ID   CAH2_MOUSE              Reviewed;         260 AA.
AC   P00920; Q6LDQ7; Q7TPE1; Q9DCT3; Q9DCY9;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2007, sequence version 4.
DT   02-SEP-2026, entry version 205.
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; Synonyms=Car2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=6420240; DOI=10.1016/0378-1119(83)90237-8;
RA   Curtis P.J., Withers E., Demuth D., Watt R., Venta P.J., Tashian R.E.;
RT   "The nucleotide sequence and derived amino acid sequence of cDNA coding for
RT   mouse carbonic anhydrase II.";
RL   Gene 25:325-332(1983).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2995362; DOI=10.1016/s0021-9258(17)38996-2;
RA   Venta P.J., Montgomery J.C., Hewett-Emmett D., Wiebauer K., Tashian R.E.;
RT   "Structure and exon to protein domain relationships of the mouse carbonic
RT   anhydrase II gene.";
RL   J. Biol. Chem. 260:12130-12135(1985).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Kidney;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Colon;
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   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-77.
RX   PubMed=3000449; DOI=10.1016/0167-4781(85)90006-5;
RA   Venta P.J., Montgomery J.C., Hewett-Emmett D., Tashian R.E.;
RT   "Comparison of the 5' regions of human and mouse carbonic anhydrase II
RT   genes and identification of possible regulatory elements.";
RL   Biochim. Biophys. Acta 826:195-201(1985).
RN   [6]
RP   PROTEIN SEQUENCE OF 19-53; 58-80; 90-111; 114-126; 133-167 AND 213-226, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=C57BL/6J; TISSUE=Brain, and Hippocampus;
RA   Lubec G., Klug S., Kang S.U.;
RL   Submitted (APR-2007) to UniProtKB.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 155-178 AND 214-240.
RX   PubMed=6187736; DOI=10.1016/s0021-9258(18)32645-0;
RA   Curtis P.J.;
RT   "Cloning of mouse carbonic anhydrase mRNA and its induction in mouse
RT   erythroleukemic cells.";
RL   J. Biol. Chem. 258:4459-4463(1983).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 241-260.
RX   PubMed=6331255; DOI=10.1111/j.1749-6632.1984.tb12355.x;
RA   Venta P.J., Montgomery J.C., Wiebauer K., Hewett-Emmett D., Tashian R.E.;
RT   "Organization of the mouse and human carbonic anhydrase II genes.";
RL   Ann. N. Y. Acad. Sci. 429:309-323(1984).
RN   [9]
RP   FUNCTION.
RX   PubMed=20150244; DOI=10.1152/ajpgi.00293.2009;
RA   Simpson J.E., Walker N.M., Supuran C.T., Soleimani M., Clarke L.L.;
RT   "Putative anion transporter-1 (Pat-1, Slc26a6) contributes to intracellular
RT   pH regulation during H+-dipeptide transport in duodenal villous
RT   epithelium.";
RL   Am. J. Physiol. 298:G683-G691(2010).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-87, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Catalyzes the reversible hydration of carbon dioxide (By
CC       similarity). Can also hydrate cyanamide to urea (By similarity).
CC       Involved in the regulation of fluid secretion into the anterior chamber
CC       of the eye (By similarity). Essential for bone resorption and
CC       osteoclast differentiation (By similarity). Contributes to
CC       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}.
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 (By similarity). Interaction with SLC4A7
CC       regulates SLC4A7 transporter activity (By similarity). Interacts with
CC       SLC26A6 (By similarity). {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.
CC       {ECO:0000250|UniProtKB:P00918}.
CC   -!- SIMILARITY: Belongs to the alpha-carbonic anhydrase family.
CC       {ECO:0000305}.
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DR   EMBL; K00811; AAA37356.1; -; mRNA.
DR   EMBL; M81022; AAA37357.1; -; Genomic_DNA.
DR   EMBL; M81016; AAA37357.1; JOINED; Genomic_DNA.
DR   EMBL; M81017; AAA37357.1; JOINED; Genomic_DNA.
DR   EMBL; M81018; AAA37357.1; JOINED; Genomic_DNA.
DR   EMBL; M81019; AAA37357.1; JOINED; Genomic_DNA.
DR   EMBL; M81020; AAA37357.1; JOINED; Genomic_DNA.
DR   EMBL; M81021; AAA37357.1; JOINED; Genomic_DNA.
DR   EMBL; AK002333; BAB22019.1; -; mRNA.
DR   EMBL; AK002498; BAB22146.2; -; mRNA.
DR   EMBL; BC055291; AAH55291.1; -; mRNA.
DR   EMBL; M25944; AAA39505.1; -; mRNA.
DR   CCDS; CCDS17251.1; -.
DR   PIR; A23900; CRMS2.
DR   RefSeq; NP_033931.4; NM_009801.5.
DR   AlphaFoldDB; P00920; -.
DR   SMR; P00920; -.
DR   BioGRID; 198483; 13.
DR   FunCoup; P00920; 424.
DR   IntAct; P00920; 2.
DR   STRING; 10090.ENSMUSP00000029078; -.
DR   ChEMBL; CHEMBL3689; -.
DR   GlyGen; P00920; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P00920; -.
DR   PhosphoSitePlus; P00920; -.
DR   SwissPalm; P00920; -.
DR   CPTAC; non-CPTAC-3303; -.
DR   CPTAC; non-CPTAC-3365; -.
DR   jPOST; P00920; -.
DR   PaxDb; 10090-ENSMUSP00000029078; -.
DR   PeptideAtlas; P00920; -.
DR   ProteomicsDB; 265421; -.
DR   Pumba; P00920; -.
DR   Antibodypedia; 677; 719 antibodies from 46 providers.
DR   DNASU; 12349; -.
DR   Ensembl; ENSMUST00000029078.9; ENSMUSP00000029078.8; ENSMUSG00000027562.13.
DR   GeneID; 12349; -.
DR   UCSC; uc008oqt.2; mouse.
DR   AGR; MGI:88269; -.
DR   CTD; 12349; -.
DR   MGI; MGI:88269; Car2.
DR   VEuPathDB; HostDB:ENSMUSG00000027562; -.
DR   eggNOG; KOG0382; Eukaryota.
DR   GeneTree; ENSGT00940000160385; -.
DR   HOGENOM; CLU_039326_2_1_1; -.
DR   InParanoid; P00920; -.
DR   OMA; INPHWKV; -.
DR   OrthoDB; 429145at2759; -.
DR   PhylomeDB; P00920; -.
DR   Reactome; R-MMU-1237044; Erythrocytes take up carbon dioxide and release oxygen.
DR   Reactome; R-MMU-1247673; Erythrocytes take up oxygen and release carbon dioxide.
DR   Reactome; R-MMU-1475029; Reversible hydration of carbon dioxide.
DR   BioGRID-ORCS; 12349; 2 hits in 78 CRISPR screens.
DR   PRO; PR:P00920; -.
DR   Proteomes; UP000000589; Chromosome 3.
DR   RNAct; P00920; protein.
DR   Bgee; ENSMUSG00000027562; Expressed in fetal liver hematopoietic progenitor cell and 274 other cell types or tissues.
DR   ExpressionAtlas; P00920; baseline and differential.
DR   GO; GO:0045177; C:apical part of cell; ISO:GO_Central.
DR   GO; GO:0030424; C:axon; ISO:GO_Central.
DR   GO; GO:0016323; C:basolateral plasma membrane; ISO:GO_Central.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; ISO:GO_Central.
DR   GO; GO:0005902; C:microvillus; ISO:GO_Central.
DR   GO; GO:0043209; C:myelin sheath; IDA:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0004064; F:arylesterase activity; ISO:GO_Central.
DR   GO; GO:0004089; F:carbonate dehydratase activity; IDA:MGI.
DR   GO; GO:0018820; F:cyanamide hydratase activity; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; ISO:GO_Central.
DR   GO; GO:0038166; P:angiotensin-activated signaling pathway; ISS:UniProtKB.
DR   GO; GO:0015670; P:carbon dioxide transport; IMP:MGI.
DR   GO; GO:0071498; P:cellular response to fluid shear stress; IEA:Ensembl.
DR   GO; GO:0044849; P:estrous cycle; IEA:Ensembl.
DR   GO; GO:0051454; P:intracellular pH elevation; ISO:GO_Central.
DR   GO; GO:0051452; P:intracellular pH reduction; IMP:MGI.
DR   GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR   GO; GO:0002009; P:morphogenesis of an epithelium; IMP:MGI.
DR   GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR   GO; GO:0036035; P:osteoclast development; ISO:GO_Central.
DR   GO; GO:0045780; P:positive regulation of bone resorption; ISO:GO_Central.
DR   GO; GO:2001150; P:positive regulation of dipeptide transmembrane transport; IMP:UniProtKB.
DR   GO; GO:0045672; P:positive regulation of osteoclast differentiation; ISO:GO_Central.
DR   GO; GO:0032230; P:positive regulation of synaptic transmission, GABAergic; IGI:MGI.
DR   GO; GO:2001225; P:regulation of chloride transport; IMP:MGI.
DR   GO; GO:0051453; P:regulation of intracellular pH; IMP:UniProtKB.
DR   GO; GO:0044070; P:regulation of monoatomic anion transport; ISS:UniProtKB.
DR   GO; GO:0006885; P:regulation of pH; IC:MGI.
DR   GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR   GO; GO:1904404; P:response to formaldehyde; IEA:Ensembl.
DR   GO; GO:0009268; P:response to pH; IEA:Ensembl.
DR   GO; GO:0048545; P:response to steroid hormone; IEA:Ensembl.
DR   GO; GO:0010043; P:response to zinc ion; IEA:Ensembl.
DR   GO; GO:0046903; P:secretion; IMP:MGI.
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:0000250|UniProtKB:P00918"
FT   CHAIN           2..260
FT                   /note="Carbonic anhydrase 2"
FT                   /id="PRO_0000077419"
FT   DOMAIN          3..259
FT                   /note="Alpha-carbonic anhydrase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01134"
FT   ACT_SITE        64
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   ACT_SITE        67
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   ACT_SITE        127
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   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   MOD_RES         2
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P27139"
FT   MOD_RES         87
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         165
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   CONFLICT        39
FT                   /note="Q -> H (in Ref. 1; AAA37356 and 4; AAH55291)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        145
FT                   /note="I -> Y (in Ref. 1; AAA37356 and 2; AAA37357)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        213
FT                   /note="E -> D (in Ref. 2; AAA37357)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   260 AA;  29033 MW;  095760368D446AA6 CRC64;
     MSHHWGYSKH NGPENWHKDF PIANGDRQSP VDIDTATAQH DPALQPLLIS YDKAASKSIV
     NNGHSFNVEF DDSQDNAVLK GGPLSDSYRL IQFHFHWGSS DGQGSEHTVN KKKYAAELHL
     VHWNTKYGDF GKAVQQPDGL AVLGIFLKIG PASQGLQKVL EALHSIKTKG KRAAFANFDP
     CSLLPGNLDY WTYPGSLTTP PLLECVTWIV LREPITVSSE QMSHFRTLNF NEEGDAEEAM
     VDNWRPAQPL KNRKIKASFK
//