Q14CN2 (CLCA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calcium-activated chloride channel regulator 4

Alternative name(s):
Calcium-activated chloride channel family member 4
Short name=hCLCA4
Calcium-activated chloride channel protein 2
Short name=CaCC-2
Short name=hCaCC-2

Cleaved into the following 2 chains:

1. Calcium-activated chloride channel regulator 4, 110 kDa form
2. Calcium-activated chloride channel regulator 4, 30 kDa form

Gene names

Name:	CLCA4
Synonyms:	CaCC2
ORF Names:	UNQ562/PRO1124

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	919 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.
Subcellular location	Cell membrane; Single-pass membrane protein By similarity. Apical cell membrane By similarity. Secreted By similarity. Note: The C-terminus 30 kDa form is anchored to the membrane By similarity. The N-terminus 110 kDa form is released from the membrane triggered by an unknown stimulus By similarity.
Tissue specificity	Primarily expressed in the digestive tract, mainly in colon. Detected in smaller amounts in brain, urogenital organs, testis, and salivary and mammary glands. Highly expressed in the epithelial layer and submucosal gland of the inferior turbinate mucosa. Lower levels in the epithelial layer of nasal polyp. Ref.1 Ref.5 Ref.6
Induction	Down-regulated in oral tongue squamous cell carcinomas. Ref.8
Post-translational modification	Processed at a monobasic residue to yield a larger N-terminal and a smaller C-terminal cleavage products of 90 to 110 and 30 to 35 kDa, respectively By similarity.
Sequence similarities	Belongs to the CLCR family. Contains 1 VWFA domain.

Ontologies

Keywords
Biological process	Transport
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Ligand	Chloride
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	apical plasma membrane 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
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 – 919	898	Calcium-activated chloride channel regulator 4		PRO_0000345389
	Chain	22 – ?		Calcium-activated chloride channel regulator 4, 110 kDa form		PRO_0000345390
	Chain	? – 919		Calcium-activated chloride channel regulator 4, 30 kDa form		PRO_0000345391
Regions
	Transmembrane	895 – 915	21	Helical; Potential
	Domain	306 – 476	171	VWFA
Amino acid modifications
	Glycosylation	75	1	N-linked (GlcNAc...) Potential
	Glycosylation	340	1	N-linked (GlcNAc...) Potential
	Glycosylation	504	1	N-linked (GlcNAc...) Potential
	Glycosylation	542	1	N-linked (GlcNAc...) Potential
	Glycosylation	588	1	N-linked (GlcNAc...) Potential
	Glycosylation	628	1	N-linked (GlcNAc...) Potential
	Glycosylation	811	1	N-linked (GlcNAc...) Ref.7
	Glycosylation	832	1	N-linked (GlcNAc...) Potential
	Glycosylation	837	1	N-linked (GlcNAc...) Potential
	Glycosylation	852	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	43	1	P → S. Corresponds to variant rs2231580 [ dbSNP | Ensembl ].		VAR_045816
	Natural variant	443	1	D → V. Corresponds to variant rs2839932 [ dbSNP | Ensembl ].		VAR_045817
	Natural variant	449	1	M → L. Corresponds to variant rs1011048 [ dbSNP | Ensembl ].		VAR_045818
	Natural variant	810	1	V → L. Ref.4 Corresponds to variant rs2231604 [ dbSNP | Ensembl ].		VAR_045819
	Natural variant	877 – 878	2	Missing.		VAR_045820
Experimental info
	Sequence conflict	303	1	S → R in AAD48398. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q14CN2 [UniParc]. Last modified July 22, 2008. Version 2. Checksum: 47C0DF125A319810	FASTA	919	101,283
	10 20 30 40 50 60 MGLFRGFVFL LVLCLLHQSN TSFIKLNNNG FEDIVIVIDP SVPEDEKIIE QIEDMVTTAS 70 80 90 100 110 120 TYLFEATEKR FFFKNVSILI PENWKENPQY KRPKHENHKH ADVIVAPPTL PGRDEPYTKQ 130 140 150 160 170 180 FTECGEKGEY IHFTPDLLLG KKQNEYGPPG KLFVHEWAHL RWGVFDEYNE DQPFYRAKSK 190 200 210 220 230 240 KIEATRCSAG ISGRNRVYKC QGGSCLSRAC RIDSTTKLYG KDCQFFPDKV QTEKASIMFM 250 260 270 280 290 300 QSIDSVVEFC NEKTHNQEAP SLQNIKCNFR STWEVISNSE DFKNTIPMVT PPPPPVFSLL 310 320 330 340 350 360 KISQRIVCLV LDKSGSMGGK DRLNRMNQAA KHFLLQTVEN GSWVGMVHFD STATIVNKLI 370 380 390 400 410 420 QIKSSDERNT LMAGLPTYPL GGTSICSGIK YAFQVIGELH SQLDGSEVLL LTDGEDNTAS 430 440 450 460 470 480 SCIDEVKQSG AIVHFIALGR AADEAVIEMS KITGGSHFYV SDEAQNNGLI DAFGALTSGN 490 500 510 520 530 540 TDLSQKSLQL ESKGLTLNSN AWMNDTVIID STVGKDTFFL ITWNSLPPSI SLWDPSGTIM 550 560 570 580 590 600 ENFTVDATSK MAYLSIPGTA KVGTWAYNLQ AKANPETLTI TVTSRAANSS VPPITVNAKM 610 620 630 640 650 660 NKDVNSFPSP MIVYAEILQG YVPVLGANVT AFIESQNGHT EVLELLDNGA GADSFKNDGV 670 680 690 700 710 720 YSRYFTAYTE NGRYSLKVRA HGGANTARLK LRPPLNRAAY IPGWVVNGEI EANPPRPEID 730 740 750 760 770 780 EDTQTTLEDF SRTASGGAFV VSQVPSLPLP DQYPPSQITD LDATVHEDKI ILTWTAPGDN 790 800 810 820 830 840 FDVGKVQRYI IRISASILDL RDSFDDALQV NTTDLSPKEA NSKESFAFKP ENISEENATH 850 860 870 880 890 900 IFIAIKSIDK SNLTSKVSNI AQVTLFIPQA NPDDIDPTPT PTPTPTPDKS HNSGVNISTL 910 VLSVIGSVVI VNFILSTTI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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], VARIANT 877-PRO-THR-878 DEL, TISSUE SPECIFICITY. Tissue: Colon.
[2]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"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].
[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], VARIANTS LEU-810 AND 877-PRO-THR-878 DEL.
[5]	"The CLCA gene locus as a modulator of the gastrointestinal basic defect in cystic fibrosis." Ritzka M., Stanke F., Jansen S., Gruber A.D., Pusch L., Woelfl S., Veeze H.J., Halley D.J., Tummler B. Hum. Genet. 115:483-491(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"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.
[7]	"Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry." Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A. J. Proteome Res. 5:1493-1503(2006) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-811, MASS SPECTROMETRY. Tissue: Saliva.
[8]	"Transcriptomic dissection of tongue squamous cell carcinoma." Ye H., Yu T., Temam S., Ziober B.L., Wang J., Schwartz J.L., Mao L., Wong D.T., Zhou X. BMC Genomics 9:69-69(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF127035 mRNA. Translation: AAD48398.1. AY358470 mRNA. Translation: AAQ88834.1. AL122002 Genomic DNA. Translation: CAI22170.1. BC113687 mRNA. Translation: AAI13688.1. BC113689 mRNA. Translation: AAI13690.1.
IPI	IPI01018986.
RefSeq	NP_036260.2. NM_012128.3.
UniGene	Hs.567422.
3D structure databases
ProteinModelPortal	Q14CN2.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000359594.
Protein family/group databases
MEROPS	M87.002.
TCDB	1.A.13.1.2. epithelial chloride channel (E-ClC) family. 1.A.14.1.1. non-selective cation channel-1 (NSCC1) family.
Polymorphism databases
DMDM	205831469.
Proteomic databases
PaxDb	Q14CN2.
PRIDE	Q14CN2.
Protocols and materials databases
DNASU	22802.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000370563; ENSP00000359594; ENSG00000016602.
GeneID	22802.
KEGG	hsa:22802.
UCSC	uc009wcs.3. human.
Organism-specific databases
CTD	22802.
GeneCards	GC01P087012.
H-InvDB	HIX0000752.
HGNC	HGNC:2018. CLCA4.
HPA	HPA017045.
neXtProt	NX_Q14CN2.
PharmGKB	PA26545.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG42884.
HOGENOM	HOG000015107.
HOVERGEN	HBG005560.
KO	K05030.
OMA	SNRLNRM.
OrthoDB	EOG4Z8XVR.
Gene expression databases
ArrayExpress	Q14CN2.
Bgee	Q14CN2.
CleanEx	HS_CLCA4.
Genevestigator	Q14CN2.
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
GenomeRNAi	22802.
NextBio	43156.

Entry information

Entry name

CLCA4_HUMAN

Accession

Primary (citable) accession number: Q14CN2
Secondary accession number(s): Q6UX81, Q9UNF7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 22, 2008
Last sequence update:	July 22, 2008
Last modified:	May 1, 2013
This is version 59 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.