ID   CAH4_MOUSE              Reviewed;         305 AA.
AC   Q64444;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 1.
DT   24-JAN-2024, entry version 180.
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; Synonyms=Car4;
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 [GENOMIC DNA].
RC   STRAIN=129/SvJ; TISSUE=Liver;
RX   PubMed=8935991; DOI=10.1007/bf02396238;
RA   Tamai S., Cody L.B., Sly W.S.;
RT   "Molecular cloning of the mouse gene coding for carbonic anhydrase IV.";
RL   Biochem. Genet. 34:31-43(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   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   [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).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue, Heart, Kidney, and Lung;
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).
RN   [5]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH INHIBITOR AND ZINC
RP   ION, COFACTOR, AND DISULFIDE BONDS.
RX   PubMed=9541386; DOI=10.1002/pro.5560070303;
RA   Stams T., Chen Y., Boriack-Sjodin P.A., Hurt J.D., Liao J., May J.A.,
RA   Dean T., Laipis P., Silverman D.N., Christianson D.W.;
RT   "Structures of murine carbonic anhydrase IV and human carbonic anhydrase II
RT   complexed with brinzolamide: molecular basis of isozyme-drug
RT   discrimination.";
RL   Protein Sci. 7:556-563(1998).
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=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: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:0000269|PubMed:9541386};
CC   -!- ACTIVITY REGULATION: Inhibited by acetazolamide. {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with SLC4A4. {ECO:0000269|PubMed:14567693}.
CC   -!- INTERACTION:
CC       Q64444; O88343: Slc4a4; NbExp=2; IntAct=EBI-6859308, EBI-771342;
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; U37091; AAC52569.1; -; Genomic_DNA.
DR   EMBL; BC012704; AAH12704.1; -; mRNA.
DR   CCDS; CCDS25190.1; -.
DR   RefSeq; NP_031633.1; NM_007607.2.
DR   PDB; 2ZNC; X-ray; 2.80 A; A=22-279.
DR   PDB; 3ZNC; X-ray; 2.80 A; A=22-279.
DR   PDBsum; 2ZNC; -.
DR   PDBsum; 3ZNC; -.
DR   AlphaFoldDB; Q64444; -.
DR   SMR; Q64444; -.
DR   IntAct; Q64444; 1.
DR   STRING; 10090.ENSMUSP00000099483; -.
DR   GlyConnect; 2181; 4 N-Linked glycans (2 sites).
DR   GlyCosmos; Q64444; 2 sites, 4 glycans.
DR   GlyGen; Q64444; 2 sites, 4 N-linked glycans (2 sites).
DR   iPTMnet; Q64444; -.
DR   PhosphoSitePlus; Q64444; -.
DR   SwissPalm; Q64444; -.
DR   jPOST; Q64444; -.
DR   MaxQB; Q64444; -.
DR   PaxDb; 10090-ENSMUSP00000099483; -.
DR   PeptideAtlas; Q64444; -.
DR   ProteomicsDB; 265422; -.
DR   Antibodypedia; 2592; 361 antibodies from 33 providers.
DR   DNASU; 12351; -.
DR   Ensembl; ENSMUST00000103194.10; ENSMUSP00000099483.4; ENSMUSG00000000805.19.
DR   GeneID; 12351; -.
DR   KEGG; mmu:12351; -.
DR   UCSC; uc007krg.2; mouse.
DR   AGR; MGI:1096574; -.
DR   CTD; 12351; -.
DR   MGI; MGI:1096574; Car4.
DR   VEuPathDB; HostDB:ENSMUSG00000000805; -.
DR   eggNOG; KOG0382; Eukaryota.
DR   GeneTree; ENSGT00940000155690; -.
DR   HOGENOM; CLU_039326_2_0_1; -.
DR   InParanoid; Q64444; -.
DR   OMA; TGSGDWC; -.
DR   OrthoDB; 49814at2759; -.
DR   PhylomeDB; Q64444; -.
DR   TreeFam; TF316425; -.
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; 12351; 2 hits in 79 CRISPR screens.
DR   ChiTaRS; Car4; mouse.
DR   EvolutionaryTrace; Q64444; -.
DR   PRO; PR:Q64444; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; Q64444; Protein.
DR   Bgee; ENSMUSG00000000805; Expressed in placenta labyrinth and 208 other cell types or tissues.
DR   ExpressionAtlas; Q64444; baseline and differential.
DR   GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR   GO; GO:0031526; C:brush border membrane; ISO:MGI.
DR   GO; GO:0009986; C:cell surface; ISO:MGI.
DR   GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISO:MGI.
DR   GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR   GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR   GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0005791; C:rough endoplasmic reticulum; ISO:MGI.
DR   GO; GO:0042383; C:sarcolemma; ISO:MGI.
DR   GO; GO:0016529; C:sarcoplasmic reticulum; ISO:MGI.
DR   GO; GO:0030667; C:secretory granule membrane; ISO:MGI.
DR   GO; GO:0005802; C:trans-Golgi network; ISO:MGI.
DR   GO; GO:0030658; C:transport vesicle membrane; ISO:MGI.
DR   GO; GO:0004089; F:carbonate dehydratase activity; IDA:MGI.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0015701; P:bicarbonate transport; ISO:MGI.
DR   GO; GO:0015670; P:carbon dioxide transport; IC:MGI.
DR   GO; GO:0006730; P:one-carbon metabolic process; IBA:GO_Central.
DR   GO; GO:0006885; P:regulation of pH; IC:MGI.
DR   CDD; cd03117; alpha_CA_IV_XV_like; 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   InterPro; IPR018338; Carbonic_anhydrase_a-class_CS.
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; PS00162; ALPHA_CA_1; 1.
DR   PROSITE; PS51144; ALPHA_CA_2; 1.
DR   Genevisible; Q64444; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Disulfide bond; Glycoprotein; GPI-anchor;
KW   Lipoprotein; Lyase; Membrane; Metal-binding; Reference proteome; Signal;
KW   Zinc.
FT   SIGNAL          1..17
FT                   /evidence="ECO:0000255"
FT   CHAIN           18..277
FT                   /note="Carbonic anhydrase 4"
FT                   /id="PRO_0000004228"
FT   PROPEP          278..305
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000250|UniProtKB:P22748"
FT                   /id="PRO_0000004229"
FT   DOMAIN          20..278
FT                   /note="Alpha-carbonic anhydrase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01134"
FT   ACT_SITE        87
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   BINDING         114
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:9541386"
FT   BINDING         116
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:9541386"
FT   BINDING         139
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:9541386"
FT   BINDING         218..219
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   LIPID           277
FT                   /note="GPI-anchor amidated serine"
FT                   /evidence="ECO:0000250|UniProtKB:P22748"
FT   CARBOHYD        123
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        214
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        23..35
FT                   /evidence="ECO:0000269|PubMed:9541386"
FT   DISULFID        45..222
FT                   /evidence="ECO:0000269|PubMed:9541386"
FT   HELIX           25..29
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   STRAND          30..33
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   HELIX           38..40
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   HELIX           43..46
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   STRAND          47..49
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   HELIX           57..59
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   STRAND          70..73
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   STRAND          78..84
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   STRAND          86..92
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   STRAND          96..100
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   STRAND          108..117
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   STRAND          119..123
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   STRAND          125..129
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   STRAND          135..144
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   STRAND          156..168
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   HELIX           171..173
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   HELIX           174..179
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   HELIX           180..182
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   STRAND          189..195
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   HELIX           198..200
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   HELIX           204..206
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   STRAND          210..215
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   STRAND          226..233
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   STRAND          235..238
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   HELIX           239..248
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   STRAND          250..252
FT                   /evidence="ECO:0007829|PDB:2ZNC"
FT   STRAND          275..277
FT                   /evidence="ECO:0007829|PDB:2ZNC"
SQ   SEQUENCE   305 AA;  34351 MW;  EEE988FF52732884 CRC64;
     MQLLLALLAL AYVAPSTEDS GWCYEIQTKD PRSSCLGPEK WPGACKENQQ SPINIVTART
     KVNPRLTPFI LVGYDQKQQW PIKNNQHTVE MTLGGGACII GGDLPARYEA VQLHLHWSNG
     NDNGSEHSID GRHFAMEMHI VHKKLTSSKE DSKDKFAVLA FMIEVGDKVN KGFQPLVEAL
     PSISKPHSTS TVRESSLQDM LPPSTKMYTY FRYNGSLTTP NCDETVIWTV YKQPIKIHKN
     QFLEFSKNLY YDEDQKLNMK DNVRPLQPLG KRQVFKSHAP GQLLSLPLPT LLVPTLTCLV
     ANFLQ
//