ID   ADA2_PONAB              Reviewed;         511 AA.
AC   Q5RC46;
DT   09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   03-AUG-2022, entry version 67.
DE   RecName: Full=Adenosine deaminase 2 {ECO:0000250|UniProtKB:Q9NZK5};
DE            EC=3.5.4.4 {ECO:0000250|UniProtKB:Q9NZK5};
DE   AltName: Full=Cat eye syndrome critical region protein 1;
DE   Flags: Precursor;
GN   Name=ADA2 {ECO:0000250|UniProtKB:Q9NZK5}; Synonyms=CECR1;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). {ECO:0000250}.
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   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- SUBUNIT: Homodimer. Interacts with adenosine receptors. Binds heparin
CC       (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
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:0000250}.
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:0000250}.
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; CR858435; CAH90664.1; -; mRNA.
DR   RefSeq; NP_001125360.1; NM_001131888.1.
DR   AlphaFoldDB; Q5RC46; -.
DR   SMR; Q5RC46; -.
DR   STRING; 9601.ENSPPYP00000022304; -.
DR   GeneID; 100172262; -.
DR   KEGG; pon:100172262; -.
DR   CTD; 51816; -.
DR   eggNOG; KOG1097; Eukaryota.
DR   InParanoid; Q5RC46; -.
DR   Proteomes; UP000001595; Unplaced.
DR   GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR   GO; GO:0004000; F:adenosine deaminase activity; ISS:UniProtKB.
DR   GO; GO:0031685; F:adenosine receptor binding; ISS:UniProtKB.
DR   GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR   GO; GO:0043394; F:proteoglycan binding; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR   GO; GO:0006154; P:adenosine catabolic process; ISS:UniProtKB.
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   2: Evidence at transcript level;
KW   Disulfide bond; 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_0000269717"
FT   REGION          30..100
FT                   /note="Dimerization"
FT                   /evidence="ECO:0000250"
FT   REGION          127..185
FT                   /note="PRB domain"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        359
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        384
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         112
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         114
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         115
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         204..211
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         293
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         326
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         356
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         441
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         442
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        127
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        174
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        185
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        378
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        137..159
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   511 AA;  58867 MW;  24EF664E283A4A1F CRC64;
     MLVDGPSEWP ALRFLLLAVA MSFFGSALSI DETRAHLLLK EKMMRLGGRL VLNTKEEQAN
     ERLMMLKIAE MKEAMRTLIF PPSMHFFQAK HLIERSQVFN ILRMMPKGAA LHLHDIGIVT
     MDWLVRNVTY RPHCHICFTP KGIMQFRFAH PTPRTSEKCS KWILLEDYRK RVQNVTEFDD
     SLLRNFTLVT QHPEVIYTNQ NVVWSKFETI FFTISGLIHY APVFRDYVFQ SMQEFYEDNV
     LYMEIRARLL PVYELSGEHH DEEWSVKTYQ EVAQKFVETH PEFIGIKIIY SDHRSKDVAV
     IAESIRTAMG LRTKFPTVVA GFDLVGREDT GHSLQDYKEA LMIPAKGGVK LPYFFHAGET
     DWQGTSIDRN ILDALMLNTT RIGHGFALSK HPAVRAYSWK KDIPIEVCPI SNQVLKLVSD
     LRNHPVATLM ATGHPMVISS DDPAIFGAKG LSYDFYEVFM GIGGMKADLR TLKQLAMNSI
     KYSALLEIEK NTFMEIWKKR WDKFIADVAT K