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Protein

Calcium-activated chloride channel regulator 2

Gene

Clca2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Plays a role in modulating chloride current across the plasma membrane in a calcium-dependent manner, and cell adhesion. Involved in basal cell adhesion and/or stratification of squamous epithelia. May act as a tumor suppressor in breast and colorectal cancer. Plays a key role for cell adhesion in the beginning stages of lung metastasis via the binding to ITGB4.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi164Zinc; catalyticBy similarity1
Active sitei165By similarity1
Metal bindingi168Zinc; catalyticBy similarity1
Metal bindingi175Zinc; catalyticBy similarity1

GO - Molecular functioni

  • chloride channel activity Source: MGI
  • intracellular calcium activated chloride channel activity Source: GO_Central
  • ligand-gated ion channel activity Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • metallopeptidase activity Source: UniProtKB-KW

GO - Biological processi

  • cell adhesion Source: UniProtKB-KW
  • chloride transport Source: MGI

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-2672351 Stimuli-sensing channels

Protein family/group databases

MEROPSiM87.003

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium-activated chloride channel regulator 2 (EC:3.4.-.-By similarity)
Alternative name(s):
Calcium-activated chloride channel family member 5
Short name:
mCLCA5
Gene namesi
Name:Clca2
Synonyms:Clca5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:2139758 Clca2

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini33 – 905ExtracellularSequence analysisAdd BLAST873
Transmembranei906 – 926HelicalSequence analysisAdd BLAST21
Topological domaini927 – 942CytoplasmicSequence analysisAdd BLAST16

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 32Sequence analysisAdd BLAST32
ChainiPRO_000033369633 – 942Calcium-activated chloride channel regulator 2Add BLAST910

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi74N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi97N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi231N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi235N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi254N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi286N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi522N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi580N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi637N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi821N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

The translation product is autoproteolytically cleaved by the metalloprotease domain in the endoplasmic reticulum into a N-terminal and a C-terminal products that remain physically associated with each other. The cleavage is necessary for calcium-activated chloride channel (CaCC) activation activity.By similarity
N-glycosylated.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei708 – 709Cleavage; by autolysisBy similarity2

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein

Proteomic databases

PaxDbiQ8BG22
PRIDEiQ8BG22

PTM databases

PhosphoSitePlusiQ8BG22

Expressioni

Tissue specificityi

Highly expressed in eye, spleen, lung, kidney, uterus, and endothelial cells. Weakly expressed in heart and throughout the gastrointestinal tract. Highly expressed in mammary cell lines. Its expression in immortalized cell line HC11 correlates with slow or arrested growth. Re-expression in mammary tumor cells reduces colony survival.2 Publications

Inductioni

By 30-fold when cells are deprived of growth factors or anchorage in mammary epithelial cell. Down-regulated in metastatic mammary tumor cell lines.1 Publication

Gene expression databases

BgeeiENSMUSG00000036960 Expressed in 56 organ(s), highest expression level in ear
GenevisibleiQ8BG22 MM

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000036029

Structurei

3D structure databases

ProteinModelPortaliQ8BG22
SMRiQ8BG22
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini311 – 483VWFAPROSITE-ProRule annotationAdd BLAST173

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni54 – 205Metalloprotease domainBy similarityAdd BLAST152

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, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IEPS Eukaryota
ENOG410XPSZ LUCA
GeneTreeiENSGT00390000004810
HOGENOMiHOG000015107
HOVERGENiHBG005560
InParanoidiQ8BG22
KOiK05028
OMAiNIQMNAP
OrthoDBiEOG091G09E6
PhylomeDBiQ8BG22
TreeFamiTF328396

Family and domain databases

Gene3Di3.40.50.410, 1 hit
InterProiView protein in InterPro
IPR004727 CLCA_chordata
IPR013642 CLCA_N
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

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q8BG22-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MTHRDSTGPV IGLKLVTLLF TLSPELLFLG AGLKLKENGY DGLLVAINPR
60 70 80 90 100
VPEDLKLITN IKEMITEASF YLFNATKRRV FFRNVQILVP ATWTDHNYSR
110 120 130 140 150
VRQESYDKAN VIVAEQSEEH GDDPYTLQHR GCGQEGRYIH FTPSFLLNDE
160 170 180 190 200
LAAGYGARGR VFVHEWAHLR WGVFDEYNND KPFYVNGRNE IQVTRCSSDI
210 220 230 240 250
TGVFVCEKGL CPHEDCIISK IFREGCTFLY NSTQNATGSI MFMPSLPSVV
260 270 280 290 300
EFCNESTHNQ EAPNLQNQVC SLRSTWDVIT ASSDLNHSLP VHGVGLPAPP
310 320 330 340 350
TFSLLQAGDR VVCLVIDVSR KMAEGDRLLR LQQAAELYLM QVVEAHTFVG
360 370 380 390 400
IVTFDSKGEI RASLQQIYSD DDRKLLVSYL PTAVSTDAET NICAGVKKGF
410 420 430 440 450
EVVEERNGRA DGSVLILVTS GADEHIANCL LTSMNSGSTI HSMALGSSAA
460 470 480 490 500
RKVGELSRLT GGLKFFIPDK FTSNGMTEAF VRISSGTGDI FQQSLQVESV
510 520 530 540 550
CETVQPQHQL ADTMTVDSAV GNDTLFLVTW QTGGPPEIAL LDPSGRKYNT
560 570 580 590 600
GDFIINLAFR TASLKIPGTA KHGHWTYTLN NTHHSPQALK VTVASRASSL
610 620 630 640 650
AMSPATLEAF VERDSTYFPQ PVIIYANVRK GLHPILNATV VATVEPEAGD
660 670 680 690 700
PVVLQLLDGG AGADVIRNDG IYSRYFSSFA VSGSYSLTVH VRHSPSTSTL
710 720 730 740 750
ALPVPGNHAM YVPGYITNDN IQMNAPKNLG HRPVKERWGF SRVSSGGSFS
760 770 780 790 800
VLGVPDGPHP DMFPPCKITD LEAMKVEDDV VLSWTAPGED FDQGQTTSYE
810 820 830 840 850
IRMSRSLWNI RDDFDNAILV NSSELVPQHA GTRETFTFSP KLVTHELDHE
860 870 880 890 900
LAEDAQEPYI VYVALRAMDR SSLRSAVSNI ALVSMSLPPN SSPVVSRDDL
910 920 930 940
ILKGVLTTVG LIAILCLIMV VAHCIFNRKK RPSRKENETK FL
Length:942
Mass (Da):103,626
Last modified:March 1, 2003 - v1
Checksum:iD0511E33CF317E4F
GO
Isoform 2 (identifier: Q8BG22-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     675-942: Missing.

Note: No experimental confirmation available.
Show »
Length:674
Mass (Da):73,983
Checksum:i190E0E58E4C6D0F1
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_033515675 – 942Missing in isoform 2. 1 PublicationAdd BLAST268

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY161007 mRNA Translation: AAO18366.1
AK028704 mRNA Translation: BAC26076.1
AK035512 mRNA Translation: BAC29086.1
AK048276 mRNA Translation: BAC33291.1
BC096379 mRNA Translation: AAH96379.1
CCDSiCCDS17890.1 [Q8BG22-1]
RefSeqiNP_848812.1, NM_178697.5 [Q8BG22-1]
XP_006501498.1, XM_006501435.1 [Q8BG22-2]
UniGeneiMm.331420

Genome annotation databases

EnsembliENSMUST00000040465; ENSMUSP00000036029; ENSMUSG00000036960 [Q8BG22-1]
ENSMUST00000198993; ENSMUSP00000143161; ENSMUSG00000036960 [Q8BG22-2]
GeneIDi229933
KEGGimmu:229933
UCSCiuc008rqg.1 mouse [Q8BG22-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY161007 mRNA Translation: AAO18366.1
AK028704 mRNA Translation: BAC26076.1
AK035512 mRNA Translation: BAC29086.1
AK048276 mRNA Translation: BAC33291.1
BC096379 mRNA Translation: AAH96379.1
CCDSiCCDS17890.1 [Q8BG22-1]
RefSeqiNP_848812.1, NM_178697.5 [Q8BG22-1]
XP_006501498.1, XM_006501435.1 [Q8BG22-2]
UniGeneiMm.331420

3D structure databases

ProteinModelPortaliQ8BG22
SMRiQ8BG22
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000036029

Protein family/group databases

MEROPSiM87.003

PTM databases

PhosphoSitePlusiQ8BG22

Proteomic databases

PaxDbiQ8BG22
PRIDEiQ8BG22

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000040465; ENSMUSP00000036029; ENSMUSG00000036960 [Q8BG22-1]
ENSMUST00000198993; ENSMUSP00000143161; ENSMUSG00000036960 [Q8BG22-2]
GeneIDi229933
KEGGimmu:229933
UCSCiuc008rqg.1 mouse [Q8BG22-1]

Organism-specific databases

CTDi9635
MGIiMGI:2139758 Clca2

Phylogenomic databases

eggNOGiENOG410IEPS Eukaryota
ENOG410XPSZ LUCA
GeneTreeiENSGT00390000004810
HOGENOMiHOG000015107
HOVERGENiHBG005560
InParanoidiQ8BG22
KOiK05028
OMAiNIQMNAP
OrthoDBiEOG091G09E6
PhylomeDBiQ8BG22
TreeFamiTF328396

Enzyme and pathway databases

ReactomeiR-MMU-2672351 Stimuli-sensing channels

Miscellaneous databases

ChiTaRSiClca1 mouse
PROiPR:Q8BG22
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000036960 Expressed in 56 organ(s), highest expression level in ear
GenevisibleiQ8BG22 MM

Family and domain databases

Gene3Di3.40.50.410, 1 hit
InterProiView protein in InterPro
IPR004727 CLCA_chordata
IPR013642 CLCA_N
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 nameiCLCA2_MOUSE
AccessioniPrimary (citable) accession number: Q8BG22
Secondary accession number(s): Q8BZF7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: March 1, 2003
Last modified: September 12, 2018
This is version 121 of the entry and version 1 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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