Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Calcium-activated chloride channel regulator 4

Gene

CLCA4

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi155ZincBy similarity1
Metal bindingi159ZincBy similarity1
Metal bindingi166ZincBy similarity1

GO - Molecular functioni

GO - Biological processi

  • ion transmembrane transport Source: Reactome
  • transport Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Transport

Keywords - Ligandi

Chloride, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-2672351. Stimuli-sensing channels.

Protein family/group databases

MEROPSiM87.002.
TCDBi1.A.13.1.2. the epithelial chloride channel (e-clc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium-activated chloride channel regulator 4 (EC:3.4.-.-By similarity)
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
Chloride channel accessory 4
Cleaved into the following 2 chains:
Gene namesi
Name:CLCA4
Synonyms:CaCC2
ORF Names:UNQ562/PRO1124
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:2018. CLCA4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei895 – 915HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB-SubCell
  • extracellular exosome Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi22802.
MalaCardsiCLCA4.
OpenTargetsiENSG00000016602.
Orphaneti586. Cystic fibrosis.
PharmGKBiPA26545.

Polymorphism and mutation databases

BioMutaiCLCA4.
DMDMi205831469.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000345391? – 919Calcium-activated chloride channel regulator 4, 30 kDa form
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000034538922 – 919Calcium-activated chloride channel regulator 4Add BLAST898
ChainiPRO_000034539022 – ?Calcium-activated chloride channel regulator 4, 110 kDa form

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi75N-linked (GlcNAc...)Sequence analysis1
Glycosylationi340N-linked (GlcNAc...)Sequence analysis1
Glycosylationi504N-linked (GlcNAc...)Sequence analysis1
Glycosylationi542N-linked (GlcNAc...)Sequence analysis1
Glycosylationi588N-linked (GlcNAc...)Sequence analysis1
Glycosylationi628N-linked (GlcNAc...)Sequence analysis1
Glycosylationi811N-linked (GlcNAc...)1 Publication1
Glycosylationi832N-linked (GlcNAc...)Sequence analysis1
Glycosylationi837N-linked (GlcNAc...)Sequence analysis1
Glycosylationi852N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

The translation product is autoproteolytically cleaved by the metalloprotease domain in the endoplasmic reticulum into a N-terminal and a C-terminal products that remain physically associated with each other. The cleavage is necessary for calcium-activated chloride channel (CaCC) activation activity.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei697 – 698Cleavage; by autolysisBy similarity2

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein

Proteomic databases

PaxDbiQ14CN2.
PeptideAtlasiQ14CN2.
PRIDEiQ14CN2.

PTM databases

iPTMnetiQ14CN2.
PhosphoSitePlusiQ14CN2.

Expressioni

Tissue specificityi

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.3 Publications

Inductioni

Down-regulated in oral tongue squamous cell carcinomas.1 Publication

Gene expression databases

BgeeiENSG00000016602.
CleanExiHS_CLCA4.
GenevisibleiQ14CN2. HS.

Organism-specific databases

HPAiHPA017045.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000359594.

Structurei

3D structure databases

ProteinModelPortaliQ14CN2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini306 – 476VWFAPROSITE-ProRule annotationAdd BLAST171

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni45 – 199Metalloprotease domainBy similarityAdd BLAST155

Domaini

The metalloprotease region is responsible for autoproteolytic processing. It can also cross-cleave other CLCA Substrates.By similarity

Sequence similaritiesi

Belongs to the CLCR family.Curated
Contains 1 VWFA domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IEPS. Eukaryota.
ENOG410XPSZ. LUCA.
GeneTreeiENSGT00390000004810.
HOGENOMiHOG000015107.
HOVERGENiHBG005560.
InParanoidiQ14CN2.
KOiK05030.
OMAiTIMENFT.
OrthoDBiEOG091G09E6.
PhylomeDBiQ14CN2.
TreeFamiTF328396.

Family and domain databases

Gene3Di3.40.50.410. 1 hit.
InterProiIPR013642. CLCA.
IPR004727. CLCA_chordata.
IPR002035. VWF_A.
[Graphical view]
PfamiPF08434. CLCA. 1 hit.
PF00092. VWA. 1 hit.
[Graphical view]
SMARTiSM00327. VWA. 1 hit.
[Graphical view]
SUPFAMiSSF53300. SSF53300. 1 hit.
TIGRFAMsiTIGR00868. hCaCC. 1 hit.
PROSITEiPS50234. VWFA. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q14CN2-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGLFRGFVFL LVLCLLHQSN TSFIKLNNNG FEDIVIVIDP SVPEDEKIIE
60 70 80 90 100
QIEDMVTTAS TYLFEATEKR FFFKNVSILI PENWKENPQY KRPKHENHKH
110 120 130 140 150
ADVIVAPPTL PGRDEPYTKQ FTECGEKGEY IHFTPDLLLG KKQNEYGPPG
160 170 180 190 200
KLFVHEWAHL RWGVFDEYNE DQPFYRAKSK KIEATRCSAG ISGRNRVYKC
210 220 230 240 250
QGGSCLSRAC RIDSTTKLYG KDCQFFPDKV QTEKASIMFM QSIDSVVEFC
260 270 280 290 300
NEKTHNQEAP SLQNIKCNFR STWEVISNSE DFKNTIPMVT PPPPPVFSLL
310 320 330 340 350
KISQRIVCLV LDKSGSMGGK DRLNRMNQAA KHFLLQTVEN GSWVGMVHFD
360 370 380 390 400
STATIVNKLI QIKSSDERNT LMAGLPTYPL GGTSICSGIK YAFQVIGELH
410 420 430 440 450
SQLDGSEVLL LTDGEDNTAS SCIDEVKQSG AIVHFIALGR AADEAVIEMS
460 470 480 490 500
KITGGSHFYV SDEAQNNGLI DAFGALTSGN TDLSQKSLQL ESKGLTLNSN
510 520 530 540 550
AWMNDTVIID STVGKDTFFL ITWNSLPPSI SLWDPSGTIM ENFTVDATSK
560 570 580 590 600
MAYLSIPGTA KVGTWAYNLQ AKANPETLTI TVTSRAANSS VPPITVNAKM
610 620 630 640 650
NKDVNSFPSP MIVYAEILQG YVPVLGANVT AFIESQNGHT EVLELLDNGA
660 670 680 690 700
GADSFKNDGV YSRYFTAYTE NGRYSLKVRA HGGANTARLK LRPPLNRAAY
710 720 730 740 750
IPGWVVNGEI EANPPRPEID EDTQTTLEDF SRTASGGAFV VSQVPSLPLP
760 770 780 790 800
DQYPPSQITD LDATVHEDKI ILTWTAPGDN FDVGKVQRYI IRISASILDL
810 820 830 840 850
RDSFDDALQV NTTDLSPKEA NSKESFAFKP ENISEENATH IFIAIKSIDK
860 870 880 890 900
SNLTSKVSNI AQVTLFIPQA NPDDIDPTPT PTPTPTPDKS HNSGVNISTL
910
VLSVIGSVVI VNFILSTTI
Length:919
Mass (Da):101,283
Last modified:July 22, 2008 - v2
Checksum:i47C0DF125A319810
GO
Isoform 2 (identifier: Q14CN2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-287: Missing.
     490-524: LESKGLTLNSNAWMNDTVIIDSTVGKDTFFLITWN → VRVLIPWVFMFTFATRKNHLVVISFEFHIFLKVNF
     525-919: Missing.

Note: No experimental confirmation available.
Show »
Length:237
Mass (Da):25,849
Checksum:i0B3A1F1D60877BA6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti303S → R in AAD48398 (PubMed:10437792).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04581643P → S.Corresponds to variant rs2231580dbSNPEnsembl.1
Natural variantiVAR_045817443D → V.Corresponds to variant rs2839932dbSNPEnsembl.1
Natural variantiVAR_045818449M → L.Corresponds to variant rs1011048dbSNPEnsembl.1
Natural variantiVAR_045819810V → L.1 PublicationCorresponds to variant rs2231604dbSNPEnsembl.1
Natural variantiVAR_045820877 – 878Missing .2 Publications2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0561171 – 287Missing in isoform 2. 1 PublicationAdd BLAST287
Alternative sequenceiVSP_056118490 – 524LESKG…LITWN → VRVLIPWVFMFTFATRKNHL VVISFEFHIFLKVNF in isoform 2. 1 PublicationAdd BLAST35
Alternative sequenceiVSP_056119525 – 919Missing in isoform 2. 1 PublicationAdd BLAST395

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF127035 mRNA. Translation: AAD48398.1.
AY358470 mRNA. Translation: AAQ88834.1.
AK293766 mRNA. Translation: BAH11591.1.
AL122002 Genomic DNA. Translation: CAI22170.1.
BC113687 mRNA. Translation: AAI13688.1.
BC113689 mRNA. Translation: AAI13690.1.
CCDSiCCDS41355.1. [Q14CN2-1]
RefSeqiNP_036260.2. NM_012128.3. [Q14CN2-1]
UniGeneiHs.567422.

Genome annotation databases

EnsembliENST00000370563; ENSP00000359594; ENSG00000016602. [Q14CN2-1]
GeneIDi22802.
KEGGihsa:22802.
UCSCiuc009wcs.4. human. [Q14CN2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF127035 mRNA. Translation: AAD48398.1.
AY358470 mRNA. Translation: AAQ88834.1.
AK293766 mRNA. Translation: BAH11591.1.
AL122002 Genomic DNA. Translation: CAI22170.1.
BC113687 mRNA. Translation: AAI13688.1.
BC113689 mRNA. Translation: AAI13690.1.
CCDSiCCDS41355.1. [Q14CN2-1]
RefSeqiNP_036260.2. NM_012128.3. [Q14CN2-1]
UniGeneiHs.567422.

3D structure databases

ProteinModelPortaliQ14CN2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000359594.

Protein family/group databases

MEROPSiM87.002.
TCDBi1.A.13.1.2. the epithelial chloride channel (e-clc) family.

PTM databases

iPTMnetiQ14CN2.
PhosphoSitePlusiQ14CN2.

Polymorphism and mutation databases

BioMutaiCLCA4.
DMDMi205831469.

Proteomic databases

PaxDbiQ14CN2.
PeptideAtlasiQ14CN2.
PRIDEiQ14CN2.

Protocols and materials databases

DNASUi22802.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000370563; ENSP00000359594; ENSG00000016602. [Q14CN2-1]
GeneIDi22802.
KEGGihsa:22802.
UCSCiuc009wcs.4. human. [Q14CN2-1]

Organism-specific databases

CTDi22802.
DisGeNETi22802.
GeneCardsiCLCA4.
H-InvDBHIX0000752.
HGNCiHGNC:2018. CLCA4.
HPAiHPA017045.
MalaCardsiCLCA4.
MIMi616857. gene.
neXtProtiNX_Q14CN2.
OpenTargetsiENSG00000016602.
Orphaneti586. Cystic fibrosis.
PharmGKBiPA26545.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEPS. Eukaryota.
ENOG410XPSZ. LUCA.
GeneTreeiENSGT00390000004810.
HOGENOMiHOG000015107.
HOVERGENiHBG005560.
InParanoidiQ14CN2.
KOiK05030.
OMAiTIMENFT.
OrthoDBiEOG091G09E6.
PhylomeDBiQ14CN2.
TreeFamiTF328396.

Enzyme and pathway databases

ReactomeiR-HSA-2672351. Stimuli-sensing channels.

Miscellaneous databases

GeneWikiiCLCA4.
GenomeRNAii22802.
PROiQ14CN2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000016602.
CleanExiHS_CLCA4.
GenevisibleiQ14CN2. HS.

Family and domain databases

Gene3Di3.40.50.410. 1 hit.
InterProiIPR013642. CLCA.
IPR004727. CLCA_chordata.
IPR002035. VWF_A.
[Graphical view]
PfamiPF08434. CLCA. 1 hit.
PF00092. VWA. 1 hit.
[Graphical view]
SMARTiSM00327. VWA. 1 hit.
[Graphical view]
SUPFAMiSSF53300. SSF53300. 1 hit.
TIGRFAMsiTIGR00868. hCaCC. 1 hit.
PROSITEiPS50234. VWFA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCLCA4_HUMAN
AccessioniPrimary (citable) accession number: Q14CN2
Secondary accession number(s): A8MQC9
, B7Z1Q5, Q6UX81, Q9UNF7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 22, 2008
Last sequence update: July 22, 2008
Last modified: November 30, 2016
This is version 96 of the entry and version 2 of the sequence. [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, 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.