ADA_HUMAN
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 03-AUG-2022, entry version 238.
DE RecName: Full=Adenosine deaminase;
DE EC=3.5.4.4 {ECO:0000269|PubMed:16670267, ECO:0000269|PubMed:23193172, ECO:0000269|PubMed:8452534};
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, AND CHARACTERIZATION OF VARIANT
RP ILE-233.
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;
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, AND FUNCTION.
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). Plays an important
CC role in purine metabolism and in adenosine homeostasis. Modulates
CC signaling by extracellular adenosine, and so contributes indirectly to
CC cellular signaling events. Acts as a positive regulator of T-cell
CC coactivation, by binding DPP4 (PubMed:20959412). Its interaction with
CC DPP4 regulates lymphocyte-epithelial cell adhesion (PubMed:11772392).
CC Enhances dendritic cell immunogenicity by affecting dendritic cell
CC costimulatory molecule expression and cytokines and chemokines
CC secretion (By similarity). Enhances CD4+ T-cell differentiation and
CC proliferation (PubMed:20959412). Acts as a positive modulator of
CC adenosine receptors ADORA1 and ADORA2A, by enhancing their ligand
CC affinity via conformational change (PubMed:23193172). Stimulates
CC plasminogen activation (PubMed:15016824). Plays a role in male
CC fertility (PubMed:21919946, PubMed:26166670). Plays a protective role
CC in early 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 -!- 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:8452534};
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 -!- 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 ---------------------------------------------------------------------------
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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; 57.
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; P00813; -.
DR PeptideAtlas; P00813; -.
DR PRIDE; P00813; -.
DR ProteomicsDB; 51289; -.
DR TopDownProteomics; P00813; -.
DR Antibodypedia; 700; 516 antibodies from 44 providers.
DR CPTC; P00813; 1 antibody.
DR DNASU; 100; -.
DR Ensembl; ENST00000372874.9; ENSP00000361965.4; ENSG00000196839.13.
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 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; 1045809at2759; -.
DR PhylomeDB; P00813; -.
DR TreeFam; TF314270; -.
DR BioCyc; MetaCyc:HS02191-MON; -.
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 SABIO-RK; P00813; -.
DR SignaLink; P00813; -.
DR SIGNOR; P00813; -.
DR BioGRID-ORCS; 100; 12 hits in 1075 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 125 other tissues.
DR ExpressionAtlas; P00813; baseline and differential.
DR Genevisible; P00813; HS.
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; IEA:Ensembl.
DR GO; GO:0004000; F:adenosine deaminase activity; IDA:UniProtKB.
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: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:0110148; P:biomineralization; IDA:MGI.
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 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; 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; unknown pathological
FT significance; loss of activity on its own; total loss of
FT activity; when 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; unknown pathological
FT significance; 30% of activity; total loss of activity; when
FT associated with 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
