ADA_RAT
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 03-AUG-2022, entry version 136.
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, AND TISSUE SPECIFICITY.
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. Plays an important role in purine metabolism and in
CC adenosine homeostasis. Modulates signaling by extracellular adenosine,
CC and so contributes indirectly to cellular signaling events. Acts as a
CC positive regulator of T-cell coactivation, by binding DPP4. Its
CC interaction with DPP4 regulates lymphocyte-epithelial cell adhesion.
CC Enhances dendritic cell immunogenicity by affecting dendritic cell
CC costimulatory molecule expression and cytokines and chemokines
CC secretion. Enhances CD4+ T-cell differentiation and proliferation. Acts
CC as a positive modulator of adenosine receptors ADORA1 and ADORA2A, by
CC enhancing their ligand affinity via conformational change. Stimulates
CC plasminogen activation. Plays a role in male fertility. Plays a
CC protective role in early postimplantation embryonic development.
CC {ECO:0000250|UniProtKB:P00813, ECO:0000250|UniProtKB:P03958,
CC ECO:0000250|UniProtKB:P56658}.
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 -!- 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}; Peripheral membrane
CC protein {ECO:0000250}; Extracellular side {ECO:0000250}. Cell junction
CC {ECO:0000250|UniProtKB:P00813}. Cytoplasmic vesicle lumen
CC {ECO:0000269|PubMed:19900420, ECO:0000269|PubMed:8783262}. Cytoplasm
CC {ECO:0000250}. Lysosome {ECO:0000250|UniProtKB:P00813}.
CC Note=Colocalized with DPP4 at the cell surface.
CC {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}.
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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; Q920P6; -.
DR PRIDE; Q920P6; -.
DR DNASU; 24165; -.
DR Ensembl; ENSRNOT00000014151; ENSRNOP00000014151; ENSRNOG00000010265.
DR GeneID; 24165; -.
DR KEGG; rno:24165; -.
DR UCSC; RGD:2031; rat.
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 OMA; NHFTIHA; -.
DR OrthoDB; 1045809at2759; -.
DR PhylomeDB; Q920P6; -.
DR TreeFam; TF314270; -.
DR Reactome; R-RNO-74217; Purine salvage.
DR PRO; PR:Q920P6; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000010265; Expressed in esophagus and 19 other tissues.
DR Genevisible; Q920P6; RN.
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; IDA: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: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; ISS:UniProtKB.
DR GO; GO:0046085; P:adenosine metabolic process; IDA:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0000255; P:allantoin metabolic 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:0110148; P:biomineralization; 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: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: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: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: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: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:0043278; P:response to morphine; IMP: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:0042110; P:T cell activation; 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 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 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
