PUR9_PONAB
ID PUR9_PONAB Reviewed; 592 AA.
AC Q5R5C2;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 86.
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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=(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. 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 -!- 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; CR860940; CAH93044.1; -; mRNA.
DR RefSeq; NP_001126800.1; NM_001133328.1.
DR AlphaFoldDB; Q5R5C2; -.
DR SMR; Q5R5C2; -.
DR STRING; 9601.ENSPPYP00000014690; -.
DR GeneID; 100173804; -.
DR KEGG; pon:100173804; -.
DR CTD; 471; -.
DR eggNOG; KOG2555; Eukaryota.
DR InParanoid; Q5R5C2; -.
DR OrthoDB; 324473at2759; -.
DR UniPathway; UPA00074; UER00133.
DR UniPathway; UPA00074; UER00135.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0003937; F:IMP cyclohydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0004643; F:phosphoribosylaminoimidazolecarboxamide formyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0006189; P:'de novo' IMP biosynthetic process; IEA:UniProtKB-UniPathway.
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 2: Evidence at transcript level;
KW Acetylation; Hydrolase; Multifunctional enzyme; Purine biosynthesis;
KW Reference proteome; Transferase.
FT CHAIN 1..592
FT /note="Bifunctional purine biosynthesis protein ATIC"
FT /id="PRO_0000270213"
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"
SQ SEQUENCE 592 AA; 64693 MW; 4991DDFCCD8D0E7B CRC64;
MAPGHLALFS VSDKTGLVEF ARNLTALGLN LVASGGTAKA LRDAGLAVRD VSELTGFPEM
LGGRVKTLHP AVHAGILARN IPEDNADMAR LDFNLIRVVA CNLYPFVKTV ASPGVTVEEA
VEQIDIGGVT LLRAAAKNHA RVTVVCEPED YVVVSTEMKS SEIKDTSLET RRQLALKAFT
HTAQYDEAIS DYFRKQYSKG ISQMPLRYGM NPHQTPAQLY TLKPKLPITV LNGAPGFINL
CDALNAWQLV KELKEALGIP AAASFKHVSP AGAAVGIPLS EDEAKVCMVY DLYKTLTPIS
AAYARARGAD RMSSFGDFVA LSDVCDVPTA KIISREVSDG IIAPGYEEEA LKILSKKKNG
NYCVLQMDQS YKPDENEVRT LFGLHLSQKR NNGVVDKSLF SNVVTKNKDL PESALRDLIV
ATIAVKYTQS NSVCYAKNGQ VIGIGAGQQS RIHCTRLAGD KANYWWLRHH PQVLSMKFKT
GVKRAEISNA IDQYVTGTIG EDEDLIKWEA LFEEVPELLT EAEKKEWVEK LTEVSISSDA
FFPFRDNVDR AKRSGVAYIA APSGSAADKV VIEACDELGI ILAHTNLRLF HH
