Q9UQC9 (CLCA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calcium-activated chloride channel regulator 2

Alternative name(s):
Calcium-activated chloride channel family member 2
Short name=hCLCA2
Calcium-activated chloride channel protein 3
Short name=CaCC-3
Short name=hCaCC-3

Cleaved into the following 2 chains:

1. Calcium-activated chloride channel regulator 2, 109 kDa form
2. Calcium-activated chloride channel regulator 2, 35 kDa form

Gene names

Name:	CLCA2
Synonyms:	CACC3

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	943 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	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. Ref.7 Ref.8 Ref.9 Ref.11 Ref.12
Subcellular location	Cell membrane; Single-pass type I membrane protein. Basal cell membrane; Single-pass type I membrane protein. Cell junction Ref.1 Ref.10 Ref.11 Ref.13. Calcium-activated chloride channel regulator 2, 109 kDa form: Secreted. Note: Remains associated to the 35 kDa form until an unidentified event triggers the release. Ref.1 Ref.10 Ref.11 Ref.13
Tissue specificity	Expressed in cornea, skin, vagina, esophagus, and larynx (at protein level). Expressed in trachea and mammary gland. Weakly expressed in testis and kidney. Highly expressed in corneal epithelium, colon and trachea. Moderately expressed in brain, urogenital organs, bladder, uterus and prostate. Highly expressed in tissues containing stratified epithelium including cornea, esophagus, larynx, skin and vagina than those tissues which contain only epithelial monolayers. Expressed in normal breast epithelium but not in breast cancer. Highly expressed during epithelial stratification. Expressed in endothelial cells of lung. Expressed selectively in endothelia of small pulmonary arteries, arterioles, and subpleural and interlobular venules. Ref.1 Ref.2 Ref.3 Ref.7 Ref.9 Ref.10 Ref.11 Ref.12
Induction	Significantly down-regulated in breast and colorectal cancer. Ref.7 Ref.8
Post-translational modification	The 141 kDa mature form is shedded, producing a 109 kDa form and a 35 kDa form. N-glycosylated. Ref.1 Ref.13
Sequence similarities	Belongs to the CLCR family. Contains 1 VWFA domain.

Ontologies

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 31	31	Potential
	Chain	32 – 943	912	Calcium-activated chloride channel regulator 2		PRO_0000333694
	Chain	33 – ?		Calcium-activated chloride channel regulator 2, 109 kDa form		PRO_0000333695
	Chain	? – 943		Calcium-activated chloride channel regulator 2, 35 kDa form		PRO_0000344502
Regions
	Topological domain	32 – 901	870	Extracellular Potential
	Transmembrane	902 – 922	21	Helical; Potential
	Topological domain	923 – 943	21	Cytoplasmic Potential
	Domain	311 – 483	173	VWFA
Amino acid modifications
	Glycosylation	74	1	N-linked (GlcNAc...) Potential
	Glycosylation	150	1	N-linked (GlcNAc...)
	Glycosylation	231	1	N-linked (GlcNAc...) Potential
	Glycosylation	522	1	N-linked (GlcNAc...)
	Glycosylation	822	1	N-linked (GlcNAc...)
Natural variations
	Natural variant	80	1	V → I. Corresponds to variant rs11580625 [ dbSNP | Ensembl ].		VAR_054057
	Natural variant	306	1	Q → E. Corresponds to variant rs17409304 [ dbSNP | Ensembl ].		VAR_043148
	Natural variant	534	1	G → D. Corresponds to variant rs1413426 [ dbSNP | Ensembl ].		VAR_054058
	Natural variant	754	1	G → E in a breast cancer sample; somatic mutation. Ref.14		VAR_043149
Experimental info
	Mutagenesis	150	1	N → Q: Reduction in size by around 2 kDa. Ref.1
	Mutagenesis	292	1	N → Q: No change in size. Ref.1
	Mutagenesis	522	1	N → Q: Reduction in size by around 2 kDa. Ref.1
	Mutagenesis	637	1	N → Q: No change in size. Ref.1
	Mutagenesis	822	1	N → Q: Reduction in size by around 2 kDa. Ref.1
	Mutagenesis	938	1	N → Q: No change in size. Ref.1
	Sequence conflict	178	1	N → I in BAA77810. Ref.3
	Sequence conflict	830	1	Q → R in BAF83037. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q9UQC9 [UniParc]. Last modified May 20, 2008. Version 2. Checksum: 0E09A09090D2529B	FASTA	943	103,941
	10 20 30 40 50 60 MTQRSIAGPI CNLKFVTLLV ALSSELPFLG AGVQLQDNGY NGLLIAINPQ VPENQNLISN 70 80 90 100 110 120 IKEMITEASF YLFNATKRRV FFRNIKILIP ATWKANNNSK IKQESYEKAN VIVTDWYGAH 130 140 150 160 170 180 GDDPYTLQYR GCGKEGKYIH FTPNFLLNDN LTAGYGSRGR VFVHEWAHLR WGVFDEYNND 190 200 210 220 230 240 KPFYINGQNQ IKVTRCSSDI TGIFVCEKGP CPQENCIISK LFKEGCTFIY NSTQNATASI 250 260 270 280 290 300 MFMQSLSSVV EFCNASTHNQ EAPNLQNQMC SLRSAWDVIT DSADFHHSFP MNGTELPPPP 310 320 330 340 350 360 TFSLVQAGDK VVCLVLDVSS KMAEADRLLQ LQQAAEFYLM QIVEIHTFVG IASFDSKGEI 370 380 390 400 410 420 RAQLHQINSN DDRKLLVSYL PTTVSAKTDI SICSGLKKGF EVVEKLNGKA YGSVMILVTS 430 440 450 460 470 480 GDDKLLGNCL PTVLSSGSTI HSIALGSSAA PNLEELSRLT GGLKFFVPDI SNSNSMIDAF 490 500 510 520 530 540 SRISSGTGDI FQQHIQLEST GENVKPHHQL KNTVTVDNTV GNDTMFLVTW QASGPPEIIL 550 560 570 580 590 600 FDPDGRKYYT NNFITNLTFR TASLWIPGTA KPGHWTYTLN NTHHSLQALK VTVTSRASNS 610 620 630 640 650 660 AVPPATVEAF VERDSLHFPH PVMIYANVKQ GFYPILNATV TATVEPETGD PVTLRLLDDG 670 680 690 700 710 720 AGADVIKNDG IYSRYFFSFA ANGRYSLKVH VNHSPSISTP AHSIPGSHAM YVPGYTANGN 730 740 750 760 770 780 IQMNAPRKSV GRNEEERKWG FSRVSSGGSF SVLGVPAGPH PDVFPPCKII DLEAVKVEEE 790 800 810 820 830 840 LTLSWTAPGE DFDQGQATSY EIRMSKSLQN IQDDFNNAIL VNTSKRNPQQ AGIREIFTFS 850 860 870 880 890 900 PQISTNGPEH QPNGETHESH RIYVAIRAMD RNSLQSAVSN IAQAPLFIPP NSDPVPARDY 910 920 930 940 LILKGVLTAM GLIGIICLII VVTHHTLSRK KRADKKENGT KLL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and transmembrane structure of hCLCA2 from human lung, trachea, and mammary gland." Gruber A.D., Schreur K.D., Ji H.-L., Fuller C.M., Pauli B.U. Am. J. Physiol. 276:C1261-C1270(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION, MUTAGENESIS OF ASN-150; ASN-292; ASN-522; ASN-637; ASN-822 AND ASN-938. Tissue: Lung.
[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.
[3]	"Isolation and characterization of a Ca(2+)-activated chloride channel from human corneal epithelium." Itoh R., Kawamoto S., Miyamoto Y., Kinoshita S., Okubo K. Curr. Eye Res. 21:918-925(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Corneal epithelium.
[4]	"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]. Tissue: Tongue.
[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].
[6]	"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]. Tissue: Brain.
[7]	"Tumorigenicity of human breast cancer is associated with loss of the Ca2+-activated chloride channel CLCA2." Gruber A.D., Pauli B.U. Cancer Res. 59:5488-5491(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION, TISSUE SPECIFICITY, FUNCTION.
[8]	"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: INDUCTION, FUNCTION.
[9]	"The breast cancer beta 4 integrin and endothelial human CLCA2 mediate lung metastasis." Abdel-Ghany M., Cheng H.-C., Elble R.C., Pauli B.U. J. Biol. Chem. 276:25438-25446(2001) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, FUNCTION.
[10]	"Calcium-activated chloride channel-2 in human epithelia." Connon C.J., Yamasaki K., Kawasaki S., Quantock A.J., Koizumi N., Kinoshita S. J. Histochem. Cytochem. 52:415-418(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[11]	"The quantification of hCLCA2 and colocalisation with integrin beta4 in stratified human epithelia." Connon C.J., Kawasaki S., Yamasaki K., Quantock A.J., Kinoshita S. Acta Histochem. 106:421-425(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, FUNCTION, TISSUE SPECIFICITY.
[12]	"Gene expression and immunolocalisation of a calcium-activated chloride channel during the stratification of cultivated and developing corneal epithelium." Connon C.J., Kawasaki S., Liles M., Koizumi N., Yamasaki K., Nakamura T., Quantock A.J., Kinoshita S. Cell Tissue Res. 323:177-182(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, FUNCTION.
[13]	"The putative chloride channel hCLCA2 has a single C-terminal transmembrane segment." Elble R.C., Walia V., Cheng H.-C., Connon C.J., Mundhenk L., Gruber A.D., Pauli B.U. J. Biol. Chem. 281:29448-29454(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, SHEDDING, GLYCOSYLATION, TOPOLOGY.
[14]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-754.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF043977 mRNA. Translation: AAD40367.1. AF127980 mRNA. Translation: AAD48397.1. AB026833 mRNA. Translation: BAA77810.1. AK290348 mRNA. Translation: BAF83037.1. CH471097 Genomic DNA. Translation: EAW73187.1. BC041096 mRNA. Translation: AAH41096.1.
IPI	IPI00299094.
RefSeq	NP_006527.1. NM_006536.5.
UniGene	Hs.241551.
3D structure databases
ProteinModelPortal	Q9UQC9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UQC9. 1 interaction.
STRING	9606.ENSP00000359596.
Protein family/group databases
MEROPS	M87.003.
Polymorphism databases
DMDM	189082520.
Proteomic databases
PaxDb	Q9UQC9.
PRIDE	Q9UQC9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000370565; ENSP00000359596; ENSG00000137975.
GeneID	9635.
KEGG	hsa:9635.
UCSC	uc001dlr.4. human.
Organism-specific databases
CTD	9635.
GeneCards	GC01P086889.
HGNC	HGNC:2016. CLCA2.
MIM	604003. gene.
neXtProt	NX_Q9UQC9.
PharmGKB	PA26543.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG42884.
HOGENOM	HOG000015107.
HOVERGEN	HBG005560.
InParanoid	Q9UQC9.
KO	K05028.
OMA	EKGPCPQ.
OrthoDB	EOG469QT1.
PhylomeDB	Q9UQC9.
Gene expression databases
Bgee	Q9UQC9.
CleanEx	HS_CLCA2.
Genevestigator	Q9UQC9.
Family and domain databases
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
ChiTaRS	CLCA2. human.
GenomeRNAi	9635.
NextBio	36163.
SOURCE	Search...

Entry information

Entry name

CLCA2_HUMAN

Accession

Primary (citable) accession number: Q9UQC9
Secondary accession number(s): A8K2T3, Q9Y6N2

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 20, 2008
Last sequence update:	May 20, 2008
Last modified:	April 3, 2013
This is version 85 of the entry and version 2 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.