ID PUR9_BOVIN Reviewed; 592 AA. AC Q0VCK0; DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot. DT 05-SEP-2006, sequence version 1. DT 04-NOV-2026, entry version 126. DE RecName: Full=Bifunctional purine biosynthesis protein ATIC; DE AltName: Full=AICAR transformylase/inosine monophosphate cyclohydrolase; DE Short=ATIC; DE Includes: DE RecName: Full=Phosphoribosylaminoimidazolecarboxamide formyltransferase; DE EC=2.1.2.3 {ECO:0000250|UniProtKB:P31939}; DE AltName: Full=5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase; DE Short=AICAR formyltransferase; DE AltName: Full=AICAR transformylase; DE Includes: DE RecName: Full=Inosine 5'-monophosphate cyclohydrolase {ECO:0000305}; DE Short=IMP cyclohydrolase {ECO:0000305}; DE EC=3.5.4.10 {ECO:0000250|UniProtKB:P31939}; DE AltName: Full=IMP synthase; DE AltName: Full=Inosinicase; GN Name=ATIC; Synonyms=PURH; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Hereford; TISSUE=Fetal lung; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Bifunctional enzyme that catalyzes the last two steps of CC purine biosynthesis. Acts as a transformylase that incorporates a CC formyl group to the AMP analog AICAR (5-amino-1-(5-phospho-beta-D- CC ribosyl)imidazole-4-carboxamide) to produce the intermediate formyl- CC AICAR (FAICAR). Can use both 10-formyldihydrofolate and 10- CC formyltetrahydrofolate as the formyl donor in this reaction. Also CC catalyzes the cyclization of FAICAR to IMP. Promotes insulin CC receptor/INSR autophosphorylation and is involved in INSR CC internalization. {ECO:0000250|UniProtKB:P31939}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(6R)-10-formyltetrahydrofolate + 5-amino-1-(5-phospho-beta-D- CC ribosyl)imidazole-4-carboxamide = 5-formamido-1-(5-phospho-D- CC ribosyl)imidazole-4-carboxamide + (6S)-5,6,7,8-tetrahydrofolate; CC Xref=Rhea:RHEA:22192, ChEBI:CHEBI:57453, ChEBI:CHEBI:58467, CC ChEBI:CHEBI:58475, ChEBI:CHEBI:195366; EC=2.1.2.3; CC Evidence={ECO:0000250|UniProtKB:P31939}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22193; CC Evidence={ECO:0000250|UniProtKB:P31939}; CC -!- CATALYTIC ACTIVITY: CC Reaction=10-formyldihydrofolate + 5-amino-1-(5-phospho-beta-D- CC ribosyl)imidazole-4-carboxamide = 5-formamido-1-(5-phospho-D- CC ribosyl)imidazole-4-carboxamide + 7,8-dihydrofolate; CC Xref=Rhea:RHEA:59144, ChEBI:CHEBI:57451, ChEBI:CHEBI:57452, CC ChEBI:CHEBI:58467, ChEBI:CHEBI:58475; CC Evidence={ECO:0000250|UniProtKB:P31939}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59145; CC Evidence={ECO:0000250|UniProtKB:P31939}; CC -!- CATALYTIC ACTIVITY: CC Reaction=IMP + H2O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4- CC carboxamide; Xref=Rhea:RHEA:18445, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:58053, ChEBI:CHEBI:58467; EC=3.5.4.10; CC Evidence={ECO:0000250|UniProtKB:P31939}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18447; CC Evidence={ECO:0000250|UniProtKB:P31939}; CC -!- ACTIVITY REGULATION: AMP and XMP inhibit AICAR formyltransferase CC activity. {ECO:0000250|UniProtKB:P31939}. CC -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway; 5- CC formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino- CC 1-(5-phospho-D-ribosyl)imidazole-4-carboxamide (10-formyl THF route): CC step 1/1. {ECO:0000250|UniProtKB:P31939}. CC -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway; IMP CC from 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide: step CC 1/1. {ECO:0000250|UniProtKB:P31939}. CC -!- SUBUNIT: Homodimer. Associates with internalized INSR complexes on CC Golgi/endosomal membranes. Interacts with INSR; ATIC together with CC PRKAA2/AMPK2 and HACD3/PTPLAD1 is proposed to be part of a signaling CC network regulating INSR autophosphorylation and endocytosis. CC {ECO:0000250|UniProtKB:P31939}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:P54113}. CC -!- DOMAIN: The IMP cyclohydrolase activity resides in the N-terminal CC region. {ECO:0000250|UniProtKB:P31939}. CC -!- MISCELLANEOUS: The de novo purine synthesis pathway includes 10 CC sequential steps, beginning with phosphoribosyl pyrophosphate and CC ending with inosine monophosphate (IMP), the first purine compound of CC the pathway. {ECO:0000250|UniProtKB:P31939}. CC -!- SIMILARITY: Belongs to the PurH family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BC120131; AAI20132.1; -; mRNA. DR RefSeq; NP_001068722.1; NM_001075254.2. DR AlphaFoldDB; Q0VCK0; -. DR SMR; Q0VCK0; -. DR FunCoup; Q0VCK0; 3179. DR STRING; 9913.ENSBTAP00000025662; -. DR PaxDb; 9913-ENSBTAP00000025662; -. DR PeptideAtlas; Q0VCK0; -. DR Ensembl; ENSBTAT00085004833; ENSBTAP00085027608; ENSBTAG00085021076. DR GeneID; 506343; -. DR KEGG; bta:506343; -. DR CTD; 471; -. DR VEuPathDB; HostDB:ENSBTAG00000019274; -. DR VGNC; VGNC:26264; ATIC. DR eggNOG; KOG2555; Eukaryota. DR HOGENOM; CLU_016316_3_2_1; -. DR InParanoid; Q0VCK0; -. DR OMA; AAAMKPY; -. DR OrthoDB; 6017153at2759; -. DR Reactome; R-BTA-73817; Purine ribonucleoside monophosphate biosynthesis. DR UniPathway; UPA00074; UER00133. DR UniPathway; UPA00074; UER00135. DR Proteomes; UP000009136; Chromosome 2. DR Bgee; ENSBTAG00000019274; Expressed in biceps femoris and 107 other cell types or tissues. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0003937; F:IMP cyclohydrolase activity; ISS:UniProtKB. DR GO; GO:0004643; F:phosphoribosylaminoimidazolecarboxamide formyltransferase activity; ISS:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0044208; P:'de novo' AMP biosynthetic process; IEA:UniProtKB-ARBA. DR GO; GO:0006189; P:'de novo' IMP biosynthetic process; IBA:GO_Central. DR GO; GO:0097294; P:'de novo' XMP biosynthetic process; IEA:UniProtKB-ARBA. DR GO; GO:0006177; P:GMP biosynthetic process; IEA:UniProtKB-ARBA. DR CDD; cd01421; IMPCH; 1. DR FunFam; 3.40.50.1380:FF:000003; Bifunctional purine biosynthesis protein; 1. DR FunFam; 1.10.287.440:FF:000001; Bifunctional purine biosynthesis protein PURH; 1. DR FunFam; 3.40.140.20:FF:000008; Bifunctional purine biosynthesis protein PURH; 1. DR Gene3D; 1.10.287.440; -; 1. DR Gene3D; 3.40.140.20; -; 2. DR Gene3D; 3.40.50.1380; Methylglyoxal synthase-like domain; 1. DR HAMAP; MF_00139; PurH; 1. DR InterPro; IPR024051; AICAR_Tfase_dup_dom_sf. DR InterPro; IPR024050; AICAR_Tfase_insert_dom_sf. DR InterPro; IPR016193; Cytidine_deaminase-like. DR InterPro; IPR011607; MGS-like_dom. DR InterPro; IPR036914; MGS-like_dom_sf. DR InterPro; IPR002695; PurH-like. DR NCBIfam; NF005492; PRK07106.1; 1. DR NCBIfam; TIGR00355; purH; 1. DR PANTHER; PTHR11692:SF0; BIFUNCTIONAL PURINE BIOSYNTHESIS PROTEIN ATIC; 1. DR PANTHER; PTHR11692; BIFUNCTIONAL PURINE BIOSYNTHESIS PROTEIN PURH; 1. DR Pfam; PF01808; AICARFT_IMPCHas; 1. DR Pfam; PF02142; MGS; 1. DR PIRSF; PIRSF000414; AICARFT_IMPCHas; 1. DR SMART; SM00798; AICARFT_IMPCHas; 1. DR SMART; SM00851; MGS; 1. DR SUPFAM; SSF53927; Cytidine deaminase-like; 1. DR SUPFAM; SSF52335; Methylglyoxal synthase-like; 1. DR PROSITE; PS51855; MGS; 1. PE 2: Evidence at transcript level; KW Acetylation; Cytoplasm; Hydrolase; Multifunctional enzyme; KW Purine biosynthesis; Reference proteome; Transferase. FT CHAIN 1..592 FT /note="Bifunctional purine biosynthesis protein ATIC" FT /id="PRO_0000270212" FT DOMAIN 1..146 FT /note="MGS-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01202" FT REGION 1..198 FT /note="IMP cyclohydrolase" FT /evidence="ECO:0000250|UniProtKB:P31335" FT REGION 199..592 FT /note="AICAR formyltransferase" FT /evidence="ECO:0000250|UniProtKB:P31335" FT ACT_SITE 137 FT /note="Proton donor/acceptor; for FAICAR cyclization FT activity" FT /evidence="ECO:0000250|UniProtKB:P31939" FT ACT_SITE 267 FT /note="Proton acceptor; for AICAR formyltransferase FT activity" FT /evidence="ECO:0000250|UniProtKB:P31939" FT BINDING 12..14 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /evidence="ECO:0000250|UniProtKB:P31939" FT BINDING 34..37 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /evidence="ECO:0000250|UniProtKB:P31939" FT BINDING 64..67 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /evidence="ECO:0000250|UniProtKB:P31939" FT BINDING 101..102 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /evidence="ECO:0000250|UniProtKB:P31939" FT BINDING 125..126 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /evidence="ECO:0000250|UniProtKB:P31939" FT BINDING 207..208 FT /ligand="5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4- FT carboxamide" FT /ligand_id="ChEBI:CHEBI:58475" FT /ligand_note="ligand shared between dimeric partners" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:P31939" FT BINDING 267 FT /ligand="5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4- FT carboxamide" FT /ligand_id="ChEBI:CHEBI:58475" FT /ligand_note="ligand shared between dimeric partners" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:P31939" FT BINDING 316 FT /ligand="5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4- FT carboxamide" FT /ligand_id="ChEBI:CHEBI:58475" FT /ligand_note="ligand shared between dimeric partners" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:P31939" FT BINDING 339 FT /ligand="5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4- FT carboxamide" FT /ligand_id="ChEBI:CHEBI:58475" FT /ligand_note="ligand shared between dimeric partners" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:P31939" FT BINDING 431 FT /ligand="5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4- FT carboxamide" FT /ligand_id="ChEBI:CHEBI:58475" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:P31939" FT BINDING 451 FT /ligand="5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4- FT carboxamide" FT /ligand_id="ChEBI:CHEBI:58475" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:P31939" FT BINDING 452 FT /ligand="(6R)-10-formyltetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:195366" FT /evidence="ECO:0000250|UniProtKB:P31335" FT BINDING 541 FT /ligand="5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4- FT carboxamide" FT /ligand_id="ChEBI:CHEBI:58475" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:P31939" FT BINDING 546 FT /ligand="(6R)-10-formyltetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:195366" FT /evidence="ECO:0000250|UniProtKB:P31335" FT BINDING 565..566 FT /ligand="(6R)-10-formyltetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:195366" FT /evidence="ECO:0000250|UniProtKB:P31335" FT BINDING 588 FT /ligand="5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4- FT carboxamide" FT /ligand_id="ChEBI:CHEBI:58475" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:P31939" FT SITE 266 FT /note="Transition state stabilizer" FT /evidence="ECO:0000250|UniProtKB:P31939" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000250|UniProtKB:P31939" FT MOD_RES 199 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P31939" SQ SEQUENCE 592 AA; 64483 MW; EBD94993555935D7 CRC64; MAPGQLALFS VSDKNGLVEF ARNLASVGLN LIASGGTAKA LRDAGLAVRD VSELTGFPEM LGGRVKTLHP AVHAGILARD IPEDSADMAK LDFNLIRVVV CNLYPFGKTV ASPGVTVEEA VEHIDIGGVT LLRAAAKNHA RVTVVCEPED YAAVASEMQD SDSKDTSLET RRQLALKAFT HTAQYDEAIS DYFRKEYSKG VSQMPLRYGM NPHQTPAQLY TLKPKLPITV LNGAPGFINL CDALNAWQLV KELKEALGLP AAASFKHVSP AGAAVGIPLS EDEANVCMVY DLYKTLTPVA TAYARARGAD RMSSFGDFVA LSDVCDVPTA KIISREVSDG IIAPGYENEA LKILSKKKNG NYCVLQMDQS YIPDENEVRT LFGLRLSQKR NNSVVNRSLF SNIVTKNKDL PESALRDLIV ATIAVKYTQS NSVCYAKNGQ VIGIGAGQQS RIHCTRLAGD KANCWWLRHH PQVLSMKFKT GVKRAEISNA IDQYVTGTIG EGEDLIKWKA LFEEVPELLT ETEKKEWIDK LNEVSISSDA FFPFRDNVDR AKRSGVAYIA APSGSAADKV VIEACDELGI ILAHTNLRLF HH //