[1]	NUCLEOTIDE SEQUENCE [MRNA]. PubMed=1311094 [NCBI, ExPASy, EBI, Israel, Japan] Okuyama T., Sato S., Zhu X.L., Waheed A., Sly W.S.; "Human carbonic anhydrase IV: cDNA cloning, sequence comparison, and expression in COS cell membranes."; Proc. Natl. Acad. Sci. U.S.A. 89:1315-1319(1992).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. DOI=10.1006/geno.1993.1247; PubMed=8325641 [NCBI, ExPASy, EBI, Israel, Japan] Okuyama T., Batanian J.R., Sly W.S.; "Genomic organization and localization of gene for human carbonic anhydrase IV to chromosome 17q."; Genomics 16:678-684(1993).
[3]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. TISSUE=Brain, and Placenta; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[4]	PROTEIN SEQUENCE OF 19-35; 113-123 AND 233-239. TISSUE=Lung; PubMed=2111324 [NCBI, ExPASy, EBI, Israel, Japan] Zhu X.L., Sly W.S.; "Carbonic anhydrase IV from human lung. Purification, characterization, and comparison with membrane carbonic anhydrase from human kidney."; J. Biol. Chem. 265:8795-8801(1990).
[5]	DISULFIDE BONDS. DOI=10.1006/abbi.1996.0412; PubMed=8809084 [NCBI, ExPASy, EBI, Israel, Japan] Waheed A., Okuyama T., Heyduk T., Sly W.S.; "Carbonic anhydrase IV: purification of a secretory form of the recombinant human enzyme and identification of the positions and importance of its disulfide bonds."; Arch. Biochem. Biophys. 333:432-438(1996).
[6]	GPI-ANCHOR AT SER-284, AND MUTAGENESIS OF SER-284. DOI=10.1016/0003-9861(95)90015-2; PubMed=7625839 [NCBI, ExPASy, EBI, Israel, Japan] Okuyama T., Waheed A., Kusumoto W., Zhu X.L., Sly W.S.; "Carbonic anhydrase IV: role of removal of C-terminal domain in glycosylphosphatidylinositol anchoring and realization of enzyme activity."; Arch. Biochem. Biophys. 320:315-322(1995).
[7]	X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 19-284. DOI=10.1073/pnas.93.24.13589; PubMed=8942978 [NCBI, ExPASy, EBI, Israel, Japan] Stams T., Nair S.K., Okuyama T., Waheed A., Sly W.S., Christianson D.W.; "Crystal structure of the secretory form of membrane-associated human carbonic anhydrase IV at 2.8-A resolution."; Proc. Natl. Acad. Sci. U.S.A. 93:13589-13594(1996).
[8]	VARIANTS RP17 TRP-14 AND SER-219, FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH SLC4A4. DOI=10.1093/hmg/ddi023; PubMed=15563508 [NCBI, ExPASy, EBI, Israel, Japan] Yang Z., Alvarez B.V., Chakarova C., Jiang L., Karan G., Frederick J.M., Zhao Y., Sauve Y., Li X., Zrenner E., Wissinger B., Den Hollander A.I., Katz B., Baehr W., Cremers F.P., Casey J.R., Bhattacharya S.S., Zhang K.; "Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration."; Hum. Mol. Genet. 14:255-265(2005).

Comments

FUNCTION: Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4.
CATALYTIC ACTIVITY: H₂CO₃ = CO₂ + H₂O.
COFACTOR: Zinc.
ENZYME REGULATION: Inhibited by acetazolamide.
SUBUNIT: Interacts with SLC4A4.
SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor.
TISSUE SPECIFICITY: Expressed in the endothelium of the choriocapillaris in eyes (at protein level).
DISEASE: Defects in CA4 are the cause of retinitis pigmentosa type 17 (RP17) [MIM:600852]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP17 inheritance is autosomal dominant.
SIMILARITY: Belongs to the alpha-carbonic anhydrase family.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M83670; AAA35630.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
L10955; AAA35625.1; ALT_SEQ; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
L10951; AAA35625.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
L10953; AAA35625.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
L10954; AAA35625.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
L10955; AAA35626.1; ALT_SEQ; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
L10954; AAA35626.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC057792; AAH57792.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC069649; AAH69649.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC074768; AAH74768.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

A45745; CRHU4.

NP_000708.1; -.

3D structure databases

PDB

1ZNC; X-ray; 2.80 A; A/B=19-284.

[ExPASy / RCSB / EBI]

PDBsum

1ZNC; -.

ModBase

P22748.

Organism-specific databases

HIX0039194; -.

HGNC:1375; CA4.

CA4.

HPA011089; -.
HPA017258; -.

MIM

114760; gene. [NCBI / EBI]
600852; phenotype. [NCBI / EBI]

Orphanet

791; Retinitis pigmentosa.

PharmGKB

PA24379; -.

GeneCards

P22748.

Gene expression databases

ArrayExpress

P22748; -.

CleanEx

HS_CA4; -.

GermOnline

ENSG00000167434; Homo sapiens.

Ontologies

GO:0031225;	Cellular component: anchored to membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0005624;	Cellular component: membrane fraction (traceable author statement from ProtInc).
GO:0005886;	Cellular component: plasma membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0004089;	Molecular function: carbonate dehydratase activity (traceable author statement from ProtInc).
GO:0008270;	Molecular function: zinc ion binding (inferred from electronic annotation from InterPro).
GO:0006730;	Biological process: one-carbon compound metabolic process (inferred from electronic annotation from InterPro).
GO:0050896;	Biological process: response to stimulus (inferred from electronic annotation from UniProtKB-KW).
GO:0007601;	Biological process: visual perception (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR001148; Euk_COanhd.
Graphical view of domain structure.

Gene3D

G3DSA:3.10.200.10; Euk_COanhd; 1.

PANTHER

PTHR18952; Euk_COanhd; 1.

Pfam

PF00194; Carb_anhydrase; 1.
Pfam graphical view of domain structure.

ProDom

PD000865; Euk_COanhd; 1.
[Domain structure / List of seq. sharing at least 1 domain]

PROSITE

PS00162; ALPHA_CA_1; 1.
PS51144; ALPHA_CA_2; 1.
PROSITE graphical view of domain structure (profiles).

ProtoNet

P22748.

Genome annotation databases

Ensembl

ENSG00000167434; Homo sapiens. [Contig view]

GeneID

762; -.

KEGG

hsa:762; -.

Phylogenomic databases

HOGENOM

P22748; -.

HOVERGEN

P22748; -.

Other

BindingDB

P22748; -.

DrugBank

DB00436; Bendroflumethiazide.
DB00562; Benzthiazide.
DB00880; Chlorothiazide.
DB00606; Cyclothiazide.
DB01119; Diazoxide.
DB00999; Hydrochlorothiazide.
DB00774; Hydroflumethiazide.
DB00232; Methyclothiazide.
DB01325; Quinethazone.
DB00273; Topiramate.
DB01021; Trichlormethiazide.

P22748; -.

3082; -.

CA4; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Cell membrane; Direct protein sequencing; Disease mutation; Glycoprotein; GPI-anchor; Lipoprotein; Lyase; Membrane; Metal-binding; Retinitis pigmentosa; Sensory transduction; Signal; Vision; Zinc.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`SIGNAL`	`1 18`	`18`
`CHAIN`	`19 284`	`266`	`Carbonic anhydrase 4.`	`PRO_0000004226`
`PROPEP`	`285 312`	`28`	`Removed in mature form.`	`PRO_0000004227`
`METAL`	`115 115`		`Zinc; catalytic.`
`METAL`	`117 117`		`Zinc; catalytic.`
`METAL`	`140 140`		`Zinc; catalytic.`
`LIPID`	`284 284`		`GPI-anchor amidated serine.`
`DISULFID`	`24 36`
`DISULFID`	`46 229`
`VARIANT`	`14 14`	`1`	`R -> W (in RP17; abolishes interaction with SLC4A4. Impaired SLC4A4 cotransporter activity stimulation).`	`VAR_024749`
`VARIANT`	`219 219`	`1`	`R -> S (in RP17; no catalytic activity. Impaired SLC4A4 cotransporter activity stimulation).`	`VAR_024750`
`MUTAGEN`	`284 284`		`S->F: Loss of C-terminal domain removal and inactivation.`
`CONFLICT`	`24 24`		`C -> E (in Ref. 4; AA sequence).`
`HELIX`	`26 31`	`6`
`HELIX`	`39 41`	`3`
`HELIX`	`44 47`	`4`
`STRAND`	`48 50`	`3`
`HELIX`	`58 60`	`3`
`STRAND`	`61 63`	`3`
`STRAND`	`70 74`	`5`
`STRAND`	`79 85`	`7`
`STRAND`	`87 93`	`7`
`STRAND`	`99 102`	`4`
`STRAND`	`109 118`	`10`
`STRAND`	`127 130`	`4`
`STRAND`	`136 147`	`12`
`STRAND`	`162 175`	`14`
`TURN`	`178 180`	`3`
`HELIX`	`181 186`	`6`
`HELIX`	`187 189`	`3`
`STRAND`	`196 202`	`7`
`HELIX`	`204 206`	`3`
`HELIX`	`211 215`	`5`
`STRAND`	`217 222`	`6`
`STRAND`	`233 240`	`8`
`STRAND`	`242 245`	`4`
`HELIX`	`246 255`	`10`
`STRAND`	`257 259`	`3`

Sequence information

Length: 312 AA [This is the length of the unprocessed precursor]

Molecular weight: 35032 Da [This is the MW of the unprocessed precursor]

CRC64: EF5F182474ABE9B0 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MRMLLALLAL SAARPSASAE SHWCYEVQAE SSNYPCLVPV KWGGNCQKDR QSPINIVTTK 

        70         80         90        100        110        120 
AKVDKKLGRF FFSGYDKKQT WTVQNNGHSV MMLLENKASI SGGGLPAPYQ AKQLHLHWSD 

       130        140        150        160        170        180 
LPYKGSEHSL DGEHFAMEMH IVHEKEKGTS RNVKEAQDPE DEIAVLAFLV EAGTQVNEGF 

       190        200        210        220        230        240 
QPLVEALSNI PKPEMSTTMA ESSLLDLLPK EEKLRHYFRY LGSLTTPTCD EKVVWTVFRE 

       250        260        270        280        290        300 
PIQLHREQIL AFSQKLYYDK EQTVSMKDNV RPLQQLGQRT VIKSGAPGRP LPWALPALLG 

       310 
PMLACLLAGF LR

P22748 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools