CAH2_RAT
ID CAH2_RAT Reviewed; 260 AA.
AC P27139;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 167.
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;
GN Name=Ca2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=1765271; DOI=10.1016/0378-1119(91)90619-m;
RA Stolle C.A., McGowan M.H., Heim R.A., Varia M., Neubauer J.A.;
RT "Nucleotide sequence of a cDNA encoding rat brain carbonic anhydrase II and
RT its deduced amino acid sequence.";
RL Gene 109:265-267(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9074494; DOI=10.1016/s0378-1119(96)00700-7;
RA McGowan M.H., Neubauer J.A., Stolle C.A.;
RT "Characterization of the rat carbonic anhydrase II gene structure: sequence
RT analysis of the 5' flanking region and 3' UTR.";
RL Gene 186:181-188(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 58-80; 81-110; 114-126; 133-158 AND 213-226, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain, Hippocampus, and Spinal cord;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Kang S.U.;
RL Submitted (JUL-2007) to UniProtKB.
RN [5]
RP FUNCTION.
RX PubMed=9665810; DOI=10.1006/excr.1998.4071;
RA Lehenkari P., Hentunen T.A., Laitala-Leinonen T., Tuukkanen J.,
RA Vaeaenaenen H.K.;
RT "Carbonic anhydrase II plays a major role in osteoclast differentiation and
RT bone resorption by effecting the steady state intracellular pH and Ca2+.";
RL Exp. Cell Res. 242:128-137(1998).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2 AND SER-232, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Catalyzes the reversible hydration of carbon dioxide (By
CC similarity). Involved in the regulation of fluid secretion into the
CC anterior chamber of the eye (By similarity). Essential for bone
CC resorption and osteoclast differentiation (PubMed:9665810). Contributes
CC to intracellular pH regulation in the duodenal upper villous epithelium
CC during proton-coupled peptide absorption (By similarity). Stimulates
CC the chloride-bicarbonate exchange activity of SLC26A6 (By similarity).
CC {ECO:0000250|UniProtKB:P00918, ECO:0000269|PubMed:9665810}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hydrogencarbonate = 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 -!- 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 -!- SIMILARITY: Belongs to the alpha-carbonic anhydrase family.
CC {ECO:0000305}.
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DR EMBL; X58294; CAA41227.1; -; mRNA.
DR EMBL; AH006769; AAC53104.1; -; Genomic_DNA.
DR EMBL; BC065577; AAH65577.1; -; mRNA.
DR PIR; JH0527; JH0527.
DR RefSeq; NP_062164.1; NM_019291.1.
DR AlphaFoldDB; P27139; -.
DR SMR; P27139; -.
DR BioGRID; 248454; 1.
DR IntAct; P27139; 2.
DR STRING; 10116.ENSRNOP00000013354; -.
DR BindingDB; P27139; -.
DR ChEMBL; CHEMBL4706; -.
DR DrugCentral; P27139; -.
DR iPTMnet; P27139; -.
DR PhosphoSitePlus; P27139; -.
DR SwissPalm; P27139; -.
DR World-2DPAGE; 0004:P27139; -.
DR PaxDb; P27139; -.
DR PRIDE; P27139; -.
DR Ensembl; ENSRNOT00000013354; ENSRNOP00000013354; ENSRNOG00000009629.
DR GeneID; 54231; -.
DR KEGG; rno:54231; -.
DR UCSC; RGD:2240; rat.
DR CTD; 12349; -.
DR RGD; 2240; Ca2.
DR eggNOG; KOG0382; Eukaryota.
DR GeneTree; ENSGT00940000160385; -.
DR HOGENOM; CLU_039326_2_1_1; -.
DR InParanoid; P27139; -.
DR OMA; SADFPNF; -.
DR OrthoDB; 1377476at2759; -.
DR PhylomeDB; P27139; -.
DR TreeFam; TF316425; -.
DR Reactome; R-RNO-1237044; Erythrocytes take up carbon dioxide and release oxygen.
DR Reactome; R-RNO-1247673; Erythrocytes take up oxygen and release carbon dioxide.
DR Reactome; R-RNO-1475029; Reversible hydration of carbon dioxide.
DR PRO; PR:P27139; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000009629; Expressed in stomach and 20 other tissues.
DR Genevisible; P27139; RN.
DR GO; GO:0045177; C:apical part of cell; IDA:RGD.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005902; C:microvillus; IDA:RGD.
DR GO; GO:0043209; C:myelin sheath; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0004064; F:arylesterase activity; ISO:RGD.
DR GO; GO:0004089; F:carbonate dehydratase activity; IDA:RGD.
DR GO; GO:0016836; F:hydro-lyase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; ISO:RGD.
DR GO; GO:0038166; P:angiotensin-activated signaling pathway; ISS:UniProtKB.
DR GO; GO:0015670; P:carbon dioxide transport; ISO:RGD.
DR GO; GO:0071498; P:cellular response to fluid shear stress; IEP:RGD.
DR GO; GO:0001822; P:kidney development; IEP:RGD.
DR GO; GO:0002009; P:morphogenesis of an epithelium; ISO:RGD.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEP:RGD.
DR GO; GO:0006730; P:one-carbon metabolic process; IBA:GO_Central.
DR GO; GO:0030316; P:osteoclast differentiation; TAS:RGD.
DR GO; GO:0045780; P:positive regulation of bone resorption; IMP:RGD.
DR GO; GO:0032849; P:positive regulation of cellular pH reduction; IMP:RGD.
DR GO; GO:2001150; P:positive regulation of dipeptide transmembrane transport; ISS:UniProtKB.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IMP:RGD.
DR GO; GO:0032230; P:positive regulation of synaptic transmission, GABAergic; ISO:RGD.
DR GO; GO:0044070; P:regulation of anion transport; ISS:UniProtKB.
DR GO; GO:0045124; P:regulation of bone resorption; TAS:RGD.
DR GO; GO:0030641; P:regulation of cellular pH; TAS:RGD.
DR GO; GO:2001225; P:regulation of chloride transport; ISO:RGD.
DR GO; GO:0051453; P:regulation of intracellular pH; ISS:UniProtKB.
DR GO; GO:0043627; P:response to estrogen; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0009268; P:response to pH; IEP:RGD.
DR GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
DR GO; GO:0010043; P:response to zinc ion; IEP:RGD.
DR GO; GO:0046903; P:secretion; ISO:RGD.
DR Gene3D; 3.10.200.10; -; 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; PTHR18952; 1.
DR Pfam; PF00194; Carb_anhydrase; 1.
DR SMART; SM01057; Carb_anhydrase; 1.
DR SUPFAM; SSF51069; SSF51069; 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:0000250|UniProtKB:P00918"
FT CHAIN 2..260
FT /note="Carbonic anhydrase 2"
FT /id="PRO_0000077421"
FT DOMAIN 3..259
FT /note="Alpha-carbonic anhydrase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01134"
FT REGION 16..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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:0000250|UniProtKB:P00918"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 87
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P00920"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P00918"
FT MOD_RES 232
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 260 AA; 29114 MW; 8263A3C0B9B5753D CRC64;
MSHHWGYSKS NGPENWHKEF PIANGDRQSP VDIDTGTAQH DPSLQPLLIC YDKVASKSIV
NNGHSFNVEF DDSQDFAVLK EGPLSGSYRL IQFHFHWGSS DGQGSEHTVN KKKYAAELHL
VHWNTKYGDF GKAVQHPDGL AVLGIFLKIG PASQGLQKIT EALHSIKTKG KRAAFANFDP
CSLLPGNLDY WTYPGSLTTP PLLECVTWIV LKEPITVSSE QMSHFRKLNF NSEGEAEELM
VDNWRPAQPL KNRKIKASFK
