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Protein

Calcium-activated chloride channel regulator 1

Gene

CLCA1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi156Zinc; catalytic1 Publication1
Active sitei1571 Publication1
Metal bindingi160Zinc; catalytic1 Publication1
Metal bindingi167Zinc; catalytic1 Publication1

GO - Molecular functioni

GO - Biological processi

  • calcium ion transport Source: UniProtKB-KW
  • cellular response to hypoxia Source: Ensembl
  • ion transmembrane transport Source: Reactome
  • transport Source: ProtInc

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
Biological processCalcium transport, Ion transport, Transport
LigandCalcium, Chloride, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-2672351. Stimuli-sensing channels.

Protein family/group databases

MEROPSiM87.001.
TCDBi1.A.13.1.6. the epithelial chloride channel (e-clc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium-activated chloride channel regulator 1 (EC:3.4.-.-1 Publication)
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 namesi
Name:CLCA1
Synonyms:CACC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000016490.15.
HGNCiHGNC:2015. CLCA1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi150Q → A: Reduces proteolytic cleavage. 1 Publication1
Mutagenesisi156H → A: Abolishes proteolytic cleavage. 1 Publication1
Mutagenesisi157E → Q: Abolishes proteolytic cleavage. 1 Publication1
Mutagenesisi160H → A: Abolishes proteolytic cleavage. 1 Publication1
Mutagenesisi167D → A: Abolishes proteolytic cleavage. 1 Publication1
Mutagenesisi168E → A: Abolishes proteolytic cleavage. 1 Publication1

Organism-specific databases

DisGeNETi1179.
OpenTargetsiENSG00000016490.
PharmGKBiPA26542.

Chemistry databases

ChEMBLiCHEMBL2364708.

Polymorphism and mutation databases

BioMutaiCLCA1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000033369022 – 914Calcium-activated chloride channel regulator 1Add BLAST893

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi503N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi585N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi770N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi804N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi810N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi831N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi836N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi890N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Glycosylated.1 Publication
The 125-kDa product is autoproteolytically processed by the metalloprotease domain and yields to two cell-surface-associated subunits, a 90-kDa protein and a group of 37-to 41-kDa proteins. The cleavage is necessary for calcium-activated chloride channel (CaCC) activation activity.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei694 – 695Cleavage; by autolysis1 Publication2

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein

Proteomic databases

PaxDbiA8K7I4.
PRIDEiA8K7I4.

PTM databases

iPTMnetiA8K7I4.
PhosphoSitePlusiA8K7I4.

Expressioni

Tissue specificityi

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.5 Publications

Inductioni

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.7 Publications

Gene expression databases

BgeeiENSG00000016490.
CleanExiHS_CLCA1.
GenevisibleiA8K7I4. HS.

Organism-specific databases

HPAiHPA052787.
HPA059301.

Interactioni

Protein-protein interaction databases

BioGridi107593. 2 interactors.
IntActiA8K7I4. 1 interactor.
STRINGi9606.ENSP00000234701.

Structurei

3D structure databases

ProteinModelPortaliA8K7I4.
SMRiA8K7I4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini306 – 475VWFAAdd BLAST170

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni46 – 199Metalloprotease domain1 PublicationAdd BLAST154

Domaini

The metalloprotease region is responsible for autoproteolytic processing. It can also cross-cleave other CLCA substrates.1 Publication

Sequence similaritiesi

Belongs to the CLCR family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IEPS. Eukaryota.
ENOG410XPSZ. LUCA.
GeneTreeiENSGT00390000004810.
HOGENOMiHOG000015107.
HOVERGENiHBG005560.
InParanoidiA8K7I4.
KOiK05027.
OMAiKQVCFSR.
OrthoDBiEOG091G09E6.
PhylomeDBiA8K7I4.
TreeFamiTF328396.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.40.50.410. 1 hit.
InterProiView protein in InterPro
IPR004727. CLCA_chordata.
IPR013642. CLCA_N.
IPR013783. Ig-like_fold.
IPR002035. VWF_A.
IPR036465. vWFA_dom_sf.
PfamiView protein in Pfam
PF08434. CLCA. 1 hit.
PF13519. VWA_2. 1 hit.
SMARTiView protein in SMART
SM00327. VWA. 1 hit.
SUPFAMiSSF53300. SSF53300. 1 hit.
TIGRFAMsiTIGR00868. hCaCC. 1 hit.
PROSITEiView protein in PROSITE
PS50234. VWFA. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

A8K7I4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGPFKSSVFI LILHLLEGAL SNSLIQLNNN GYEGIVVAID PNVPEDETLI
60 70 80 90 100
QQIKDMVTQA SLYLLEATGK RFYFKNVAIL IPETWKTKAD YVRPKLETYK
110 120 130 140 150
NADVLVAEST PPGNDEPYTE QMGNCGEKGE RIHLTPDFIA GKKLAEYGPQ
160 170 180 190 200
GRAFVHEWAH LRWGVFDEYN NDEKFYLSNG RIQAVRCSAG ITGTNVVKKC
210 220 230 240 250
QGGSCYTKRC TFNKVTGLYE KGCEFVLQSR QTEKASIMFA QHVDSIVEFC
260 270 280 290 300
TEQNHNKEAP NKQNQKCNLR STWEVIRDSE DFKKTTPMTT QPPNPTFSLL
310 320 330 340 350
QIGQRIVCLV LDKSGSMATG NRLNRLNQAG QLFLLQTVEL GSWVGMVTFD
360 370 380 390 400
SAAHVQNELI QINSGSDRDT LAKRLPAAAS GGTSICSGLR SAFTVIRKKY
410 420 430 440 450
PTDGSEIVLL TDGEDNTISG CFNEVKQSGA IIHTVALGPS AAQELEELSK
460 470 480 490 500
MTGGLQTYAS DQVQNNGLID AFGALSSGNG AVSQRSIQLE SKGLTLQNSQ
510 520 530 540 550
WMNGTVIVDS TVGKDTLFLI TWTMQPPQIL LWDPSGQKQG GFVVDKNTKM
560 570 580 590 600
AYLQIPGIAK VGTWKYSLQA SSQTLTLTVT SRASNATLPP ITVTSKTNKD
610 620 630 640 650
TSKFPSPLVV YANIRQGASP ILRASVTALI ESVNGKTVTL ELLDNGAGAD
660 670 680 690 700
ATKDDGVYSR YFTTYDTNGR YSVKVRALGG VNAARRRVIP QQSGALYIPG
710 720 730 740 750
WIENDEIQWN PPRPEINKDD VQHKQVCFSR TSSGGSFVAS DVPNAPIPDL
760 770 780 790 800
FPPGQITDLK AEIHGGSLIN LTWTAPGDDY DHGTAHKYII RISTSILDLR
810 820 830 840 850
DKFNESLQVN TTALIPKEAN SEEVFLFKPE NITFENGTDL FIAIQAVDKV
860 870 880 890 900
DLKSEISNIA RVSLFIPPQT PPETPSPDET SAPCPNIHIN STIPGIHILK
910
IMWKWIGELQ LSIA
Length:914
Mass (Da):100,226
Last modified:November 2, 2010 - v3
Checksum:i8D8999E855822711
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti393F → S in BAF84688 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05465465L → F4 PublicationsCorresponds to variant dbSNP:rs2145412Ensembl.1
Natural variantiVAR_054655152R → K1 PublicationCorresponds to variant dbSNP:rs2753386Ensembl.1
Natural variantiVAR_043146357N → S4 PublicationsCorresponds to variant dbSNP:rs2734705Ensembl.1
Natural variantiVAR_054656406E → V. Corresponds to variant dbSNP:rs1142185Ensembl.1
Natural variantiVAR_054657426K → R. Corresponds to variant dbSNP:rs4647852Ensembl.1
Natural variantiVAR_043147524M → T4 PublicationsCorresponds to variant dbSNP:rs2791494Ensembl.1
Natural variantiVAR_054658661Y → H. Corresponds to variant dbSNP:rs5744409Ensembl.1
Natural variantiVAR_054659760K → N1 PublicationCorresponds to variant dbSNP:rs2791483Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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. No translation available.
CH471097 Genomic DNA. Translation: EAW73186.1.
CCDSiCCDS709.1.
RefSeqiNP_001276.2. NM_001285.3.
UniGeneiHs.194659.

Genome annotation databases

EnsembliENST00000234701; ENSP00000234701; ENSG00000016490.
ENST00000394711; ENSP00000378200; ENSG00000016490.
GeneIDi1179.
KEGGihsa:1179.
UCSCiuc001dlt.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCLCA1_HUMAN
AccessioniPrimary (citable) accession number: A8K7I4
Secondary accession number(s): B2RAV5
, O95151, Q5TDF4, Q9UNF6, Q9UPC6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: November 2, 2010
Last modified: October 25, 2017
This is version 90 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families