ID   CAH4_RABIT              Reviewed;         308 AA.
AC   P48283;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   02-SEP-2026, entry version 139.
DE   RecName: Full=Carbonic anhydrase 4;
DE            EC=4.2.1.1 {ECO:0000250|UniProtKB:P22748};
DE   AltName: Full=Carbonate dehydratase IV;
DE   AltName: Full=Carbonic anhydrase IV;
DE            Short=CA-IV;
DE   Flags: Precursor;
GN   Name=CA4;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=New Zealand white; TISSUE=Kidney cortex;
RX   PubMed=9140058; DOI=10.1152/ajprenal.1997.272.4.f551;
RA   Winkler C.A., Kittelberger A.M., Schwartz G.J.;
RT   "Expression of carbonic anhydrase IV mRNA in rabbit kidney: stimulation by
RT   metabolic acidosis.";
RL   Am. J. Physiol. 272:F551-F560(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=New Zealand white; TISSUE=Kidney cortex;
RA   Tamai S.;
RL   Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   INTERACTION WITH SLC4A4.
RX   PubMed=14567693; DOI=10.1021/bi0353124;
RA   Alvarez B.V., Loiselle F.B., Supuran C.T., Schwartz G.J., Casey J.R.;
RT   "Direct extracellular interaction between carbonic anhydrase IV and the
RT   human NBC1 sodium/bicarbonate co-transporter.";
RL   Biochemistry 42:12321-12329(2003).
CC   -!- FUNCTION: Catalyzes the reversible hydration of carbon dioxide into
CC       bicarbonate and protons and thus is essential to maintaining
CC       intracellular and extracellular pH. May stimulate the
CC       sodium/bicarbonate transporter activity of SLC4A4 that acts in pH
CC       homeostasis. It is essential for acid overload removal from the retina
CC       and retina epithelium, and acid release in the choriocapillaris in the
CC       choroid. {ECO:0000250|UniProtKB:P22748}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=hydrogencarbonate + H(+) = CO2 + H2O; Xref=Rhea:RHEA:10748,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC         ChEBI:CHEBI:17544; EC=4.2.1.1;
CC         Evidence={ECO:0000250|UniProtKB:P22748};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10749;
CC         Evidence={ECO:0000250|UniProtKB:P22748};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10750;
CC         Evidence={ECO:0000250|UniProtKB:P22748};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:P22748};
CC   -!- ACTIVITY REGULATION: Inhibited by acetazolamide. {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with SLC4A4. {ECO:0000269|PubMed:14567693}.
CC   -!- INTERACTION:
CC       P48283; Q9Y6R1-1: SLC4A4; Xeno; NbExp=2; IntAct=EBI-6859264, EBI-6859278;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P22748};
CC       Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P22748}.
CC   -!- SIMILARITY: Belongs to the alpha-carbonic anhydrase family.
CC       {ECO:0000305}.
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DR   EMBL; L48928; AAC37337.1; -; mRNA.
DR   EMBL; U58871; AAB09467.1; -; mRNA.
DR   RefSeq; NP_001075841.1; NM_001082372.1.
DR   AlphaFoldDB; P48283; -.
DR   SMR; P48283; -.
DR   FunCoup; P48283; 49.
DR   IntAct; P48283; 1.
DR   STRING; 9986.ENSOCUP00000046147; -.
DR   GlyCosmos; P48283; 2 sites, No reported glycans.
DR   PaxDb; 9986-ENSOCUP00000046147; -.
DR   GeneID; 100009226; -.
DR   KEGG; ocu:100009226; -.
DR   CTD; 762; -.
DR   eggNOG; KOG0382; Eukaryota.
DR   InParanoid; P48283; -.
DR   OrthoDB; 429145at2759; -.
DR   Proteomes; UP000001811; Unplaced.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0004089; F:carbonate dehydratase activity; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   CDD; cd03117; alpha_CA_IV_XV_like; 1.
DR   FunFam; 3.10.200.10:FF:000003; Carbonic anhydrase 12; 1.
DR   Gene3D; 3.10.200.10; Alpha carbonic anhydrase; 1.
DR   InterPro; IPR041874; CA4/CA15.
DR   InterPro; IPR001148; CA_dom.
DR   InterPro; IPR036398; CA_dom_sf.
DR   InterPro; IPR023561; Carbonic_anhydrase_a-class.
DR   PANTHER; PTHR18952; CARBONIC ANHYDRASE; 1.
DR   PANTHER; PTHR18952:SF95; CARBONIC ANHYDRASE 4; 1.
DR   Pfam; PF00194; Carb_anhydrase; 1.
DR   SMART; SM01057; Carb_anhydrase; 1.
DR   SUPFAM; SSF51069; Carbonic anhydrase; 1.
DR   PROSITE; PS51144; ALPHA_CA_2; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Disulfide bond; Glycoprotein; GPI-anchor; Lipoprotein;
KW   Lyase; Membrane; Metal-binding; Reference proteome; Signal; Zinc.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   CHAIN           19..280
FT                   /note="Carbonic anhydrase 4"
FT                   /id="PRO_0000004230"
FT   PROPEP          281..308
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000250|UniProtKB:P22748"
FT                   /id="PRO_0000004231"
FT   DOMAIN          21..281
FT                   /note="Alpha-carbonic anhydrase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01134"
FT   ACT_SITE        86
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   BINDING         113
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:Q64444"
FT   BINDING         115
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:Q64444"
FT   BINDING         138
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:Q64444"
FT   BINDING         221..222
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   LIPID           280
FT                   /note="GPI-anchor amidated serine"
FT                   /evidence="ECO:0000250|UniProtKB:P22748"
FT   CARBOHYD        31
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        192
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        24..34
FT                   /evidence="ECO:0000250|UniProtKB:Q64444"
FT   DISULFID        44..225
FT                   /evidence="ECO:0000250|UniProtKB:Q64444"
SQ   SEQUENCE   308 AA;  34394 MW;  CDB29AED9D8CDEBC CRC64;
     MQLLFALLAL GALRPLAGEE LHWCYEIQAS NYSCLGPDKW QEDCQKSRQS PINIVTTKAE
     VDHSLGRFHF SGYDQREARL VENNGHSVMV SLGDEISISG GGLPARYRAT QLHLHWSQEL
     DRGSEHSLDG ERSAMEMHIV HQKETGTSGN EVQDSDDSIA VLAFLVEAGP TMNEGFQPLV
     TALSAISIPG TNTTMAPSSL WDLLPAEEEL RHYFRYMGSL TTPACSETVV WTVFQEPIRL
     HRDQILEFSS KLYYDQERKM NMKDNVRPLQ RLGDRSVFKS QAAGQLLPLP LPTLLVPTLA
     CVMAGLLR
//