ID   PUR9_DICDI              Reviewed;         542 AA.
AC   Q86L14; Q550I9;
DT   08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2003, sequence version 1.
DT   27-MAR-2024, entry version 116.
DE   RecName: Full=Bifunctional purine biosynthesis protein purH;
DE   Includes:
DE     RecName: Full=Phosphoribosylaminoimidazolecarboxamide formyltransferase;
DE              EC=2.1.2.3 {ECO:0000250|UniProtKB:P54113};
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:P54113};
DE     AltName: Full=ATIC;
DE     AltName: Full=IMP synthase;
DE     AltName: Full=Inosinicase;
GN   Name=purH; ORFNames=DDB_G0277087;
OS   Dictyostelium discoideum (Social amoeba).
OC   Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC   Dictyosteliaceae; Dictyostelium.
OX   NCBI_TaxID=44689;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=AX4;
RX   PubMed=12097910; DOI=10.1038/nature00847;
RA   Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA   Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA   Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA   Noegel A.A.;
RT   "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL   Nature 418:79-85(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=AX4;
RX   PubMed=15875012; DOI=10.1038/nature03481;
RA   Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA   Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA   Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA   Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA   Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA   Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA   Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA   Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA   Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA   Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA   Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA   Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA   Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA   Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA   Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA   Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA   Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT   "The genome of the social amoeba Dictyostelium discoideum.";
RL   Nature 435:43-57(2005).
RN   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=AX2;
RX   PubMed=16926386; DOI=10.1074/mcp.m600113-mcp200;
RA   Gotthardt D., Blancheteau V., Bosserhoff A., Ruppert T., Delorenzi M.,
RA   Soldati T.;
RT   "Proteomics fingerprinting of phagosome maturation and evidence for the
RT   role of a Galpha during uptake.";
RL   Mol. Cell. Proteomics 5:2228-2243(2006).
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). Also catalyzes the cyclization of FAICAR to IMP.
CC       {ECO:0000250|UniProtKB:P54113}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6R)-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:58467,
CC         ChEBI:CHEBI:58475, ChEBI:CHEBI:195366; EC=2.1.2.3;
CC         Evidence={ECO:0000250|UniProtKB:P54113};
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:P54113};
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.
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.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P54113}.
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   -!- 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; AAFI02000019; EAL69045.1; -; Genomic_DNA.
DR   RefSeq; XP_642943.1; XM_637851.1.
DR   AlphaFoldDB; Q86L14; -.
DR   SMR; Q86L14; -.
DR   STRING; 44689.Q86L14; -.
DR   PaxDb; 44689-DDB0230095; -.
DR   EnsemblProtists; EAL69045; EAL69045; DDB_G0277087.
DR   GeneID; 8620812; -.
DR   KEGG; ddi:DDB_G0277087; -.
DR   dictyBase; DDB_G0277087; purH.
DR   eggNOG; KOG2555; Eukaryota.
DR   HOGENOM; CLU_016316_5_2_1; -.
DR   InParanoid; Q86L14; -.
DR   OMA; IKHNNPC; -.
DR   PhylomeDB; Q86L14; -.
DR   Reactome; R-DDI-73817; Purine ribonucleoside monophosphate biosynthesis.
DR   UniPathway; UPA00074; UER00133.
DR   UniPathway; UPA00074; UER00135.
DR   PRO; PR:Q86L14; -.
DR   Proteomes; UP000002195; Chromosome 2.
DR   GO; GO:0005829; C:cytosol; ISS:dictyBase.
DR   GO; GO:0045335; C:phagocytic vesicle; HDA:dictyBase.
DR   GO; GO:0003937; F:IMP cyclohydrolase activity; ISS:dictyBase.
DR   GO; GO:0004643; F:phosphoribosylaminoimidazolecarboxamide formyltransferase activity; ISS:dictyBase.
DR   GO; GO:0006189; P:'de novo' IMP biosynthetic process; ISS:dictyBase.
DR   GO; GO:0006164; P:purine nucleotide biosynthetic process; ISS:dictyBase.
DR   CDD; cd01421; IMPCH; 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; IPR016193; Cytidine_deaminase-like.
DR   InterPro; IPR011607; MGS-like_dom.
DR   InterPro; IPR036914; MGS-like_dom_sf.
DR   InterPro; IPR002695; PurH-like.
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   1: Evidence at protein level;
KW   Cytoplasm; Hydrolase; Multifunctional enzyme; Purine biosynthesis;
KW   Reference proteome; Transferase.
FT   CHAIN           1..542
FT                   /note="Bifunctional purine biosynthesis protein purH"
FT                   /id="PRO_0000329022"
FT   DOMAIN          1..143
FT                   /note="MGS-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01202"
FT   ACT_SITE        134
FT                   /note="Proton donor/acceptor; for FAICAR cyclization
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   ACT_SITE        295
FT                   /note="Proton acceptor; for AICAR formyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   BINDING         30..33
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   BINDING         60..63
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   BINDING         122..123
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   BINDING         236..237
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         295
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         327
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         350
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         446
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         466
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         491
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         496
FT                   /ligand="(6R)-10-formyltetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:195366"
FT                   /evidence="ECO:0000250|UniProtKB:P31335"
FT   BINDING         538
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            294
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
SQ   SEQUENCE   542 AA;  59087 MW;  B2EC8F2D199D04F1 CRC64;
     MQALLSVYNK SGIVEFSKIL SSKGFNLIST GGTAKSLVDN GLKVQQVSDV TEYPEMLDGR
     VKTLHPKIHG GLLARPELAH HQADLNKYNI KPISIVVVNL YPFVETVSKE STTLEEAIEN
     IDIGGHTLIR ASSKNFQNVL IIVDPSDYKW IGERIQSSTD STNVLSSITL EERKKLALKA
     FQHGCSYDAA VSQYLSKVEL TNATTIQGVK GTDSASVNVE FPQTFLPLYE KKNDLRYGEN
     PHQKAALYQC PGTGGIANAQ LLHGPALSYN NILDGDAALK AVREFDRCAC VVIKHTNPCG
     LSVGVNDSEQ AEVYKRAFNG DPKSAYGGIL GFNRTLTLET ATALKSVFYE VIIAPDYTED
     ALALLSKKEK LRILRIPEAA NQIQFTQPDI RTITGGALLQ SPNPIIRGDL AEATKNWKVV
     TENKPTEQQM KDLLFAWRVS KHVKSNAIVL SKDETIVAIG AGQPNRSQSV DICMKVGGDK
     VKGSVLASDA FFPFADSIDL AHQGNIACIV QPGGSIRDQE VIDAANKYGI PMVFTGNRNF
     LH
//