P31335 · PUR9_CHICK
- ProteinBifunctional purine biosynthesis protein ATIC
- GeneATIC
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids593 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Bifunctional enzyme that catalyzes the last two steps of purine biosynthesis (PubMed:12501179).
Acts as a transformylase that incorporates a formyl group to the AMP analog AICAR (5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide) to produce the intermediate formyl-AICAR (FAICAR) (PubMed:12501179).
Can use both 10-formyldihydrofolate and 10-formyltetrahydrofolate as the formyl donor in this reaction. Also catalyzes the cyclization of FAICAR to IMP. Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (By similarity).
Acts as a transformylase that incorporates a formyl group to the AMP analog AICAR (5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide) to produce the intermediate formyl-AICAR (FAICAR) (PubMed:12501179).
Can use both 10-formyldihydrofolate and 10-formyltetrahydrofolate as the formyl donor in this reaction. Also catalyzes the cyclization of FAICAR to IMP. Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (By similarity).
Miscellaneous
The de novo purine synthesis pathway includes 10 sequential steps, beginning with phosphoribosyl pyrophosphate and ending with inositol monophosphate (IMP), the first purin compound of the pathway.
Catalytic activity
- (6R)-10-formyltetrahydrofolate + 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide = (6S)-5,6,7,8-tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamideThis reaction proceeds in the forward direction.
- 10-formyldihydrofolate + 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide + 7,8-dihydrofolateThis reaction proceeds in the forward direction.
Activity regulation
AMP and XMP inhibit AICAR formyltransferase activity (By similarity).
AICAR formyltransferase activity is competitively inhibited by 2-[5-hydroxy-3-methyl-1-(2-methyl-4-sulfo-phenyl)-1H-pyrazol-4-ylazo]-4-sulfo-benzoic acid (326203-A) (PubMed:15355974).
FAICAR cyclization is competitively inhibited by 1,5-dihydroimidazo[4,5-c][1,2,6]thiadiazin-4(3H)-one-2,2-dioxide and the corresponding nucleoside and nucleoside monophosphate (PubMed:17324932).
AICAR formyltransferase activity is competitively inhibited by 2-[5-hydroxy-3-methyl-1-(2-methyl-4-sulfo-phenyl)-1H-pyrazol-4-ylazo]-4-sulfo-benzoic acid (326203-A) (PubMed:15355974).
FAICAR cyclization is competitively inhibited by 1,5-dihydroimidazo[4,5-c][1,2,6]thiadiazin-4(3H)-one-2,2-dioxide and the corresponding nucleoside and nucleoside monophosphate (PubMed:17324932).
Pathway
Purine metabolism; IMP biosynthesis via de novo pathway; 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide (10-formyl THF route): step 1/1.
Purine metabolism; IMP biosynthesis via de novo pathway; IMP from 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide: step 1/1.
Features
Showing features for binding site, active site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 13-15 | IMP (UniProtKB | ChEBI) | ||||
Sequence: SEK | ||||||
Binding site | 35-38 | IMP (UniProtKB | ChEBI) | ||||
Sequence: SGGT | ||||||
Binding site | 65-68 | IMP (UniProtKB | ChEBI) | ||||
Sequence: RVKT | ||||||
Binding site | 102-103 | IMP (UniProtKB | ChEBI) | ||||
Sequence: CN | ||||||
Binding site | 126-127 | IMP (UniProtKB | ChEBI) | ||||
Sequence: DI | ||||||
Active site | 138 | Proton donor/acceptor; for FAICAR cyclization activity | ||||
Sequence: K | ||||||
Binding site | 208-209 | 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain | ||||
Sequence: RY | ||||||
Site | 267 | Transition state stabilizer | ||||
Sequence: K | ||||||
Active site | 268 | Proton acceptor; for AICAR formyltransferase activity | ||||
Sequence: H | ||||||
Binding site | 268 | 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain | ||||
Sequence: H | ||||||
Binding site | 317 | 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain | ||||
Sequence: G | ||||||
Binding site | 340 | 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain | ||||
Sequence: D | ||||||
Binding site | 432 | 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (UniProtKB | ChEBI); ligand shared between dimeric partners | ||||
Sequence: N | ||||||
Binding site | 452 | 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (UniProtKB | ChEBI); ligand shared between dimeric partners | ||||
Sequence: R | ||||||
Binding site | 453 | (6R)-10-formyltetrahydrofolate (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 542 | 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (UniProtKB | ChEBI); ligand shared between dimeric partners | ||||
Sequence: F | ||||||
Binding site | 547 | (6R)-10-formyltetrahydrofolate (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 566-567 | (6R)-10-formyltetrahydrofolate (UniProtKB | ChEBI) | ||||
Sequence: SA | ||||||
Binding site | 589 | 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (UniProtKB | ChEBI); ligand shared between dimeric partners | ||||
Sequence: R |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Molecular Function | IMP cyclohydrolase activity | |
Molecular Function | phosphoribosylaminoimidazolecarboxamide formyltransferase activity | |
Molecular Function | protein homodimerization activity | |
Biological Process | 'de novo' IMP biosynthetic process |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameBifunctional purine biosynthesis protein ATIC
- Alternative names
Including 2 domains:
- Recommended namePhosphoribosylaminoimidazolecarboxamide formyltransferase
- EC number
- Alternative names
- Recommended nameInosine 5'-monophosphate cyclohydrolase
- EC number
- Short namesIMP cyclohydrolase
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Archelosauria > Archosauria > Dinosauria > Saurischia > Theropoda > Coelurosauria > Aves > Neognathae > Galloanserae > Galliformes > Phasianidae > Phasianinae > Gallus
Accessions
- Primary accessionP31335
Proteomes
Organism-specific databases
Subcellular Location
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000192155 | 1-593 | Bifunctional purine biosynthesis protein ATIC | |||
Sequence: MAARQQLALLSVSEKAGLVEFARSLNALGLGLIASGGTATALRDAGLPVRDVSDLTGFPEMLGGRVKTLHPAVHAGILARNIPEDNADMNKQDFSLVRVVVCNLYPFVKTVSSPGVTVPEAVEKIDIGGVALLRAAAKNHARVTVVCDPADYSSVAKEMAASKDKDTSVETRRHLALKAFTHTAQYDAAISDYFRKEYSKGVSQLPLRYGMNPHQSPAQLYTTRPKLPLTVVNGSPGFINLCDALNAWQLVKELKQALGIPAAASFKHVSPAGAAVGIPLSEEEAQVCMVHDLHKTLTPLASAYARSRGADRMSSFGDFIALSDICDVPTAKIISREVSDGVVAPGYEEEALKILSKKKNGGYCVLQMDPNYEPDDNEIRTLYGLQLMQKRNNAVIDRSLFKNIVTKNKTLPESAVRDLIVASIAVKYTQSNSVCYAKDGQVIGIGAGQQSRIHCTRLAGDKANSWWLRHHPRVLSMKFKAGVKRAEVSNAIDQYVTGTIGEDEDLVKWQAMFEEVPAQLTEAEKKQWIAKLTAVSLSSDAFFPFRDNVDRAKRIGVQFIVAPSGSAADEVVIEACNELGITLIHTNLRLFHH | ||||||
Modified residue | 200 | N6-acetyllysine | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
Interaction
Subunit
Homodimer (PubMed:11323713, PubMed:12501179).
Associates with internalized INSR complexes on Golgi/endosomal membranes. Interacts with INSR; ATIC together with PRKAA2/AMPK2 and HACD3/PTPLAD1 is proposed to be part of a signaling network regulating INSR autophosphorylation and endocytosis (By similarity).
Associates with internalized INSR complexes on Golgi/endosomal membranes. Interacts with INSR; ATIC together with PRKAA2/AMPK2 and HACD3/PTPLAD1 is proposed to be part of a signaling network regulating INSR autophosphorylation and endocytosis (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 1-147 | MGS-like | ||||
Sequence: MAARQQLALLSVSEKAGLVEFARSLNALGLGLIASGGTATALRDAGLPVRDVSDLTGFPEMLGGRVKTLHPAVHAGILARNIPEDNADMNKQDFSLVRVVVCNLYPFVKTVSSPGVTVPEAVEKIDIGGVALLRAAAKNHARVTVVC | ||||||
Region | 1-199 | IMP cyclohydrolase | ||||
Sequence: MAARQQLALLSVSEKAGLVEFARSLNALGLGLIASGGTATALRDAGLPVRDVSDLTGFPEMLGGRVKTLHPAVHAGILARNIPEDNADMNKQDFSLVRVVVCNLYPFVKTVSSPGVTVPEAVEKIDIGGVALLRAAAKNHARVTVVCDPADYSSVAKEMAASKDKDTSVETRRHLALKAFTHTAQYDAAISDYFRKEYS | ||||||
Region | 200-593 | AICAR formyltransferase | ||||
Sequence: KGVSQLPLRYGMNPHQSPAQLYTTRPKLPLTVVNGSPGFINLCDALNAWQLVKELKQALGIPAAASFKHVSPAGAAVGIPLSEEEAQVCMVHDLHKTLTPLASAYARSRGADRMSSFGDFIALSDICDVPTAKIISREVSDGVVAPGYEEEALKILSKKKNGGYCVLQMDPNYEPDDNEIRTLYGLQLMQKRNNAVIDRSLFKNIVTKNKTLPESAVRDLIVASIAVKYTQSNSVCYAKDGQVIGIGAGQQSRIHCTRLAGDKANSWWLRHHPRVLSMKFKAGVKRAEVSNAIDQYVTGTIGEDEDLVKWQAMFEEVPAQLTEAEKKQWIAKLTAVSLSSDAFFPFRDNVDRAKRIGVQFIVAPSGSAADEVVIEACNELGITLIHTNLRLFHH |
Domain
The IMP cyclohydrolase activity resides in the N-terminal region.
Sequence similarities
Belongs to the PurH family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length593
- Mass (Da)64,415
- Last updated1993-07-01 v1
- ChecksumBD1A34F03D96A136
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
S64492 EMBL· GenBank· DDBJ | AAB20309.1 EMBL· GenBank· DDBJ | mRNA |