UniProtKB - P56658 (ADA_BOVIN)
Protein
Adenosine deaminase
Gene
ADA
Organism
Bos taurus (Bovine)
Status
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
- EC:3.5.4.4By similarity
Cofactori
Zn2+4 PublicationsNote: Binds 1 zinc ion per subunit.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 15 | Zinc; catalyticCombined sources9 Publications | 1 | |
Metal bindingi | 17 | Zinc; catalyticCombined sources9 Publications | 1 | |
Binding sitei | 17 | SubstrateCombined sources6 Publications | 1 | |
Binding sitei | 19 | SubstrateCombined sources7 Publications | 1 | |
Sitei | 58 | Important for interaction with adenosine receptors and increasing their affinity for agonistsBy similarity | 1 | |
Sitei | 62 | Important for interaction with adenosine receptors and increasing their affinity for agonistsBy similarity | 1 | |
Binding sitei | 184 | Substrate; via amide nitrogen and carbonyl oxygenCombined sources2 Publications | 1 | |
Metal bindingi | 214 | Zinc; catalyticCombined sources9 Publications | 1 | |
Active sitei | 217 | Proton donorBy similarity | 1 | |
Sitei | 238 | Important for catalytic activityBy similarity | 1 | |
Metal bindingi | 295 | Zinc; catalyticCombined sources9 Publications | 1 | |
Binding sitei | 296 | SubstrateCombined sources6 Publications | 1 |
GO - Molecular functioni
- adenosine deaminase activity Source: UniProtKB
- zinc ion binding Source: UniProtKB
GO - Biological processi
- adenosine catabolic process Source: UniProtKB
- cell adhesion Source: UniProtKB-KW
- hypoxanthine salvage Source: GO_Central
- inosine biosynthetic process Source: UniProtKB
- negative regulation of adenosine receptor signaling pathway Source: GO_Central
- nucleotide metabolic process Source: UniProtKB-KW
- purine ribonucleoside monophosphate biosynthetic process Source: InterPro
- T cell activation Source: GO_Central
Keywordsi
Molecular function | Hydrolase |
Biological process | Cell adhesion, Nucleotide metabolism |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 3.5.4.4 908 |
Names & Taxonomyi
Protein namesi | Recommended name: Adenosine deaminase (EC:3.5.4.4By similarity)Alternative name(s): Adenosine aminohydrolase |
Gene namesi | Name:ADA |
Organismi | Bos taurus (Bovine) |
Taxonomic identifieri | 9913 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos |
Proteomesi |
|
Subcellular locationi
Lysosome
- Lysosome By similarity
Plasma membrane
- Cell membrane By similarity; Peripheral membrane protein By similarity; Extracellular side By similarity
Other locations
- Cell junction By similarity
- Cytoplasmic vesicle lumen By similarity
- Cytoplasm By similarity
Note: Colocalized with DPP4 at the cell surface.By similarity
Cytosol
- cytosol Source: GO_Central
Lysosome
- lysosome Source: UniProtKB-SubCell
Plasma Membrane
- external side of plasma membrane Source: GO_Central
Other locations
- cell junction Source: UniProtKB-SubCell
- cytoplasmic vesicle lumen Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell junction, Cell membrane, Cytoplasm, Cytoplasmic vesicle, Lysosome, MembranePathology & 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
ChEMBLi | CHEMBL2966 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedBy similarity1 Publication | |||
ChainiPRO_0000194351 | 2 – 363 | Adenosine deaminaseAdd BLAST | 362 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineBy similarity | 1 | |
Modified residuei | 54 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 232 | N6-acetyllysineBy similarity | 1 |
Keywords - PTMi
AcetylationProteomic databases
PaxDbi | P56658 |
PeptideAtlasi | P56658 |
PRIDEi | P56658 |
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
With | Entry | #Exp. | IntAct | Notes |
---|---|---|---|---|
DPP4 | P27487 | 5 | EBI-7475530,EBI-2871277 | From Homo sapiens. |
Protein-protein interaction databases
IntActi | P56658, 1 interactor |
MINTi | P56658 |
STRINGi | 9913.ENSBTAP00000006947 |
Chemistry databases
BindingDBi | P56658 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1KRM | X-ray | 2.50 | A | 2-357 | [»] | |
1NDV | X-ray | 2.30 | A | 2-357 | [»] | |
1NDW | X-ray | 2.00 | A | 2-357 | [»] | |
1NDY | X-ray | 2.00 | A | 2-357 | [»] | |
1NDZ | X-ray | 2.00 | A | 2-357 | [»] | |
1O5R | X-ray | 2.35 | A | 2-357 | [»] | |
1QXL | X-ray | 2.25 | A | 2-357 | [»] | |
1UML | X-ray | 2.50 | A | 2-357 | [»] | |
1V79 | X-ray | 2.50 | A | 2-357 | [»] | |
1V7A | X-ray | 2.50 | A | 2-357 | [»] | |
1VFL | X-ray | 1.80 | A | 2-357 | [»] | |
1W1I | X-ray | 3.03 | E/F/G/H | 1-357 | [»] | |
1WXY | X-ray | 2.50 | A | 2-357 | [»] | |
1WXZ | X-ray | 2.80 | A | 2-357 | [»] | |
2BGN | X-ray | 3.15 | E/F/G/H | 2-363 | [»] | |
2E1W | X-ray | 2.50 | A | 2-357 | [»] | |
2Z7G | X-ray | 2.52 | A | 2-357 | [»] | |
ProteinModelPortali | P56658 | |||||
SMRi | P56658 | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P56658 |
Family & Domainsi
Sequence similaritiesi
Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family.Curated
Phylogenomic databases
eggNOGi | KOG1097 Eukaryota COG1816 LUCA |
HOGENOMi | HOG000218816 |
HOVERGENi | HBG001718 |
InParanoidi | P56658 |
KOi | K01488 |
OrthoDBi | 1045809at2759 |
Family and domain databases
CDDi | cd01320 ADA, 1 hit |
HAMAPi | MF_00540 A_deaminase, 1 hit |
InterProi | View protein in InterPro IPR006650 A/AMP_deam_AS IPR001365 A/AMP_deaminase_dom IPR028893 A_deaminase IPR006330 Ado/ade_deaminase IPR032466 Metal_Hydrolase |
Pfami | View protein in Pfam PF00962 A_deaminase, 1 hit |
SUPFAMi | SSF51556 SSF51556, 1 hit |
TIGRFAMsi | TIGR01430 aden_deam, 1 hit |
PROSITEi | View protein in PROSITE PS00485 A_DEAMINASE, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P56658-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 8 | N → D AA sequence (PubMed:8877857).Curated | 1 | |
Sequence conflicti | 32 – 33 | RK → KR AA sequence (PubMed:8877857).Curated | 2 | |
Sequence conflicti | 57 | S → T AA sequence (PubMed:8877857).Curated | 1 | |
Sequence conflicti | 60 | E → D AA sequence (PubMed:8877857).Curated | 1 | |
Sequence conflicti | 77 – 79 | EAV → DAI AA sequence (PubMed:8877857).Curated | 3 | |
Sequence conflicti | 261 | V → I AA sequence (PubMed:8877857).Curated | 1 | |
Sequence conflicti | 279 – 281 | PVV → AVI AA sequence (PubMed:8877857).Curated | 3 | |
Sequence conflicti | 313 – 314 | NE → KD AA sequence (PubMed:8877857).Curated | 2 |
Mass spectrometryi
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 199 | K → Q. | 1 | |
Natural varianti | 246 | A → T. | 1 | |
Natural varianti | 352 | G → R. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF280603 mRNA Translation: AAF91430.1 |
RefSeqi | NP_776312.1, NM_173887.2 |
UniGenei | Bt.4303 |
Genome annotation databases
GeneIDi | 280712 |
KEGGi | bta:280712 |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Web resourcesi
Worthington enzyme manual |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF280603 mRNA Translation: AAF91430.1 |
RefSeqi | NP_776312.1, NM_173887.2 |
UniGenei | Bt.4303 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1KRM | X-ray | 2.50 | A | 2-357 | [»] | |
1NDV | X-ray | 2.30 | A | 2-357 | [»] | |
1NDW | X-ray | 2.00 | A | 2-357 | [»] | |
1NDY | X-ray | 2.00 | A | 2-357 | [»] | |
1NDZ | X-ray | 2.00 | A | 2-357 | [»] | |
1O5R | X-ray | 2.35 | A | 2-357 | [»] | |
1QXL | X-ray | 2.25 | A | 2-357 | [»] | |
1UML | X-ray | 2.50 | A | 2-357 | [»] | |
1V79 | X-ray | 2.50 | A | 2-357 | [»] | |
1V7A | X-ray | 2.50 | A | 2-357 | [»] | |
1VFL | X-ray | 1.80 | A | 2-357 | [»] | |
1W1I | X-ray | 3.03 | E/F/G/H | 1-357 | [»] | |
1WXY | X-ray | 2.50 | A | 2-357 | [»] | |
1WXZ | X-ray | 2.80 | A | 2-357 | [»] | |
2BGN | X-ray | 3.15 | E/F/G/H | 2-363 | [»] | |
2E1W | X-ray | 2.50 | A | 2-357 | [»] | |
2Z7G | X-ray | 2.52 | A | 2-357 | [»] | |
ProteinModelPortali | P56658 | |||||
SMRi | P56658 | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Protein-protein interaction databases
IntActi | P56658, 1 interactor |
MINTi | P56658 |
STRINGi | 9913.ENSBTAP00000006947 |
Chemistry databases
BindingDBi | P56658 |
ChEMBLi | CHEMBL2966 |
Proteomic databases
PaxDbi | P56658 |
PeptideAtlasi | P56658 |
PRIDEi | P56658 |
Protocols and materials databases
Structural Biology Knowledgebase | Search... |
Genome annotation databases
GeneIDi | 280712 |
KEGGi | bta:280712 |
Organism-specific databases
CTDi | 100 |
Phylogenomic databases
eggNOGi | KOG1097 Eukaryota COG1816 LUCA |
HOGENOMi | HOG000218816 |
HOVERGENi | HBG001718 |
InParanoidi | P56658 |
KOi | K01488 |
OrthoDBi | 1045809at2759 |
Enzyme and pathway databases
BRENDAi | 3.5.4.4 908 |
Miscellaneous databases
EvolutionaryTracei | P56658 |
PROi | PR:P56658 |
Family and domain databases
CDDi | cd01320 ADA, 1 hit |
HAMAPi | MF_00540 A_deaminase, 1 hit |
InterProi | View protein in InterPro IPR006650 A/AMP_deam_AS IPR001365 A/AMP_deaminase_dom IPR028893 A_deaminase IPR006330 Ado/ade_deaminase IPR032466 Metal_Hydrolase |
Pfami | View protein in Pfam PF00962 A_deaminase, 1 hit |
SUPFAMi | SSF51556 SSF51556, 1 hit |
TIGRFAMsi | TIGR01430 aden_deam, 1 hit |
PROSITEi | View protein in PROSITE PS00485 A_DEAMINASE, 1 hit |
ProtoNeti | Search... |
Entry informationi
Entry namei | ADA_BOVIN | |
Accessioni | P56658Primary (citable) accession number: P56658 Secondary accession number(s): Q9MYY1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1999 |
Last sequence update: | January 23, 2007 | |
Last modified: | January 16, 2019 | |
This is version 133 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Direct protein sequencing, Pharmaceutical, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - PDB cross-references
Index of Protein Data Bank (PDB) cross-references