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A8K7I4 (CLCA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 57. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calcium-activated chloride channel regulator 1
Alternative name(s):
Calcium-activated chloride channel family member 1
Short name=hCLCA1
Calcium-activated chloride channel protein 1
Short name=CaCC-1
Short name=hCaCC-1
Gene names
Name:CLCA1
Synonyms:CACC1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length914 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.1 Ref.6 Ref.7 Ref.8

Subcellular location

Secretedextracellular space. Cell membrane; Peripheral membrane protein; Extracellular side. Note: Protein that remains attached to the plasma membrane appeared to be predominantly localized to microvilli. Ref.11

Tissue specificity

Highly expressed in small intestine and colon namely in intestinal basal crypt epithelia and goblet cells, and appendix. Weakly expressed in uterus, testis and kidney. Expressed in the airways epithelium of both asthmatic and healthy patients. Expressed in the bronchial epithelium, especially in mucus-producing goblet cells. Expressed in normal turbinate mucosa and nasal polyp. Expressed in. Ref.1 Ref.2 Ref.7 Ref.8 Ref.9

Induction

By IL13/interleukin-13 in tracheobronchial epithelial cells. Up-regulated by histamine in a dose-dependent manner. Significantly down-regulated in colorectal cancer. Significantly up-regulated in the IL9-responsive mucus-producing epithelium of asthmatic patients. Significantly decreased in nasal polyp. Significantly increased by TNF in upper airway mucosa. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13

Post-translational modification

Glycosylated. Ref.1

The 125-kDa product is processed and yields to two cell-surface-associated subunits, a 90-kDa protein and a group of 37-to 41-kDa proteins.

Sequence similarities

Belongs to the CLCR family.

Contains 1 VWFA domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 914893Calcium-activated chloride channel regulator 1
PRO_0000333690

Regions

Domain306 – 475170VWFA

Amino acid modifications

Glycosylation5031N-linked (GlcNAc...) Potential
Glycosylation5851N-linked (GlcNAc...) Potential
Glycosylation7701N-linked (GlcNAc...) Potential
Glycosylation8041N-linked (GlcNAc...) Potential
Glycosylation8101N-linked (GlcNAc...) Potential
Glycosylation8311N-linked (GlcNAc...) Potential
Glycosylation8361N-linked (GlcNAc...) Potential
Glycosylation8901N-linked (GlcNAc...) Potential

Natural variations

Natural variant651L → F. Ref.1 Ref.2 Ref.3 Ref.5
Corresponds to variant rs2145412 [ dbSNP | Ensembl ].
VAR_054654
Natural variant1521R → K. Ref.1
Corresponds to variant rs2753386 [ dbSNP | Ensembl ].
VAR_054655
Natural variant3571N → S. Ref.1 Ref.2 Ref.3 Ref.5
Corresponds to variant rs2734705 [ dbSNP | Ensembl ].
VAR_043146
Natural variant4061E → V.
Corresponds to variant rs1142185 [ dbSNP | Ensembl ].
VAR_054656
Natural variant4261K → R.
Corresponds to variant rs4647852 [ dbSNP | Ensembl ].
VAR_054657
Natural variant5241M → T. Ref.1 Ref.2 Ref.3 Ref.5
Corresponds to variant rs2791494 [ dbSNP | Ensembl ].
VAR_043147
Natural variant6611Y → H.
Corresponds to variant rs5744409 [ dbSNP | Ensembl ].
VAR_054658
Natural variant7601K → N. Ref.1
Corresponds to variant rs2791483 [ dbSNP | Ensembl ].
VAR_054659

Experimental info

Sequence conflict3931F → S in BAF84688. Ref.3

Sequences

Sequence LengthMass (Da)Tools
A8K7I4 [UniParc].

Last modified November 2, 2010. Version 3.
Checksum: 8D8999E855822711

FASTA914100,226
        10         20         30         40         50         60 
MGPFKSSVFI LILHLLEGAL SNSLIQLNNN GYEGIVVAID PNVPEDETLI QQIKDMVTQA 

        70         80         90        100        110        120 
SLYLLEATGK RFYFKNVAIL IPETWKTKAD YVRPKLETYK NADVLVAEST PPGNDEPYTE 

       130        140        150        160        170        180 
QMGNCGEKGE RIHLTPDFIA GKKLAEYGPQ GRAFVHEWAH LRWGVFDEYN NDEKFYLSNG 

       190        200        210        220        230        240 
RIQAVRCSAG ITGTNVVKKC QGGSCYTKRC TFNKVTGLYE KGCEFVLQSR QTEKASIMFA 

       250        260        270        280        290        300 
QHVDSIVEFC TEQNHNKEAP NKQNQKCNLR STWEVIRDSE DFKKTTPMTT QPPNPTFSLL 

       310        320        330        340        350        360 
QIGQRIVCLV LDKSGSMATG NRLNRLNQAG QLFLLQTVEL GSWVGMVTFD SAAHVQNELI 

       370        380        390        400        410        420 
QINSGSDRDT LAKRLPAAAS GGTSICSGLR SAFTVIRKKY PTDGSEIVLL TDGEDNTISG 

       430        440        450        460        470        480 
CFNEVKQSGA IIHTVALGPS AAQELEELSK MTGGLQTYAS DQVQNNGLID AFGALSSGNG 

       490        500        510        520        530        540 
AVSQRSIQLE SKGLTLQNSQ WMNGTVIVDS TVGKDTLFLI TWTMQPPQIL LWDPSGQKQG 

       550        560        570        580        590        600 
GFVVDKNTKM AYLQIPGIAK VGTWKYSLQA SSQTLTLTVT SRASNATLPP ITVTSKTNKD 

       610        620        630        640        650        660 
TSKFPSPLVV YANIRQGASP ILRASVTALI ESVNGKTVTL ELLDNGAGAD ATKDDGVYSR 

       670        680        690        700        710        720 
YFTTYDTNGR YSVKVRALGG VNAARRRVIP QQSGALYIPG WIENDEIQWN PPRPEINKDD 

       730        740        750        760        770        780 
VQHKQVCFSR TSSGGSFVAS DVPNAPIPDL FPPGQITDLK AEIHGGSLIN LTWTAPGDDY 

       790        800        810        820        830        840 
DHGTAHKYII RISTSILDLR DKFNESLQVN TTALIPKEAN SEEVFLFKPE NITFENGTDL 

       850        860        870        880        890        900 
FIAIQAVDKV DLKSEISNIA RVSLFIPPQT PPETPSPDET SAPCPNIHIN STIPGIHILK 

       910 
IMWKWIGELQ LSIA 

« Hide

References

« Hide 'large scale' references
[1]"Genomic cloning, molecular characterization, and functional analysis of human CLCA1, the first human member of the family of Ca2+-activated Cl- channel proteins."
Gruber A.D., Elble R.C., Ji H.-L., Schreur K.D., Fuller C.M., Pauli B.U.
Genomics 54:200-214(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, TISSUE SPECIFICITY, GLYCOSYLATION, PROTEOLYTIC PROCESSING, VARIANTS PHE-65; LYS-152; SER-357; THR-524 AND ASN-760.
Tissue: Small intestine.
[2]"Identification of three novel members of the calcium-dependent chloride channel (CaCC) family predominantly expressed in the digestive tract and trachea."
Agnel M., Vermat T., Culouscou J.-M.
FEBS Lett. 455:295-301(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANTS PHE-65; SER-357 AND THR-524.
Tissue: Small intestine.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS PHE-65; SER-357 AND THR-524.
Tissue: Colon and Small intestine.
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS PHE-65; SER-357 AND THR-524.
[6]"Expression of the Ca2+-activated chloride channel genes CLCA1 and CLCA2 is downregulated in human colorectal cancer."
Bustin S.A., Li S.-R., Dorudi S.
DNA Cell Biol. 20:331-338(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[7]"Increased expression of the human Ca2+-activated Cl- channel 1 (CaCC1) gene in the asthmatic airway."
Hoshino M., Morita S., Iwashita H., Sagiya Y., Nagi T., Nakanishi A., Ashida Y., Nishimura O., Fujisawa Y., Fujino M.
Am. J. Respir. Crit. Care Med. 165:1132-1136(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION, TISSUE SPECIFICITY.
[8]"A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma."
Toda M., Tulic M.K., Levitt R.C., Hamid Q.
J. Allergy Clin. Immunol. 109:246-250(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION, TISSUE SPECIFICITY.
[9]"Expression and distribution of ion transport mRNAs in human nasal mucosa and nasal polyps."
Lee S.H., Park J.H., Jung H.H., Lee S.H., Oh J.W., Lee H.M., Jun H.S., Cho W.J., Lee J.Y.
Acta Oto-Laryngol. 125:745-752(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INDUCTION.
[10]"Niflumic acid and MSI-2216 reduce TNF-alpha-induced mucin expression in human airway mucosa."
Hauber H.-P., Daigneault P., Frenkiel S., Lavigne F., Hung H.-L., Levitt R.C., Hamid Q.
J. Allergy Clin. Immunol. 115:266-271(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[11]"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.
[12]"Differential regulation of MUC5AC/Muc5ac and hCLCA-1/mGob-5 expression in airway epithelium."
Thai P., Chen Y., Dolganov G., Wu R.
Am. J. Respir. Cell Mol. Biol. 33:523-530(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[13]"Histamine induces MUC5AC expression via a hCLCA1 pathway."
Kim Y.M., Won T.-B., Kim S.W., Min Y.-G., Lee C.H., Rhee C.-S.
Pharmacology 80:219-226(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF039400 mRNA. Translation: AAC95428.1.
AF039401 Genomic DNA. Translation: AAC95429.1.
AF127036 mRNA. Translation: AAD25487.1.
AK291999 mRNA. Translation: BAF84688.1.
AK314375 mRNA. Translation: BAG37002.1.
AL122002 Genomic DNA. Translation: CAI22169.1.
CH471097 Genomic DNA. Translation: EAW73186.1.
RefSeqNP_001276.2. NM_001285.3.
UniGeneHs.194659.

3D structure databases

ProteinModelPortalA8K7I4.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107593. 2 interactions.
IntActA8K7I4. 1 interaction.
STRING9606.ENSP00000234701.

Chemistry

ChEMBLCHEMBL2364708.

Protein family/group databases

MEROPSM87.001.

PTM databases

PhosphoSiteA8K7I4.

Proteomic databases

PaxDbA8K7I4.
PRIDEA8K7I4.

Protocols and materials databases

DNASU1179.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000234701; ENSP00000234701; ENSG00000016490.
ENST00000394711; ENSP00000378200; ENSG00000016490.
GeneID1179.
KEGGhsa:1179.
UCSCuc001dls.1. human.

Organism-specific databases

CTD1179.
GeneCardsGC01P086934.
HGNCHGNC:2015. CLCA1.
HPAHPA052787.
MIM603906. gene.
neXtProtNX_A8K7I4.
PharmGKBPA26542.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG42884.
HOGENOMHOG000015107.
HOVERGENHBG005560.
InParanoidA8K7I4.
KOK05027.
OMAEPYTEQM.
OrthoDBEOG78WKR1.
PhylomeDBA8K7I4.
TreeFamTF328396.

Gene expression databases

BgeeA8K7I4.
CleanExHS_CLCA1.
GenevestigatorA8K7I4.

Family and domain databases

Gene3D3.40.50.410. 1 hit.
InterProIPR004727. CaCC_prot.
IPR013642. Cl_channel_Ca.
IPR015394. DUF1973.
IPR002035. VWF_A.
[Graphical view]
PfamPF08434. CLCA_N. 1 hit.
PF09315. DUF1973. 1 hit.
[Graphical view]
SMARTSM00327. VWA. 1 hit.
[Graphical view]
SUPFAMSSF53300. SSF53300. 1 hit.
TIGRFAMsTIGR00868. hCaCC. 1 hit.
PROSITEPS50234. VWFA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCLCA1.
GenomeRNAi1179.
NextBio4872.
PROA8K7I4.
SOURCESearch...

Entry information

Entry nameCLCA1_HUMAN
AccessionPrimary (citable) accession number: A8K7I4
Secondary accession number(s): B2RAV5 expand/collapse secondary AC list , O95151, Q5TDF4, Q9UNF6, Q9UPC6
Entry history
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: November 2, 2010
Last modified: April 16, 2014
This is version 57 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM