CAH4_RAT
ID CAH4_RAT Reviewed; 309 AA.
AC P48284; Q4QR97;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 157.
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;
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=Lung;
RX PubMed=8279579; DOI=10.1152/ajplung.1993.265.6.l627;
RA Fleming R.E., Crouch E.C., Ruzicka C.A., Sly W.S.;
RT "Pulmonary carbonic anhydrase IV: developmental regulation and cell-
RT specific expression in the capillary endothelium.";
RL Am. J. Physiol. 265:L627-L635(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 PROTEIN SEQUENCE OF 19-22; 24-33 AND 36-38, TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, AND GLYCOSYLATION.
RC TISSUE=Lung;
RX PubMed=1737787; DOI=10.1016/s0021-9258(19)50732-3;
RA Waheed A., Zhu X.L., Sly W.S.;
RT "Membrane-associated carbonic anhydrase from rat lung. Purification,
RT characterization, tissue distribution, and comparison with carbonic
RT anhydrase IVs of other mammals.";
RL J. Biol. Chem. 267:3308-3311(1992).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-193, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24090084; DOI=10.1021/pr400783j;
RA Parker B.L., Thaysen-Andersen M., Solis N., Scott N.E., Larsen M.R.,
RA Graham M.E., Packer N.H., Cordwell S.J.;
RT "Site-specific glycan-peptide analysis for determination of N-glycoproteome
RT heterogeneity.";
RL J. Proteome Res. 12:5791-5800(2013).
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:0000250|UniProtKB:P22748};
CC -!- ACTIVITY REGULATION: Inhibited by acetazolamide. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with SLC4A4. {ECO:0000250|UniProtKB:P22748}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1737787};
CC Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:1737787}.
CC -!- TISSUE SPECIFICITY: Present in kidney and lung. Also particularly
CC abundant in brain, muscle, heart and liver. Not detected in skin or
CC spleen. {ECO:0000269|PubMed:1737787}.
CC -!- PTM: The N-terminus is blocked.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:1737787}.
CC -!- SIMILARITY: Belongs to the alpha-carbonic anhydrase family.
CC {ECO:0000305}.
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DR EMBL; S68245; AAB29505.1; -; mRNA.
DR EMBL; BC097329; AAH97329.1; -; mRNA.
DR PIR; I51900; I51900.
DR RefSeq; NP_062047.1; NM_019174.3.
DR AlphaFoldDB; P48284; -.
DR SMR; P48284; -.
DR BioGRID; 247918; 2.
DR IntAct; P48284; 1.
DR MINT; P48284; -.
DR STRING; 10116.ENSRNOP00000003908; -.
DR GlyGen; P48284; 1 site, 4 N-linked glycans (1 site).
DR iPTMnet; P48284; -.
DR PhosphoSitePlus; P48284; -.
DR PaxDb; P48284; -.
DR PRIDE; P48284; -.
DR GeneID; 29242; -.
DR KEGG; rno:29242; -.
DR CTD; 762; -.
DR RGD; 2242; Ca4.
DR eggNOG; KOG0382; Eukaryota.
DR HOGENOM; CLU_039326_2_0_1; -.
DR InParanoid; P48284; -.
DR OrthoDB; 1377476at2759; -.
DR PhylomeDB; P48284; -.
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:P48284; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; P48284; RN.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; ISO:RGD.
DR GO; GO:0046658; C:anchored component of plasma membrane; ISO:RGD.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0031526; C:brush border membrane; ISO:RGD.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISO:RGD.
DR GO; GO:0070062; C:extracellular exosome; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0005791; C:rough endoplasmic reticulum; ISO:RGD.
DR GO; GO:0042383; C:sarcolemma; IDA:RGD.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:RGD.
DR GO; GO:0030667; C:secretory granule membrane; ISO:RGD.
DR GO; GO:0005802; C:trans-Golgi network; ISO:RGD.
DR GO; GO:0030658; C:transport vesicle membrane; 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; IEA:InterPro.
DR GO; GO:0048513; P:animal organ development; IEP:RGD.
DR GO; GO:0015701; P:bicarbonate transport; ISO:RGD.
DR GO; GO:0006730; P:one-carbon metabolic process; IBA:GO_Central.
DR GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
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 Cell membrane; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW GPI-anchor; Lipoprotein; Lyase; Membrane; Metal-binding;
KW Reference proteome; Signal; Zinc.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..281
FT /note="Carbonic anhydrase 4"
FT /id="PRO_0000004232"
FT PROPEP 282..309
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P22748"
FT /id="PRO_0000004233"
FT DOMAIN 20..282
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:0000250|UniProtKB:Q64444"
FT BINDING 116
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q64444"
FT BINDING 139
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q64444"
FT BINDING 222..223
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00918"
FT LIPID 281
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000250|UniProtKB:P22748"
FT CARBOHYD 193
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PubMed:24090084"
FT DISULFID 23..35
FT /evidence="ECO:0000250|UniProtKB:Q64444"
FT DISULFID 45..226
FT /evidence="ECO:0000250|UniProtKB:Q64444"
SQ SEQUENCE 309 AA; 35076 MW; 9EBD1315348CFC8C CRC64;
MQLLLALLAL AYVAPSTEDS HWCYEIQAKE PNSHCSGPEQ WTGDCKKNQQ SPINIVTSKT
KLNPSLTPFT FVGYDQKKKW EVKNNQHSVE MSLGEDIYIF GGDLPTQYKA IQLHLHWSEE
SNKGSEHSID GKHFAMEMHV VHKKMTTGDK VQDSDSKDKI AVLAFMVEVG NEVNEGFQPL
VEALSRLSKP FTNSTVSESC LQDMLPEKKK LSAYFRYQGS LTTPGCDETV IWTVFEEPIK
IHKDQFLEFS KKLYYDQEQK LNMKDNVRPL QPLGNRQVFR SHASGRLLSL PLPTLLVPTL
TCLVASFLH
