ID ADA_RAT Reviewed; 352 AA. AC Q920P6; DT 05-MAR-2002, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 24-JAN-2024, entry version 144. DE RecName: Full=Adenosine deaminase; DE EC=3.5.4.4 {ECO:0000269|PubMed:19900420}; DE AltName: Full=Adenosine aminohydrolase; GN Name=Ada; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Sprague-Dawley; TISSUE=Leptomeninges; RA Okada T., Mochizuki T., Huag Z., Sugita Y., Urade Y., Hayaishi O.; RT "Restricted expression of adenosine deaminase in rat leptomeninges and its RT role in the regulation of sleep."; RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Thymus; 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 [3] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=8783262; DOI=10.1016/0306-4522(96)00049-8; RA Nagy J.I., Yamamoto T., Uemura H., Schrader W.P.; RT "Adenosine deaminase in rodent median eminence: detection by antibody to RT the mouse enzyme and co-localization with adenosine deaminase-complexing RT protein (CD26)."; RL Neuroscience 73:459-471(1996). RN [4] RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND FUNCTION. RX PubMed=19900420; DOI=10.1016/j.brainres.2009.10.073; RA Kaminsky Y., Kosenko E.; RT "AMP deaminase and adenosine deaminase activities in liver and brain RT regions in acute ammonia intoxication and subacute toxic hepatitis."; RL Brain Res. 1311:175-181(2010). CC -!- FUNCTION: Catalyzes the hydrolytic deamination of adenosine and 2- CC deoxyadenosine (PubMed:19900420). 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. Its interaction with DPP4 regulates lymphocyte- CC epithelial cell adhesion. Enhances dendritic cell immunogenicity by CC affecting dendritic cell costimulatory molecule expression and CC cytokines and chemokines secretion. Enhances CD4+ T-cell CC differentiation and proliferation. Acts as a positive modulator of CC adenosine receptors ADORA1 and ADORA2A, by enhancing their ligand CC affinity via conformational change. Stimulates plasminogen activation. CC Plays a role in male fertility. Plays a protective role in early CC postimplantation embryonic development. {ECO:0000250|UniProtKB:P00813, CC ECO:0000250|UniProtKB:P03958, ECO:0000250|UniProtKB:P56658, CC ECO:0000269|PubMed:19900420}. 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:19900420}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24409; CC Evidence={ECO:0000305|PubMed:19900420}; 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:0000250|UniProtKB:P00813}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28191; CC Evidence={ECO:0000250|UniProtKB:P00813}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:P00813}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P00813}; CC -!- SUBUNIT: Interacts with DPP4 (via extracellular domain). Interacts with CC PLG (via Kringle 4 domain); the interaction stimulates PLG activation CC when in complex with DPP4. {ECO:0000250|UniProtKB:P00813}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P00813}; CC Peripheral membrane protein {ECO:0000250}; Extracellular side CC {ECO:0000250}. Cell junction {ECO:0000250|UniProtKB:P00813}. CC Cytoplasmic vesicle lumen {ECO:0000269|PubMed:19900420, CC ECO:0000269|PubMed:8783262}. Cytoplasm {ECO:0000250}. Lysosome CC {ECO:0000250|UniProtKB:P00813}. Note=Colocalized with DPP4 at the cell CC surface. {ECO:0000250|UniProtKB:P00813}. CC -!- TISSUE SPECIFICITY: Detected in brain and liver (at protein level). CC {ECO:0000269|PubMed:19900420, ECO:0000269|PubMed:8783262}. CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily. CC Adenosine and AMP deaminases family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB059655; BAB69691.1; -; mRNA. DR EMBL; BC088116; AAH88116.1; -; mRNA. DR RefSeq; NP_569083.1; NM_130399.2. DR AlphaFoldDB; Q920P6; -. DR SMR; Q920P6; -. DR IntAct; Q920P6; 1. DR STRING; 10116.ENSRNOP00000014151; -. DR ChEMBL; CHEMBL4630846; -. DR iPTMnet; Q920P6; -. DR PhosphoSitePlus; Q920P6; -. DR jPOST; Q920P6; -. DR PaxDb; 10116-ENSRNOP00000014151; -. DR DNASU; 24165; -. DR Ensembl; ENSRNOT00000014151.7; ENSRNOP00000014151.3; ENSRNOG00000010265.7. DR Ensembl; ENSRNOT00055006244; ENSRNOP00055004764; ENSRNOG00055003913. DR Ensembl; ENSRNOT00060002310; ENSRNOP00060001496; ENSRNOG00060001531. DR Ensembl; ENSRNOT00065044013; ENSRNOP00065036097; ENSRNOG00065025525. DR GeneID; 24165; -. DR KEGG; rno:24165; -. DR UCSC; RGD:2031; rat. DR AGR; RGD:2031; -. DR CTD; 100; -. DR RGD; 2031; Ada. DR eggNOG; KOG1097; Eukaryota. DR GeneTree; ENSGT00950000183113; -. DR HOGENOM; CLU_039228_0_1_1; -. DR InParanoid; Q920P6; -. DR OrthoDB; 36100at2759; -. DR PhylomeDB; Q920P6; -. DR TreeFam; TF314270; -. DR Reactome; R-RNO-74217; Purine salvage. DR Reactome; R-RNO-9755088; Ribavirin ADME. DR PRO; PR:Q920P6; -. DR Proteomes; UP000002494; Chromosome 3. DR Bgee; ENSRNOG00000010265; Expressed in esophagus and 19 other cell types or tissues. DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell. DR GO; GO:0009986; C:cell surface; ISO:RGD. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0060205; C:cytoplasmic vesicle lumen; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; ISO:RGD. DR GO; GO:0032839; C:dendrite cytoplasm; IDA:RGD. DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD. DR GO; GO:0005615; C:extracellular space; IDA:RGD. DR GO; GO:0005764; C:lysosome; ISO:RGD. DR GO; GO:0016020; C:membrane; ISO:RGD. DR GO; GO:0043025; C:neuronal cell body; IDA:RGD. DR GO; GO:0046936; F:2'-deoxyadenosine deaminase activity; ISO:RGD. DR GO; GO:0004000; F:adenosine deaminase activity; IDA:UniProtKB. DR GO; GO:0019239; F:deaminase activity; ISO:RGD. DR GO; GO:0001883; F:purine nucleoside binding; IDA:RGD. DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB. DR GO; GO:0006154; P:adenosine catabolic process; IMP:RGD. DR GO; GO:0046085; P:adenosine metabolic process; IDA:RGD. DR GO; GO:0000255; P:allantoin metabolic process; ISO:RGD. DR GO; GO:0046632; P:alpha-beta T cell differentiation; ISO:RGD. DR GO; GO:0043605; P:amide catabolic process; ISO:RGD. DR GO; GO:0006196; P:AMP catabolic process; ISO:RGD. DR GO; GO:0044209; P:AMP salvage; ISO:RGD. DR GO; GO:0006915; P:apoptotic process; ISO:RGD. DR GO; GO:0042100; P:B cell proliferation; ISO:RGD. DR GO; GO:0019722; P:calcium-mediated signaling; ISO:RGD. DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW. DR GO; GO:0046059; P:dAMP catabolic process; ISO:RGD. DR GO; GO:0046061; P:dATP catabolic process; ISO:RGD. DR GO; GO:0006157; P:deoxyadenosine catabolic process; ISO:RGD. DR GO; GO:0048566; P:embryonic digestive tract development; ISO:RGD. DR GO; GO:0002314; P:germinal center B cell differentiation; ISO:RGD. DR GO; GO:0002467; P:germinal center formation; ISO:RGD. DR GO; GO:0032263; P:GMP salvage; ISO:RGD. DR GO; GO:0001821; P:histamine secretion; IMP:RGD. DR GO; GO:0046101; P:hypoxanthine biosynthetic process; ISO:RGD. DR GO; GO:0043103; P:hypoxanthine salvage; IBA:GO_Central. DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD. DR GO; GO:0046103; P:inosine biosynthetic process; ISS:UniProtKB. DR GO; GO:0050900; P:leukocyte migration; ISO:RGD. DR GO; GO:0001889; P:liver development; ISO:RGD. DR GO; GO:0048286; P:lung alveolus development; ISO:RGD. DR GO; GO:0030324; P:lung development; ISO:RGD. DR GO; GO:0002901; P:mature B cell apoptotic process; ISO:RGD. DR GO; GO:0070254; P:mucus secretion; ISO:RGD. DR GO; GO:0060169; P:negative regulation of adenosine receptor signaling pathway; ISO:RGD. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD. DR GO; GO:0042323; P:negative regulation of circadian sleep/wake cycle, non-REM sleep; IMP:RGD. DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD. DR GO; GO:0002686; P:negative regulation of leukocyte migration; ISO:RGD. DR GO; GO:0002906; P:negative regulation of mature B cell apoptotic process; ISO:RGD. DR GO; GO:0070256; P:negative regulation of mucus secretion; ISO:RGD. DR GO; GO:0060407; P:negative regulation of penile erection; ISO:RGD. DR GO; GO:0070244; P:negative regulation of thymocyte apoptotic process; ISO:RGD. DR GO; GO:0043084; P:penile erection; ISO:RGD. DR GO; GO:0048541; P:Peyer's patch development; ISO:RGD. DR GO; GO:0001890; P:placenta development; ISO:RGD. DR GO; GO:0046638; P:positive regulation of alpha-beta T cell differentiation; ISO:RGD. DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISO:RGD. DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; ISO:RGD. DR GO; GO:0002636; P:positive regulation of germinal center formation; ISO:RGD. DR GO; GO:0010460; P:positive regulation of heart rate; ISO:RGD. DR GO; GO:0045987; P:positive regulation of smooth muscle contraction; ISO:RGD. DR GO; GO:0050870; P:positive regulation of T cell activation; ISO:RGD. DR GO; GO:0045582; P:positive regulation of T cell differentiation; ISO:RGD. DR GO; GO:0033089; P:positive regulation of T cell differentiation in thymus; ISO:RGD. DR GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; ISO:RGD. DR GO; GO:0032261; P:purine nucleotide salvage; ISO:RGD. DR GO; GO:0033632; P:regulation of cell-cell adhesion mediated by integrin; ISO:RGD. DR GO; GO:0045187; P:regulation of circadian sleep/wake cycle, sleep; IEP:RGD. DR GO; GO:0045580; P:regulation of T cell differentiation; ISO:RGD. DR GO; GO:0033081; P:regulation of T cell differentiation in thymus; IMP:RGD. DR GO; GO:0046686; P:response to cadmium ion; IEP:RGD. DR GO; GO:0042542; P:response to hydrogen peroxide; IEP:RGD. DR GO; GO:0001666; P:response to hypoxia; IMP:RGD. DR GO; GO:0010035; P:response to inorganic substance; ISO:RGD. DR GO; GO:1903576; P:response to L-arginine; IEP:RGD. DR GO; GO:0014074; P:response to purine-containing compound; ISO:RGD. DR GO; GO:0033197; P:response to vitamin E; IDA:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD. DR GO; GO:0006939; P:smooth muscle contraction; ISO:RGD. DR GO; GO:0042110; P:T cell activation; ISO:RGD. DR GO; GO:0030217; P:T cell differentiation; ISO:RGD. DR GO; GO:0033077; P:T cell differentiation in thymus; ISO:RGD. DR GO; GO:0050852; P:T cell receptor signaling pathway; ISO:RGD. DR GO; GO:0070242; P:thymocyte apoptotic process; ISO:RGD. DR GO; GO:0001829; P:trophectodermal cell differentiation; ISO:RGD. DR GO; GO:0046111; P:xanthine biosynthetic process; ISO:RGD. 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; Q920P6; RN. PE 1: Evidence at protein level; KW Acetylation; Cell adhesion; Cell junction; Cell membrane; Cytoplasm; KW Cytoplasmic vesicle; Hydrolase; Lysosome; Membrane; Metal-binding; KW Nucleotide metabolism; Reference proteome; Zinc. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P00813" FT CHAIN 2..352 FT /note="Adenosine deaminase" FT /id="PRO_0000194354" 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:0000250|UniProtKB:P56658" FT BINDING 17 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P56658" FT BINDING 17 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P56658" FT BINDING 19 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P56658" FT BINDING 184 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P56658" FT BINDING 214 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P56658" FT BINDING 295 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P56658" FT BINDING 296 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P56658" FT SITE 58 FT /note="Important for interaction with adenosine receptors FT and increasing their affinity for agonists" FT /evidence="ECO:0000250|UniProtKB:P00813" FT SITE 62 FT /note="Important for interaction with adenosine receptors FT and increasing their affinity for agonists" FT /evidence="ECO:0000250|UniProtKB:P00813" FT SITE 238 FT /note="Important for catalytic activity" FT /evidence="ECO:0000250|UniProtKB:P03958" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:P00813" FT MOD_RES 54 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P00813" FT MOD_RES 232 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P00813" SQ SEQUENCE 352 AA; 39899 MW; F689ADFD39682FC6 CRC64; MAQTPAFNKP KVELHVHLDG AIKPETILYY GKKRGIDLPA DTVEGLRNII GMDKPLSLPD FLAKFDYYMP AIAGCREAIK RIAYEFVEMK AKEGVVYVEV RYSPHLLANS KVDPIPWNQA EGDLTPDEVV DLVNQGLQEG EQAFGIKVRS ILCCMRHQPS WSPEVLELCK KYHQKTVVAM DLAGDETIEG SSLFPGHVEA YEGAVKDGIH RTVHAGEVGS AEVVREAVDI LKTERVGHGY HTIEDEALYN RLLKENMHFE VCPWSSYLTG AWNPKTTHAV VRFKDDQANY SLNSDDPLIF KSTVDTDYQM VKKDMGFTEE EFKRLNINAA KSSFLPEDEK KELLERLYKE YQ //