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Q8BG22

- CLCA2_MOUSE

UniProt

Q8BG22 - CLCA2_MOUSE

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Protein

Calcium-activated chloride channel regulator 2

Gene

Clca2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- 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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi164 – 1641ZincBy similarity
Metal bindingi168 – 1681ZincBy similarity
Metal bindingi175 – 1751ZincBy similarity
Sitei708 – 7092Cleavage; by autoproteolysisBy similarity

GO - Molecular functioni

  1. chloride channel activity Source: MGI
  2. ligand-gated ion channel activity Source: MGI

GO - Biological processi

  1. cell adhesion Source: UniProtKB-KW
  2. chloride transmembrane transport Source: GOC
  3. chloride transport Source: MGI
  4. ion transmembrane transport Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Cell adhesion, Ion transport, Transport

Keywords - Ligandi

Calcium, Chloride, Metal-binding, Zinc

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 3

Organism-specific databases

MGIiMGI:2139758. Clca5.

Subcellular locationi

Cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication. Basal cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication. Cell junction 1 Publication

GO - Cellular componenti

  1. cell junction Source: UniProtKB-KW
  2. integral component of membrane Source: UniProtKB-KW
  3. plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3232Sequence AnalysisAdd
BLAST
Chaini33 – 942910Calcium-activated chloride channel regulator 2PRO_0000333696Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi74 – 741N-linked (GlcNAc...)Sequence Analysis
Glycosylationi97 – 971N-linked (GlcNAc...)Sequence Analysis
Glycosylationi231 – 2311N-linked (GlcNAc...)Sequence Analysis
Glycosylationi235 – 2351N-linked (GlcNAc...)Sequence Analysis
Glycosylationi254 – 2541N-linked (GlcNAc...)Sequence Analysis
Glycosylationi286 – 2861N-linked (GlcNAc...)Sequence Analysis
Glycosylationi522 – 5221N-linked (GlcNAc...)Sequence Analysis
Glycosylationi580 – 5801N-linked (GlcNAc...)Sequence Analysis
Glycosylationi637 – 6371N-linked (GlcNAc...)Sequence Analysis
Glycosylationi821 – 8211N-linked (GlcNAc...)Sequence Analysis

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

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein

Proteomic databases

PaxDbiQ8BG22.
PRIDEiQ8BG22.

PTM databases

PhosphoSiteiQ8BG22.

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

BgeeiQ8BG22.
GenevestigatoriQ8BG22.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000036029.

Structurei

3D structure databases

ProteinModelPortaliQ8BG22.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini33 – 905873ExtracellularSequence AnalysisAdd
BLAST
Topological domaini927 – 94216CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei906 – 92621HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini311 – 483173VWFAPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni54 – 205152Metalloprotease 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, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG42884.
GeneTreeiENSGT00390000004810.
HOGENOMiHOG000015107.
HOVERGENiHBG005560.
InParanoidiQ8BG22.
KOiK05028.
OMAiEKGPCPQ.
OrthoDBiEOG78WKR1.
PhylomeDBiQ8BG22.
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]

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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei675 – 942268Missing in isoform 2. 1 PublicationVSP_033515Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_178697.4. [Q8BG22-1]
XP_006501498.1. XM_006501435.1. [Q8BG22-2]
UniGeneiMm.331420.

Genome annotation databases

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

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS17890.1. [Q8BG22-1 ]
RefSeqi NP_848812.1. NM_178697.4. [Q8BG22-1 ]
XP_006501498.1. XM_006501435.1. [Q8BG22-2 ]
UniGenei Mm.331420.

3D structure databases

ProteinModelPortali Q8BG22.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10090.ENSMUSP00000036029.

Protein family/group databases

MEROPSi M87.003.

PTM databases

PhosphoSitei Q8BG22.

Proteomic databases

PaxDbi Q8BG22.
PRIDEi Q8BG22.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000040465 ; ENSMUSP00000036029 ; ENSMUSG00000036960 . [Q8BG22-1 ]
GeneIDi 229933.
KEGGi mmu:229933.
UCSCi uc008rqg.1. mouse. [Q8BG22-1 ]

Organism-specific databases

CTDi 229933.
MGIi MGI:2139758. Clca5.

Phylogenomic databases

eggNOGi NOG42884.
GeneTreei ENSGT00390000004810.
HOGENOMi HOG000015107.
HOVERGENi HBG005560.
InParanoidi Q8BG22.
KOi K05028.
OMAi EKGPCPQ.
OrthoDBi EOG78WKR1.
PhylomeDBi Q8BG22.
TreeFami TF328396.

Miscellaneous databases

NextBioi 379743.
PROi Q8BG22.
SOURCEi Search...

Gene expression databases

Bgeei Q8BG22.
Genevestigatori Q8BG22.

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. "Re-expression of detachment-inducible chloride channel mCLCA5 suppresses growth of metastatic breast cancer cells."
    Beckley J.R., Pauli B.U., Elble R.C.
    J. Biol. Chem. 279:41634-41641(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INDUCTION.
    Strain: BALB/c.
  2. "Molecular and functional analyses of two new calcium-activated chloride channel family members from mouse eye and intestine."
    Evans S.R., Thoreson W.B., Beck C.L.
    J. Biol. Chem. 279:41792-41800(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Tissue: Eye.
  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] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J.
    Tissue: Head and Skin.
  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] (ISOFORM 1).
    Strain: 129.
    Tissue: Mammary tumor.

Entry informationi

Entry nameiCLCA2_MOUSE
AccessioniPrimary (citable) accession number: Q8BG22
Secondary accession number(s): Q8BZF7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: March 1, 2003
Last modified: October 29, 2014
This is version 89 of the entry and version 1 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