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Protein

Adenosine deaminase

Gene

ADA

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine (By similarity). Plays an important role in purine metabolism and in adenosine homeostasis (By similarity). Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events (By similarity). Acts as a positive regulator of T-cell coactivation, by binding DPP4 (By similarity). Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion (By similarity). Enhances dendritic cell immunogenicity by affecting dendritic cell costimulatory molecule expression and cytokines and chemokines secretion (PubMed:23240012). Enhances CD4+ T-cell differentiation and proliferation (By similarity). Acts as a positive modulator of adenosine receptors ADORA1 and ADORA2A, by enhancing their ligand affinity via conformational change (By similarity). Stimulates plasminogen activation (By similarity). Plays a role in male fertility (By similarity). Plays a protective role in early postimplantation embryonic development (By similarity).By similarity1 Publication

Catalytic activityi

Adenosine + H2O = inosine + NH3.By similarity

Cofactori

Zn2+4 PublicationsNote: Binds 1 zinc ion per subunit.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi15Zinc; catalyticCombined sources9 Publications1
Metal bindingi17Zinc; catalyticCombined sources9 Publications1
Binding sitei17SubstrateCombined sources6 Publications1
Binding sitei19SubstrateCombined sources7 Publications1
Sitei58Important for interaction with adenosine receptors and increasing their affinity for agonistsBy similarity1
Sitei62Important for interaction with adenosine receptors and increasing their affinity for agonistsBy similarity1
Binding sitei184Substrate; via amide nitrogen and carbonyl oxygenCombined sources2 Publications1
Metal bindingi214Zinc; catalyticCombined sources9 Publications1
Active sitei217Proton donorBy similarity1
Sitei238Important for catalytic activityBy similarity1
Metal bindingi295Zinc; catalyticCombined sources9 Publications1
Binding sitei296SubstrateCombined sources6 Publications1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processCell adhesion, Nucleotide metabolism
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.5.4.4 908

Names & Taxonomyi

Protein namesi
Recommended name:
Adenosine deaminase (EC:3.5.4.4By similarity)
Alternative name(s):
Adenosine aminohydrolase
Gene namesi
Name:ADA
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Cytoplasmic vesicle, Lysosome, Membrane

Pathology & Biotechi

Pharmaceutical usei

Available under the name Adagen (Enzon). This is a PEG-conjugated form (pegademase). Used to treat patients with severe combined immunodeficiency diseases (SCID).

Chemistry databases

ChEMBLiCHEMBL2966

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity1 Publication
ChainiPRO_00001943512 – 363Adenosine deaminaseAdd BLAST362

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei54N6-acetyllysineBy similarity1
Modified residuei232N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiP56658
PeptideAtlasiP56658
PRIDEiP56658

Expressioni

Tissue specificityi

Expressed in gastrointestinal tissues (at protein level).1 Publication

Interactioni

Subunit structurei

Interacts with DPP4 (via extracellular domain). Interacts with PLG (via Kringle 4 domain); the interaction stimulates PLG activation when in complex with DPP4.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
DPP4P274875EBI-7475530,EBI-2871277From Homo sapiens.

Protein-protein interaction databases

IntActiP56658, 1 interactor
MINTiP56658
STRINGi9913.ENSBTAP00000006947

Chemistry databases

BindingDBiP56658

Structurei

Secondary structure

1363
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP56658
SMRiP56658
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP56658

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1097 Eukaryota
COG1816 LUCA
HOGENOMiHOG000218816
HOVERGENiHBG001718
InParanoidiP56658
KOiK01488

Family and domain databases

CDDicd01320 ADA, 1 hit
HAMAPiMF_00540 A_deaminase, 1 hit
InterProiView protein in InterPro
IPR006650 A/AMP_deam_AS
IPR001365 A/AMP_deaminase_dom
IPR028893 A_deaminase
IPR006330 Ado/ade_deaminase
IPR032466 Metal_Hydrolase
PfamiView protein in Pfam
PF00962 A_deaminase, 1 hit
SUPFAMiSSF51556 SSF51556, 1 hit
TIGRFAMsiTIGR01430 aden_deam, 1 hit
PROSITEiView protein in PROSITE
PS00485 A_DEAMINASE, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P56658-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAQTPAFNKP KVELHVHLDG AIKPETILYY GRKRGIALPA DTPEELQNII
60 70 80 90 100
GMDKPLSLPE FLAKFDYYMP AIAGCREAVK RIAYEFVEMK AKDGVVYVEV
110 120 130 140 150
RYSPHLLANS KVEPIPWNQA EGDLTPDEVV SLVNQGLQEG ERDFGVKVRS
160 170 180 190 200
ILCCMRHQPS WSSEVVELCK KYREQTVVAI DLAGDETIEG SSLFPGHVKA
210 220 230 240 250
YAEAVKSGVH RTVHAGEVGS ANVVKEAVDT LKTERLGHGY HTLEDATLYN
260 270 280 290 300
RLRQENMHFE VCPWSSYLTG AWKPDTEHPV VRFKNDQVNY SLNTDDPLIF
310 320 330 340 350
KSTLDTDYQM TKNEMGFTEE EFKRLNINAA KSSFLPEDEK KELLDLLYKA
360
YGMPSPASAE QCL
Length:363
Mass (Da):40,919
Last modified:January 23, 2007 - v3
Checksum:i69F6D25ACFF2A3E5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti8N → D AA sequence (PubMed:8877857).Curated1
Sequence conflicti32 – 33RK → KR AA sequence (PubMed:8877857).Curated2
Sequence conflicti57S → T AA sequence (PubMed:8877857).Curated1
Sequence conflicti60E → D AA sequence (PubMed:8877857).Curated1
Sequence conflicti77 – 79EAV → DAI AA sequence (PubMed:8877857).Curated3
Sequence conflicti261V → I AA sequence (PubMed:8877857).Curated1
Sequence conflicti279 – 281PVV → AVI AA sequence (PubMed:8877857).Curated3
Sequence conflicti313 – 314NE → KD AA sequence (PubMed:8877857).Curated2

Mass spectrometryi

Molecular mass is 40549±16 Da from positions 2 - 363. Determined by ESI. 1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti199K → Q. 1
Natural varianti246A → T. 1
Natural varianti352G → R. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF280603 mRNA Translation: AAF91430.1
RefSeqiNP_776312.1, NM_173887.2
UniGeneiBt.4303

Genome annotation databases

GeneIDi280712
KEGGibta:280712

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Worthington enzyme manual

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF280603 mRNA Translation: AAF91430.1
RefSeqiNP_776312.1, NM_173887.2
UniGeneiBt.4303

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KRMX-ray2.50A2-357[»]
1NDVX-ray2.30A2-357[»]
1NDWX-ray2.00A2-357[»]
1NDYX-ray2.00A2-357[»]
1NDZX-ray2.00A2-357[»]
1O5RX-ray2.35A2-357[»]
1QXLX-ray2.25A2-357[»]
1UMLX-ray2.50A2-357[»]
1V79X-ray2.50A2-357[»]
1V7AX-ray2.50A2-357[»]
1VFLX-ray1.80A2-357[»]
1W1IX-ray3.03E/F/G/H1-357[»]
1WXYX-ray2.50A2-357[»]
1WXZX-ray2.80A2-357[»]
2BGNX-ray3.15E/F/G/H2-363[»]
2E1WX-ray2.50A2-357[»]
2Z7GX-ray2.52A2-357[»]
ProteinModelPortaliP56658
SMRiP56658
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP56658, 1 interactor
MINTiP56658
STRINGi9913.ENSBTAP00000006947

Chemistry databases

BindingDBiP56658
ChEMBLiCHEMBL2966

Proteomic databases

PaxDbiP56658
PeptideAtlasiP56658
PRIDEiP56658

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi280712
KEGGibta:280712

Organism-specific databases

CTDi100

Phylogenomic databases

eggNOGiKOG1097 Eukaryota
COG1816 LUCA
HOGENOMiHOG000218816
HOVERGENiHBG001718
InParanoidiP56658
KOiK01488

Enzyme and pathway databases

BRENDAi3.5.4.4 908

Miscellaneous databases

EvolutionaryTraceiP56658
PROiPR:P56658

Family and domain databases

CDDicd01320 ADA, 1 hit
HAMAPiMF_00540 A_deaminase, 1 hit
InterProiView protein in InterPro
IPR006650 A/AMP_deam_AS
IPR001365 A/AMP_deaminase_dom
IPR028893 A_deaminase
IPR006330 Ado/ade_deaminase
IPR032466 Metal_Hydrolase
PfamiView protein in Pfam
PF00962 A_deaminase, 1 hit
SUPFAMiSSF51556 SSF51556, 1 hit
TIGRFAMsiTIGR01430 aden_deam, 1 hit
PROSITEiView protein in PROSITE
PS00485 A_DEAMINASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiADA_BOVIN
AccessioniPrimary (citable) accession number: P56658
Secondary accession number(s): Q9MYY1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 23, 2007
Last modified: February 28, 2018
This is version 131 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Pharmaceutical, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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