A8K7I4 (CLCA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	914 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Secreted › extracellular 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.

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Calcium Chloride
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	calcium ion transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc secretory granule Inferred from electronic annotation. Source: Compara
Molecular_function	chloride channel activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 914	893	Calcium-activated chloride channel regulator 1		PRO_0000333690
Regions
	Domain	306 – 475	170	VWFA
Amino acid modifications
	Glycosylation	503	1	N-linked (GlcNAc...) Potential
	Glycosylation	585	1	N-linked (GlcNAc...) Potential
	Glycosylation	770	1	N-linked (GlcNAc...) Potential
	Glycosylation	804	1	N-linked (GlcNAc...) Potential
	Glycosylation	810	1	N-linked (GlcNAc...) Potential
	Glycosylation	831	1	N-linked (GlcNAc...) Potential
	Glycosylation	836	1	N-linked (GlcNAc...) Potential
	Glycosylation	890	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	65	1	L → F. Ref.1 Ref.2 Ref.3 Ref.5 Corresponds to variant rs2145412 [ dbSNP | Ensembl ].		VAR_054654
	Natural variant	152	1	R → K. Ref.1 Corresponds to variant rs2753386 [ dbSNP | Ensembl ].		VAR_054655
	Natural variant	357	1	N → S. Ref.1 Ref.2 Ref.3 Ref.5 Corresponds to variant rs2734705 [ dbSNP | Ensembl ].		VAR_043146
	Natural variant	406	1	E → V. Corresponds to variant rs1142185 [ dbSNP | Ensembl ].		VAR_054656
	Natural variant	426	1	K → R. Corresponds to variant rs4647852 [ dbSNP | Ensembl ].		VAR_054657
	Natural variant	524	1	M → T. Ref.1 Ref.2 Ref.3 Ref.5 Corresponds to variant rs2791494 [ dbSNP | Ensembl ].		VAR_043147
	Natural variant	661	1	Y → H. Corresponds to variant rs5744409 [ dbSNP | Ensembl ].		VAR_054658
	Natural variant	760	1	K → N. Ref.1 Corresponds to variant rs2791483 [ dbSNP | Ensembl ].		VAR_054659
Experimental info
	Sequence conflict	393	1	F → S in BAF84688. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	A8K7I4 [UniParc]. Last modified November 2, 2010. Version 3. Checksum: 8D8999E855822711	FASTA	914	100,226
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.
IPI	IPI00014625.
RefSeq	NP_001276.2. NM_001285.3.
UniGene	Hs.194659.
3D structure databases
ProteinModelPortal	A8K7I4.
ModBase	Search...
Protein-protein interaction databases
IntAct	A8K7I4. 1 interaction.
STRING	9606.ENSP00000234701.
Protein family/group databases
MEROPS	M87.001.
PTM databases
PhosphoSite	A8K7I4.
Proteomic databases
PaxDb	A8K7I4.
PRIDE	A8K7I4.
Protocols and materials databases
DNASU	1179.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000234701; ENSP00000234701; ENSG00000016490. ENST00000394711; ENSP00000378200; ENSG00000016490.
GeneID	1179.
KEGG	hsa:1179.
UCSC	uc001dls.1. human.
Organism-specific databases
CTD	1179.
GeneCards	GC01P086934.
HGNC	HGNC:2015. CLCA1.
HPA	HPA052787.
MIM	603906. gene.
neXtProt	NX_A8K7I4.
PharmGKB	PA26542.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG42884.
HOGENOM	HOG000015107.
HOVERGEN	HBG005560.
InParanoid	A8K7I4.
KO	K05027.
OMA	EPYTEQM.
OrthoDB	EOG4Z8XVR.
PhylomeDB	A8K7I4.
Gene expression databases
Bgee	A8K7I4.
CleanEx	HS_CLCA1.
Genevestigator	A8K7I4.
Family and domain databases
Gene3D	3.40.50.410. 1 hit.
InterPro	IPR004727. CaCC_prot. IPR013642. Cl_channel_Ca. IPR015394. DUF1973. IPR002035. VWF_A. [Graphical view]
Pfam	PF08434. CLCA_N. 1 hit. PF09315. DUF1973. 1 hit. [Graphical view]
SMART	SM00327. VWA. 1 hit. [Graphical view]
TIGRFAMs	TIGR00868. hCaCC. 1 hit.
PROSITE	PS50234. VWFA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	1179.
NextBio	4872.
SOURCE	Search...

Entry information

Entry name

CLCA1_HUMAN

Accession

Primary (citable) accession number: A8K7I4
Secondary accession number(s): B2RAV5 , O95151, Q5TDF4, Q9UNF6, Q9UPC6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 20, 2008
Last sequence update:	November 2, 2010
Last modified:	May 29, 2013
This is version 50 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.