CAH4_MOUSE
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 03-AUG-2022, entry version 172.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 GlyGen; Q64444; 2 sites, 4 N-linked glycans (2 sites).
DR PhosphoSitePlus; Q64444; -.
DR jPOST; Q64444; -.
DR MaxQB; Q64444; -.
DR PaxDb; Q64444; -.
DR PeptideAtlas; Q64444; -.
DR PRIDE; Q64444; -.
DR ProteomicsDB; 265422; -.
DR Antibodypedia; 2592; 321 antibodies from 33 providers.
DR DNASU; 12351; -.
DR Ensembl; ENSMUST00000103194; ENSMUSP00000099483; ENSMUSG00000000805.
DR GeneID; 12351; -.
DR KEGG; mmu:12351; -.
DR UCSC; uc007krg.2; mouse.
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; SHWCYEI; -.
DR OrthoDB; 1377476at2759; -.
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 74 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 205 other tissues.
DR ExpressionAtlas; Q64444; baseline and differential.
DR Genevisible; Q64444; MM.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; ISO:MGI.
DR GO; GO:0046658; C:anchored component of plasma membrane; IDA:MGI.
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: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; ISO: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:0016836; F:hydro-lyase activity; IBA:GO_Central.
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; -; 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 InterPro; IPR018343; Carbonic_anhydrase_CA4.
DR PANTHER; PTHR18952; PTHR18952; 1.
DR PANTHER; PTHR18952:SF95; PTHR18952:SF95; 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 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
