SESLIQLNNN GYEGIVIAID HDVPEDEALI QHIKDMVTQA 70 80 90 100 110 120 SPYLFEATGK RFYFKNVAIL IPESWKAKPE YTRPKLETFK NADVLVSTTS PLGNDEPYTE 130 140 150 160 170 180 HIGACGEKGI RIHLTPDFLA GKKLTQYGPQ DRTFVHEWAH FRWGVFNEYN NDEKFYLSKG 190 200 210 220 230 240 KPQAVRCSAA ITGKNQVRRC QGGSCITNGK CVIDRVTGLY KDNCVFVPDP HQNEKASIMF 250 260 270 280 290 300 NQNINSVVEF CTEKNHNQEA PNDQNQRCNL RSTWEVIQES EDFKQTTPMT AQPPAPTFSL 310 320 330 340 350 360 LQIGQRIVCL VLDKSGSMLN DDRLNRMNQA SRLFLLQTVE QGSWVGMVTF DSAAYVQSEL 370 380 390 400 410 420 KQLNSGADRD LLIKHLPTVS AGGTSICSGL RTAFTVIKKK YPTDGSEIVL LTDGEDNTIS 430 440 450 460 470 480 SCFDLVKQSG AIIHTVALGP AAAKELEQLS KMTGGLQTYS SDQVQNNGLV DAFAALSSGN 490 500 510 520 530 540 AAIAQHSIQL ESRGVNLQNN QWMNGSVIVD SSVGKDTLFL ITWTTHPPTI FIWDPSGVEQ 550 560 570 580 590 600 NGFILDTTTK VAYLQVPGTA KVGFWKYSIQ ASSQTLTLTV TSRAASATLP PITVTPVVNK 610 620 630 640 650 660 NTGKFPSPVT VYASIRQGAS PILRASVTAL IESVNGKTVT LELLDNGAGA DATKNDGVYS 670 680 690 700 710 720 RFFTAFDANG RYSVKIWALG GVTSDRQRAA PPKNRAMYID GWIEDGEVRM NPPRPETSYV 730 740 750 760 770 780 QDKQLCFSRT SSGGSFVATN VPAAAPIPDL FPPCQITDLK ASIQGQNLVN LTWTAPGDDY 790 800 810 820 830 840 DHGRASNYII RMSTSIVDLR DHFNTSLQVN TTGLIPKEAS SEEIFEFELG GNTFGNGTDI 850 860 870 880 890 900 FIAIQAVDKS NLKSEISNIA RVSVFIPAQE PPIPEDSTPP CPDISINSTI PGIHVLKIMW 910 KWLGEMQVTL GLH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and identification of the gene gob-5, which is expressed in intestinal goblet cells in mice." Komiya T., Tanigawa Y., Hirohashi S. Biochem. Biophys. Res. Commun. 255:347-351(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Intestine.
[2]	"Characterization of a calcium-activated chloride channel as a shared target of Th2 cytokine pathways and its potential involvement in asthma." Zhou Y., Dong Q., Louahed J., Dragwa C., Savio D., Huang M., Weiss C., Tomer Y., McLane M.P., Nicolaides N.C., Levitt R.C. Am. J. Respir. Cell Mol. Biol. 25:486-491(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Colon and Stomach.
[4]	"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]. Strain: FVB/N. Tissue: Colon.
[5]	"Role of gob-5 in mucus overproduction and airway hyperresponsiveness in asthma." Nakanishi A., Morita S., Iwashita H., Sagiya Y., Ashida Y., Shirafuji H., Fujisawa Y., Nishimura O., Fujino M. Proc. Natl. Acad. Sci. U.S.A. 98:5175-5180(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[6]	"The murine mCLCA3 (alias gob-5) protein is located in the mucin granule membranes of intestinal, respiratory, and uterine goblet cells." Leverkoehne I., Gruber A.D. J. Histochem. Cytochem. 50:829-838(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PROTEOLYTIC PROCESSING, GLYCOSYLATION.
[7]	"Gene expression profiles reveal increased mClca3 (Gob5) expression and mucin production in a murine model of asbestos-induced fibrogenesis." Sabo-Attwood T., Ramos-Nino M., Bond J., Butnor K.J., Heintz N., Gruber A.D., Steele C., Taatjes D.J., Vacek P., Mossman B.T. Am. J. Pathol. 167:1243-1256(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[8]	"hCLCA1 and mCLCA3 are secreted non-integral membrane proteins and therefore are not ion channels." Gibson A., Lewis A.P., Affleck K., Aitken A.J., Meldrum E., Thompson N. J. Biol. Chem. 280:27205-27212(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"Blue native/SDS-PAGE analysis reveals reduced expression of the mClCA3 protein in cystic fibrosis knock-out mice." Brouillard F., Bensalem N., Hinzpeter A., Tondelier D., Trudel S., Gruber A.D., Ollero M., Edelman A. Mol. Cell. Proteomics 4:1762-1775(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[10]	"Gob-5 contributes to goblet cell hyperplasia and modulates pulmonary tissue inflammation." Long A.J., Sypek J.P., Askew R., Fish S.C., Mason L.E., Williams C.M.M., Goldman S.J. Am. J. Respir. Cell Mol. Biol. 35:357-365(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[11]	"Both cleavage products of the mCLCA3 protein are secreted soluble proteins." Mundhenk L., Alfalah M., Elble R.C., Pauli B.U., Naim H.Y., Gruber A.D. J. Biol. Chem. 281:30072-30080(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION, PROCESSING.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB017156 mRNA. Translation: BAA33743.1. AK008659 mRNA. Translation: BAB25815.2. AK136476 mRNA. Translation: BAE22995.1. BC028343 mRNA. Translation: AAH28343.1. BC116318 mRNA. Translation: AAI16319.1. BC116319 mRNA. Translation: AAI16320.1.
IPI	IPI00471289.
PIR	JG0168.
RefSeq	NP_059502.1. NM_017474.2.
UniGene	Mm.33483.
3D structure databases
ProteinModelPortal	Q9D7Z6.
ModBase	Search...
Protein family/group databases
MEROPS	M87.001.
PTM databases
PhosphoSite	Q9D7Z6.
Proteomic databases
PaxDb	Q9D7Z6.
PRIDE	Q9D7Z6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000029919; ENSMUSP00000029919; ENSMUSG00000028255.
GeneID	23844.
KEGG	mmu:23844.
UCSC	uc008rqf.2. mouse.
Organism-specific databases
CTD	23844.
MGI	MGI:1346342. Clca3.
Phylogenomic databases
eggNOG	NOG42884.
GeneTree	ENSGT00390000004810.
HOGENOM	HOG000015107.
HOVERGEN	HBG005560.
InParanoid	Q9D7Z6.
KO	K05027.
OMA	EPYTEQM.
OrthoDB	EOG4Z8XVR.
Gene expression databases
Bgee	Q9D7Z6.
Genevestigator	Q9D7Z6.
Family and domain databases
InterPro	IPR004727. CaCC_prot. IPR013642. Cl_channel_Ca. IPR015394. DUF1973. IPR002035. VWF_A. [Graphical view]
Pfam	PF08434. CLCA_N. 1 hit. PF09315. DUF1973. 1 hit. [Graphical view]
SMART	SM00327. VWA. 1 hit. [Graphical view]
TIGRFAMs	TIGR00868. hCaCC. 1 hit.
PROSITE	PS50234. VWFA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	303523.
SOURCE	Search...

Entry information

Entry name

CLCA1_MOUSE

Accession

Primary (citable) accession number: Q9D7Z6
Secondary accession number(s): O88826, Q8R049

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 20, 2008
Last sequence update:	December 1, 2001
Last modified:	April 3, 2013
This is version 88 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program