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Q9D7Z6

- CLCA1_MOUSE

UniProt

Q9D7Z6 - CLCA1_MOUSE

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Protein

Calcium-activated chloride channel regulator 1

Gene

Clca1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi156 – 1561ZincBy similarity
Metal bindingi160 – 1601ZincBy similarity
Metal bindingi167 – 1671ZincBy similarity
Sitei695 – 6962Cleavage; by autoproteolysisBy similarity

GO - Molecular functioni

  1. chloride channel activity Source: MGI

GO - Biological processi

  1. calcium ion transport Source: UniProtKB-KW
  2. cellular response to hypoxia Source: Ensembl
  3. chloride transmembrane transport Source: GOC
  4. chloride transport Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Calcium transport, Ion transport, Transport

Keywords - Ligandi

Calcium, Chloride, Metal-binding, Zinc

Protein family/group databases

MEROPSiM87.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium-activated chloride channel regulator 1 (EC:3.4.-.-By similarity)
Alternative name(s):
Calcium-activated chloride channel family member 3
Short name:
mCLCA3
Protein gob-5
Gene namesi
Name:Clca1
Synonyms:Clca3, Gob5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 3

Organism-specific databases

MGIiMGI:1346342. Clca3.

Subcellular locationi

Secretedextracellular space 3 Publications
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.

GO - Cellular componenti

  1. extracellular region Source: UniProtKB-KW
  2. integral component of membrane Source: MGI
  3. microvillus Source: MGI
  4. secretory granule Source: MGI
  5. zymogen granule membrane Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence AnalysisAdd
BLAST
Chaini22 – 913892Calcium-activated chloride channel regulator 1PRO_0000333692Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi504 – 5041N-linked (GlcNAc...)Sequence Analysis
Glycosylationi770 – 7701N-linked (GlcNAc...)Sequence Analysis
Glycosylationi804 – 8041N-linked (GlcNAc...)Sequence Analysis
Glycosylationi810 – 8101N-linked (GlcNAc...)Sequence Analysis
Glycosylationi836 – 8361N-linked (GlcNAc...)Sequence Analysis
Glycosylationi887 – 8871N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

The 110 kDa translation product is autoproteolytically cleaved by the metalloprotease domain in the endoplasmic reticulum into a 75 kDa N-terminal and a 35 kDa C-terminal products that remain physically associated with each other. The cleavage is necessary for calcium-activated chloride channel (CaCC) activation activity.By similarity1 Publication
Glycosylated.2 Publications

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein

Proteomic databases

MaxQBiQ9D7Z6.
PaxDbiQ9D7Z6.
PRIDEiQ9D7Z6.

PTM databases

PhosphoSiteiQ9D7Z6.

Expressioni

Tissue specificityi

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).3 Publications

Inductioni

By IL3, IL4 and IL9 in the lung. Increases in the bronchiolar epithelium of asbestos-induced fibrogenesis. Decreases in cystic fibrosis knockout mice.3 Publications

Gene expression databases

BgeeiQ9D7Z6.
GenevestigatoriQ9D7Z6.

Structurei

3D structure databases

ProteinModelPortaliQ9D7Z6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini307 – 476170VWFAPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni46 – 199154Metalloprotease domainBy similarityAdd
BLAST

Domaini

The metalloprotease region is responsible for autoproteolytic processing. It can also cross-cleave other CLCA Substrates.By similarity

Sequence similaritiesi

Belongs to the CLCR family.Curated
Contains 1 VWFA domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG42884.
GeneTreeiENSGT00390000004810.
HOGENOMiHOG000015107.
HOVERGENiHBG005560.
InParanoidiQ9D7Z6.
KOiK05027.
OMAiEPYTEQM.
OrthoDBiEOG78WKR1.
PhylomeDBiQ9D7Z6.
TreeFamiTF328396.

Family and domain databases

Gene3Di3.40.50.410. 1 hit.
InterProiIPR004727. CaCC_prot.
IPR013642. Cl_channel_Ca.
IPR015394. DUF1973.
IPR002035. VWF_A.
[Graphical view]
PfamiPF08434. CLCA_N. 1 hit.
PF09315. DUF1973. 1 hit.
[Graphical view]
SMARTiSM00327. VWA. 1 hit.
[Graphical view]
SUPFAMiSSF53300. SSF53300. 1 hit.
TIGRFAMsiTIGR00868. hCaCC. 1 hit.
PROSITEiPS50234. VWFA. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9D7Z6-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MESLKSPVFL LILHLLEGVL SESLIQLNNN GYEGIVIAID HDVPEDEALI
60 70 80 90 100
QHIKDMVTQA SPYLFEATGK RFYFKNVAIL IPESWKAKPE YTRPKLETFK
110 120 130 140 150
NADVLVSTTS PLGNDEPYTE HIGACGEKGI RIHLTPDFLA GKKLTQYGPQ
160 170 180 190 200
DRTFVHEWAH FRWGVFNEYN NDEKFYLSKG KPQAVRCSAA ITGKNQVRRC
210 220 230 240 250
QGGSCITNGK CVIDRVTGLY KDNCVFVPDP HQNEKASIMF NQNINSVVEF
260 270 280 290 300
CTEKNHNQEA PNDQNQRCNL RSTWEVIQES EDFKQTTPMT AQPPAPTFSL
310 320 330 340 350
LQIGQRIVCL VLDKSGSMLN DDRLNRMNQA SRLFLLQTVE QGSWVGMVTF
360 370 380 390 400
DSAAYVQSEL KQLNSGADRD LLIKHLPTVS AGGTSICSGL RTAFTVIKKK
410 420 430 440 450
YPTDGSEIVL LTDGEDNTIS SCFDLVKQSG AIIHTVALGP AAAKELEQLS
460 470 480 490 500
KMTGGLQTYS SDQVQNNGLV DAFAALSSGN AAIAQHSIQL ESRGVNLQNN
510 520 530 540 550
QWMNGSVIVD SSVGKDTLFL ITWTTHPPTI FIWDPSGVEQ NGFILDTTTK
560 570 580 590 600
VAYLQVPGTA KVGFWKYSIQ ASSQTLTLTV TSRAASATLP PITVTPVVNK
610 620 630 640 650
NTGKFPSPVT VYASIRQGAS PILRASVTAL IESVNGKTVT LELLDNGAGA
660 670 680 690 700
DATKNDGVYS RFFTAFDANG RYSVKIWALG GVTSDRQRAA PPKNRAMYID
710 720 730 740 750
GWIEDGEVRM NPPRPETSYV QDKQLCFSRT SSGGSFVATN VPAAAPIPDL
760 770 780 790 800
FPPCQITDLK ASIQGQNLVN LTWTAPGDDY DHGRASNYII RMSTSIVDLR
810 820 830 840 850
DHFNTSLQVN TTGLIPKEAS SEEIFEFELG GNTFGNGTDI FIAIQAVDKS
860 870 880 890 900
NLKSEISNIA RVSVFIPAQE PPIPEDSTPP CPDISINSTI PGIHVLKIMW
910
KWLGEMQVTL GLH
Length:913
Mass (Da):100,071
Last modified:December 1, 2001 - v2
Checksum:iA7FA2F9E1089806D
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti469 – 4691L → F in AAH28343. (PubMed:15489334)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS17889.1.
PIRiJG0168.
RefSeqiNP_059502.1. NM_017474.2.
UniGeneiMm.33483.

Genome annotation databases

EnsembliENSMUST00000029919; ENSMUSP00000029919; ENSMUSG00000028255.
GeneIDi23844.
KEGGimmu:23844.
UCSCiuc008rqf.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS17889.1.
PIRi JG0168.
RefSeqi NP_059502.1. NM_017474.2.
UniGenei Mm.33483.

3D structure databases

ProteinModelPortali Q9D7Z6.
ModBasei Search...
MobiDBi Search...

Protein family/group databases

MEROPSi M87.001.

PTM databases

PhosphoSitei Q9D7Z6.

Proteomic databases

MaxQBi Q9D7Z6.
PaxDbi Q9D7Z6.
PRIDEi Q9D7Z6.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000029919 ; ENSMUSP00000029919 ; ENSMUSG00000028255 .
GeneIDi 23844.
KEGGi mmu:23844.
UCSCi uc008rqf.2. mouse.

Organism-specific databases

CTDi 23844.
MGIi MGI:1346342. Clca3.

Phylogenomic databases

eggNOGi NOG42884.
GeneTreei ENSGT00390000004810.
HOGENOMi HOG000015107.
HOVERGENi HBG005560.
InParanoidi Q9D7Z6.
KOi K05027.
OMAi EPYTEQM.
OrthoDBi EOG78WKR1.
PhylomeDBi Q9D7Z6.
TreeFami TF328396.

Miscellaneous databases

NextBioi 303523.
PROi Q9D7Z6.
SOURCEi Search...

Gene expression databases

Bgeei Q9D7Z6.
Genevestigatori Q9D7Z6.

Family and domain databases

Gene3Di 3.40.50.410. 1 hit.
InterProi IPR004727. CaCC_prot.
IPR013642. Cl_channel_Ca.
IPR015394. DUF1973.
IPR002035. VWF_A.
[Graphical view ]
Pfami PF08434. CLCA_N. 1 hit.
PF09315. DUF1973. 1 hit.
[Graphical view ]
SMARTi SM00327. VWA. 1 hit.
[Graphical view ]
SUPFAMi SSF53300. SSF53300. 1 hit.
TIGRFAMsi TIGR00868. hCaCC. 1 hit.
PROSITEi PS50234. VWFA. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiCLCA1_MOUSE
AccessioniPrimary (citable) accession number: Q9D7Z6
Secondary accession number(s): O88826, Q8R049
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: December 1, 2001
Last modified: October 29, 2014
This is version 100 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3