位置:首页 > 蛋白库 > CAH4_HUMAN
CAH4_HUMAN
ID   CAH4_HUMAN              Reviewed;         312 AA.
AC   P22748; B4DQA4; Q6FHI7;
DT   01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 2.
DT   03-AUG-2022, entry version 215.
DE   RecName: Full=Carbonic anhydrase 4;
DE            EC=4.2.1.1 {ECO:0000269|PubMed:15563508, ECO:0000269|PubMed:16686544, ECO:0000269|PubMed:16807956, ECO:0000269|PubMed:17127057, ECO:0000269|PubMed:17652713, ECO:0000269|PubMed:17705204, ECO:0000269|PubMed:7625839};
DE   AltName: Full=Carbonate dehydratase IV;
DE   AltName: Full=Carbonic anhydrase IV;
DE            Short=CA-IV;
DE   Flags: Precursor;
GN   Name=CA4 {ECO:0000312|HGNC:HGNC:1375};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=1311094; DOI=10.1073/pnas.89.4.1315;
RA   Okuyama T., Sato S., Zhu X.L., Waheed A., Sly W.S.;
RT   "Human carbonic anhydrase IV: cDNA cloning, sequence comparison, and
RT   expression in COS cell membranes.";
RL   Proc. Natl. Acad. Sci. U.S.A. 89:1315-1319(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8325641; DOI=10.1006/geno.1993.1247;
RA   Okuyama T., Batanian J.R., Sly W.S.;
RT   "Genomic organization and localization of gene for human carbonic anhydrase
RT   IV to chromosome 17q.";
RL   Genomics 16:678-684(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Brain;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16625196; DOI=10.1038/nature04689;
RA   Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA   Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA   Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA   Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA   DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA   Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA   Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA   LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA   Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA   Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA   Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA   Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA   Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT   "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT   human lineage.";
RL   Nature 440:1045-1049(2006).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain, and 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   [8]
RP   PROTEIN SEQUENCE OF 19-35; 113-123 AND 233-239.
RC   TISSUE=Lung;
RX   PubMed=2111324; DOI=10.1016/s0021-9258(19)38958-6;
RA   Zhu X.L., Sly W.S.;
RT   "Carbonic anhydrase IV from human lung. Purification, characterization, and
RT   comparison with membrane carbonic anhydrase from human kidney.";
RL   J. Biol. Chem. 265:8795-8801(1990).
RN   [9]
RP   DISULFIDE BONDS.
RX   PubMed=8809084; DOI=10.1006/abbi.1996.0412;
RA   Waheed A., Okuyama T., Heyduk T., Sly W.S.;
RT   "Carbonic anhydrase IV: purification of a secretory form of the recombinant
RT   human enzyme and identification of the positions and importance of its
RT   disulfide bonds.";
RL   Arch. Biochem. Biophys. 333:432-438(1996).
RN   [10]
RP   GPI-ANCHOR AT SER-284, MUTAGENESIS OF SER-284, CATALYTIC ACTIVITY, AND
RP   FUNCTION.
RX   PubMed=7625839; DOI=10.1016/0003-9861(95)90015-2;
RA   Okuyama T., Waheed A., Kusumoto W., Zhu X.L., Sly W.S.;
RT   "Carbonic anhydrase IV: role of removal of C-terminal domain in
RT   glycosylphosphatidylinositol anchoring and realization of enzyme
RT   activity.";
RL   Arch. Biochem. Biophys. 320:315-322(1995).
RN   [11]
RP   ACTIVITY REGULATION, CATALYTIC ACTIVITY, AND FUNCTION.
RX   PubMed=16807956; DOI=10.1002/chem.200600159;
RA   Temperini C., Scozzafava A., Vullo D., Supuran C.T.;
RT   "Carbonic anhydrase activators. Activation of isozymes I, II, IV, VA, VII,
RT   and XIV with l- and d-histidine and crystallographic analysis of their
RT   adducts with isoform II: engineering proton-transfer processes within the
RT   active site of an enzyme.";
RL   Chemistry 12:7057-7066(2006).
RN   [12]
RP   ACTIVITY REGULATION, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=16686544; DOI=10.1021/jm0603320;
RA   Temperini C., Scozzafava A., Vullo D., Supuran C.T.;
RT   "Carbonic anhydrase activators. Activation of isoforms I, II, IV, VA, VII,
RT   and XIV with L- and D-phenylalanine and crystallographic analysis of their
RT   adducts with isozyme II: stereospecific recognition within the active site
RT   of an enzyme and its consequences for the drug design.";
RL   J. Med. Chem. 49:3019-3027(2006).
RN   [13]
RP   ACTIVITY REGULATION, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=17705204; DOI=10.1002/anie.200701189;
RA   Koehler K., Hillebrecht A., Schulze Wischeler J., Innocenti A., Heine A.,
RA   Supuran C.T., Klebe G.;
RT   "Saccharin inhibits carbonic anhydrases: possible explanation for its
RT   unpleasant metallic aftertaste.";
RL   Angew. Chem. Int. Ed. Engl. 46:7697-7699(2007).
RN   [14]
RP   ACTIVITY REGULATION, FUNCTION, CATALYTIC ACTIVITY, AND ALTERNATIVE
RP   SPLICING.
RX   PubMed=17127057; DOI=10.1016/j.bmcl.2006.11.027;
RA   Temperini C., Innocenti A., Scozzafava A., Mastrolorenzo A., Supuran C.T.;
RT   "Carbonic anhydrase activators: L-Adrenaline plugs the active site entrance
RT   of isozyme II, activating better isoforms I, IV, VA, VII, and XIV.";
RL   Bioorg. Med. Chem. Lett. 17:628-635(2007).
RN   [15]
RP   ACTIVITY REGULATION, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=17314045; DOI=10.1016/j.bmcl.2007.01.113;
RA   Temperini C., Innocenti A., Guerri A., Scozzafava A., Rusconi S.,
RA   Supuran C.T.;
RT   "Phosph(on)ate as a zinc-binding group in metalloenzyme inhibitors: X-ray
RT   crystal structure of the antiviral drug foscarnet complexed to human
RT   carbonic anhydrase I.";
RL   Bioorg. Med. Chem. Lett. 17:2210-2215(2007).
RN   [16]
RP   ACTIVITY REGULATION, AND CATALYTIC ACTIVITY.
RX   PubMed=19186056; DOI=10.1016/j.bmcl.2009.01.038;
RA   Crocetti L., Maresca A., Temperini C., Hall R.A., Scozzafava A.,
RA   Muehlschlegel F.A., Supuran C.T.;
RT   "A thiabendazole sulfonamide shows potent inhibitory activity against
RT   mammalian and nematode alpha-carbonic anhydrases.";
RL   Bioorg. Med. Chem. Lett. 19:1371-1375(2009).
RN   [17]
RP   ACTIVITY REGULATION, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=19206230; DOI=10.1021/ja809683v;
RA   Maresca A., Temperini C., Vu H., Pham N.B., Poulsen S.-A., Scozzafava A.,
RA   Quinn R.J., Supuran C.T.;
RT   "Non-zinc mediated inhibition of carbonic anhydrases: coumarins are a new
RT   class of suicide inhibitors.";
RL   J. Am. Chem. Soc. 131:3057-3062(2009).
RN   [18]
RP   CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND
RP   FUNCTION.
RX   PubMed=18618712; DOI=10.1002/prot.22144;
RA   Di Fiore A., Monti S.M., Hilvo M., Parkkila S., Romano V., Scaloni A.,
RA   Pedone C., Scozzafava A., Supuran C.T., De Simone G.;
RT   "Crystal structure of human carbonic anhydrase XIII and its complex with
RT   the inhibitor acetazolamide.";
RL   Proteins 74:164-175(2009).
RN   [19]
RP   X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 19-284 IN COMPLEX WITH ZINC ION.
RX   PubMed=8942978; DOI=10.1073/pnas.93.24.13589;
RA   Stams T., Nair S.K., Okuyama T., Waheed A., Sly W.S., Christianson D.W.;
RT   "Crystal structure of the secretory form of membrane-associated human
RT   carbonic anhydrase IV at 2.8-A resolution.";
RL   Proc. Natl. Acad. Sci. U.S.A. 93:13589-13594(1996).
RN   [20]
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 19-284 IN COMPLEX WITH
RP   INHIBITORS.
RX   PubMed=20363633; DOI=10.1016/j.bmc.2010.03.014;
RA   Vernier W.F., Chong W., Rewolinski D., Greasley S., Pauly T.A., Shaw M.,
RA   Dinh D.M., Ferre R.A.A., Meador J.W. III, Nukui S., Ornelas M., Paz R.L.,
RA   Reyner E.;
RT   "Thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV:
RT   structure-based drug design, synthesis, and biological evaluation.";
RL   Bioorg. Med. Chem. 18:3307-3319(2010).
RN   [21]
RP   INVOLVEMENT IN RP17, VARIANTS RP17 TRP-14 AND SER-219, FUNCTION, CATALYTIC
RP   ACTIVITY, TISSUE SPECIFICITY, INTERACTION WITH SLC4A4, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=15563508; DOI=10.1093/hmg/ddi023;
RA   Yang Z., Alvarez B.V., Chakarova C., Jiang L., Karan G., Frederick J.M.,
RA   Zhao Y., Sauve Y., Li X., Zrenner E., Wissinger B., Den Hollander A.I.,
RA   Katz B., Baehr W., Cremers F.P., Casey J.R., Bhattacharya S.S., Zhang K.;
RT   "Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal
RT   photoreceptor degeneration.";
RL   Hum. Mol. Genet. 14:255-265(2005).
RN   [22]
RP   INTERACTION WITH SLC4A4, VARIANT RP17 HIS-69, VARIANT LYS-177,
RP   CHARACTERIZATION OF VARIANT RP17 HIS-69, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=17652713; DOI=10.1167/iovs.06-1515;
RA   Alvarez B.V., Vithana E.N., Yang Z., Koh A.H., Yeung K., Yong V.,
RA   Shandro H.J., Chen Y., Kolatkar P., Palasingam P., Zhang K., Aung T.,
RA   Casey J.R.;
RT   "Identification and characterization of a novel mutation in the carbonic
RT   anhydrase IV gene that causes retinitis pigmentosa.";
RL   Invest. Ophthalmol. Vis. Sci. 48:3459-3468(2007).
RN   [23]
RP   VARIANT RP17 THR-12.
RX   PubMed=20450258; DOI=10.3109/02713680903503512;
RA   Tian Y., Tang L., Cui J., Zhu X.;
RT   "Screening for the carbonic anhydrase IV gene mutations in Chinese
RT   retinitis pigmentosa patients.";
RL   Curr. Eye Res. 35:440-444(2010).
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 (PubMed:15563508, PubMed:17652713,
CC       PubMed:7625839, PubMed:16807956, PubMed:16686544, PubMed:17705204,
CC       PubMed:17127057, PubMed:17314045, PubMed:19186056, PubMed:19206230,
CC       PubMed:18618712). May stimulate the sodium/bicarbonate transporter
CC       activity of SLC4A4 that acts in pH homeostasis (PubMed:15563508). It is
CC       essential for acid overload removal from the retina and retina
CC       epithelium, and acid release in the choriocapillaris in the choroid
CC       (PubMed:15563508). {ECO:0000269|PubMed:15563508,
CC       ECO:0000269|PubMed:16686544, ECO:0000269|PubMed:16807956,
CC       ECO:0000269|PubMed:17127057, ECO:0000269|PubMed:17314045,
CC       ECO:0000269|PubMed:17652713, ECO:0000269|PubMed:17705204,
CC       ECO:0000269|PubMed:18618712, ECO:0000269|PubMed:19186056,
CC       ECO:0000269|PubMed:19206230, ECO:0000269|PubMed:7625839}.
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; Evidence={ECO:0000269|PubMed:15563508,
CC         ECO:0000269|PubMed:16686544, ECO:0000269|PubMed:16807956,
CC         ECO:0000269|PubMed:17127057, ECO:0000269|PubMed:17314045,
CC         ECO:0000269|PubMed:17652713, ECO:0000269|PubMed:17705204,
CC         ECO:0000269|PubMed:18618712, ECO:0000269|PubMed:19186056,
CC         ECO:0000269|PubMed:19206230, ECO:0000269|PubMed:7625839};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10749;
CC         Evidence={ECO:0000305|PubMed:17652713};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10750;
CC         Evidence={ECO:0000305|PubMed:17652713};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000269|PubMed:8942978};
CC   -!- ACTIVITY REGULATION: Activated by histamine, L-adrenaline, D-
CC       phenylalanine, L- and D-histidine. Inhibited by coumarins, saccharin,
CC       sulfonamide derivatives such as acetazolamide and Foscarnet
CC       (phosphonoformate trisodium salt). {ECO:0000269|PubMed:16686544,
CC       ECO:0000269|PubMed:16807956, ECO:0000269|PubMed:17127057,
CC       ECO:0000269|PubMed:17314045, ECO:0000269|PubMed:17705204,
CC       ECO:0000269|PubMed:18618712, ECO:0000269|PubMed:19186056,
CC       ECO:0000269|PubMed:19206230}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=21.5 mM for CO(2) {ECO:0000269|PubMed:18618712};
CC   -!- SUBUNIT: Interacts with SLC4A4. {ECO:0000269|PubMed:15563508,
CC       ECO:0000269|PubMed:17652713, ECO:0000269|PubMed:20363633,
CC       ECO:0000269|PubMed:8942978}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15563508};
CC       Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:7625839}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P22748-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P22748-2; Sequence=VSP_055973, VSP_055974;
CC   -!- TISSUE SPECIFICITY: Expressed in the endothelium of the
CC       choriocapillaris in eyes (at protein level). Not expressed in the
CC       retinal epithelium at detectable levels. {ECO:0000269|PubMed:15563508}.
CC   -!- DISEASE: Retinitis pigmentosa 17 (RP17) [MIM:600852]: A retinal
CC       dystrophy belonging to the group of pigmentary retinopathies. Retinitis
CC       pigmentosa is characterized by retinal pigment deposits visible on
CC       fundus examination and primary loss of rod photoreceptor cells followed
CC       by secondary loss of cone photoreceptors. Patients typically have night
CC       vision blindness and loss of midperipheral visual field. As their
CC       condition progresses, they lose their far peripheral visual field and
CC       eventually central vision as well. {ECO:0000269|PubMed:15563508,
CC       ECO:0000269|PubMed:17652713, ECO:0000269|PubMed:20450258}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry. Defective acid overload removal from retina and retinal
CC       epithelium, due to mutant CA4, is responsible for photoreceptor
CC       degeneration, indicating that impaired pH homeostasis is the most
CC       likely cause underlying the RP17 phenotype.
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; M83670; AAA35630.1; -; mRNA.
DR   EMBL; L10955; AAA35625.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; L10951; AAA35625.1; JOINED; Genomic_DNA.
DR   EMBL; L10953; AAA35625.1; JOINED; Genomic_DNA.
DR   EMBL; L10954; AAA35625.1; JOINED; Genomic_DNA.
DR   EMBL; L10955; AAA35626.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; L10954; AAA35626.1; JOINED; Genomic_DNA.
DR   EMBL; AK289715; BAF82404.1; -; mRNA.
DR   EMBL; AK298710; BAG60866.1; -; mRNA.
DR   EMBL; CR541766; CAG46565.1; -; mRNA.
DR   EMBL; AC025048; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471109; EAW94362.1; -; Genomic_DNA.
DR   EMBL; BC057792; AAH57792.1; -; mRNA.
DR   EMBL; BC069649; AAH69649.1; -; mRNA.
DR   EMBL; BC074768; AAH74768.1; -; mRNA.
DR   CCDS; CCDS11624.1; -. [P22748-1]
DR   PIR; A45745; CRHU4.
DR   RefSeq; NP_000708.1; NM_000717.4. [P22748-1]
DR   RefSeq; XP_016880501.1; XM_017025012.1.
DR   PDB; 1ZNC; X-ray; 2.80 A; A/B=19-284.
DR   PDB; 3F7B; X-ray; 2.05 A; A/B=19-284.
DR   PDB; 3F7U; X-ray; 2.00 A; A/B/C/D=19-284.
DR   PDB; 3FW3; X-ray; 1.72 A; A/B=19-284.
DR   PDB; 5IPZ; X-ray; 2.10 A; A/B/C/D=19-284.
DR   PDB; 5JN8; X-ray; 1.85 A; A/B/C/D=19-284.
DR   PDB; 5JN9; X-ray; 2.10 A; A/B/C/D=19-284.
DR   PDB; 5JNA; X-ray; 2.00 A; A/B/C/D=19-284.
DR   PDB; 5JNC; X-ray; 2.00 A; A/B/C/D=19-284.
DR   PDB; 5KU6; X-ray; 1.80 A; A/B/C/D=19-284.
DR   PDBsum; 1ZNC; -.
DR   PDBsum; 3F7B; -.
DR   PDBsum; 3F7U; -.
DR   PDBsum; 3FW3; -.
DR   PDBsum; 5IPZ; -.
DR   PDBsum; 5JN8; -.
DR   PDBsum; 5JN9; -.
DR   PDBsum; 5JNA; -.
DR   PDBsum; 5JNC; -.
DR   PDBsum; 5KU6; -.
DR   AlphaFoldDB; P22748; -.
DR   SMR; P22748; -.
DR   BioGRID; 107217; 9.
DR   IntAct; P22748; 6.
DR   STRING; 9606.ENSP00000300900; -.
DR   BindingDB; P22748; -.
DR   ChEMBL; CHEMBL3729; -.
DR   DrugBank; DB00819; Acetazolamide.
DR   DrugBank; DB00436; Bendroflumethiazide.
DR   DrugBank; DB00562; Benzthiazide.
DR   DrugBank; DB01194; Brinzolamide.
DR   DrugBank; DB00606; Cyclothiazide.
DR   DrugBank; DB01144; Diclofenamide.
DR   DrugBank; DB00869; Dorzolamide.
DR   DrugBank; DB08846; Ellagic acid.
DR   DrugBank; DB00311; Ethoxzolamide.
DR   DrugBank; DB00774; Hydroflumethiazide.
DR   DrugBank; DB00703; Methazolamide.
DR   DrugBank; DB00232; Methyclothiazide.
DR   DrugBank; DB09460; Sodium carbonate.
DR   DrugBank; DB00273; Topiramate.
DR   DrugBank; DB01021; Trichlormethiazide.
DR   DrugBank; DB00909; Zonisamide.
DR   DrugCentral; P22748; -.
DR   GuidetoPHARMACOLOGY; 2599; -.
DR   iPTMnet; P22748; -.
DR   PhosphoSitePlus; P22748; -.
DR   BioMuta; CA4; -.
DR   DMDM; 115465; -.
DR   EPD; P22748; -.
DR   jPOST; P22748; -.
DR   MassIVE; P22748; -.
DR   PaxDb; P22748; -.
DR   PeptideAtlas; P22748; -.
DR   PRIDE; P22748; -.
DR   ProteomicsDB; 54034; -. [P22748-1]
DR   Antibodypedia; 2592; 321 antibodies from 33 providers.
DR   DNASU; 762; -.
DR   Ensembl; ENST00000300900.9; ENSP00000300900.3; ENSG00000167434.10. [P22748-1]
DR   Ensembl; ENST00000586876.1; ENSP00000467465.1; ENSG00000167434.10. [P22748-2]
DR   GeneID; 762; -.
DR   KEGG; hsa:762; -.
DR   MANE-Select; ENST00000300900.9; ENSP00000300900.3; NM_000717.5; NP_000708.1.
DR   UCSC; uc002iym.5; human. [P22748-1]
DR   CTD; 762; -.
DR   DisGeNET; 762; -.
DR   GeneCards; CA4; -.
DR   GeneReviews; CA4; -.
DR   HGNC; HGNC:1375; CA4.
DR   HPA; ENSG00000167434; Tissue enhanced (intestine).
DR   MalaCards; CA4; -.
DR   MIM; 114760; gene.
DR   MIM; 600852; phenotype.
DR   neXtProt; NX_P22748; -.
DR   OpenTargets; ENSG00000167434; -.
DR   Orphanet; 791; Retinitis pigmentosa.
DR   PharmGKB; PA25991; -.
DR   VEuPathDB; HostDB:ENSG00000167434; -.
DR   eggNOG; KOG0382; Eukaryota.
DR   GeneTree; ENSGT00940000155690; -.
DR   HOGENOM; CLU_039326_2_2_1; -.
DR   InParanoid; P22748; -.
DR   OMA; SHWCYEI; -.
DR   OrthoDB; 1377476at2759; -.
DR   PhylomeDB; P22748; -.
DR   TreeFam; TF316425; -.
DR   BRENDA; 4.2.1.1; 2681.
DR   PathwayCommons; P22748; -.
DR   Reactome; R-HSA-1237044; Erythrocytes take up carbon dioxide and release oxygen.
DR   Reactome; R-HSA-1247673; Erythrocytes take up oxygen and release carbon dioxide.
DR   Reactome; R-HSA-1475029; Reversible hydration of carbon dioxide.
DR   SABIO-RK; P22748; -.
DR   SignaLink; P22748; -.
DR   BioGRID-ORCS; 762; 16 hits in 1070 CRISPR screens.
DR   ChiTaRS; CA4; human.
DR   EvolutionaryTrace; P22748; -.
DR   GeneWiki; Carbonic_anhydrase_4; -.
DR   GenomeRNAi; 762; -.
DR   Pharos; P22748; Tclin.
DR   PRO; PR:P22748; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; P22748; protein.
DR   Bgee; ENSG00000167434; Expressed in mucosa of transverse colon and 177 other tissues.
DR   ExpressionAtlas; P22748; baseline and differential.
DR   Genevisible; P22748; HS.
DR   GO; GO:0031362; C:anchored component of external side of plasma membrane; IDA:DFLAT.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:DFLAT.
DR   GO; GO:0031526; C:brush border membrane; IDA:DFLAT.
DR   GO; GO:0009986; C:cell surface; IDA:DFLAT.
DR   GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:DFLAT.
DR   GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:DFLAT.
DR   GO; GO:0016020; C:membrane; TAS:ProtInc.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:DFLAT.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005791; C:rough endoplasmic reticulum; IDA:DFLAT.
DR   GO; GO:0030667; C:secretory granule membrane; IDA:DFLAT.
DR   GO; GO:0005802; C:trans-Golgi network; IDA:DFLAT.
DR   GO; GO:0030658; C:transport vesicle membrane; IDA:DFLAT.
DR   GO; GO:0004089; F:carbonate dehydratase activity; IBA:GO_Central.
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; IMP:DFLAT.
DR   GO; GO:0006730; P:one-carbon metabolic process; IBA:GO_Central.
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; Alternative splicing; Cell membrane;
KW   Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein;
KW   GPI-anchor; Lipoprotein; Lyase; Membrane; Metal-binding;
KW   Reference proteome; Retinitis pigmentosa; Signal; Zinc.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000269|PubMed:2111324"
FT   CHAIN           19..284
FT                   /note="Carbonic anhydrase 4"
FT                   /id="PRO_0000004226"
FT   PROPEP          285..312
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000269|PubMed:7625839"
FT                   /id="PRO_0000004227"
FT   DOMAIN          21..285
FT                   /note="Alpha-carbonic anhydrase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01134"
FT   ACT_SITE        88
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   BINDING         115
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:8942978"
FT   BINDING         117
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:8942978"
FT   BINDING         140
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:8942978"
FT   BINDING         225..226
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00918"
FT   LIPID           284
FT                   /note="GPI-anchor amidated serine"
FT                   /evidence="ECO:0000269|PubMed:7625839"
FT   DISULFID        24..36
FT                   /evidence="ECO:0000269|PubMed:8809084"
FT   DISULFID        46..229
FT                   /evidence="ECO:0000269|PubMed:8809084"
FT   VAR_SEQ         90..106
FT                   /note="VMMLLENKASISGGGLP -> GWNPGERGLPATGGGTV (in isoform
FT                   2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_055973"
FT   VAR_SEQ         107..312
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_055974"
FT   VARIANT         12
FT                   /note="A -> T (in RP17; dbSNP:rs1245199379)"
FT                   /evidence="ECO:0000269|PubMed:20450258"
FT                   /id="VAR_071430"
FT   VARIANT         14
FT                   /note="R -> W (in RP17; abolishes interaction with SLC4A4;
FT                   impaired SLC4A4 cotransporter activity stimulation;
FT                   dbSNP:rs104894559)"
FT                   /evidence="ECO:0000269|PubMed:15563508"
FT                   /id="VAR_024749"
FT   VARIANT         69
FT                   /note="R -> H (in RP17; has no effect on carbonate
FT                   dehydratase activity; loss of interaction with SLC4A4;
FT                   dbSNP:rs121434552)"
FT                   /evidence="ECO:0000269|PubMed:17652713"
FT                   /id="VAR_071431"
FT   VARIANT         177
FT                   /note="N -> K (in dbSNP:rs185942554)"
FT                   /evidence="ECO:0000269|PubMed:17652713"
FT                   /id="VAR_071432"
FT   VARIANT         219
FT                   /note="R -> S (in RP17; abolishes carbonate dehydratase
FT                   activity; impaired SLC4A4 cotransporter activity
FT                   stimulation; dbSNP:rs121434551)"
FT                   /evidence="ECO:0000269|PubMed:15563508"
FT                   /id="VAR_024750"
FT   VARIANT         237
FT                   /note="V -> L (in dbSNP:rs2229178)"
FT                   /id="VAR_048680"
FT   MUTAGEN         284
FT                   /note="S->F: Loss of C-terminal domain removal and
FT                   abolishes carbonate dehydratase activity."
FT                   /evidence="ECO:0000269|PubMed:7625839"
FT   CONFLICT        24
FT                   /note="C -> E (in Ref. 8; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   HELIX           26..29
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   HELIX           39..41
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   TURN            44..47
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   STRAND          48..50
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   HELIX           58..60
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   STRAND          61..63
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   STRAND          70..77
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   STRAND          82..85
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   STRAND          87..93
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   STRAND          99..102
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   STRAND          109..118
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   TURN            122..124
FT                   /evidence="ECO:0007829|PDB:5IPZ"
FT   STRAND          127..130
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   STRAND          136..145
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   HELIX           153..157
FT                   /evidence="ECO:0007829|PDB:5KU6"
FT   STRAND          162..175
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   HELIX           178..180
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   HELIX           181..186
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   HELIX           187..189
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   STRAND          196..198
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   HELIX           205..207
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   HELIX           211..214
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   STRAND          217..222
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   STRAND          233..240
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   STRAND          242..245
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   HELIX           246..255
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   STRAND          257..259
FT                   /evidence="ECO:0007829|PDB:3FW3"
FT   STRAND          264..266
FT                   /evidence="ECO:0007829|PDB:5KU6"
SQ   SEQUENCE   312 AA;  35032 MW;  EF5F182474ABE9B0 CRC64;
     MRMLLALLAL SAARPSASAE SHWCYEVQAE SSNYPCLVPV KWGGNCQKDR QSPINIVTTK
     AKVDKKLGRF FFSGYDKKQT WTVQNNGHSV MMLLENKASI SGGGLPAPYQ AKQLHLHWSD
     LPYKGSEHSL DGEHFAMEMH IVHEKEKGTS RNVKEAQDPE DEIAVLAFLV EAGTQVNEGF
     QPLVEALSNI PKPEMSTTMA ESSLLDLLPK EEKLRHYFRY LGSLTTPTCD EKVVWTVFRE
     PIQLHREQIL AFSQKLYYDK EQTVSMKDNV RPLQQLGQRT VIKSGAPGRP LPWALPALLG
     PMLACLLAGF LR
 
 
维奥蛋白资源库 - 中文蛋白资源 CopyRight © 2010-2024