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Protein

Calcium-activated chloride channel regulator 1

Gene

Clca1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Metal bindingi156Zinc; catalyticBy similarity1
Active sitei157By similarity1
Metal bindingi160Zinc; catalyticBy similarity1
Metal bindingi167Zinc; catalyticBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
Biological processCalcium transport, Ion transport, Transport
LigandCalcium, Chloride, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-2672351 Stimuli-sensing channels

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1346342 Clca1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000033369222 – 913Calcium-activated chloride channel regulator 1Add BLAST892

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi504N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi770N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi804N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi810N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi836N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi887N-linked (GlcNAc...) asparagineSequence analysis1

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei695 – 696Cleavage; by autolysisBy similarity2

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein

Proteomic databases

MaxQBiQ9D7Z6
PaxDbiQ9D7Z6
PeptideAtlasiQ9D7Z6
PRIDEiQ9D7Z6

PTM databases

iPTMnetiQ9D7Z6
PhosphoSitePlusiQ9D7Z6

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

BgeeiENSMUSG00000028255 Expressed in 71 organ(s), highest expression level in large intestine
GenevisibleiQ9D7Z6 MM

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000029919

Structurei

3D structure databases

ProteinModelPortaliQ9D7Z6
SMRiQ9D7Z6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini307 – 476VWFAPROSITE-ProRule annotationAdd BLAST170

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni46 – 199Metalloprotease domainBy similarityAdd BLAST154

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

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IEPS Eukaryota
ENOG410XPSZ LUCA
GeneTreeiENSGT00390000004810
HOGENOMiHOG000015107
HOVERGENiHBG005560
InParanoidiQ9D7Z6
KOiK05027
OMAiLFPPCQI
OrthoDBiEOG091G09E6
PhylomeDBiQ9D7Z6
TreeFamiTF328396

Family and domain databases

Gene3Di2.60.40.10, 1 hit
3.40.50.410, 1 hit
InterProiView protein in InterPro
IPR004727 CLCA_chordata
IPR013642 CLCA_N
IPR013783 Ig-like_fold
IPR002035 VWF_A
IPR036465 vWFA_dom_sf
PfamiView protein in Pfam
PF08434 CLCA, 1 hit
PF13519 VWA_2, 1 hit
SMARTiView protein in SMART
SM00327 VWA, 1 hit
SUPFAMiSSF53300 SSF53300, 1 hit
TIGRFAMsiTIGR00868 hCaCC, 1 hit
PROSITEiView protein in PROSITE
PS50234 VWFA, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti469L → F in AAH28343 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

3D structure databases

ProteinModelPortaliQ9D7Z6
SMRiQ9D7Z6
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000029919

Protein family/group databases

MEROPSiM87.001

PTM databases

iPTMnetiQ9D7Z6
PhosphoSitePlusiQ9D7Z6

Proteomic databases

MaxQBiQ9D7Z6
PaxDbiQ9D7Z6
PeptideAtlasiQ9D7Z6
PRIDEiQ9D7Z6

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi1179
MGIiMGI:1346342 Clca1

Phylogenomic databases

eggNOGiENOG410IEPS Eukaryota
ENOG410XPSZ LUCA
GeneTreeiENSGT00390000004810
HOGENOMiHOG000015107
HOVERGENiHBG005560
InParanoidiQ9D7Z6
KOiK05027
OMAiLFPPCQI
OrthoDBiEOG091G09E6
PhylomeDBiQ9D7Z6
TreeFamiTF328396

Enzyme and pathway databases

ReactomeiR-MMU-2672351 Stimuli-sensing channels

Miscellaneous databases

ChiTaRSiClca1 mouse
PROiPR:Q9D7Z6
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028255 Expressed in 71 organ(s), highest expression level in large intestine
GenevisibleiQ9D7Z6 MM

Family and domain databases

Gene3Di2.60.40.10, 1 hit
3.40.50.410, 1 hit
InterProiView protein in InterPro
IPR004727 CLCA_chordata
IPR013642 CLCA_N
IPR013783 Ig-like_fold
IPR002035 VWF_A
IPR036465 vWFA_dom_sf
PfamiView protein in Pfam
PF08434 CLCA, 1 hit
PF13519 VWA_2, 1 hit
SMARTiView protein in SMART
SM00327 VWA, 1 hit
SUPFAMiSSF53300 SSF53300, 1 hit
TIGRFAMsiTIGR00868 hCaCC, 1 hit
PROSITEiView protein in PROSITE
PS50234 VWFA, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCLCA1_MOUSE
AccessioniPrimary (citable) accession number: Q9D7Z6
Secondary accession number(s): O88826, Q8R049
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: December 1, 2001
Last modified: November 7, 2018
This is version 132 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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