ID   ADA2_PIG                Reviewed;         510 AA.
AC   P58780; Q8WND6;
DT   16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2002, sequence version 1.
DT   03-AUG-2022, entry version 88.
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   Sus scrofa (Pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX   NCBI_TaxID=9823;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=11738815; DOI=10.1016/s0378-1119(01)00762-4;
RA   Maier S.A., Podemski L., Graham S.W., McDermid H.E., Locke J.;
RT   "Characterization of the adenosine deaminase-related growth factor (ADGF)
RT   gene family in Drosophila.";
RL   Gene 280:27-36(2001).
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 25-40, 386-393,
CC       and 419-425. {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; AF384216; AAL40921.1; -; mRNA.
DR   RefSeq; NP_999181.1; NM_214016.2.
DR   AlphaFoldDB; P58780; -.
DR   SMR; P58780; -.
DR   STRING; 9823.ENSSSCP00000027144; -.
DR   PaxDb; P58780; -.
DR   PRIDE; P58780; -.
DR   GeneID; 397079; -.
DR   KEGG; ssc:397079; -.
DR   CTD; 51816; -.
DR   eggNOG; KOG1097; Eukaryota.
DR   InParanoid; P58780; -.
DR   OrthoDB; 430357at2759; -.
DR   BRENDA; 3.5.4.4; 6170.
DR   Proteomes; UP000008227; Unplaced.
DR   Proteomes; UP000314985; 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   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   2: Evidence at transcript level;
KW   Disulfide bond; Glycoprotein; Heparin-binding; Hydrolase; Metal-binding;
KW   Reference proteome; Secreted; Signal; Zinc.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   CHAIN           25..510
FT                   /note="Adenosine deaminase 2"
FT                   /id="PRO_0000006726"
FT   REGION          25..95
FT                   /note="Dimerization"
FT                   /evidence="ECO:0000250"
FT   REGION          122..182
FT                   /note="PRB domain"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        356
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        381
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         107
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         109
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         110
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         201..208
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         290
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         323
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         353
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         438
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         439
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        122
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        171
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        375
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        132..156
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   510 AA;  58190 MW;  7C9C360E1E65EBBD CRC64;
     MSGWPVLPAL LLAVAMSSFH SATSRDEERN RLLMREKMMQ VGGQLVLQEE EERANGRLQA
     LKEAEMQEAK RTGIFPPSLH FFQAKGLMEK SAVFNILKKM PKGAALHVHD FGMVSMDWLV
     KNATYRPYCY FCLTPKGATQ FKFAHPPPPT PKQEECSEWV LLEKFRKGLP NVTEFDNSLL
     RTFTLMTENP QETYANQDMV WKKFKTIFFA ISGLVNYAPV FRDFIFLGLE EFYQDQVLYL
     ELRAMLYPVY ELNGMVHSRE WSVRTYEEVA RTFAKTHPGF IGIKLIYSDH RSKDVSLIKE
     SVQRAMELRA KFPQMVAGFD LVGREDTGHS LYDYKEALMI PASRGVKLPY FFHAGETDWQ
     GTSADRNLLD ALILNSTRIG HGFALSKHPA VWADAWRKDI PLEVCPISNQ VLKLVSDLRN
     HPAAVLMATG YPMVISSDDP AAFGAKGLSY DFYEAFMGLG GLTADLRTLK QLAMNSIRYS
     ALSETEKKVA METWEERWHR FVAELTRGPK