ADA_MOUSE
ID ADA_MOUSE Reviewed; 352 AA.
AC P03958;
DT 23-OCT-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Adenosine deaminase;
DE EC=3.5.4.4 {ECO:0000269|PubMed:8634299, ECO:0000269|PubMed:8672487, ECO:0000269|PubMed:8942668, ECO:0000269|PubMed:9272950, ECO:0000269|PubMed:9622483};
DE AltName: Full=Adenosine aminohydrolase;
GN Name=Ada;
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=2410423; DOI=10.1016/s0021-9258(17)39247-5;
RA Yeung C.-Y., Ingolia D.E., Roth D.B., Shoemaker C., Al-Ubaidi M.R.,
RA Yen J.-Y., Ching C., Bobonis C., Kaufman R.J., Kellems R.E.;
RT "Identification of functional murine adenosine deaminase cDNA clones by
RT complementation in Escherichia coli.";
RL J. Biol. Chem. 260:10299-10307(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2387582; DOI=10.1016/0888-7543(90)90189-2;
RA Al-Ubaidi M.R., Ramamurthy V., Maa M.C., Ingolia D.E., Chinsky J.M.,
RA Martin B.D., Kellems R.E.;
RT "Structural and functional analysis of the murine adenosine deaminase
RT gene.";
RL Genomics 7:476-485(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Xu P., Winston J.W., Lu J., Muzny D.M., Gibbs R.A., Kellems R.E.;
RT "The comparative sequence analysis of murine and human ADA genes.";
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ILS, and ISS;
RX PubMed=11471062; DOI=10.1007/s00335-001-1001-x;
RA Ehringer M.A., Thompson J., Conroy O., Xu Y., Yang F., Canniff J.,
RA Beeson M., Gordon L., Bennett B., Johnson T.E., Sikela J.M.;
RT "High-throughput sequence identification of gene coding variants within
RT alcohol-related QTLs.";
RL Mamm. Genome 12:657-663(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Tongue;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor;
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 [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=7670465; DOI=10.1038/ng0795-279;
RA Migchielsen A.A., Breuer M.L., van Roon M.A., te Riele H., Zurcher C.,
RA Ossendorp F., Toutain S., Hershfield M.S., Berns A., Valerio D.;
RT "Adenosine-deaminase-deficient mice die perinatally and exhibit liver-cell
RT degeneration, atelectasis and small intestinal cell death.";
RL Nat. Genet. 10:279-287(1995).
RN [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=7731963; DOI=10.1073/pnas.92.9.3673;
RA Wakamiya M., Blackburn M.R., Jurecic R., McArthur M.J., Geske R.S.,
RA Cartwright J. Jr., Mitani K., Vaishnav S., Belmont J.W., Kellems R.E.,
RA Finegold M.J., Montgomery C.A. Jr., Bradley A., Caskey C.T.;
RT "Disruption of the adenosine deaminase gene causes hepatocellular
RT impairment and perinatal lethality in mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:3673-3677(1995).
RN [9]
RP MUTAGENESIS OF GLU-217, CIRCULAR DICHROISM, BIOPHYSICOCHEMICAL PROPERTIES,
RP COFACTOR, ACTIVE SITE, AND PROPOSED ENZYME MECHANISM.
RX PubMed=8634299; DOI=10.1021/bi9514119;
RA Mohamedali K.A., Kurz L.C., Rudolph F.B.;
RT "Site-directed mutagenesis of active site glutamate-217 in mouse adenosine
RT deaminase.";
RL Biochemistry 35:1672-1680(1996).
RN [10]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=8783262; DOI=10.1016/0306-4522(96)00049-8;
RA Nagy J.I., Yamamoto T., Uemura H., Schrader W.P.;
RT "Adenosine deaminase in rodent median eminence: detection by antibody to
RT the mouse enzyme and co-localization with adenosine deaminase-complexing
RT protein (CD26).";
RL Neuroscience 73:459-471(1996).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=9272950; DOI=10.1242/dev.124.16.3089;
RA Blackburn M.R., Knudsen T.B., Kellems R.E.;
RT "Genetically engineered mice demonstrate that adenosine deaminase is
RT essential for early postimplantation development.";
RL Development 124:3089-3097(1997).
RN [12]
RP FUNCTION.
RX PubMed=10720488; DOI=10.1006/bbrc.2000.2357;
RA Xu P.A., Kellems R.E.;
RT "Function of murine adenosine deaminase in the gastrointestinal tract.";
RL Biochem. Biophys. Res. Commun. 269:749-757(2000).
RN [13]
RP DISRUPTION PHENOTYPE.
RX PubMed=10899903; DOI=10.1084/jem.192.2.159;
RA Blackburn M.R., Volmer J.B., Thrasher J.L., Zhong H., Crosby J.R.,
RA Lee J.J., Kellems R.E.;
RT "Metabolic consequences of adenosine deaminase deficiency in mice are
RT associated with defects in alveogenesis, pulmonary inflammation, and airway
RT obstruction.";
RL J. Exp. Med. 192:159-170(2000).
RN [14]
RP FUNCTION.
RX PubMed=11435465; DOI=10.1172/jci200110360;
RA Apasov S.G., Blackburn M.R., Kellems R.E., Smith P.T., Sitkovsky M.V.;
RT "Adenosine deaminase deficiency increases thymic apoptosis and causes
RT defective T cell receptor signaling.";
RL J. Clin. Invest. 108:131-141(2001).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, Lung, 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).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH ZINC IONS AND
RP TRANSITION STATE ANALOG 6-HYDROXYL-1,6-DIHYDROPURINE RIBONUCLEOTIDE,
RP COFACTOR, AND PROPOSED ENZYME MECHANISM.
RX PubMed=1925539; DOI=10.1126/science.1925539;
RA Wilson D.K., Rudolph F.B., Quiocho F.A.;
RT "Atomic structure of adenosine deaminase complexed with a transition-state
RT analog: understanding catalysis and immunodeficiency mutations.";
RL Science 252:1278-1284(1991).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 4-352 OF MUTANTS GLU-295 AND
RP ALA-296 IN COMPLEXES WITH ZINC IONS; 6-HYDROXYL-1,6-DIHYDROPURINE
RP RIBONUCLEOTIDE AND PURINE RIBOSIDE, CIRCULAR DICHROISM, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND MUTAGENESIS OF ASP-295 AND ASP-296.
RX PubMed=8672487; DOI=10.1021/bi952920d;
RA Sideraki V., Mohamedali K.A., Wilson D.K., Chang Z., Kellems R.E.,
RA Quiocho F.A., Rudolph F.B.;
RT "Probing the functional role of two conserved active site aspartates in
RT mouse adenosine deaminase.";
RL Biochemistry 35:7862-7872(1996).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF MUTANTS ALA-238 AND GLU-238 IN
RP COMPLEXES WITH ZINC IONS; 6-HYDROXYL-1,6-DIHYDROPURINE RIBONUCLEOTIDE AND
RP PURINE RIBOSIDE, AND MUTAGENESIS OF HIS-238.
RX PubMed=8942668; DOI=10.1021/bi961427e;
RA Sideraki V., Wilson D.K., Kurz L.C., Quiocho F.A., Rudolph F.B.;
RT "Site-directed mutagenesis of histidine 238 in mouse adenosine deaminase:
RT substitution of histidine 238 does not impede hydroxylate formation.";
RL Biochemistry 35:15019-15028(1996).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH ZINC IONS AND
RP INHIBITOR, COFACTOR, AND ACTIVE SITE.
RX PubMed=9622483; DOI=10.1021/bi980324o;
RA Wang Z., Quiocho F.A.;
RT "Complexes of adenosine deaminase with two potent inhibitors: X-ray
RT structures in four independent molecules at pH of maximum activity.";
RL Biochemistry 37:8314-8324(1998).
CC -!- FUNCTION: Catalyzes the hydrolytic deamination of adenosine and 2-
CC deoxyadenosine (PubMed:9272950). Plays an important role in purine
CC metabolism and in adenosine homeostasis (PubMed:9272950,
CC PubMed:10720488). Modulates signaling by extracellular adenosine, and
CC so contributes indirectly to cellular signaling events
CC (PubMed:11435465). Acts as a positive regulator of T-cell coactivation,
CC by binding DPP4. Its interaction with DPP4 regulates lymphocyte-
CC epithelial cell adhesion (By similarity). Enhances dendritic cell
CC immunogenicity by affecting dendritic cell costimulatory molecule
CC expression and cytokines and chemokines secretion (By similarity).
CC Enhances CD4+ T-cell differentiation and proliferation (By similarity).
CC Acts as a positive modulator of adenosine receptors ADORA1 and ADORA2A,
CC by enhancing their ligand affinity via conformational change (By
CC similarity). Stimulates plasminogen activation (By similarity). Plays a
CC role in male fertility (By similarity). Plays a protective role in
CC early postimplantation embryonic development (PubMed:9272950).
CC {ECO:0000250|UniProtKB:P00813, ECO:0000250|UniProtKB:P56658,
CC ECO:0000269|PubMed:10720488, ECO:0000269|PubMed:11435465,
CC ECO:0000269|PubMed:9272950}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine + H(+) + H2O = inosine + NH4(+);
CC Xref=Rhea:RHEA:24408, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16335, ChEBI:CHEBI:17596, ChEBI:CHEBI:28938; EC=3.5.4.4;
CC Evidence={ECO:0000269|PubMed:8634299, ECO:0000269|PubMed:8672487,
CC ECO:0000269|PubMed:8942668, ECO:0000269|PubMed:9272950,
CC ECO:0000269|PubMed:9622483};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:1925539, ECO:0000269|PubMed:8634299,
CC ECO:0000269|PubMed:9622483};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:1925539,
CC ECO:0000269|PubMed:8634299, ECO:0000269|PubMed:9622483};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=20 uM for adenosine {ECO:0000269|PubMed:8634299,
CC ECO:0000269|PubMed:8672487};
CC pH dependence:
CC Optimum pH is 6-8.5. {ECO:0000269|PubMed:8634299,
CC ECO:0000269|PubMed:8672487};
CC -!- SUBUNIT: Interacts with DPP4 (via extracellular domain). Interacts with
CC PLG (via Kringle 4 domain); the interaction stimulates PLG activation
CC when in complex with DPP4. {ECO:0000250|UniProtKB:P00813}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}; Extracellular side {ECO:0000250}. Cell junction
CC {ECO:0000250|UniProtKB:P00813}. Cytoplasmic vesicle lumen
CC {ECO:0000269|PubMed:8783262}. Cytoplasm {ECO:0000250}. Lysosome
CC {ECO:0000250|UniProtKB:P00813}. Note=Colocalized with DPP4 at the cell
CC surface. {ECO:0000250|UniProtKB:P00813}.
CC -!- TISSUE SPECIFICITY: Detected in brain neurons in the median emninence
CC (at protein level) (PubMed:8783262). Expressed in secondary deciduum
CC (at protein level) (PubMed:9272950). Found in all tissues, occurs in
CC large amounts in T-lymphocytes and, at the time of weaning, in
CC gastrointestinal tissues. {ECO:0000269|PubMed:8783262,
CC ECO:0000269|PubMed:9272950}.
CC -!- DEVELOPMENTAL STAGE: Expressed in trophoblast at 7.5 dpc and 9.5 dpc.
CC {ECO:0000269|PubMed:9272950}.
CC -!- DISRUPTION PHENOTYPE: Lethal at perinatal stages. Fetuses are viable up
CC to 18 dpc, but after this survival decreases rapidly. Fewer that 10% of
CC mutant pups are born live, and these die within hours after birth.
CC Mutant fetuses display much higher than normal levels of adenosine and
CC dATP, respiratory distress, hepatocellular degeneration and necrosis.
CC Prenatal lethality can be avoided using an ADA expression vector with a
CC trophoblast-specific promoter. Mutant mice die after about three weeks
CC due to immunodeficiency, disturbances in purine metabolism and severe
CC lung inflammation. {ECO:0000269|PubMed:10899903,
CC ECO:0000269|PubMed:7670465, ECO:0000269|PubMed:7731963}.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Adenosine and AMP deaminases family. {ECO:0000305}.
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DR EMBL; M10319; AAA37173.1; -; mRNA.
DR EMBL; M34251; AAB07142.1; -; Genomic_DNA.
DR EMBL; M34242; AAB07142.1; JOINED; Genomic_DNA.
DR EMBL; M34243; AAB07142.1; JOINED; Genomic_DNA.
DR EMBL; M34244; AAB07142.1; JOINED; Genomic_DNA.
DR EMBL; M34246; AAB07142.1; JOINED; Genomic_DNA.
DR EMBL; M34247; AAB07142.1; JOINED; Genomic_DNA.
DR EMBL; M34248; AAB07142.1; JOINED; Genomic_DNA.
DR EMBL; M34249; AAB07142.1; JOINED; Genomic_DNA.
DR EMBL; M34250; AAB07142.1; JOINED; Genomic_DNA.
DR EMBL; U73107; AAC08442.1; -; Genomic_DNA.
DR EMBL; AF483480; AAL90754.1; -; mRNA.
DR EMBL; AF483481; AAL90755.1; -; mRNA.
DR EMBL; AK075899; BAC36039.1; -; mRNA.
DR EMBL; BC002075; AAH02075.1; -; mRNA.
DR CCDS; CCDS17015.1; -.
DR PIR; A01010; DUMSA.
DR RefSeq; NP_001258981.1; NM_001272052.1.
DR RefSeq; NP_031424.1; NM_007398.4.
DR PDB; 1A4L; X-ray; 2.60 A; A/B/C/D=4-352.
DR PDB; 1A4M; X-ray; 1.95 A; A/B/C/D=4-352.
DR PDB; 1ADD; X-ray; 2.40 A; A=4-352.
DR PDB; 1FKW; X-ray; 2.40 A; A=4-352.
DR PDB; 1FKX; X-ray; 2.40 A; A=4-352.
DR PDB; 1UIO; X-ray; 2.40 A; A=4-352.
DR PDB; 1UIP; X-ray; 2.40 A; A=4-352.
DR PDB; 2ADA; X-ray; 2.40 A; A=1-352.
DR PDB; 3KM8; X-ray; 2.00 A; A/B=1-352.
DR PDB; 3MVI; X-ray; 1.60 A; A/B=4-352.
DR PDB; 3MVT; X-ray; 2.20 A; A/C=4-352.
DR PDB; 3T1G; X-ray; 2.35 A; A=4-352.
DR PDBsum; 1A4L; -.
DR PDBsum; 1A4M; -.
DR PDBsum; 1ADD; -.
DR PDBsum; 1FKW; -.
DR PDBsum; 1FKX; -.
DR PDBsum; 1UIO; -.
DR PDBsum; 1UIP; -.
DR PDBsum; 2ADA; -.
DR PDBsum; 3KM8; -.
DR PDBsum; 3MVI; -.
DR PDBsum; 3MVT; -.
DR PDBsum; 3T1G; -.
DR AlphaFoldDB; P03958; -.
DR SMR; P03958; -.
DR BioGRID; 197959; 9.
DR IntAct; P03958; 1.
DR STRING; 10090.ENSMUSP00000017841; -.
DR BindingDB; P03958; -.
DR ChEMBL; CHEMBL3206; -.
DR iPTMnet; P03958; -.
DR PhosphoSitePlus; P03958; -.
DR REPRODUCTION-2DPAGE; P03958; -.
DR EPD; P03958; -.
DR jPOST; P03958; -.
DR PaxDb; P03958; -.
DR PeptideAtlas; P03958; -.
DR PRIDE; P03958; -.
DR ProteomicsDB; 296065; -.
DR Antibodypedia; 700; 516 antibodies from 44 providers.
DR DNASU; 11486; -.
DR Ensembl; ENSMUST00000017841; ENSMUSP00000017841; ENSMUSG00000017697.
DR GeneID; 11486; -.
DR KEGG; mmu:11486; -.
DR UCSC; uc008ntl.2; mouse.
DR CTD; 100; -.
DR MGI; MGI:87916; Ada.
DR VEuPathDB; HostDB:ENSMUSG00000017697; -.
DR eggNOG; KOG1097; Eukaryota.
DR GeneTree; ENSGT00950000183113; -.
DR HOGENOM; CLU_039228_0_1_1; -.
DR InParanoid; P03958; -.
DR OMA; NHFTIHA; -.
DR OrthoDB; 1045809at2759; -.
DR PhylomeDB; P03958; -.
DR TreeFam; TF314270; -.
DR BRENDA; 3.5.4.4; 3474.
DR Reactome; R-MMU-74217; Purine salvage.
DR SABIO-RK; P03958; -.
DR BioGRID-ORCS; 11486; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Ada; mouse.
DR EvolutionaryTrace; P03958; -.
DR PRO; PR:P03958; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P03958; protein.
DR Bgee; ENSMUSG00000017697; Expressed in decidua and 194 other tissues.
DR ExpressionAtlas; P03958; baseline and differential.
DR Genevisible; P03958; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0060205; C:cytoplasmic vesicle lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0032839; C:dendrite cytoplasm; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0046936; F:2'-deoxyadenosine deaminase activity; IMP:MGI.
DR GO; GO:0004000; F:adenosine deaminase activity; IDA:UniProtKB.
DR GO; GO:0001883; F:purine nucleoside binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0006154; P:adenosine catabolic process; IDA:UniProtKB.
DR GO; GO:0046085; P:adenosine metabolic process; ISO:MGI.
DR GO; GO:0000255; P:allantoin metabolic process; IDA:MGI.
DR GO; GO:0046632; P:alpha-beta T cell differentiation; IMP:MGI.
DR GO; GO:0006196; P:AMP catabolic process; IDA:MGI.
DR GO; GO:0044209; P:AMP salvage; IDA:MGI.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0042100; P:B cell proliferation; IMP:MGI.
DR GO; GO:0110148; P:biomineralization; ISO:MGI.
DR GO; GO:0019722; P:calcium-mediated signaling; IMP:MGI.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0046059; P:dAMP catabolic process; IMP:MGI.
DR GO; GO:0046061; P:dATP catabolic process; IDA:MGI.
DR GO; GO:0006157; P:deoxyadenosine catabolic process; IDA:MGI.
DR GO; GO:0048566; P:embryonic digestive tract development; IMP:MGI.
DR GO; GO:0002314; P:germinal center B cell differentiation; IMP:MGI.
DR GO; GO:0002467; P:germinal center formation; IMP:MGI.
DR GO; GO:0032263; P:GMP salvage; IDA:MGI.
DR GO; GO:0001821; P:histamine secretion; ISO:MGI.
DR GO; GO:0046101; P:hypoxanthine biosynthetic process; IMP:MGI.
DR GO; GO:0043103; P:hypoxanthine salvage; IBA:GO_Central.
DR GO; GO:0032264; P:IMP salvage; TAS:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0046103; P:inosine biosynthetic process; IDA:UniProtKB.
DR GO; GO:0050900; P:leukocyte migration; IMP:MGI.
DR GO; GO:0001889; P:liver development; IMP:MGI.
DR GO; GO:0048286; P:lung alveolus development; IMP:MGI.
DR GO; GO:0030324; P:lung development; IMP:MGI.
DR GO; GO:0002901; P:mature B cell apoptotic process; IMP:MGI.
DR GO; GO:0070254; P:mucus secretion; IMP:MGI.
DR GO; GO:0060169; P:negative regulation of adenosine receptor signaling pathway; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:MGI.
DR GO; GO:0042323; P:negative regulation of circadian sleep/wake cycle, non-REM sleep; ISO:MGI.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:MGI.
DR GO; GO:0002686; P:negative regulation of leukocyte migration; IMP:MGI.
DR GO; GO:0002906; P:negative regulation of mature B cell apoptotic process; IMP:MGI.
DR GO; GO:0070256; P:negative regulation of mucus secretion; IMP:MGI.
DR GO; GO:0060407; P:negative regulation of penile erection; IMP:MGI.
DR GO; GO:0070244; P:negative regulation of thymocyte apoptotic process; IMP:MGI.
DR GO; GO:0043084; P:penile erection; IMP:MGI.
DR GO; GO:0048541; P:Peyer's patch development; IMP:MGI.
DR GO; GO:0001890; P:placenta development; IMP:MGI.
DR GO; GO:0046638; P:positive regulation of alpha-beta T cell differentiation; IMP:MGI.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IMP:MGI.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IMP:MGI.
DR GO; GO:0002636; P:positive regulation of germinal center formation; IMP:MGI.
DR GO; GO:0010460; P:positive regulation of heart rate; IMP:MGI.
DR GO; GO:0045987; P:positive regulation of smooth muscle contraction; IMP:MGI.
DR GO; GO:0050870; P:positive regulation of T cell activation; IMP:MGI.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; IMP:MGI.
DR GO; GO:0033089; P:positive regulation of T cell differentiation in thymus; IMP:MGI.
DR GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; IMP:MGI.
DR GO; GO:0032261; P:purine nucleotide salvage; ISO:MGI.
DR GO; GO:0033632; P:regulation of cell-cell adhesion mediated by integrin; ISO:MGI.
DR GO; GO:0045580; P:regulation of T cell differentiation; IMP:MGI.
DR GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR GO; GO:0010035; P:response to inorganic substance; IMP:MGI.
DR GO; GO:0043278; P:response to morphine; ISO:MGI.
DR GO; GO:0014074; P:response to purine-containing compound; ISO:MGI.
DR GO; GO:0033197; P:response to vitamin E; ISO:MGI.
DR GO; GO:0006939; P:smooth muscle contraction; IMP:MGI.
DR GO; GO:0042110; P:T cell activation; IMP:MGI.
DR GO; GO:0030217; P:T cell differentiation; IMP:MGI.
DR GO; GO:0033077; P:T cell differentiation in thymus; IMP:MGI.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:MGI.
DR GO; GO:0070242; P:thymocyte apoptotic process; IMP:MGI.
DR GO; GO:0001829; P:trophectodermal cell differentiation; IMP:MGI.
DR GO; GO:0046111; P:xanthine biosynthetic process; IMP:MGI.
DR CDD; cd01320; ADA; 1.
DR HAMAP; MF_00540; A_deaminase; 1.
DR InterPro; IPR006650; A/AMP_deam_AS.
DR InterPro; IPR028893; A_deaminase.
DR InterPro; IPR001365; A_deaminase_dom.
DR InterPro; IPR006330; Ado/ade_deaminase.
DR InterPro; IPR032466; Metal_Hydrolase.
DR PANTHER; PTHR11409; PTHR11409; 1.
DR Pfam; PF00962; A_deaminase; 1.
DR SUPFAM; SSF51556; SSF51556; 1.
DR TIGRFAMs; TIGR01430; aden_deam; 1.
DR PROSITE; PS00485; A_DEAMINASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell adhesion; Cell junction; Cell membrane;
KW Cytoplasm; Cytoplasmic vesicle; Hydrolase; Lysosome; Membrane;
KW Metal-binding; Nucleotide metabolism; Reference proteome; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P00813"
FT CHAIN 2..352
FT /note="Adenosine deaminase"
FT /id="PRO_0000194353"
FT ACT_SITE 217
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:8634299,
FT ECO:0000305|PubMed:9622483"
FT BINDING 15
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:1925539,
FT ECO:0000269|PubMed:8672487, ECO:0000269|PubMed:8942668,
FT ECO:0000269|PubMed:9622483, ECO:0007744|PDB:1A4L,
FT ECO:0007744|PDB:1A4M, ECO:0007744|PDB:1FKW,
FT ECO:0007744|PDB:1FKX, ECO:0007744|PDB:1UIO,
FT ECO:0007744|PDB:1UIP, ECO:0007744|PDB:2ADA"
FT BINDING 17
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:1925539,
FT ECO:0000269|PubMed:8672487, ECO:0000269|PubMed:8942668,
FT ECO:0000269|PubMed:9622483, ECO:0007744|PDB:1A4L,
FT ECO:0007744|PDB:1A4M, ECO:0007744|PDB:1FKW,
FT ECO:0007744|PDB:1FKX"
FT BINDING 17
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:1925539,
FT ECO:0000269|PubMed:8672487, ECO:0000269|PubMed:8942668,
FT ECO:0000269|PubMed:9622483, ECO:0007744|PDB:1A4L,
FT ECO:0007744|PDB:1A4M, ECO:0007744|PDB:1FKW,
FT ECO:0007744|PDB:1FKX, ECO:0007744|PDB:1UIO,
FT ECO:0007744|PDB:1UIP, ECO:0007744|PDB:2ADA"
FT BINDING 19
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:1925539,
FT ECO:0000269|PubMed:8672487, ECO:0000269|PubMed:8942668,
FT ECO:0000269|PubMed:9622483, ECO:0007744|PDB:1A4L,
FT ECO:0007744|PDB:1A4M, ECO:0007744|PDB:1FKW,
FT ECO:0007744|PDB:1FKX"
FT BINDING 184
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:1925539,
FT ECO:0000269|PubMed:8672487, ECO:0000269|PubMed:8942668,
FT ECO:0000269|PubMed:9622483, ECO:0007744|PDB:1A4M,
FT ECO:0007744|PDB:1FKX, ECO:0007744|PDB:1UIO,
FT ECO:0007744|PDB:1UIP, ECO:0007744|PDB:2ADA"
FT BINDING 214
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:1925539,
FT ECO:0000269|PubMed:8672487, ECO:0000269|PubMed:8942668,
FT ECO:0000269|PubMed:9622483, ECO:0007744|PDB:1A4L,
FT ECO:0007744|PDB:1A4M, ECO:0007744|PDB:1FKW,
FT ECO:0007744|PDB:1FKX, ECO:0007744|PDB:1UIO,
FT ECO:0007744|PDB:1UIP, ECO:0007744|PDB:2ADA"
FT BINDING 295
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:1925539,
FT ECO:0000269|PubMed:8672487, ECO:0000269|PubMed:8942668,
FT ECO:0000269|PubMed:9622483, ECO:0007744|PDB:1A4L,
FT ECO:0007744|PDB:1A4M, ECO:0007744|PDB:1FKW,
FT ECO:0007744|PDB:1FKX, ECO:0007744|PDB:1UIO,
FT ECO:0007744|PDB:1UIP, ECO:0007744|PDB:2ADA"
FT BINDING 296
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:8672487,
FT ECO:0000269|PubMed:8942668, ECO:0007744|PDB:1FKW,
FT ECO:0007744|PDB:1UIP"
FT SITE 58
FT /note="Important for interaction with adenosine receptors
FT and increasing their affinity for agonists"
FT /evidence="ECO:0000250|UniProtKB:P00813"
FT SITE 62
FT /note="Important for interaction with adenosine receptors
FT and increasing their affinity for agonists"
FT /evidence="ECO:0000250|UniProtKB:P00813"
FT SITE 238
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000269|PubMed:8942668,
FT ECO:0000269|PubMed:9622483"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P00813"
FT MOD_RES 54
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00813"
FT MOD_RES 232
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00813"
FT MUTAGEN 217
FT /note="E->D: Reduces catalytic activity 700-fold. No effect
FT on affinity for adenosine."
FT /evidence="ECO:0000269|PubMed:8634299"
FT MUTAGEN 217
FT /note="E->G: Reduces catalytic activity 3200-fold. No
FT effect on affinity for adenosine."
FT /evidence="ECO:0000269|PubMed:8634299"
FT MUTAGEN 217
FT /note="E->Q: Reduces catalytic activity 4800-fold, and
FT slightly increases affinity for substrate."
FT /evidence="ECO:0000269|PubMed:8634299"
FT MUTAGEN 217
FT /note="E->S: Loss of activity."
FT /evidence="ECO:0000269|PubMed:8634299"
FT MUTAGEN 238
FT /note="H->A: Increases affinity for adenosine 20-fold.
FT Reduces enzyme activity 500-fold."
FT /evidence="ECO:0000269|PubMed:8942668"
FT MUTAGEN 238
FT /note="H->E: Nearly abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:8942668"
FT MUTAGEN 238
FT /note="H->R: Reduces enzyme activity 1500-fold. No effect
FT on affinity for adenosine."
FT /evidence="ECO:0000269|PubMed:8942668"
FT MUTAGEN 295
FT /note="D->E: No effect on affinity for adenosine. Reduces
FT enzyme activity 2750-fold."
FT /evidence="ECO:0000269|PubMed:8672487"
FT MUTAGEN 296
FT /note="D->A: Reduces affinity for adenosine 70-fold.
FT Reduces enzyme activity 110000-fold."
FT /evidence="ECO:0000269|PubMed:8672487"
FT MUTAGEN 296
FT /note="D->N: Reduces affinity for adenosine 10-fold.
FT Reduces enzyme activity 100-fold."
FT /evidence="ECO:0000269|PubMed:8672487"
FT CONFLICT 141
FT /note="E -> R (in Ref. 2; AAB07142)"
FT /evidence="ECO:0000305"
FT STRAND 11..13
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 18..20
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 24..34
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 43..50
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 58..62
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 65..72
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 76..92
FT /evidence="ECO:0007829|PDB:3MVI"
FT STRAND 95..102
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:3MVI"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:3T1G"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 126..144
FT /evidence="ECO:0007829|PDB:3MVI"
FT STRAND 147..155
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 162..171
FT /evidence="ECO:0007829|PDB:3MVI"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:3MVI"
FT STRAND 177..184
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 195..207
FT /evidence="ECO:0007829|PDB:3MVI"
FT STRAND 210..219
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 221..229
FT /evidence="ECO:0007829|PDB:3MVI"
FT STRAND 234..238
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 240..244
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 246..254
FT /evidence="ECO:0007829|PDB:3MVI"
FT STRAND 258..261
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 263..268
FT /evidence="ECO:0007829|PDB:3MVI"
FT STRAND 270..272
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 279..285
FT /evidence="ECO:0007829|PDB:3MVI"
FT STRAND 289..292
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 297..300
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 304..315
FT /evidence="ECO:0007829|PDB:3MVI"
FT HELIX 319..332
FT /evidence="ECO:0007829|PDB:3MVI"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:1A4L"
FT HELIX 337..350
FT /evidence="ECO:0007829|PDB:3MVI"
SQ SEQUENCE 352 AA; 39992 MW; E53A8A1FABA148CD CRC64;
MAQTPAFNKP KVELHVHLDG AIKPETILYF GKKRGIALPA DTVEELRNII GMDKPLSLPG
FLAKFDYYMP VIAGCREAIK RIAYEFVEMK AKEGVVYVEV RYSPHLLANS KVDPMPWNQT
EGDVTPDDVV DLVNQGLQEG EQAFGIKVRS ILCCMRHQPS WSLEVLELCK KYNQKTVVAM
DLAGDETIEG SSLFPGHVEA YEGAVKNGIH RTVHAGEVGS PEVVREAVDI LKTERVGHGY
HTIEDEALYN RLLKENMHFE VCPWSSYLTG AWDPKTTHAV VRFKNDKANY SLNTDDPLIF
KSTLDTDYQM TKKDMGFTEE EFKRLNINAA KSSFLPEEEK KELLERLYRE YQ
