PUR9_RAT
ID PUR9_RAT Reviewed; 592 AA.
AC O35567; Q6IN16;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 146.
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=IMP cyclohydrolase;
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Donryu; TISSUE=Liver;
RX PubMed=9332377; DOI=10.1016/s0378-1119(97)00273-4;
RA Akira T., Komatsu M., Nango R., Tomooka A., Konaka K., Yamauchi M.,
RA Kitamura Y., Nomura S., Tsukamoto I.;
RT "Molecular cloning and expression of a rat cDNA encoding 5-aminoimidazole-
RT 4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase.";
RL Gene 197:289-293(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 178-194; 531-545 AND 570-588, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (NOV-2006) to UniProtKB.
RN [4]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH INSR.
RX PubMed=25687571; DOI=10.1074/mcp.m114.047159;
RA Boutchueng-Djidjou M., Collard-Simard G., Fortier S., Hebert S.S.,
RA Kelly I., Landry C.R., Faure R.L.;
RT "The last enzyme of the de novo purine synthesis pathway 5-aminoimidazole-
RT 4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC)
RT plays a central role in insulin signaling and the Golgi/endosomes protein
RT network.";
RL Mol. Cell. Proteomics 14:1079-1092(2015).
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 (By similarity). Promotes
CC insulin receptor/INSR autophosphorylation and is involved in INSR
CC internalization (PubMed:25687571). {ECO:0000250|UniProtKB:P31939,
CC ECO:0000269|PubMed:25687571}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-10-formyltetrahydrofolate + 5-amino-1-(5-phospho-beta-D-
CC ribosyl)imidazole-4-carboxamide = (6S)-5,6,7,8-tetrahydrofolate + 5-
CC formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide;
CC Xref=Rhea:RHEA:22192, ChEBI:CHEBI:57453, ChEBI:CHEBI:57454,
CC ChEBI:CHEBI:58467, ChEBI:CHEBI:58475; 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=H2O + IMP = 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 (By similarity). Associates with internalized INSR
CC complexes on Golgi/endosomal membranes (PubMed:25687571). Interacts
CC with INSR; ATIC together with PRKAA2/AMPK2 and HACD3/PTPLAD1 is
CC proposed to be part of a signaling network regulating INSR
CC autophosphorylation and endocytosis (PubMed:25687571).
CC {ECO:0000250|UniProtKB:P31939, ECO:0000269|PubMed:25687571}.
CC -!- INTERACTION:
CC O35567; PRO_0000016698 [P15127]: Insr; NbExp=3; IntAct=EBI-10768817, EBI-10768746;
CC -!- TISSUE SPECIFICITY: Expressed in liver. {ECO:0000269|PubMed:9332377}.
CC -!- DOMAIN: The IMP cyclohydrolase activity resides in the N-terminal
CC region.
CC -!- MISCELLANEOUS: The de novo purine synthesis pathway includes 10
CC sequential steps, beginning with phosphoribosyl pyrophosphate and
CC ending with inositol monophosphate (IMP), the first purin compound of
CC the pathway. {ECO:0000250|UniProtKB:P31939}.
CC -!- SIMILARITY: Belongs to the PurH family. {ECO:0000305}.
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DR EMBL; D89514; BAA22837.1; -; mRNA.
DR EMBL; BC072496; AAH72496.1; -; mRNA.
DR RefSeq; NP_112276.2; NM_031014.2.
DR AlphaFoldDB; O35567; -.
DR SMR; O35567; -.
DR BioGRID; 249543; 3.
DR IntAct; O35567; 3.
DR MINT; O35567; -.
DR STRING; 10116.ENSRNOP00000021105; -.
DR iPTMnet; O35567; -.
DR PhosphoSitePlus; O35567; -.
DR jPOST; O35567; -.
DR PaxDb; O35567; -.
DR PRIDE; O35567; -.
DR Ensembl; ENSRNOT00000098789; ENSRNOP00000084375; ENSRNOG00000015511.
DR Ensembl; ENSRNOT00000116844; ENSRNOP00000078278; ENSRNOG00000015511.
DR GeneID; 81643; -.
DR KEGG; rno:81643; -.
DR UCSC; RGD:70879; rat.
DR CTD; 471; -.
DR RGD; 70879; Atic.
DR eggNOG; KOG2555; Eukaryota.
DR GeneTree; ENSGT00390000004553; -.
DR HOGENOM; CLU_016316_3_2_1; -.
DR InParanoid; O35567; -.
DR OMA; WRVAKFV; -.
DR OrthoDB; 324473at2759; -.
DR PhylomeDB; O35567; -.
DR TreeFam; TF105642; -.
DR BRENDA; 2.1.2.3; 5301.
DR BRENDA; 3.5.4.10; 5301.
DR Reactome; R-RNO-73817; Purine ribonucleoside monophosphate biosynthesis.
DR UniPathway; UPA00074; UER00133.
DR UniPathway; UPA00074; UER00135.
DR PRO; PR:O35567; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Bgee; ENSRNOG00000015511; Expressed in thymus and 19 other tissues.
DR Genevisible; O35567; RN.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0003937; F:IMP cyclohydrolase activity; IDA:RGD.
DR GO; GO:0004643; F:phosphoribosylaminoimidazolecarboxamide formyltransferase activity; IDA:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0044208; P:'de novo' AMP biosynthetic process; ISO:RGD.
DR GO; GO:0006189; P:'de novo' IMP biosynthetic process; IDA:RGD.
DR GO; GO:0097294; P:'de novo' XMP biosynthetic process; ISO:RGD.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR GO; GO:0003360; P:brainstem development; IEP:RGD.
DR GO; GO:0098761; P:cellular response to interleukin-7; ISO:RGD.
DR GO; GO:0021549; P:cerebellum development; IEP:RGD.
DR GO; GO:0021987; P:cerebral cortex development; IEP:RGD.
DR GO; GO:0009235; P:cobalamin metabolic process; TAS:RGD.
DR GO; GO:0046452; P:dihydrofolate metabolic process; IDA:RGD.
DR GO; GO:0006177; P:GMP biosynthetic process; ISO:RGD.
DR GO; GO:0009116; P:nucleoside metabolic process; IDA:RGD.
DR GO; GO:0010035; P:response to inorganic substance; IEP:RGD.
DR GO; GO:0009259; P:ribonucleotide metabolic process; IDA:RGD.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IDA:RGD.
DR Gene3D; 1.10.287.440; -; 1.
DR Gene3D; 3.40.140.20; -; 2.
DR Gene3D; 3.40.50.1380; -; 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 PANTHER; PTHR11692; PTHR11692; 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; SSF52335; SSF52335; 1.
DR SUPFAM; SSF53927; SSF53927; 1.
DR TIGRFAMs; TIGR00355; purH; 1.
DR PROSITE; PS51855; MGS; 1.
PE 1: Evidence at protein level;
KW Acetylation; Direct protein sequencing; Hydrolase; Multifunctional enzyme;
KW Purine biosynthesis; Reference proteome; Transferase.
FT CHAIN 1..592
FT /note="Bifunctional purine biosynthesis protein ATIC"
FT /id="PRO_0000270214"
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="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
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="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000250|UniProtKB:P31335"
FT BINDING 565..566
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
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"
FT CONFLICT 24
FT /note="L -> H (in Ref. 1; BAA22837)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 592 AA; 64208 MW; D9D710794BB12B95 CRC64;
MASSQLALFS VSDKTGLVEF ARNLASLGLS LVASGGTAKA IRDAGLAVRD VSELTGFPEM
LGGRVKTLHP AVHAGILARN IPEDAADMAR LDFNLIRVVV CNLYPFVKTV ASPDVTVEAA
VEQIDIGGVT LLRAAAKNHA RVTVVCEPED YGAVAAEMQG SGNKDTSLET RRHLALKAFT
HTAQYDEAIS DYFRRQYSKG ISQMPLRYGM NPHQTPAQLY TLKPKLPITV LNGAPGFINL
CDALNAWQLV TELRGAVDIP AAASFKHVSP AGAAVGVPLS EDEARVCMVY DLYPTLTPLA
IAYARARGAD RMSSFGDFVA LSDVCDVPTA KIISREVSDG IVAPGYEEEA LKILSKKKNG
SYCVLQMDQS YKPDENEVRT LFGLRLSQKR NNGVVDKSLF SNIVTKNKDL PESALRDLIV
ATIAVKYTQS NSVCYAKDGQ VIGIGAGQQS RIHCTRLAGD KANSWWLRHH PRVLSMKFKA
GVKRAEVSNA IDQYVTGTIG EGEDLVKWKA LFEEVPELLT EAEKKEWVDK LSGVSVSSDA
FFPFRDNVDR AKRSGVAYIV APSGSTADKV VIEACDELGI VLAHTDLRLF HH
