P31335 · PUR9_CHICK

  • Protein
    Bifunctional purine biosynthesis protein ATIC
  • Gene
    ATIC
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

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

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).

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.

TypeIDPosition(s)Description
Binding site13-15IMP (UniProtKB | ChEBI)
Binding site35-38IMP (UniProtKB | ChEBI)
Binding site65-68IMP (UniProtKB | ChEBI)
Binding site102-103IMP (UniProtKB | ChEBI)
Binding site126-127IMP (UniProtKB | ChEBI)
Active site138Proton donor/acceptor; for FAICAR cyclization activity
Binding site208-2095-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain
Site267Transition state stabilizer
Active site268Proton acceptor; for AICAR formyltransferase activity
Binding site2685-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain
Binding site3175-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain
Binding site3405-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain
Binding site4325-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (UniProtKB | ChEBI); ligand shared between dimeric partners
Binding site4525-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (UniProtKB | ChEBI); ligand shared between dimeric partners
Binding site453(6R)-10-formyltetrahydrofolate (UniProtKB | ChEBI)
Binding site5425-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (UniProtKB | ChEBI); ligand shared between dimeric partners
Binding site547(6R)-10-formyltetrahydrofolate (UniProtKB | ChEBI)
Binding site566-567(6R)-10-formyltetrahydrofolate (UniProtKB | ChEBI)
Binding site5895-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (UniProtKB | ChEBI); ligand shared between dimeric partners

GO annotations

AspectTerm
Cellular Componentcytosol
Molecular FunctionIMP cyclohydrolase activity
Molecular Functionphosphoribosylaminoimidazolecarboxamide formyltransferase activity
Molecular Functionprotein homodimerization activity
Biological Process'de novo' IMP biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Bifunctional purine biosynthesis protein ATIC
  • Alternative names
    • AICAR transformylase/inosine monophosphate cyclohydrolase
      (ATIC
      )

Including 2 domains:

  • Recommended name
    Phosphoribosylaminoimidazolecarboxamide formyltransferase
  • EC number
  • Alternative names
    • 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICAR formyltransferase)
    • AICAR transformylase
  • Recommended name
    Inosine 5'-monophosphate cyclohydrolase
  • EC number
  • Short names
    IMP cyclohydrolase
  • Alternative names
    • IMP synthase
    • Inosinicase

Gene names

    • Name
      ATIC
    • Synonyms
      PURH

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Archelosauria > Archosauria > Dinosauria > Saurischia > Theropoda > Coelurosauria > Aves > Neognathae > Galloanserae > Galliformes > Phasianidae > Phasianinae > Gallus

Accessions

  • Primary accession
    P31335

Proteomes

Organism-specific databases

Subcellular Location

Keywords

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00001921551-593Bifunctional purine biosynthesis protein ATIC
Modified residue200N6-acetyllysine

Keywords

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).

Protein-protein interaction databases

Family & Domains

Features

Showing features for domain, region.

TypeIDPosition(s)Description
Domain1-147MGS-like
Region1-199IMP cyclohydrolase
Region200-593AICAR formyltransferase

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 status
    Complete
  • Length
    593
  • Mass (Da)
    64,415
  • Last updated
    1993-07-01 v1
  • Checksum
    BD1A34F03D96A136
MAARQQLALLSVSEKAGLVEFARSLNALGLGLIASGGTATALRDAGLPVRDVSDLTGFPEMLGGRVKTLHPAVHAGILARNIPEDNADMNKQDFSLVRVVVCNLYPFVKTVSSPGVTVPEAVEKIDIGGVALLRAAAKNHARVTVVCDPADYSSVAKEMAASKDKDTSVETRRHLALKAFTHTAQYDAAISDYFRKEYSKGVSQLPLRYGMNPHQSPAQLYTTRPKLPLTVVNGSPGFINLCDALNAWQLVKELKQALGIPAAASFKHVSPAGAAVGIPLSEEEAQVCMVHDLHKTLTPLASAYARSRGADRMSSFGDFIALSDICDVPTAKIISREVSDGVVAPGYEEEALKILSKKKNGGYCVLQMDPNYEPDDNEIRTLYGLQLMQKRNNAVIDRSLFKNIVTKNKTLPESAVRDLIVASIAVKYTQSNSVCYAKDGQVIGIGAGQQSRIHCTRLAGDKANSWWLRHHPRVLSMKFKAGVKRAEVSNAIDQYVTGTIGEDEDLVKWQAMFEEVPAQLTEAEKKQWIAKLTAVSLSSDAFFPFRDNVDRAKRIGVQFIVAPSGSAADEVVIEACNELGITLIHTNLRLFHH

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
S64492
EMBL· GenBank· DDBJ
AAB20309.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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