ID ADA_HUMAN Reviewed; 363 AA. AC P00813; Q53F92; Q6LA59; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 247. DE RecName: Full=Adenosine deaminase; DE EC=3.5.4.4 {ECO:0000269|PubMed:16670267, ECO:0000269|PubMed:23193172, ECO:0000269|PubMed:26166670, ECO:0000269|PubMed:8452534, ECO:0000269|PubMed:9361033}; DE AltName: Full=Adenosine aminohydrolase; GN Name=ADA; Synonyms=ADA1; 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]. RX PubMed=6090454; DOI=10.1016/s0021-9258(20)71325-6; RA Daddona P.E., Shewach D.S., Kelley W.N., Argos P., Markham A.F., RA Orkin S.H.; RT "Human adenosine deaminase. cDNA and complete primary amino acid RT sequence."; RL J. Biol. Chem. 259:12101-12106(1984). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=6546794; DOI=10.1093/nar/12.5.2439; RA Wiginton D.A., Adrian G.S., Hutton J.J.; RT "Sequence of human adenosine deaminase cDNA including the coding region and RT a small intron."; RL Nucleic Acids Res. 12:2439-2446(1984). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3839456; DOI=10.1002/j.1460-2075.1985.tb03648.x; RA Valerio D., Duyvesteyn M.G.C., Dekker B.M.M., Weeda G., Berkvens T.M., RA van der Voorn L., van Ormondt H., van der Eb A.J.; RT "Adenosine deaminase: characterization and expression of a gene with a RT remarkable promoter."; RL EMBO J. 4:437-443(1985). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3028473; DOI=10.1021/bi00373a017; RA Wiginton D.A., Kaplan D.J., States J.C., Akeson A.L., Perme C.M., RA Bilyk I.J., Vaughn A.J., Lattier D.L., Hutton J.J.; RT "Complete sequence and structure of the gene for human adenosine RT deaminase."; RL Biochemistry 25:8234-8244(1986). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Thymus; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 2-11, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=B-cell lymphoma; RA Bienvenut W.V.; RL Submitted (AUG-2004) to UniProtKB. RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 141-363. RX PubMed=6688808; DOI=10.1016/s0021-9258(17)44027-0; RA Orkin S.H., Daddona P.E., Shewach D.S., Markham A.F., Bruns G.A., RA Goff S.C., Kelley W.N.; RT "Molecular cloning of human adenosine deaminase gene sequences."; RL J. Biol. Chem. 258:12753-12756(1983). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL RP PROPERTIES, AND SUBCELLULAR LOCATION. RX PubMed=8452534; DOI=10.1042/bj2900457; RA Lindley E.R., Pisoni R.L.; RT "Demonstration of adenosine deaminase activity in human fibroblast RT lysosomes."; RL Biochem. J. 290:457-462(1993). RN [11] RP INTERACTION WITH DPP4, AND SUBCELLULAR LOCATION. RX PubMed=8101391; DOI=10.1126/science.8101391; RA Kameoka J., Tanaka T., Nojima Y., Schlossman S.F., Morimoto C.; RT "Direct association of adenosine deaminase with a T cell activation RT antigen, CD26."; RL Science 261:466-469(1993). RN [12] RP INTERACTION WITH DPP4. RX PubMed=7907293; DOI=10.1002/eji.1830240311; RA De Meester I., Vanham G., Kestens L., Vanhoof G., Bosmans E., Gigase P., RA Scharpe S.; RT "Binding of adenosine deaminase to the lymphocyte surface via CD26."; RL Eur. J. Immunol. 24:566-570(1994). RN [13] RP INTERACTION WITH DPP4. RX PubMed=10951221; DOI=10.1046/j.1432-1327.2000.01634.x; RA Durinx C., Lambeir A.M., Bosmans E., Falmagne J.B., Berghmans R., RA Haemers A., Scharpe S., De Meester I.; RT "Molecular characterization of dipeptidyl peptidase activity in serum: RT soluble CD26/dipeptidyl peptidase IV is responsible for the release of X- RT Pro dipeptides."; RL Eur. J. Biochem. 267:5608-5613(2000). RN [14] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=11772392; DOI=10.1042/0264-6021:3610203; RA Gines S., Marino M., Mallol J., Canela E.I., Morimoto C., Callebaut C., RA Hovanessian A., Casado V., Lluis C., Franco R.; RT "Regulation of epithelial and lymphocyte cell adhesion by adenosine RT deaminase-CD26 interaction."; RL Biochem. J. 361:203-209(2002). RN [15] RP FUNCTION, AND INTERACTION WITH DPP4 AND PLG. RX PubMed=15016824; DOI=10.1074/jbc.m401023200; RA Gonzalez-Gronow M., Hershfield M.S., Arredondo-Vega F.X., Pizzo S.V.; RT "Cell surface adenosine deaminase binds and stimulates plasminogen RT activation on 1-LN human prostate cancer cells."; RL J. Biol. Chem. 279:20993-20998(2004). RN [16] RP INTERACTION WITH DPP4. RX PubMed=14691230; DOI=10.1110/ps.03352504; RA Aertgeerts K., Ye S., Shi L., Prasad S.G., Witmer D., Chi E., Sang B.C., RA Wijnands R.A., Webb D.R., Swanson R.V.; RT "N-linked glycosylation of dipeptidyl peptidase IV (CD26): effects on RT enzyme activity, homodimer formation, and adenosine deaminase binding."; RL Protein Sci. 13:145-154(2004). RN [17] RP FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION BY HYPOXIA. RX PubMed=16670267; DOI=10.1182/blood-2006-02-001016; RA Eltzschig H.K., Faigle M., Knapp S., Karhausen J., Ibla J., Rosenberger P., RA Odegard K.C., Laussen P.C., Thompson L.F., Colgan S.P.; RT "Endothelial catabolism of extracellular adenosine during hypoxia: the role RT of surface adenosine deaminase and CD26."; RL Blood 108:1602-1610(2006). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-54 AND LYS-232, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [21] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=20959412; DOI=10.1189/jlb.1009696; RA Martinez-Navio J.M., Casanova V., Pacheco R., Naval-Macabuhay I., RA Climent N., Garcia F., Gatell J.M., Mallol J., Gallart T., Lluis C., RA Franco R.; RT "Adenosine deaminase potentiates the generation of effector, memory, and RT regulatory CD4+ T cells."; RL J. Leukoc. Biol. 89:127-136(2011). RN [22] RP FUNCTION. RX PubMed=21919946; DOI=10.1111/j.1439-0272.2011.01231.x; RA Rostampour F., Biglari M., Vaisi-Raygani A., Salimi S., Tavilani H.; RT "Adenosine deaminase activity in fertile and infertile men."; RL Andrologia 44:586-589(2012). RN [23] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MUTAGENESIS OF LEU-58; ASP-60; PHE-61; LEU-62; LYS-64; PHE-65; ASP-66; RP MET-69; ILE-115; ASN-118; MET-155; HIS-157; GLY-184; ASP-185 AND LEU-194. RX PubMed=23193172; DOI=10.1096/fj.12-212621; RA Gracia E., Farre D., Cortes A., Ferrer-Costa C., Orozco M., Mallol J., RA Lluis C., Canela E.I., McCormick P.J., Franco R., Fanelli F., Casado V.; RT "The catalytic site structural gate of adenosine deaminase allosterically RT modulates ligand binding to adenosine receptors."; RL FASEB J. 27:1048-1061(2013). RN [24] RP X-RAY CRYSTALLOGRAPHY (1.52 ANGSTROMS) OF 5-363 IN COMPLEX WITH NICKEL IONS RP AND 2-DEAOXYADENOSINE, AND COFACTOR. RG Structural genomics consortium (SGC); RT "The crystal structure of human adenosine deaminase."; RL Submitted (AUG-2009) to the PDB data bank. RN [25] RP VARIANTS ADASCID TRP-76; PRO-107; GLN-149; CYS-211; THR-215 AND LEU-274. RX PubMed=2166947; DOI=10.1073/pnas.87.16.6171; RA Hirschhorn R., Tzall S., Ellenbogen A.; RT "Hot spot mutations in adenosine deaminase deficiency."; RL Proc. Natl. Acad. Sci. U.S.A. 87:6171-6175(1990). RN [26] RP VARIANT ADA*2 ASN-8. RX PubMed=8031011; DOI=10.1111/j.1469-1809.1994.tb00720.x; RA Hirschhorn R., Yang D.R., Israni A.; RT "An Asp8Asn substitution results in the adenosine deaminase (ADA) genetic RT polymorphism (ADA 2 allozyme): occurrence on different chromosomal RT backgrounds and apparent intragenic crossover."; RL Ann. Hum. Genet. 58:1-9(1994). RN [27] RP VARIANTS ADASCID. RX PubMed=6208479; DOI=10.1128/mcb.4.9.1712-1717.1984; RA Adrian G.S., Wiginton D.A., Hutton J.; RT "Structure of adenosine deaminase mRNAs from normal and adenosine RT deaminase-deficient human cell lines."; RL Mol. Cell. Biol. 4:1712-1717(1984). RN [28] RP VARIANT ADASCID GLN-101. RX PubMed=3839802; DOI=10.1172/jci112050; RA Bonthron D.T., Markham A.F., Ginsburg D., Orkin S.H.; RT "Identification of a point mutation in the adenosine deaminase gene RT responsible for immunodeficiency."; RL J. Clin. Invest. 76:894-897(1985). RN [29] RP VARIANTS ADASCID TRP-101; HIS-211 AND VAL-329. RX PubMed=3182793; DOI=10.1016/s0021-9258(18)37591-4; RA Akeson A.L., Wiginton D.A., Dusing M.R., States J.C., Hutton J.J.; RT "Mutant human adenosine deaminase alleles and their expression by RT transfection into fibroblasts."; RL J. Biol. Chem. 263:16291-16296(1988). RN [30] RP VARIANT ADASCID GLN-297. RX PubMed=2783588; DOI=10.1172/jci113909; RA Hirschhorn R., Tzall S., Ellenbogen A., Orkin S.H.; RT "Identification of a point mutation resulting in a heat-labile adenosine RT deaminase (ADA) in two unrelated children with partial ADA deficiency."; RL J. Clin. Invest. 83:497-501(1989). RN [31] RP VARIANTS ADASCID CYS-156 AND LEU-291. RX PubMed=1284479; DOI=10.1002/humu.1380010214; RA Hirschhorn R.; RT "Identification of two new missense mutations (R156C and S291L) in two ADA- RT SCID patients unusual for response to therapy with partial exchange RT transfusions."; RL Hum. Mutat. 1:166-168(1992). RN [32] RP VARIANTS ADASCID LEU-101; HIS-156; MET-177; ARG-216 AND LEU-291. RX PubMed=8227344; DOI=10.1172/jci116833; RA Santisteban I., Arredondo-Vega F.X., Kelly S., Mary A., Fischer A., RA Hummell D.S., Lawton A., Sorensen R.U., Stiehm E.R., Uribe L., Weinberg K., RA Hershfield M.S.; RT "Novel splicing, missense, and deletion mutations in seven adenosine RT deaminase-deficient patients with late/delayed onset of combined RT immunodeficiency disease. Contribution of genotype to phenotype."; RL J. Clin. Invest. 92:2291-2302(1993). RN [33] RP VARIANT ADASCID ARG-20. RX PubMed=8299233; DOI=10.1006/clin.1994.1026; RA Yang D.R., Huie M.L., Hirschhorn R.; RT "Homozygosity for a missense mutation (G20R) associated with neonatal onset RT adenosine deaminase-deficient severe combined immunodeficiency (ADA- RT SCID)."; RL Clin. Immunol. Immunopathol. 70:171-175(1994). RN [34] RP VARIANTS ARG-80 AND GLN-142. RX PubMed=8589684; DOI=10.1093/hmg/4.11.2081; RA Santisteban I., Arredondo-Vega F.X., Kelly S., Loubser M., Meydan N., RA Roifman C., Howell P.L., Bowen T., Weinberg K.I., Schroeder M.L., RA Hershfield M.S.; RT "Three new adenosine deaminase mutations that define a splicing enhancer RT and cause severe and partial phenotypes: implications for evolution of a RT CpG hotspot and expression of a transduced ADA cDNA."; RL Hum. Mol. Genet. 4:2081-2087(1995). RN [35] RP VARIANTS ADASCID ASP-15; ASP-83 AND ASP-179. RX PubMed=7599635; DOI=10.1002/humu.1380050309; RA Santisteban I., Arredondo-Vega F.X., Kelly S., Debre M., Fisher A., RA Perignon J.L., Hilman B., Eldahr J., Dreyfus D.H., Gelfand E.W., RA Howell P.L., Hershfield M.S.; RT "Four new adenosine deaminase mutations, altering a zinc-binding histidine, RT two conserved alanines, and a 5' splice site."; RL Hum. Mutat. 5:243-250(1995). RN [36] RP VARIANTS MET-152 AND ILE-233. RX PubMed=9225964; DOI=10.1007/s004390050460; RA Hirschhorn R., Borkowsky W., Jiang C.-K., Yang D.R., Jenkins T.; RT "Two newly identified mutations (Thr233Ile and Leu152Met) in partially RT adenosine deaminase-deficient (ADA-) individuals that result in differing RT biochemical and metabolic phenotypes."; RL Hum. Genet. 100:22-29(1997). RN [37] RP VARIANTS ADASCID CYS-97 AND VAL-106, CHARACTERIZATION OF VARIANTS ADASCID RP CYS-97; VAL-106; CYS-211 AND THR-215, CHARACTERIZATION OF VARIANT ILE-233, RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=9361033; DOI=10.1093/hmg/6.13.2271; RA Jiang C., Hong R., Horowitz S.D., Kong X., Hirschhorn R.; RT "An adenosine deaminase (ADA) allele contains two newly identified RT deleterious mutations (Y97C and L106V) that interact to abolish enzyme RT activity."; RL Hum. Mol. Genet. 6:2271-2278(1997). RN [38] RP VARIANTS ADASCID CYS-74; MET-129; GLU-140; TRP-149 AND PRO-199. RX PubMed=10200056; RX DOI=10.1002/(sici)1098-1004(1998)11:6<482::aid-humu15>3.0.co;2-e; RA Arrendondo-Vega F.X., Santisteban I., Notarangelo L.D., El Dahr J., RA Buckley R., Roifman C., Conley M.E., Hershfield M.S.; RT "Seven novel mutations in the adenosine deaminase (ADA) gene in patients RT with severe and delayed onset combined immunodeficiency: G74C, V129M, RT G140E, R149W, Q199P, 462delG, and E337del."; RL Hum. Mutat. 11:482-482(1998). RN [39] RP EFFECT OF VARIANT ADA*2 ASN-8 ON SLEEP. RX PubMed=16221767; DOI=10.1073/pnas.0505414102; RA Retey J.V., Adam M., Honegger E., Khatami R., Luhmann U.F.O., Jung H.H., RA Berger W., Landolt H.-P.; RT "A functional genetic variation of adenosine deaminase affects the duration RT and intensity of deep sleep in humans."; RL Proc. Natl. Acad. Sci. U.S.A. 102:15676-15681(2005). RN [40] RP VARIANT [LARGE SCALE ANALYSIS] GLN-142. RX PubMed=18772397; DOI=10.1126/science.1164368; RA Jones S., Zhang X., Parsons D.W., Lin J.C., Leary R.J., Angenendt P., RA Mankoo P., Carter H., Kamiyama H., Jimeno A., Hong S.M., Fu B., Lin M.T., RA Calhoun E.S., Kamiyama M., Walter K., Nikolskaya T., Nikolsky Y., RA Hartigan J., Smith D.R., Hidalgo M., Leach S.D., Klein A.P., Jaffee E.M., RA Goggins M., Maitra A., Iacobuzio-Donahue C., Eshleman J.R., Kern S.E., RA Hruban R.H., Karchin R., Papadopoulos N., Parmigiani G., Vogelstein B., RA Velculescu V.E., Kinzler K.W.; RT "Core signaling pathways in human pancreatic cancers revealed by global RT genomic analyses."; RL Science 321:1801-1806(2008). RN [41] RP VARIANT ADA*2 ASN-8, AND CHARACTERIZATION OF VARIANT ASN-8. RX PubMed=21734253; DOI=10.1093/cercor/bhr173; RA Bachmann V., Klaus F., Bodenmann S., Schaefer N., Brugger P., Huber S., RA Berger W., Landolt H.P.; RT "Functional ADA polymorphism increases sleep depth and reduces vigilant RT attention in humans."; RL Cereb. Cortex 22:962-970(2012). RN [42] RP VARIANT ADA*2 ASN-8, CHARACTERIZATION OF VARIANT ASN-8, FUNCTION, AND RP CATALYTIC ACTIVITY. RX PubMed=26166670; DOI=10.1016/j.urology.2015.06.034; RA Fattahi A., Khodadadi I., Amiri I., Latifi Z., Ghorbani M., Tavilani H.; RT "The Role of G22 A Adenosine Deaminase 1 Gene Polymorphism and the RT Activities of ADA Isoenzymes in Fertile and Infertile Men."; RL Urology 86:730-734(2015). CC -!- FUNCTION: Catalyzes the hydrolytic deamination of adenosine and 2- CC deoxyadenosine (PubMed:8452534, PubMed:16670267, PubMed:23193172, CC PubMed:9361033, PubMed:26166670). Plays an important role in purine CC metabolism and in adenosine homeostasis. Modulates signaling by CC extracellular adenosine, and so contributes indirectly to cellular CC signaling events. Acts as a positive regulator of T-cell coactivation, CC by binding DPP4 (PubMed:20959412). Its interaction with DPP4 regulates CC lymphocyte-epithelial cell adhesion (PubMed:11772392). Enhances CC dendritic cell immunogenicity by affecting dendritic cell costimulatory CC molecule expression and cytokines and chemokines secretion (By CC similarity). Enhances CD4+ T-cell differentiation and proliferation CC (PubMed:20959412). Acts as a positive modulator of adenosine receptors CC ADORA1 and ADORA2A, by enhancing their ligand affinity via CC conformational change (PubMed:23193172). Stimulates plasminogen CC activation (PubMed:15016824). Plays a role in male fertility CC (PubMed:21919946, PubMed:26166670). Plays a protective role in early CC postimplantation embryonic development (By similarity). CC {ECO:0000250|UniProtKB:P03958, ECO:0000250|UniProtKB:P56658, CC ECO:0000269|PubMed:11772392, ECO:0000269|PubMed:15016824, CC ECO:0000269|PubMed:16670267, ECO:0000269|PubMed:20959412, CC ECO:0000269|PubMed:21919946, ECO:0000269|PubMed:23193172, CC ECO:0000269|PubMed:26166670, ECO:0000269|PubMed:8452534, CC ECO:0000269|PubMed:9361033}. 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:16670267, ECO:0000269|PubMed:23193172, CC ECO:0000269|PubMed:26166670, ECO:0000269|PubMed:8452534, CC ECO:0000269|PubMed:9361033}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24409; CC Evidence={ECO:0000305|PubMed:9361033}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2'-deoxyadenosine + H(+) + H2O = 2'-deoxyinosine + NH4(+); CC Xref=Rhea:RHEA:28190, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17256, ChEBI:CHEBI:28938, ChEBI:CHEBI:28997; EC=3.5.4.4; CC Evidence={ECO:0000269|PubMed:9361033}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28191; CC Evidence={ECO:0000305|PubMed:9361033}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000305|Ref.24}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000305|Ref.24}; CC -!- ACTIVITY REGULATION: Inhibited by Cu(2+) and Hg(2+), coformycin, CC deoxycoformycin (dCF), 2-deoxyadenosine, 6-methylaminopurine riboside, CC 2-3-iso-propylidene-adenosine and erythro-9-(2-hydroxy-3-nonyl)adenine. CC {ECO:0000269|PubMed:16670267, ECO:0000269|PubMed:8452534}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=37 uM for adenosine (at 25 degrees Celsius and pH 5.5) CC {ECO:0000269|PubMed:8452534}; CC Vmax=41 umol/min/mg enzyme {ECO:0000269|PubMed:23193172}; CC -!- SUBUNIT: Interacts with DPP4 (via extracellular domain) CC (PubMed:10951221, PubMed:14691230, PubMed:7907293, PubMed:8101391, CC PubMed:15016824). Interacts with PLG (via Kringle 4 domain); the CC interaction stimulates PLG activation when in complex with DPP4 CC (PubMed:15016824). {ECO:0000269|PubMed:10951221, CC ECO:0000269|PubMed:14691230, ECO:0000269|PubMed:15016824, CC ECO:0000269|PubMed:7907293, ECO:0000269|PubMed:8101391}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11772392, CC ECO:0000269|PubMed:8101391}; Peripheral membrane protein; Extracellular CC side. Cell junction {ECO:0000269|PubMed:11772392}. Cytoplasmic vesicle CC lumen {ECO:0000250|UniProtKB:P03958}. Cytoplasm {ECO:0000250}. Lysosome CC {ECO:0000269|PubMed:8452534}. Note=Colocalized with DPP4 at the cell CC surface. {ECO:0000269|PubMed:11772392}. CC -!- TISSUE SPECIFICITY: Found in all tissues, occurs in large amounts in T- CC lymphocytes (PubMed:20959412). Expressed at the time of weaning in CC gastrointestinal tissues. {ECO:0000269|PubMed:20959412}. CC -!- INDUCTION: Up-regulated by hypoxia. {ECO:0000269|PubMed:16670267}. CC -!- POLYMORPHISM: There is a common allele, ADA*2, also known as the ADA 2 CC allozyme. It is associated with the reduced metabolism of adenosine to CC inosine. It specifically enhances deep sleep and slow-wave activity CC (SWA) during sleep. {ECO:0000269|PubMed:16221767}. CC -!- DISEASE: Severe combined immunodeficiency autosomal recessive T-cell- CC negative/B-cell-negative/NK-cell-negative due to adenosine deaminase CC deficiency (ADASCID) [MIM:102700]: An autosomal recessive disorder CC accounting for about 50% of non-X-linked SCIDs. SCID refers to a CC genetically and clinically heterogeneous group of rare congenital CC disorders characterized by impairment of both humoral and cell-mediated CC immunity, leukopenia, and low or absent antibody levels. Patients with CC SCID present in infancy with recurrent, persistent infections by CC opportunistic organisms. The common characteristic of all types of SCID CC is absence of T-cell-mediated cellular immunity due to a defect in T- CC cell development. ADA deficiency has been diagnosed in chronically ill CC teenagers and adults (late or adult onset). Population and newborn CC screening programs have also identified several healthy individuals CC with normal immunity who have partial ADA deficiency. CC {ECO:0000269|PubMed:10200056, ECO:0000269|PubMed:1284479, CC ECO:0000269|PubMed:2166947, ECO:0000269|PubMed:2783588, CC ECO:0000269|PubMed:3182793, ECO:0000269|PubMed:3839802, CC ECO:0000269|PubMed:6208479, ECO:0000269|PubMed:7599635, CC ECO:0000269|PubMed:8227344, ECO:0000269|PubMed:8299233, CC ECO:0000269|PubMed:9361033}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily. CC Adenosine and AMP deaminases family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA26130.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=ADAbase; Note=ADA mutation db; CC URL="http://structure.bmc.lu.se/idbase/ADAbase/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Adenosine deaminase entry; CC URL="https://en.wikipedia.org/wiki/Adenosine_deaminase"; CC -!- WEB RESOURCE: Name=Mendelian genes adenosine deaminase (ADA); CC Note=Leiden Open Variation Database (LOVD); CC URL="https://databases.lovd.nl/shared/genes/ADA"; 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; X02994; CAA26734.1; -; mRNA. DR EMBL; X02189; CAA26130.1; ALT_SEQ; Genomic_DNA. DR EMBL; X02190; CAA26130.1; JOINED; Genomic_DNA. DR EMBL; X02191; CAA26130.1; JOINED; Genomic_DNA. DR EMBL; X02192; CAA26130.1; JOINED; Genomic_DNA. DR EMBL; X02193; CAA26130.1; JOINED; Genomic_DNA. DR EMBL; X02194; CAA26130.1; JOINED; Genomic_DNA. DR EMBL; X02195; CAA26130.1; JOINED; Genomic_DNA. DR EMBL; X02196; CAA26130.1; JOINED; Genomic_DNA. DR EMBL; X02197; CAA26130.1; JOINED; Genomic_DNA. DR EMBL; X02198; CAA26130.1; JOINED; Genomic_DNA. DR EMBL; X02199; CAA26130.1; JOINED; Genomic_DNA. DR EMBL; M13792; AAA78791.1; -; Genomic_DNA. DR EMBL; AL139352; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; Z97053; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AK223397; BAD97117.1; -; mRNA. DR EMBL; BC007678; AAH07678.1; -; mRNA. DR EMBL; BC040226; AAH40226.1; -; mRNA. DR CCDS; CCDS13335.1; -. DR PIR; A91032; DUHUA. DR RefSeq; NP_000013.2; NM_000022.3. DR PDB; 3IAR; X-ray; 1.52 A; A=5-363. DR PDB; 7RTG; X-ray; 2.59 A; A/B=1-363. DR PDBsum; 3IAR; -. DR PDBsum; 7RTG; -. DR AlphaFoldDB; P00813; -. DR SMR; P00813; -. DR BioGRID; 106614; 58. DR CORUM; P00813; -. DR DIP; DIP-371N; -. DR IntAct; P00813; 7. DR STRING; 9606.ENSP00000361965; -. DR BindingDB; P00813; -. DR ChEMBL; CHEMBL1910; -. DR DrugBank; DB07711; (2S,3R)-3-(6-amino-9H-purin-9-yl)nonan-2-ol. DR DrugBank; DB07783; 1-((1R)-1-(HYDROXYMETHYL)-3-{6-[(3-PHENYLPROPANOYL)AMINO]-1H-INDOL-1-YL}PROPYL)-1H-IMIDAZOLE-4-CARBOXAMIDE. DR DrugBank; DB07786; 1-((1R,2S)-1-{2-[2-(4-CHLOROPHENYL)-1,3-BENZOXAZOL-7-YL]ETHYL}-2-HYDROXYPROPYL)-1H-IMIDAZOLE-4-CARBOXAMIDE. DR DrugBank; DB04218; 1-Deaza-Adenosine. DR DrugBank; DB07785; 1-{(1R,2S)-2-HYDROXY-1-[2-(2-NAPHTHYLOXY)ETHYL]PROPYL}-1H-IMIDAZONE-4-CARBOXAMIDE. DR DrugBank; DB03015; 6-hydroxy-1,6-dihydro purine nucleoside. DR DrugBank; DB02472; 7,8-dihydroinosine. DR DrugBank; DB00640; Adenosine. DR DrugBank; DB00975; Dipyridamole. DR DrugBank; DB14598; Edetate calcium disodium anhydrous. DR DrugBank; DB14600; Edetate disodium anhydrous. DR DrugBank; DB00974; Edetic acid. DR DrugBank; DB05057; Erdosteine. DR DrugBank; DB03220; FR-234938. DR DrugBank; DB02616; FR117016. DR DrugBank; DB02096; FR221647. DR DrugBank; DB03572; FR230513. DR DrugBank; DB02830; FR236913. DR DrugBank; DB03370; FR239087. DR DrugBank; DB04440; Nebularine. DR DrugBank; DB01280; Nelarabine. DR DrugBank; DB00552; Pentostatin. DR DrugBank; DB00277; Theophylline. DR DrugBank; DB00194; Vidarabine. DR DrugCentral; P00813; -. DR GuidetoPHARMACOLOGY; 1230; -. DR GlyGen; P00813; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P00813; -. DR MetOSite; P00813; -. DR PhosphoSitePlus; P00813; -. DR SwissPalm; P00813; -. DR BioMuta; ADA; -. DR DMDM; 113339; -. DR EPD; P00813; -. DR jPOST; P00813; -. DR MassIVE; P00813; -. DR MaxQB; P00813; -. DR PaxDb; 9606-ENSP00000361965; -. DR PeptideAtlas; P00813; -. DR ProteomicsDB; 51289; -. DR Pumba; P00813; -. DR TopDownProteomics; P00813; -. DR Antibodypedia; 700; 570 antibodies from 44 providers. DR CPTC; P00813; 1 antibody. DR DNASU; 100; -. DR Ensembl; ENST00000372874.9; ENSP00000361965.4; ENSG00000196839.14. DR GeneID; 100; -. DR KEGG; hsa:100; -. DR MANE-Select; ENST00000372874.9; ENSP00000361965.4; NM_000022.4; NP_000013.2. DR UCSC; uc002xmj.4; human. DR AGR; HGNC:186; -. DR CTD; 100; -. DR DisGeNET; 100; -. DR GeneCards; ADA; -. DR GeneReviews; ADA; -. DR HGNC; HGNC:186; ADA. DR HPA; ENSG00000196839; Group enriched (intestine, lymphoid tissue). DR MalaCards; ADA; -. DR MIM; 102700; phenotype. DR MIM; 608958; gene. DR neXtProt; NX_P00813; -. DR OpenTargets; ENSG00000196839; -. DR Orphanet; 39041; Omenn syndrome. DR Orphanet; 277; Severe combined immunodeficiency due to adenosine deaminase deficiency. DR PharmGKB; PA24503; -. DR VEuPathDB; HostDB:ENSG00000196839; -. DR eggNOG; KOG1097; Eukaryota. DR GeneTree; ENSGT00950000183113; -. DR InParanoid; P00813; -. DR OMA; NHFTIHA; -. DR OrthoDB; 36100at2759; -. DR PhylomeDB; P00813; -. DR TreeFam; TF314270; -. DR BioCyc; MetaCyc:HS02191-MONOMER; -. DR BRENDA; 3.5.4.4; 2681. DR PathwayCommons; P00813; -. DR Reactome; R-HSA-74217; Purine salvage. DR Reactome; R-HSA-9734735; Defective ADA disrupts (deoxy)adenosine deamination. DR Reactome; R-HSA-9755088; Ribavirin ADME. DR SABIO-RK; P00813; -. DR SignaLink; P00813; -. DR SIGNOR; P00813; -. DR BioGRID-ORCS; 100; 12 hits in 1161 CRISPR screens. DR ChiTaRS; ADA; human. DR EvolutionaryTrace; P00813; -. DR GeneWiki; Adenosine_deaminase; -. DR GenomeRNAi; 100; -. DR Pharos; P00813; Tclin. DR PRO; PR:P00813; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; P00813; Protein. DR Bgee; ENSG00000196839; Expressed in jejunal mucosa and 126 other cell types or tissues. DR ExpressionAtlas; P00813; baseline and differential. DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0060205; C:cytoplasmic vesicle lumen; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0009897; C:external side of plasma membrane; IDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0046936; F:2'-deoxyadenosine deaminase activity; IMP:UniProtKB. DR GO; GO:0004000; F:adenosine deaminase activity; IDA:UniProtKB. DR GO; GO:0019239; F:deaminase activity; EXP:Reactome. DR GO; GO:0008270; F:zinc ion binding; IMP:UniProtKB. DR GO; GO:0006154; P:adenosine catabolic process; IDA:UniProtKB. DR GO; GO:0046085; P:adenosine metabolic process; IDA:MGI. DR GO; GO:0000255; P:allantoin metabolic process; IEA:Ensembl. DR GO; GO:0046632; P:alpha-beta T cell differentiation; IEA:Ensembl. DR GO; GO:0043605; P:amide catabolic process; IEA:Ensembl. DR GO; GO:0006196; P:AMP catabolic process; IEA:Ensembl. DR GO; GO:0044209; P:AMP salvage; IEA:Ensembl. DR GO; GO:0042100; P:B cell proliferation; IEA:Ensembl. DR GO; GO:0019722; P:calcium-mediated signaling; IEA:Ensembl. DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW. DR GO; GO:0046059; P:dAMP catabolic process; IEA:Ensembl. DR GO; GO:0046061; P:dATP catabolic process; IEA:Ensembl. DR GO; GO:0006157; P:deoxyadenosine catabolic process; IEA:Ensembl. DR GO; GO:0048566; P:embryonic digestive tract development; IEA:Ensembl. DR GO; GO:0002314; P:germinal center B cell differentiation; IEA:Ensembl. DR GO; GO:0002467; P:germinal center formation; IEA:Ensembl. DR GO; GO:0032263; P:GMP salvage; IEA:Ensembl. DR GO; GO:0043103; P:hypoxanthine salvage; IBA:GO_Central. DR GO; GO:0046103; P:inosine biosynthetic process; IDA:MGI. DR GO; GO:0050900; P:leukocyte migration; IEA:Ensembl. DR GO; GO:0001889; P:liver development; IEA:Ensembl. DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl. DR GO; GO:0002901; P:mature B cell apoptotic process; IEA:Ensembl. DR GO; GO:0070254; P:mucus secretion; IEA:Ensembl. DR GO; GO:0060169; P:negative regulation of adenosine receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl. DR GO; GO:0002686; P:negative regulation of leukocyte migration; IEA:Ensembl. DR GO; GO:0002906; P:negative regulation of mature B cell apoptotic process; IEA:Ensembl. DR GO; GO:0070256; P:negative regulation of mucus secretion; IEA:Ensembl. DR GO; GO:0060407; P:negative regulation of penile erection; IEA:Ensembl. DR GO; GO:0070244; P:negative regulation of thymocyte apoptotic process; IEA:Ensembl. DR GO; GO:0043084; P:penile erection; IEA:Ensembl. DR GO; GO:0048541; P:Peyer's patch development; IEA:Ensembl. DR GO; GO:0001890; P:placenta development; IEA:Ensembl. DR GO; GO:0046638; P:positive regulation of alpha-beta T cell differentiation; IEA:Ensembl. DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl. DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IEA:Ensembl. DR GO; GO:0002636; P:positive regulation of germinal center formation; IEA:Ensembl. DR GO; GO:0010460; P:positive regulation of heart rate; IEA:Ensembl. DR GO; GO:0045987; P:positive regulation of smooth muscle contraction; IEA:Ensembl. DR GO; GO:0033089; P:positive regulation of T cell differentiation in thymus; IEA:Ensembl. DR GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; IEA:Ensembl. DR GO; GO:0032261; P:purine nucleotide salvage; IMP:UniProtKB. DR GO; GO:0043101; P:purine-containing compound salvage; TAS:Reactome. DR GO; GO:0033632; P:regulation of cell-cell adhesion mediated by integrin; IDA:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB. DR GO; GO:0010035; P:response to inorganic substance; IDA:MGI. DR GO; GO:0014074; P:response to purine-containing compound; IDA:MGI. DR GO; GO:0006939; P:smooth muscle contraction; IEA:Ensembl. DR GO; GO:0042110; P:T cell activation; IDA:UniProtKB. DR GO; GO:0033077; P:T cell differentiation in thymus; IEA:Ensembl. DR GO; GO:0050852; P:T cell receptor signaling pathway; IEA:Ensembl. DR GO; GO:0070242; P:thymocyte apoptotic process; IEA:Ensembl. DR GO; GO:0001829; P:trophectodermal cell differentiation; IEA:Ensembl. DR GO; GO:0046111; P:xanthine biosynthetic process; IEA:Ensembl. DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome. DR CDD; cd01320; ADA; 1. DR Gene3D; 3.20.20.140; Metal-dependent hydrolases; 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 NCBIfam; TIGR01430; aden_deam; 1. DR PANTHER; PTHR11409; ADENOSINE DEAMINASE; 1. DR PANTHER; PTHR11409:SF43; ADENOSINE DEAMINASE; 1. DR Pfam; PF00962; A_deaminase; 1. DR SUPFAM; SSF51556; Metallo-dependent hydrolases; 1. DR PROSITE; PS00485; A_DEAMINASE; 1. DR Genevisible; P00813; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cell adhesion; Cell junction; Cell membrane; KW Cytoplasm; Cytoplasmic vesicle; Direct protein sequencing; Disease variant; KW Hereditary hemolytic anemia; Hydrolase; Lysosome; Membrane; Metal-binding; KW Nucleotide metabolism; Reference proteome; SCID; Zinc. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.8" FT CHAIN 2..363 FT /note="Adenosine deaminase" FT /id="PRO_0000194352" FT REGION 126..143 FT /note="Required for binding to DDP4" FT /evidence="ECO:0000269|PubMed:15016824" FT ACT_SITE 217 FT /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:P03958" FT BINDING 15 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000305|Ref.24" FT BINDING 17 FT /ligand="substrate" FT /evidence="ECO:0000269|Ref.24, ECO:0007744|PDB:3IAR" FT BINDING 17 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000305|Ref.24" FT BINDING 19 FT /ligand="substrate" FT /evidence="ECO:0000269|Ref.24, ECO:0007744|PDB:3IAR" FT BINDING 184 FT /ligand="substrate" FT /evidence="ECO:0000269|Ref.24, ECO:0007744|PDB:3IAR" FT BINDING 214 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000305|Ref.24" FT BINDING 295 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000305|Ref.24" FT BINDING 296 FT /ligand="substrate" FT /evidence="ECO:0000269|Ref.24, ECO:0007744|PDB:3IAR" FT SITE 58 FT /note="Important for interaction with adenosine receptors FT and increasing their affinity for agonists" FT /evidence="ECO:0000269|PubMed:23193172" FT SITE 62 FT /note="Important for interaction with adenosine receptors FT and increasing their affinity for agonists" FT /evidence="ECO:0000269|PubMed:23193172" FT SITE 238 FT /note="Important for catalytic activity" FT /evidence="ECO:0000250|UniProtKB:P03958" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|Ref.8" FT MOD_RES 54 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 232 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VARIANT 8 FT /note="D -> N (allele ADA*2; found in about 10% of the FT population; affects duration and intensity of deep sleep; FT enhances negative effects of sleep loss during sleep FT deprivation; may have a protective role against male FT infertility; 20% to 30% decrease in activity; FT dbSNP:rs73598374)" FT /evidence="ECO:0000269|PubMed:16221767, FT ECO:0000269|PubMed:21734253, ECO:0000269|PubMed:26166670, FT ECO:0000269|PubMed:8031011" FT /id="VAR_002209" FT VARIANT 15 FT /note="H -> D (in ADASCID; loss of activity; FT dbSNP:rs121908725)" FT /evidence="ECO:0000269|PubMed:7599635" FT /id="VAR_002210" FT VARIANT 20 FT /note="G -> R (in ADASCID; loss of activity; FT dbSNP:rs121908724)" FT /evidence="ECO:0000269|PubMed:8299233" FT /id="VAR_002211" FT VARIANT 74 FT /note="G -> C (in ADASCID; delayed-onset; FT dbSNP:rs121908730)" FT /evidence="ECO:0000269|PubMed:10200056" FT /id="VAR_002212" FT VARIANT 76 FT /note="R -> W (in ADASCID; dbSNP:rs121908736)" FT /evidence="ECO:0000269|PubMed:2166947" FT /id="VAR_002213" FT VARIANT 80 FT /note="K -> R (in dbSNP:rs11555566)" FT /evidence="ECO:0000269|PubMed:8589684" FT /id="VAR_002214" FT VARIANT 83 FT /note="A -> D (in ADASCID; loss of activity; FT dbSNP:rs121908726)" FT /evidence="ECO:0000269|PubMed:7599635" FT /id="VAR_002215" FT VARIANT 97 FT /note="Y -> C (in ADASCID; uncertain significance; loss of FT activity on its own; total loss of activity; when FT associated with V-106; dbSNP:rs267606634)" FT /evidence="ECO:0000269|PubMed:9361033" FT /id="VAR_076954" FT VARIANT 101 FT /note="R -> L (in ADASCID; dbSNP:rs121908714)" FT /evidence="ECO:0000269|PubMed:8227344" FT /id="VAR_002216" FT VARIANT 101 FT /note="R -> Q (in ADASCID; loss of activity; FT dbSNP:rs121908714)" FT /evidence="ECO:0000269|PubMed:3839802" FT /id="VAR_002218" FT VARIANT 101 FT /note="R -> W (in ADASCID; dbSNP:rs121908717)" FT /evidence="ECO:0000269|PubMed:3182793" FT /id="VAR_002217" FT VARIANT 106 FT /note="L -> V (in ADASCID; uncertain significance; 30% of FT activity; total loss of activity; when associated with FT C-97; dbSNP:rs267606635)" FT /evidence="ECO:0000269|PubMed:9361033" FT /id="VAR_076955" FT VARIANT 107 FT /note="L -> P (in ADASCID; dbSNP:rs121908739)" FT /evidence="ECO:0000269|PubMed:2166947" FT /id="VAR_002219" FT VARIANT 129 FT /note="V -> M (in ADASCID; delayed-onset; FT dbSNP:rs121908731)" FT /evidence="ECO:0000269|PubMed:10200056" FT /id="VAR_002220" FT VARIANT 140 FT /note="G -> E (in ADASCID; dbSNP:rs121908732)" FT /evidence="ECO:0000269|PubMed:10200056" FT /id="VAR_002221" FT VARIANT 142 FT /note="R -> Q (in a pancreatic ductal adenocarcinoma FT sample; somatic mutation; dbSNP:rs61732239)" FT /evidence="ECO:0000269|PubMed:18772397, FT ECO:0000269|PubMed:8589684" FT /id="VAR_002222" FT VARIANT 149 FT /note="R -> Q (in ADASCID; dbSNP:rs121908737)" FT /evidence="ECO:0000269|PubMed:2166947" FT /id="VAR_002223" FT VARIANT 149 FT /note="R -> W (in ADASCID; dbSNP:rs121908733)" FT /evidence="ECO:0000269|PubMed:10200056" FT /id="VAR_002224" FT VARIANT 152 FT /note="L -> M (in an individual with partial ADA deficiency FT but no immunodeficiency; 1,5% of activity; FT dbSNP:rs121908728)" FT /evidence="ECO:0000269|PubMed:9225964" FT /id="VAR_002225" FT VARIANT 156 FT /note="R -> C (in ADASCID; dbSNP:rs121908735)" FT /evidence="ECO:0000269|PubMed:1284479" FT /id="VAR_002226" FT VARIANT 156 FT /note="R -> H (in ADASCID; loss of activity; FT dbSNP:rs121908722)" FT /evidence="ECO:0000269|PubMed:8227344" FT /id="VAR_002227" FT VARIANT 177 FT /note="V -> M (in ADASCID; loss of activity; FT dbSNP:rs121908719)" FT /evidence="ECO:0000269|PubMed:8227344" FT /id="VAR_002228" FT VARIANT 179 FT /note="A -> D (in ADASCID; loss of activity; FT dbSNP:rs121908727)" FT /evidence="ECO:0000269|PubMed:7599635" FT /id="VAR_002229" FT VARIANT 199 FT /note="Q -> P (in ADASCID; delayed-onset; FT dbSNP:rs121908734)" FT /evidence="ECO:0000269|PubMed:10200056" FT /id="VAR_002230" FT VARIANT 211 FT /note="R -> C (in ADASCID; late onset; 4% of activity; FT dbSNP:rs121908740)" FT /evidence="ECO:0000269|PubMed:2166947, FT ECO:0000269|PubMed:9361033" FT /id="VAR_002231" FT VARIANT 211 FT /note="R -> H (in ADASCID; dbSNP:rs121908716)" FT /evidence="ECO:0000269|PubMed:3182793" FT /id="VAR_002232" FT VARIANT 215 FT /note="A -> T (in ADASCID; 8% of activity; FT dbSNP:rs114025668)" FT /evidence="ECO:0000269|PubMed:2166947, FT ECO:0000269|PubMed:9361033" FT /id="VAR_002233" FT VARIANT 216 FT /note="G -> R (in ADASCID; severe; dbSNP:rs121908723)" FT /evidence="ECO:0000269|PubMed:8227344" FT /id="VAR_002234" FT VARIANT 233 FT /note="T -> I (in an individual with partial ADA deficiency FT but no immunodeficiency; 20% of activity; FT dbSNP:rs121908729)" FT /evidence="ECO:0000269|PubMed:9225964, FT ECO:0000269|PubMed:9361033" FT /id="VAR_002235" FT VARIANT 274 FT /note="P -> L (in ADASCID; dbSNP:rs121908738)" FT /evidence="ECO:0000269|PubMed:2166947" FT /id="VAR_002236" FT VARIANT 291 FT /note="S -> L (in ADASCID; dbSNP:rs121908721)" FT /evidence="ECO:0000269|PubMed:1284479, FT ECO:0000269|PubMed:8227344" FT /id="VAR_002237" FT VARIANT 297 FT /note="P -> Q (in ADASCID; dbSNP:rs121908718)" FT /evidence="ECO:0000269|PubMed:2783588" FT /id="VAR_002238" FT VARIANT 304 FT /note="L -> R (in ADASCID; loss of activity; FT dbSNP:rs199422327)" FT /id="VAR_002239" FT VARIANT 329 FT /note="A -> V (in ADASCID; dbSNP:rs121908715)" FT /evidence="ECO:0000269|PubMed:3182793" FT /id="VAR_002240" FT VARIANT 337 FT /note="Missing (in ADASCID)" FT /id="VAR_002241" FT MUTAGEN 58 FT /note="L->A: Decreases enzyme activity by reducing FT substrate affinity and maximum velocity; abolishes ADORA1 FT and ADORA2A modulator function." FT /evidence="ECO:0000269|PubMed:23193172" FT MUTAGEN 60 FT /note="D->A: Moderately reduces enzyme activity; reduces FT ADORA1 and ADORA2A modulation." FT /evidence="ECO:0000269|PubMed:23193172" FT MUTAGEN 61 FT /note="F->A: Decreases enzyme activity by reducing maximum FT velocity; reduces ADORA1 modulation." FT /evidence="ECO:0000269|PubMed:23193172" FT MUTAGEN 62 FT /note="L->A: Decreases enzyme activity by reducing FT substrate affinity and maximum velocity; abolishes ADORA1 FT and ADORA2A modulator function." FT /evidence="ECO:0000269|PubMed:23193172" FT MUTAGEN 64 FT /note="K->A: Moderately reduces enzyme activity; no change FT in ADORA1 and ADORA2A modulation." FT /evidence="ECO:0000269|PubMed:23193172" FT MUTAGEN 65 FT /note="F->A: Decreases enzyme activity by reducing FT substrate affinity and maximum velocity; reduces ADORA1 and FT ADORA2A modulation." FT /evidence="ECO:0000269|PubMed:23193172" FT MUTAGEN 66 FT /note="D->A: No change in enzyme activity; no change in FT ADORA1 and ADORA2A modulation." FT /evidence="ECO:0000269|PubMed:23193172" FT MUTAGEN 69 FT /note="M->A: Decreases enzyme activity by reducing maximum FT velocity; reduces ADORA2A modulation." FT /evidence="ECO:0000269|PubMed:23193172" FT MUTAGEN 115 FT /note="I->A: No change in enzyme activity; no change in FT ADORA1 and ADORA2A modulation." FT /evidence="ECO:0000269|PubMed:23193172" FT MUTAGEN 118 FT /note="N->A: Moderately reduces enzyme activity; no change FT in ADORA1 and ADORA2A modulation." FT /evidence="ECO:0000269|PubMed:23193172" FT MUTAGEN 155 FT /note="M->A: Decreases enzyme activity by reducing FT substrate affinity and maximum velocity." FT /evidence="ECO:0000269|PubMed:23193172" FT MUTAGEN 157 FT /note="H->A: Moderately reduces enzyme activity; no change FT in ADORA1 and ADORA2A modulation." FT /evidence="ECO:0000269|PubMed:23193172" FT MUTAGEN 184 FT /note="G->Q: Moderately reduces enzyme activity." FT /evidence="ECO:0000269|PubMed:23193172" FT MUTAGEN 185 FT /note="D->A: Moderately reduces enzyme activity." FT /evidence="ECO:0000269|PubMed:23193172" FT MUTAGEN 194 FT /note="L->A: No change in enzyme activity." FT /evidence="ECO:0000269|PubMed:23193172" FT CONFLICT 340 FT /note="K -> R (in Ref. 5; BAD97117)" FT /evidence="ECO:0000305" FT STRAND 11..13 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 18..20 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 24..34 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 43..50 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 58..62 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 63..67 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 69..72 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 76..91 FT /evidence="ECO:0007829|PDB:3IAR" FT TURN 92..94 FT /evidence="ECO:0007829|PDB:3IAR" FT STRAND 95..102 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 104..107 FT /evidence="ECO:0007829|PDB:3IAR" FT STRAND 109..111 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 116..118 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 126..144 FT /evidence="ECO:0007829|PDB:3IAR" FT STRAND 147..155 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 159..161 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 162..171 FT /evidence="ECO:0007829|PDB:3IAR" FT TURN 172..176 FT /evidence="ECO:0007829|PDB:3IAR" FT STRAND 177..184 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 191..193 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 195..207 FT /evidence="ECO:0007829|PDB:3IAR" FT STRAND 210..219 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 221..229 FT /evidence="ECO:0007829|PDB:3IAR" FT STRAND 234..238 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 240..244 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 246..254 FT /evidence="ECO:0007829|PDB:3IAR" FT STRAND 258..261 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 263..268 FT /evidence="ECO:0007829|PDB:3IAR" FT STRAND 270..272 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 279..285 FT /evidence="ECO:0007829|PDB:3IAR" FT STRAND 290..292 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 297..300 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 304..315 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 319..331 FT /evidence="ECO:0007829|PDB:3IAR" FT STRAND 333..335 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 337..351 FT /evidence="ECO:0007829|PDB:3IAR" FT HELIX 355..362 FT /evidence="ECO:0007829|PDB:3IAR" SQ SEQUENCE 363 AA; 40764 MW; 786BC5085CA9AFCB CRC64; MAQTPAFDKP KVELHVHLDG SIKPETILYY GRRRGIALPA NTAEGLLNVI GMDKPLTLPD FLAKFDYYMP AIAGCREAIK RIAYEFVEMK AKEGVVYVEV RYSPHLLANS KVEPIPWNQA EGDLTPDEVV ALVGQGLQEG ERDFGVKARS ILCCMRHQPN WSPKVVELCK KYQQQTVVAI DLAGDETIPG SSLLPGHVQA YQEAVKSGIH RTVHAGEVGS AEVVKEAVDI LKTERLGHGY HTLEDQALYN RLRQENMHFE ICPWSSYLTG AWKPDTEHAV IRLKNDQANY SLNTDDPLIF KSTLDTDYQM TKRDMGFTEE EFKRLNINAA KSSFLPEDEK RELLDLLYKA YGMPPSASAG QNL //