ID   CAH2_SHEEP              Reviewed;         260 AA.
AC   P00922;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   02-SEP-2026, entry version 129.
DE   RecName: Full=Carbonic anhydrase 2;
DE            EC=4.2.1.1 {ECO:0000250|UniProtKB:P00918};
DE   AltName: Full=Carbonate dehydratase II;
DE   AltName: Full=Carbonic anhydrase II;
DE            Short=CA-II;
DE   AltName: Full=Cyanamide hydratase CA2;
DE            EC=4.2.1.69 {ECO:0000250|UniProtKB:P00918};
GN   Name=CA2;
OS   Ovis aries (Sheep).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Caprinae; Ovis.
OX   NCBI_TaxID=9940;
RN   [1]
RP   PROTEIN SEQUENCE OF 2-260, AND ACETYLATION AT SER-2.
RX   PubMed=4215456; DOI=10.1016/0005-2795(74)90050-6;
RA   Tanis R.J., Ferrell R.E., Tashian R.E.;
RT   "Amino acid sequence of sheep carbonic anhydrase C.";
RL   Biochim. Biophys. Acta 371:534-548(1974).
RN   [2]
RP   VARIANT THR-36.
RX   PubMed=106895; DOI=10.1016/0005-2795(79)90404-5;
RA   Mallet B., Gulian J.M., Sciaky M., Laurent G., Charrel M.;
RT   "Multiple molecular forms of erythrocyte carbonic anhydrase of sheep.";
RL   Biochim. Biophys. Acta 576:290-304(1979).
CC   -!- FUNCTION: Catalyzes the reversible hydration of carbon dioxide. Can
CC       also hydrate cyanamide to urea. Involved in the regulation of fluid
CC       secretion into the anterior chamber of the eye. Essential for bone
CC       resorption and osteoclast differentiation. Contributes to intracellular
CC       pH regulation in the duodenal upper villous epithelium during proton-
CC       coupled peptide absorption. Stimulates the chloride-bicarbonate
CC       exchange activity of SLC26A6. {ECO:0000250|UniProtKB:P00918}.
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:P00918};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=urea = cyanamide + H2O; Xref=Rhea:RHEA:23056,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:16199, ChEBI:CHEBI:16698; EC=4.2.1.69;
CC         Evidence={ECO:0000250|UniProtKB:P00918};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:P00921};
CC   -!- ACTIVITY REGULATION: Inhibited by acetazolamide.
CC       {ECO:0000250|UniProtKB:P00918}.
CC   -!- SUBUNIT: Interacts with SLC4A4 and SLC26A6. Interaction with SLC4A7
CC       regulates SLC4A7 transporter activity (By similarity).
CC       {ECO:0000250|UniProtKB:P00918}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P00918}. Cell
CC       membrane {ECO:0000250|UniProtKB:P00918}. Note=Colocalized with SLC26A6
CC       at the surface of the cell membrane in order to form a bicarbonate
CC       transport metabolon. Displaced from the cytosolic surface of the cell
CC       membrane by PKC in phorbol myristate acetate (PMA)-induced cells (By
CC       similarity). {ECO:0000250|UniProtKB:P00918}.
CC   -!- MISCELLANEOUS: One minor and three major forms were isolated
CC       chromatographically.
CC   -!- SIMILARITY: Belongs to the alpha-carbonic anhydrase family.
CC       {ECO:0000305}.
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DR   PIR; A01145; CRSH2.
DR   AlphaFoldDB; P00922; -.
DR   SMR; P00922; -.
DR   STRING; 9940.ENSOARP00000013878; -.
DR   iPTMnet; P00922; -.
DR   PaxDb; 9940-ENSOARP00000013878; -.
DR   eggNOG; KOG0382; Eukaryota.
DR   Proteomes; UP000809102; Unplaced.
DR   GO; GO:0045177; C:apical part of cell; IEA:TreeGrafter.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0004089; F:carbonate dehydratase activity; ISS:UniProtKB.
DR   GO; GO:0018820; F:cyanamide hydratase activity; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0038166; P:angiotensin-activated signaling pathway; ISS:UniProtKB.
DR   GO; GO:0015670; P:carbon dioxide transport; IEA:TreeGrafter.
DR   GO; GO:2001150; P:positive regulation of dipeptide transmembrane transport; ISS:UniProtKB.
DR   GO; GO:0051453; P:regulation of intracellular pH; ISS:UniProtKB.
DR   GO; GO:0044070; P:regulation of monoatomic anion transport; ISS:UniProtKB.
DR   FunFam; 3.10.200.10:FF:000001; Carbonic anhydrase 2; 1.
DR   Gene3D; 3.10.200.10; Alpha carbonic anhydrase; 1.
DR   InterPro; IPR001148; CA_dom.
DR   InterPro; IPR036398; CA_dom_sf.
DR   InterPro; IPR023561; Carbonic_anhydrase_a-class.
DR   InterPro; IPR018338; Carbonic_anhydrase_a-class_CS.
DR   PANTHER; PTHR18952; CARBONIC ANHYDRASE; 1.
DR   PANTHER; PTHR18952:SF120; CARBONIC ANHYDRASE 2; 1.
DR   Pfam; PF00194; Carb_anhydrase; 1.
DR   SMART; SM01057; Carb_anhydrase; 1.
DR   SUPFAM; SSF51069; Carbonic anhydrase; 1.
DR   PROSITE; PS00162; ALPHA_CA_1; 1.
DR   PROSITE; PS51144; ALPHA_CA_2; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Cell membrane; Cytoplasm; Direct protein sequencing; Lyase;
KW   Membrane; Metal-binding; Phosphoprotein; Reference proteome; Zinc.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:4215456"
FT   CHAIN           2..260
FT                   /note="Carbonic anhydrase 2"
FT                   /id="PRO_0000077422"
FT   DOMAIN          3..259
FT                   /note="Alpha-carbonic anhydrase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01134"
FT   ACT_SITE        64
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   BINDING         94
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   BINDING         96
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   BINDING         119
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   BINDING         198..199
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   SITE            7
FT                   /note="Fine-tunes the proton-transfer properties of H-64"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   SITE            62
FT                   /note="Fine-tunes the proton-transfer properties of H-64"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   SITE            67
FT                   /note="Fine-tunes the proton-transfer properties of H-64"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0000269|PubMed:106895,
FT                   ECO:0000269|PubMed:4215456"
FT   MOD_RES         2
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P27139"
FT   MOD_RES         165
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   MOD_RES         172
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   VARIANT         36
FT                   /note="K -> T (in one of the major forms)"
FT                   /evidence="ECO:0000269|PubMed:106895"
SQ   SEQUENCE   260 AA;  29211 MW;  5881DD762616363D CRC64;
     MSHHWGYGEH NGPEHWHKDF PIADGERQSP VDIDTKAVVP DPALKPLALL YEQAASRRMV
     NNGHSFNVEF DDSQDKAVLK DGPLTGTYRL VQFHFHWGSS DDQGSEHTVD RKKYAAELHL
     VHWNTKYGDF GTAAQQPDGL AVVGVFLKVG DANPALQKVL DVLDSIKTKG KSADFPNFDP
     SSLLKRALNY WTYPGSLTNP PLLESVTWVV LKEPTSVSSQ QMLKFRSLNF NAEGEPELLM
     LANWRPAQPL KNRQVRVFPK
//