ADA2_HUMAN
ID ADA2_HUMAN Reviewed; 511 AA.
AC Q9NZK5; A8K9H4; Q6ICF1; Q86UB6; Q8NCJ2; Q96K41;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Adenosine deaminase 2 {ECO:0000312|HGNC:HGNC:1839};
DE EC=3.5.4.4 {ECO:0000269|PubMed:15926889, ECO:0000269|PubMed:20453107};
DE AltName: Full=Cat eye syndrome critical region protein 1;
DE Flags: Precursor;
GN Name=ADA2 {ECO:0000312|HGNC:HGNC:1839}; Synonyms=ADGF, CECR1, IDGFL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ARG-335.
RX PubMed=10756095; DOI=10.1006/geno.1999.6099;
RA Riazi M.A., Brinkman-Mills P., Nguyen T., Pan H., Phan S., Ying F.,
RA Roe B.A., Tochigi J., Shimizu Y., Minoshima S., Shimizu N., Buchwald M.,
RA McDermid H.E.;
RT "The human homolog of insect-derived growth factor, CECR1, is a candidate
RT gene for features of cat eye syndrome.";
RL Genomics 64:277-285(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ARG-335.
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY,
RP IDENTIFICATION BY MASS SPECTROMETRY, HEPARIN-BINDING, AND SUBCELLULAR
RP LOCATION.
RX PubMed=15926889; DOI=10.1042/bj20050683;
RA Zavialov A.V., Engstroem A.;
RT "Human ADA2 belongs to a new family of growth factors with adenosine
RT deaminase activity.";
RL Biochem. J. 391:51-57(2005).
RN [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-174 AND ASN-378.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, HEPARIN-BINDING, AND
RP SUBUNIT.
RX PubMed=20453107; DOI=10.1189/jlb.1109764;
RA Zavialov A.V., Gracia E., Glaichenhaus N., Franco R., Zavialov A.V.,
RA Lauvau G.;
RT "Human adenosine deaminase 2 induces differentiation of monocytes into
RT macrophages and stimulates proliferation of T helper cells and
RT macrophages.";
RL J. Leukoc. Biol. 88:279-290(2010).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 29-511 IN COMPLEX WITH ZINC IONS
RP AND TRANSITION STATE ANALOG COFORMYCIN, FUNCTION, COFACTOR, SUBCELLULAR
RP LOCATION, SUBUNIT, DISULFIDE BOND, DOMAINS, GLYCOSAMINOCLYCAN BINDING,
RP MUTAGENESIS OF CYS-137 AND TRP-362, AND GLYCOSYLATION AT ASN-127; ASN-185
RP AND ASN-378.
RX PubMed=20147294; DOI=10.1074/jbc.m109.083527;
RA Zavialov A.V., Yu X., Spillmann D., Lauvau G., Zavialov A.V.;
RT "Structural basis for the growth factor activity of human adenosine
RT deaminase ADA2.";
RL J. Biol. Chem. 285:12367-12377(2010).
RN [12]
RP INVOLVEMENT IN VAIHS, AND VARIANTS VAIHS ARG-47; ASP-109; GLN-112; GLN-169
RP AND CYS-453.
RX PubMed=24552284; DOI=10.1056/nejmoa1307361;
RA Zhou Q., Yang D., Ombrello A.K., Zavialov A.V., Toro C., Zavialov A.V.,
RA Stone D.L., Chae J.J., Rosenzweig S.D., Bishop K., Barron K.S., Kuehn H.S.,
RA Hoffmann P., Negro A., Tsai W.L., Cowen E.W., Pei W., Milner J.D.,
RA Silvin C., Heller T., Chin D.T., Patronas N.J., Barber J.S., Lee C.C.,
RA Wood G.M., Ling A., Kelly S.J., Kleiner D.E., Mullikin J.C., Ganson N.J.,
RA Kong H.H., Hambleton S., Candotti F., Quezado M.M., Calvo K.R., Alao H.,
RA Barham B.K., Jones A., Meschia J.F., Worrall B.B., Kasner S.E., Rich S.S.,
RA Goldbach-Mansky R., Abinun M., Chalom E., Gotte A.C., Punaro M.,
RA Pascual V., Verbsky J.W., Torgerson T.R., Singer N.G., Gershon T.R.,
RA Ozen S., Karadag O., Fleisher T.A., Remmers E.F., Burgess S.M., Moir S.L.,
RA Gadina M., Sood R., Hershfield M.S., Boehm M., Kastner D.L.,
RA Aksentijevich I.;
RT "Early-onset stroke and vasculopathy associated with mutations in ADA2.";
RL N. Engl. J. Med. 370:911-920(2014).
RN [13]
RP VARIANTS VAIHS VAL-47; ARG-47; GLN-169; LEU-251 AND SER-264.
RX PubMed=24552285; DOI=10.1056/nejmoa1307362;
RA Navon Elkan P., Pierce S.B., Segel R., Walsh T., Barash J., Padeh S.,
RA Zlotogorski A., Berkun Y., Press J.J., Mukamel M., Voth I., Hashkes P.J.,
RA Harel L., Hoffer V., Ling E., Yalcinkaya F., Kasapcopur O., Lee M.K.,
RA Klevit R.E., Renbaum P., Weinberg-Shukron A., Sener E.F., Schormair B.,
RA Zeligson S., Marek-Yagel D., Strom T.M., Shohat M., Singer A., Rubinow A.,
RA Pras E., Winkelmann J., Tekin M., Anikster Y., King M.C., Levy-Lahad E.;
RT "Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy.";
RL N. Engl. J. Med. 370:921-931(2014).
RN [14]
RP INVOLVEMENT IN SNDNS, AND VARIANTS SNDNS ALA-119 AND SER-142.
RX PubMed=25075847; DOI=10.1056/nejmc1405506;
RA Bras J., Guerreiro R., Santo G.C.;
RT "Mutant ADA2 in vasculopathies.";
RL N. Engl. J. Med. 371:478-480(2014).
CC -!- FUNCTION: Adenosine deaminase that may contribute to the degradation of
CC extracellular adenosine, a signaling molecule that controls a variety
CC of cellular responses. Requires elevated adenosine levels for optimal
CC enzyme activity. Binds to cell surfaces via proteoglycans and may play
CC a role in the regulation of cell proliferation and differentiation,
CC independently of its enzyme activity. {ECO:0000269|PubMed:20147294,
CC ECO:0000269|PubMed:20453107}.
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:15926889, ECO:0000269|PubMed:20453107};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:20147294};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:20147294};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.25 mM for adenosine {ECO:0000269|PubMed:15926889};
CC pH dependence:
CC Optimum pH is 6.6. {ECO:0000269|PubMed:15926889};
CC -!- SUBUNIT: Homodimer. Interacts with adenosine receptors. Binds heparin.
CC {ECO:0000269|PubMed:20147294, ECO:0000269|PubMed:20453107}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15926889,
CC ECO:0000269|PubMed:20147294, ECO:0000269|PubMed:20453107}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NZK5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NZK5-2; Sequence=VSP_041509, VSP_041510;
CC -!- TISSUE SPECIFICITY: Detected in blood plasma (at protein level). Widely
CC expressed, with most abundant expression in human adult heart, lung,
CC lymphoblasts, and placenta as well as fetal lung, liver, and kidney. In
CC embryo, expressed in the outflow tract and atrium of the developing
CC heart, the VII/VIII cranial nerve ganglion, and the notochord.
CC {ECO:0000269|PubMed:15926889}.
CC -!- DOMAIN: The PRB domain is involved in receptor binding, and may be
CC responsible for the cytokine-like growth factor activity due to it's
CC sharing of several structural properties with chemokines.
CC {ECO:0000269|PubMed:20147294}.
CC -!- DOMAIN: High-affinity binding to heparin/glycosaminoclycan (GAG) is
CC mediated by a large, highly positively charged surface at the interface
CC of dimer's subunits involving approximately residues 30-45, 389-396,
CC and 422-428. {ECO:0000269|PubMed:20147294}.
CC -!- DISEASE: Vasculitis, autoinflammation, immunodeficiency, and
CC hematologic defects syndrome (VAIHS) [MIM:615688]: An autosomal
CC recessive, systemic necrotizing vasculitis that affects medium and
CC small arteries. The ensuing tissue ischemia can affect any organ,
CC including the skin, musculoskeletal system, kidneys, gastrointestinal
CC tract, and the cardiovascular and nervous systems. Organ involvement
CC and disease severity are highly variable. Clinical features include
CC recurrent ischemic stroke affecting the small vessels of the brain and
CC resulting in neurologic dysfunction, recurrent fever, myalgias,
CC livedoid rash, gastrointestinal pain and hepatosplenomegaly.
CC {ECO:0000269|PubMed:24552284, ECO:0000269|PubMed:24552285}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Sneddon syndrome (SNDNS) [MIM:182410]: An autosomal recessive,
CC systemic non-inflammatory thrombotic vasculopathy characterized by the
CC association of livedo racemosa, and in some cases livedo reticularis,
CC with cerebrovascular disease. Livedo racemosa is a persistent net-like
CC violaceous-cyanotic, mottled discoloration of the skin affecting the
CC legs, the arms, the buttocks and the trunk; livedo reticularis is
CC limited to the extremities and is visible only in the cold.
CC Cerebrovascular features include recurrent transient ischemic attacks,
CC infarcts, and rarely spinal strokes or intracranial or subarachnoid
CC hemorrhages. Headache and vertigo may precede the onset of livedo
CC racemosa and cerebrovascular manifestations by several years. Rare
CC neurologic symptoms include seizures, chorea, or myelopathies.
CC {ECO:0000269|PubMed:25075847}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Candidate gene for the Cat Eye Syndrome (CES), a
CC developmental disorder associated with the duplication of a 2 Mb region
CC of 22q11.2. Duplication usually takes in the form of a surpernumerary
CC bisatellited isodicentric chromosome, resulting in four copies of the
CC region (represents an inv dup(22)(q11)). CES is characterized
CC clinically by the combination of coloboma of the iris and anal atresia
CC with fistula, downslanting palpebral fissures, preauricular tags and/or
CC pits, frequent occurrence of heart and renal malformations, and normal
CC or near-normal mental development.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Adenosine and AMP deaminases family. ADGF subfamily. {ECO:0000305}.
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DR EMBL; AF190746; AAF65941.1; -; mRNA.
DR EMBL; CR456417; CAG30303.1; -; mRNA.
DR EMBL; AK027682; BAB55293.1; -; mRNA.
DR EMBL; AK292689; BAF85378.1; -; mRNA.
DR EMBL; AK074702; BAC11148.1; -; mRNA.
DR EMBL; AC005300; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471193; EAW57750.1; -; Genomic_DNA.
DR EMBL; BC051755; AAH51755.1; -; mRNA.
DR CCDS; CCDS13742.1; -. [Q9NZK5-1]
DR CCDS; CCDS13743.1; -. [Q9NZK5-2]
DR RefSeq; NP_001269154.1; NM_001282225.1. [Q9NZK5-1]
DR RefSeq; NP_001269155.1; NM_001282226.1. [Q9NZK5-1]
DR RefSeq; NP_001269156.1; NM_001282227.1.
DR RefSeq; NP_001269157.1; NM_001282228.1.
DR RefSeq; NP_001269158.1; NM_001282229.1.
DR RefSeq; NP_803124.1; NM_177405.2. [Q9NZK5-2]
DR RefSeq; XP_011544435.1; XM_011546133.1. [Q9NZK5-1]
DR PDB; 3LGD; X-ray; 2.00 A; A/B=29-511.
DR PDB; 3LGG; X-ray; 2.50 A; A/B=29-511.
DR PDBsum; 3LGD; -.
DR PDBsum; 3LGG; -.
DR AlphaFoldDB; Q9NZK5; -.
DR SMR; Q9NZK5; -.
DR BioGRID; 119736; 5.
DR STRING; 9606.ENSP00000382731; -.
DR GlyConnect; 1912; 8 N-Linked glycans (4 sites).
DR GlyGen; Q9NZK5; 4 sites, 8 N-linked glycans (4 sites).
DR iPTMnet; Q9NZK5; -.
DR PhosphoSitePlus; Q9NZK5; -.
DR BioMuta; ADA2; -.
DR DMDM; 122065151; -.
DR jPOST; Q9NZK5; -.
DR MassIVE; Q9NZK5; -.
DR MaxQB; Q9NZK5; -.
DR PaxDb; Q9NZK5; -.
DR PeptideAtlas; Q9NZK5; -.
DR PRIDE; Q9NZK5; -.
DR ProteomicsDB; 83424; -. [Q9NZK5-1]
DR ProteomicsDB; 83425; -. [Q9NZK5-2]
DR TopDownProteomics; Q9NZK5-1; -. [Q9NZK5-1]
DR Antibodypedia; 280; 121 antibodies from 20 providers.
DR DNASU; 51816; -.
DR Ensembl; ENST00000262607.3; ENSP00000262607.2; ENSG00000093072.18. [Q9NZK5-1]
DR Ensembl; ENST00000330232.8; ENSP00000332871.4; ENSG00000093072.18. [Q9NZK5-2]
DR Ensembl; ENST00000399837.8; ENSP00000382731.2; ENSG00000093072.18. [Q9NZK5-1]
DR Ensembl; ENST00000399839.5; ENSP00000382733.1; ENSG00000093072.18. [Q9NZK5-1]
DR GeneID; 51816; -.
DR KEGG; hsa:51816; -.
DR MANE-Select; ENST00000399837.8; ENSP00000382731.2; NM_001282225.2; NP_001269154.1.
DR UCSC; uc002zmj.3; human. [Q9NZK5-1]
DR CTD; 51816; -.
DR DisGeNET; 51816; -.
DR GeneCards; ADA2; -.
DR GeneReviews; ADA2; -.
DR HGNC; HGNC:1839; ADA2.
DR HPA; ENSG00000093072; Tissue enhanced (lymphoid).
DR MalaCards; ADA2; -.
DR MIM; 182410; phenotype.
DR MIM; 607575; gene.
DR MIM; 615688; phenotype.
DR neXtProt; NX_Q9NZK5; -.
DR OpenTargets; ENSG00000093072; -.
DR Orphanet; 124; Blackfan-Diamond anemia.
DR Orphanet; 820; Sneddon syndrome.
DR Orphanet; 404553; Vasculitis due to ADA2 deficiency.
DR PharmGKB; PA26382; -.
DR VEuPathDB; HostDB:ENSG00000093072; -.
DR eggNOG; KOG1097; Eukaryota.
DR GeneTree; ENSGT00950000183113; -.
DR HOGENOM; CLU_022829_0_0_1; -.
DR InParanoid; Q9NZK5; -.
DR OMA; IFPGMMF; -.
DR OrthoDB; 430357at2759; -.
DR PhylomeDB; Q9NZK5; -.
DR TreeFam; TF324524; -.
DR BRENDA; 3.5.4.4; 2681.
DR PathwayCommons; Q9NZK5; -.
DR Reactome; R-HSA-5683826; Surfactant metabolism.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 51816; 12 hits in 1068 CRISPR screens.
DR ChiTaRS; CECR1; human.
DR EvolutionaryTrace; Q9NZK5; -.
DR GeneWiki; CECR1; -.
DR GenomeRNAi; 51816; -.
DR Pharos; Q9NZK5; Tbio.
DR PRO; PR:Q9NZK5; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q9NZK5; protein.
DR Bgee; ENSG00000093072; Expressed in monocyte and 174 other tissues.
DR ExpressionAtlas; Q9NZK5; baseline and differential.
DR Genevisible; Q9NZK5; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0004000; F:adenosine deaminase activity; IDA:UniProtKB.
DR GO; GO:0031685; F:adenosine receptor binding; IDA:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; NAS:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0043394; F:proteoglycan binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0006154; P:adenosine catabolic process; IDA:UniProtKB.
DR GO; GO:0046103; P:inosine biosynthetic process; IBA:GO_Central.
DR InterPro; IPR001365; A_deaminase_dom.
DR InterPro; IPR013659; A_deaminase_N.
DR InterPro; IPR006331; ADGF.
DR InterPro; IPR006330; Ado/ade_deaminase.
DR InterPro; IPR032466; Metal_Hydrolase.
DR PANTHER; PTHR11409; PTHR11409; 1.
DR Pfam; PF00962; A_deaminase; 1.
DR Pfam; PF08451; A_deaminase_N; 1.
DR SUPFAM; SSF51556; SSF51556; 1.
DR TIGRFAMs; TIGR01431; adm_rel; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Disease variant; Disulfide bond;
KW Glycoprotein; Heparin-binding; Hydrolase; Metal-binding;
KW Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..511
FT /note="Adenosine deaminase 2"
FT /id="PRO_0000006725"
FT REGION 30..100
FT /note="Dimerization"
FT REGION 127..185
FT /note="PRB domain"
FT ACT_SITE 359
FT /note="Proton donor"
FT /evidence="ECO:0000305"
FT ACT_SITE 384
FT /note="Proton acceptor"
FT /evidence="ECO:0000305"
FT BINDING 112
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 114
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 115
FT /ligand="substrate"
FT BINDING 204..211
FT /ligand="substrate"
FT BINDING 293
FT /ligand="substrate"
FT BINDING 326
FT /ligand="substrate"
FT BINDING 356
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 441
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 442
FT /ligand="substrate"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20147294"
FT CARBOHYD 174
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20147294"
FT CARBOHYD 378
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:20147294"
FT DISULFID 137..159
FT /evidence="ECO:0000269|PubMed:20147294"
FT VAR_SEQ 1..241
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041509"
FT VAR_SEQ 242..251
FT /note="YMEIRARLLP -> MDSLEWNWAL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041510"
FT VARIANT 47
FT /note="G -> R (in VAIHS; there is a decreased expression of
FT the mutant protein compared to wild-type;
FT dbSNP:rs202134424)"
FT /evidence="ECO:0000269|PubMed:24552284,
FT ECO:0000269|PubMed:24552285"
FT /id="VAR_071137"
FT VARIANT 47
FT /note="G -> V (in VAIHS; dbSNP:rs200930463)"
FT /evidence="ECO:0000269|PubMed:24552285"
FT /id="VAR_071138"
FT VARIANT 109
FT /note="A -> D (in VAIHS; dbSNP:rs587777240)"
FT /evidence="ECO:0000269|PubMed:24552284"
FT /id="VAR_071139"
FT VARIANT 112
FT /note="H -> Q (in VAIHS; dbSNP:rs587777241)"
FT /evidence="ECO:0000269|PubMed:24552284"
FT /id="VAR_071140"
FT VARIANT 119
FT /note="V -> A (in SNDNS)"
FT /evidence="ECO:0000269|PubMed:25075847"
FT /id="VAR_072562"
FT VARIANT 142
FT /note="G -> S (in SNDNS)"
FT /evidence="ECO:0000269|PubMed:25075847"
FT /id="VAR_072563"
FT VARIANT 169
FT /note="R -> Q (in VAIHS; dbSNP:rs77563738)"
FT /evidence="ECO:0000269|PubMed:24552284,
FT ECO:0000269|PubMed:24552285"
FT /id="VAR_071141"
FT VARIANT 251
FT /note="P -> L (in VAIHS; dbSNP:rs148936893)"
FT /evidence="ECO:0000269|PubMed:24552285"
FT /id="VAR_071142"
FT VARIANT 264
FT /note="W -> S (in VAIHS; dbSNP:rs587777242)"
FT /evidence="ECO:0000269|PubMed:24552285"
FT /id="VAR_071143"
FT VARIANT 335
FT /note="H -> R (in dbSNP:rs2231495)"
FT /evidence="ECO:0000269|PubMed:10756095,
FT ECO:0000269|PubMed:14702039"
FT /id="VAR_029802"
FT VARIANT 453
FT /note="Y -> C (in VAIHS; dbSNP:rs376785840)"
FT /evidence="ECO:0000269|PubMed:24552284"
FT /id="VAR_071144"
FT MUTAGEN 137
FT /note="C->G: Abolishes secretion."
FT /evidence="ECO:0000269|PubMed:20147294"
FT MUTAGEN 362
FT /note="W->G: Reduces dimerization and enzyme activity."
FT /evidence="ECO:0000269|PubMed:20147294"
FT CONFLICT 359
FT /note="E -> G (in Ref. 3; BAC11148)"
FT /evidence="ECO:0000305"
FT CONFLICT 394
FT /note="V -> L (in Ref. 6; AAH51755)"
FT /evidence="ECO:0000305"
FT HELIX 30..44
FT /evidence="ECO:0007829|PDB:3LGD"
FT TURN 46..49
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 54..77
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 86..93
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 97..104
FT /evidence="ECO:0007829|PDB:3LGD"
FT STRAND 108..114
FT /evidence="ECO:0007829|PDB:3LGD"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 121..126
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:3LGD"
FT STRAND 134..138
FT /evidence="ECO:0007829|PDB:3LGD"
FT STRAND 144..148
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 165..170
FT /evidence="ECO:0007829|PDB:3LGD"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:3LGG"
FT HELIX 175..185
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 193..196
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 200..218
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 221..237
FT /evidence="ECO:0007829|PDB:3LGD"
FT STRAND 240..247
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 262..279
FT /evidence="ECO:0007829|PDB:3LGD"
FT STRAND 285..293
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 298..314
FT /evidence="ECO:0007829|PDB:3LGD"
FT TURN 316..318
FT /evidence="ECO:0007829|PDB:3LGD"
FT STRAND 319..326
FT /evidence="ECO:0007829|PDB:3LGD"
FT TURN 328..330
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 335..337
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 338..341
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 343..346
FT /evidence="ECO:0007829|PDB:3LGD"
FT TURN 366..369
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 370..376
FT /evidence="ECO:0007829|PDB:3LGD"
FT STRAND 380..384
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 388..390
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 392..400
FT /evidence="ECO:0007829|PDB:3LGD"
FT STRAND 405..407
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 409..414
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 421..423
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 426..431
FT /evidence="ECO:0007829|PDB:3LGD"
FT STRAND 436..438
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 443..446
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 452..460
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 469..481
FT /evidence="ECO:0007829|PDB:3LGD"
FT STRAND 483..485
FT /evidence="ECO:0007829|PDB:3LGD"
FT HELIX 487..509
FT /evidence="ECO:0007829|PDB:3LGD"
SQ SEQUENCE 511 AA; 58934 MW; A4AB0A83E8A0611E CRC64;
MLVDGPSERP ALCFLLLAVA MSFFGSALSI DETRAHLLLK EKMMRLGGRL VLNTKEELAN
ERLMTLKIAE MKEAMRTLIF PPSMHFFQAK HLIERSQVFN ILRMMPKGAA LHLHDIGIVT
MDWLVRNVTY RPHCHICFTP RGIMQFRFAH PTPRPSEKCS KWILLEDYRK RVQNVTEFDD
SLLRNFTLVT QHPEVIYTNQ NVVWSKFETI FFTISGLIHY APVFRDYVFR SMQEFYEDNV
LYMEIRARLL PVYELSGEHH DEEWSVKTYQ EVAQKFVETH PEFIGIKIIY SDHRSKDVAV
IAESIRMAMG LRIKFPTVVA GFDLVGHEDT GHSLHDYKEA LMIPAKDGVK LPYFFHAGET
DWQGTSIDRN ILDALMLNTT RIGHGFALSK HPAVRTYSWK KDIPIEVCPI SNQVLKLVSD
LRNHPVATLM ATGHPMVISS DDPAMFGAKG LSYDFYEVFM GIGGMKADLR TLKQLAMNSI
KYSTLLESEK NTFMEIWKKR WDKFIADVAT K
