Carbonic anhydrase 4 precursor - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P22748 (CAH4_HUMAN)

Last modified November 3, 2009. Version 109. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Carbonic anhydrase 4
    EC=4.2.1.1
Alternative name(s):
    Carbonic anhydrase IV
      Short name=CA-IV
    Carbonate dehydratase IV

Gene names

Name:

CA4

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	312 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4. Ref.8
Catalytic activity	H₂CO₃ = CO₂ + H₂O.
Cofactor	Zinc.
Enzyme regulation	Inhibited by acetazolamide.
Subunit structure	Interacts with SLC4A4. Ref.8
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor. Ref.6
Tissue specificity	Expressed in the endothelium of the choriocapillaris in eyes (at protein level). Ref.8
Involvement in 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. Ref.8
Sequence similarities	Belongs to the alpha-carbonic anhydrase family.

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Ontologies

Keywords
Biological process	Sensory transduction Vision
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Retinitis pigmentosa
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Lyase
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	one-carbon metabolic process Inferred from electronic annotation. Source: InterPro response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW visual perception Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane fraction Traceable author statement. Source: ProtInc plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	carbonate dehydratase activity Ref.1 Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

Ref.4

Chain

19 – 284

266

Carbonic anhydrase 4

PRO_0000004226

Propeptide

285 – 312

Removed in mature form

PRO_0000004227

Sites

Metal binding

115

Zinc; catalytic

Metal binding

117

Zinc; catalytic

Metal binding

140

Zinc; catalytic

Amino acid modifications

Lipidation

284

GPI-anchor amidated serine

Disulfide bond

Disulfide bond

Natural variations

Natural variant

R → W in RP17; abolishes interaction with SLC4A4. Impaired SLC4A4 cotransporter activity stimulation. Ref.8

VAR_024749

Natural variant

219

R → S in RP17; no catalytic activity. Impaired SLC4A4 cotransporter activity stimulation. Ref.8

VAR_024750

Natural variant

237

V → L: dbSNP rs2229178.

VAR_048680

Experimental info

Mutagenesis

284

S → F: Loss of C-terminal domain removal and inactivation. Ref.6

Sequence conflict

C → E AA sequence Ref.4

Secondary structure

312

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P22748-1 [UniParc].

Last modified August 1, 1992. Version 2.
Checksum: EF5F182474ABE9B0
Show »

FASTA

312

35,032

        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

« Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human carbonic anhydrase IV: cDNA cloning, sequence comparison, and expression in COS cell membranes." Okuyama T., Sato S., Zhu X.L., Waheed A., Sly W.S. Proc. Natl. Acad. Sci. U.S.A. 89:1315-1319(1992) [PubMed: 1311094] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Genomic organization and localization of gene for human carbonic anhydrase IV to chromosome 17q." Okuyama T., Batanian J.R., Sly W.S. Genomics 16:678-684(1993) [PubMed: 8325641] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Placenta.
[4]	"Carbonic anhydrase IV from human lung. Purification, characterization, and comparison with membrane carbonic anhydrase from human kidney." Zhu X.L., Sly W.S. J. Biol. Chem. 265:8795-8801(1990) [PubMed: 2111324] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-35; 113-123 AND 233-239. Tissue: Lung.
[5]	"Carbonic anhydrase IV: purification of a secretory form of the recombinant human enzyme and identification of the positions and importance of its disulfide bonds." Waheed A., Okuyama T., Heyduk T., Sly W.S. Arch. Biochem. Biophys. 333:432-438(1996) [PubMed: 8809084] [Abstract] Cited for: DISULFIDE BONDS.
[6]	"Carbonic anhydrase IV: role of removal of C-terminal domain in glycosylphosphatidylinositol anchoring and realization of enzyme activity." Okuyama T., Waheed A., Kusumoto W., Zhu X.L., Sly W.S. Arch. Biochem. Biophys. 320:315-322(1995) [PubMed: 7625839] [Abstract] Cited for: GPI-ANCHOR AT SER-284, MUTAGENESIS OF SER-284.
[7]	"Crystal structure of the secretory form of membrane-associated human carbonic anhydrase IV at 2.8-A resolution." Stams T., Nair S.K., Okuyama T., Waheed A., Sly W.S., Christianson D.W. Proc. Natl. Acad. Sci. U.S.A. 93:13589-13594(1996) [PubMed: 8942978] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 19-284.
[8]	"Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration." 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. Hum. Mol. Genet. 14:255-265(2005) [PubMed: 15563508] [Abstract] Cited for: VARIANTS RP17 TRP-14 AND SER-219, FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH SLC4A4.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

M83670 mRNA. Translation: AAA35630.1.
L10955

L10954 Genomic DNA. Translation: AAA35625.1. Sequence problems.
L10955, L10954 Genomic DNA. Translation: AAA35626.1. Sequence problems.
BC057792 mRNA. Translation: AAH57792.1.
BC069649 mRNA. Translation: AAH69649.1.
BC074768 mRNA. Translation: AAH74768.1.

IPI

IPI00027466.

PIR

CRHU4. A45745.

RefSeq

NP_000708.1.

UniGene

Hs.89485

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ZNC	X-ray	2.80	A/B	19-284	[»]
3F7B	X-ray	2.05	A/B	19-284	[»]
3F7U	X-ray	2.00	A/B/C/D	19-284	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P22748.

Proteomic databases

PRIDE

P22748.

Genome annotation databases

Ensembl

ENST00000300900; ENSP00000300900; ENSG00000167434; Homo sapiens. [Genome view]
ENST00000418816; ENSP00000405207; ENSG00000167434; Homo sapiens. [Genome view]

GeneID

762.

KEGG

hsa:762.

UCSC

uc002iym.2. human.

Organism-specific databases

CTD

762.

GeneCards

GC17P055582.

H-InvDB

HIX0039194.

HGNC

HGNC:1375. CA4.

HPA

HPA011089.
HPA017258.

MIM

114760. gene.
600852. phenotype.

Orphanet

791. Retinitis pigmentosa.

PharmGKB

PA24379.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P22748.

HOVERGEN

P22748.

OMA

EPIQLHR.

Enzyme and pathway databases

BRENDA

4.2.1.1. 247.

Gene expression databases

ArrayExpress

P22748.

Bgee

P22748.

CleanEx

HS_CA4.

Genevestigator

P22748.

GermOnline

ENSG00000167434. Homo sapiens.

Family and domain databases

InterPro

IPR001148. Carbonic_anhydrase_a-class_cat.
IPR018338. Carbonic_anhydrase_a-class_CS.
IPR018343. Carbonic_anhydrase_CA4.
[Graphical view]

Gene3D

G3DSA:3.10.200.10. Euk_COanhd. 1 hit.

PANTHER

PTHR18952:SF5. Carbonic_anhydrase_CA4. 1 hit.
PTHR18952. Euk_COanhd. 1 hit.

Pfam

PF00194. Carb_anhydrase. 1 hit.
[Graphical view]

ProDom

PD000865. Euk_COanhd. 1 hit.
[Graphical view] [Entries sharing at least one domain]

PROSITE

PS00162. ALPHA_CA_1. 1 hit.
PS51144. ALPHA_CA_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

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.

NextBio

3082.

SOURCE

Search...

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Entry information

Entry name

CAH4_HUMAN

Accession

Primary (citable) accession number: P22748

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	August 1, 1992
Last modified:	November 3, 2009
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.

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