PUR9_HUMAN
ID PUR9_HUMAN Reviewed; 592 AA.
AC P31939; A8K202; E9PBU3; Q13856; Q53S28;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2002, sequence version 3.
DT 03-AUG-2022, entry version 214.
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:0000269|PubMed:10985775, ECO:0000269|PubMed:11948179, ECO:0000269|PubMed:9378707};
DE AltName: Full=5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase {ECO:0000303|PubMed:9378707};
DE Short=AICAR formyltransferase {ECO:0000303|PubMed:9378707};
DE AltName: Full=AICAR transformylase;
DE Includes:
DE RecName: Full=Inosine 5'-monophosphate cyclohydrolase {ECO:0000303|PubMed:11948179};
DE Short=IMP cyclohydrolase {ECO:0000303|PubMed:11948179};
DE EC=3.5.4.10 {ECO:0000269|PubMed:11948179, ECO:0000269|PubMed:14756554};
DE AltName: Full=IMP synthase;
DE AltName: Full=Inosinicase;
DE Contains:
DE RecName: Full=Bifunctional purine biosynthesis protein ATIC, N-terminally processed;
GN Name=ATIC {ECO:0000312|HGNC:HGNC:794}; Synonyms=PURH; ORFNames=OK/SW-cl.86;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Hepatoma;
RX PubMed=8567683; DOI=10.1074/jbc.271.4.2225;
RA Rayl E.A., Moroson B.A., Beardsley G.P.;
RT "The human purH gene product, 5-aminoimidazole-4-carboxamide ribonucleotide
RT formyltransferase/IMP cyclohydrolase. Cloning, sequencing, expression,
RT purification, kinetic analysis, and domain mapping.";
RL J. Biol. Chem. 271:2225-2233(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=8867801; DOI=10.1093/dnares/2.6.269;
RA Yamauchi M., Seki N., Mita K., Saito T., Tsuji S., Hongo E., Morimyo M.,
RA Shiomi T., Koyama H.;
RT "Isolation of human purH gene expressed in the rodent transformant cells by
RT subtractive enrichment of 3'-untranslated region of human transcript.";
RL DNA Res. 2:269-275(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 2-9, FUNCTION,
RP TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, AND
RP MUTAGENESIS OF HIS-213 AND HIS-267.
RC TISSUE=Placenta;
RX PubMed=9378707; DOI=10.1093/oxfordjournals.jbchem.a021754;
RA Sugita T., Aya H., Ueno M., Ishizuka T., Kawashima K.;
RT "Characterization of molecularly cloned human 5-aminoimidazole-4-
RT carboxamide ribonucleotide transformylase.";
RL J. Biochem. 122:309-313(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that are recognized by tumor-reactive
RT CTL generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT SER-116.
RC TISSUE=Substantia nigra;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-116.
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
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 [9]
RP PROTEIN SEQUENCE OF 15-39; 91-97; 178-194; 208-225; 267-285 AND 417-426,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [10]
RP PROTEIN SEQUENCE OF 178-189 AND 267-281.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel protein
RT database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RX PubMed=10985775; DOI=10.1021/bi0007268;
RA Wall M., Shim J.H., Benkovic S.J.;
RT "Human AICAR transformylase: role of the 4-carboxamide of AICAR in binding
RT and catalysis.";
RL Biochemistry 39:11303-11311(2000).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=11948179; DOI=10.1074/jbc.m111964200;
RA Bulock K.G., Beardsley G.P., Anderson K.S.;
RT "The kinetic mechanism of the human bifunctional enzyme ATIC (5-amino-4-
RT imidazolecarboxamide ribonucleotide transformylase/inosine 5'-monophosphate
RT cyclohydrolase). A surprising lack of substrate channeling.";
RL J. Biol. Chem. 277:22168-22174(2002).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF LYS-66; TYR-104; ASP-125 AND LYS-137.
RX PubMed=14756554; DOI=10.1021/bi035139b;
RA Vergis J.M., Beardsley G.P.;
RT "Catalytic mechanism of the cyclohydrolase activity of human aminoimidazole
RT carboxamide ribonucleotide formyltransferase/inosine monophosphate
RT cyclohydrolase.";
RL Biochemistry 43:1184-1192(2004).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-199, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH ISNR.
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).
RN [21] {ECO:0007744|PDB:1PKX}
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH XMP, SUBUNIT, AND
RP ACTIVE SITE.
RX PubMed=14756553; DOI=10.1021/bi030162i;
RA Wolan D.W., Cheong C.-G., Greasley S.E., Wilson I.A.;
RT "Structural insights into the human and avian IMP cyclohydrolase mechanism
RT via crystal structures with the bound XMP inhibitor.";
RL Biochemistry 43:1171-1183(2004).
RN [22] {ECO:0007744|PDB:1P4R, ECO:0007744|PDB:1PL0}
RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) IN COMPLEXES WITH AICAR; XMP AND THE
RP INHIBITORS BW1540 AND BW2315, SUBUNIT, AND ACTIVE SITE.
RX PubMed=14966129; DOI=10.1074/jbc.m313691200;
RA Cheong C.-G., Wolan D.W., Greasley S.E., Horton P.A., Beardsley G.P.,
RA Wilson I.A.;
RT "Crystal structures of human bifunctional enzyme aminoimidazole-4-
RT carboxamide ribonucleotide transformylase/IMP cyclohydrolase in complex
RT with potent sulfonyl-containing antifolates.";
RL J. Biol. Chem. 279:18034-18045(2004).
RN [23] {ECO:0007744|PDB:5UY8, ECO:0007744|PDB:5UZ0}
RP X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 2-592 IN COMPLEXES WITH AICAR AND
RP LSN 3213128 INHIBITOR, AND ACTIVITY REGULATION.
RX PubMed=29072452; DOI=10.1021/acs.jmedchem.7b01046;
RA Fales K.R., Njoroge F.G., Brooks H.B., Thibodeaux S., Torrado A., Si C.,
RA Toth J.L., Mc Cowan J.R., Roth K.D., Thrasher K.J., Frimpong K., Lee M.R.,
RA Dally R.D., Shepherd T.A., Durham T.B., Margolis B.J., Wu Z., Wang Y.,
RA Atwell S., Wang J., Hui Y.H., Meier T.I., Konicek S.A., Geeganage S.;
RT "Discovery of LSN 3213128, a Potent and Selective Nonclassical Antifolate
RT Aminoimidazole-4-carboxamide Ribonucleotide Formyltransferase (AICARFT)
RT Inhibitor Effective at Tumor Suppression in a Cancer Xenograft Model.";
RL J. Med. Chem. 60:9599-9616(2017).
RN [24]
RP INVOLVEMENT IN AICAR DISEASE, VARIANT AICAR ARG-426, AND CHARACTERIZATION
RP OF VARIANT AICAR ARG-426.
RX PubMed=15114530; DOI=10.1086/421475;
RA Marie S., Heron B., Bitoun P., Timmerman T., Van Den Berghe G.,
RA Vincent M.-F.;
RT "AICA-ribosiduria: a novel, neurologically devastating inborn error of
RT purine biosynthesis caused by mutation of ATIC.";
RL Am. J. Hum. Genet. 74:1276-1281(2004).
CC -!- FUNCTION: Bifunctional enzyme that catalyzes the last two steps of
CC purine biosynthesis (PubMed:11948179, PubMed:14756554). Acts as a
CC transformylase that incorporates a formyl group to the AMP analog AICAR
CC (5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide) to
CC produce the intermediate formyl-AICAR (FAICAR) (PubMed:9378707,
CC PubMed:11948179, PubMed:10985775). Can use both 10-formyldihydrofolate
CC and 10-formyltetrahydrofolate as the formyl donor in this reaction
CC (PubMed:10985775). Also catalyzes the cyclization of FAICAR to IMP
CC (PubMed:11948179, PubMed:14756554). Is able to convert thio-AICAR to 6-
CC mercaptopurine ribonucleotide, an inhibitor of purine biosynthesis used
CC in the treatment of human leukemias (PubMed:10985775). Promotes insulin
CC receptor/INSR autophosphorylation and is involved in INSR
CC internalization (PubMed:25687571). {ECO:0000269|PubMed:10985775,
CC ECO:0000269|PubMed:11948179, ECO:0000269|PubMed:14756554,
CC ECO:0000269|PubMed:25687571, ECO:0000269|PubMed:9378707}.
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:0000269|PubMed:10985775, ECO:0000269|PubMed:11948179,
CC ECO:0000269|PubMed:9378707};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22193;
CC Evidence={ECO:0000305|PubMed:10985775, ECO:0000305|PubMed:11948179,
CC ECO:0000305|PubMed:9378707};
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:0000269|PubMed:10985775};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59145;
CC Evidence={ECO:0000305|PubMed:10985775};
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:0000269|PubMed:11948179, ECO:0000269|PubMed:14756554};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18447;
CC Evidence={ECO:0000305|PubMed:11948179, ECO:0000305|PubMed:14756554};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=10-formyldihydrofolate + 5-amino-1-(5-phospho-D-
CC ribosyl)imidazole-4-thiocarboxamide = 6-thio-IMP + 7,8-dihydrofolate
CC + H2O; Xref=Rhea:RHEA:62676, ChEBI:CHEBI:15377, ChEBI:CHEBI:57451,
CC ChEBI:CHEBI:57452, ChEBI:CHEBI:145873, ChEBI:CHEBI:145875;
CC Evidence={ECO:0000269|PubMed:10985775};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62677;
CC Evidence={ECO:0000305|PubMed:10985775};
CC -!- ACTIVITY REGULATION: AMP and XMP inhibit AICAR formyltransferase
CC activity (PubMed:10985775). AICAR formyltransferase activity is
CC inhibited by N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5- [(3R)-3-
CC hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide (LSN 3213128), which
CC acts as a tumor suppression in cancer cell lines (PubMed:29072452).
CC {ECO:0000269|PubMed:10985775, ECO:0000269|PubMed:29072452}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10 uM for 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-
CC carboxamide (with (6S)-10-formyltetrahydrofolate as cosubstrate)
CC {ECO:0000269|PubMed:11948179};
CC KM=1.5 uM for 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-
CC carboxamide (with 10-formyldihydrofolate as cosubstrate)
CC {ECO:0000269|PubMed:10985775};
CC KM=1.9 uM for 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-
CC carboxamide (with (6S)-10-formyltetrahydrofolate as cosubstrate)
CC {ECO:0000269|PubMed:10985775};
CC KM=110 uM for (6S)-10-formyltetrahydrofolate
CC {ECO:0000269|PubMed:9378707};
CC KM=100 uM for (6S)-10-formyltetrahydrofolate
CC {ECO:0000269|PubMed:11948179};
CC KM=39 uM for (6S)-10-formyltetrahydrofolate
CC {ECO:0000269|PubMed:10985775};
CC KM=11 uM for 10-formyldihydrofolate {ECO:0000269|PubMed:10985775};
CC KM=1.4 uM for 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-
CC carboxamide {ECO:0000269|PubMed:11948179};
CC KM=0.9 uM for 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-
CC carboxamide {ECO:0000269|PubMed:14756554};
CC Note=kcat is 3.7 sec(-1) for AICAR formyltransferase activity with
CC (6S)-10-formyltetrahydrofolate as substrate (PubMed:10985775). kcat
CC is 4.1 sec(-1) for AICAR formyltransferase activity with 10-
CC formyldihydrofolate as substrate (PubMed:10985775). kcat is 2.9 sec(-
CC 1) for AICAR formyltransferase activity with (6S)-10-
CC formyltetrahydrofolate as substrate (PubMed:11948179). kcat is 6.0
CC sec(-1) for FAICAR cyclization activity (PubMed:11948179). kcat is
CC 8.6 sec(-1) for FAICAR cyclization activity (PubMed:14756554).
CC {ECO:0000269|PubMed:10985775, ECO:0000269|PubMed:11948179,
CC ECO:0000269|PubMed:14756554};
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:0000269|PubMed:11948179}.
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:0000269|PubMed:11948179}.
CC -!- SUBUNIT: Homodimer (PubMed:14756553, PubMed:14966129). Associates with
CC internalized INSR complexes on Golgi/endosomal membranes
CC (PubMed:25687571). Interacts with INSR; ATIC together with PRKAA2/AMPK2
CC and HACD3/PTPLAD1 is proposed to be part of a signaling network
CC regulating INSR autophosphorylation and endocytosis (PubMed:25687571).
CC {ECO:0000269|PubMed:14756553, ECO:0000269|PubMed:14966129,
CC ECO:0000269|PubMed:25687571}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P31939-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P31939-2; Sequence=VSP_053495;
CC -!- TISSUE SPECIFICITY: Present in the heart, brain, placenta, lung, liver,
CC skeletal muscle, kidney, pancreas. {ECO:0000269|PubMed:9378707}.
CC -!- DOMAIN: The IMP cyclohydrolase activity resides in the N-terminal
CC region.
CC -!- DISEASE: AICA-ribosuria due to ATIC deficiency (AICAR) [MIM:608688]: A
CC neurologically devastating inborn error of purine biosynthesis.
CC Patients excrete massive amounts of AICA-riboside in the urine and
CC accumulate AICA-ribotide and its derivatives in erythrocytes and
CC fibroblasts. Clinical features include profound intellectual
CC disability, epilepsy, dysmorphic features and congenital blindness.
CC AICAR inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:15114530}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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:0000303|PubMed:11948179}.
CC -!- SIMILARITY: Belongs to the PurH family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ATICID227.html";
CC ---------------------------------------------------------------------------
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DR EMBL; U37436; AAA97405.1; -; mRNA.
DR EMBL; D82348; BAA11559.1; -; mRNA.
DR EMBL; D89976; BAA21762.1; -; mRNA.
DR EMBL; AB062403; BAB93490.1; -; mRNA.
DR EMBL; AK290067; BAF82756.1; -; mRNA.
DR EMBL; AC073284; AAY24062.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70529.1; -; Genomic_DNA.
DR EMBL; BC008879; AAH08879.1; -; mRNA.
DR CCDS; CCDS2398.1; -. [P31939-1]
DR PIR; JC4642; JC4642.
DR RefSeq; NP_004035.2; NM_004044.6. [P31939-1]
DR PDB; 1P4R; X-ray; 2.55 A; A/B=1-592.
DR PDB; 1PKX; X-ray; 1.90 A; A/B/C/D=1-592.
DR PDB; 1PL0; X-ray; 2.60 A; A/B/C/D=1-592.
DR PDB; 5UY8; X-ray; 2.39 A; A/B/C/D=2-592.
DR PDB; 5UZ0; X-ray; 1.79 A; A/B/C/D=2-592.
DR PDBsum; 1P4R; -.
DR PDBsum; 1PKX; -.
DR PDBsum; 1PL0; -.
DR PDBsum; 5UY8; -.
DR PDBsum; 5UZ0; -.
DR AlphaFoldDB; P31939; -.
DR SMR; P31939; -.
DR BioGRID; 106961; 115.
DR IntAct; P31939; 18.
DR MINT; P31939; -.
DR STRING; 9606.ENSP00000236959; -.
DR BindingDB; P31939; -.
DR ChEMBL; CHEMBL2518; -.
DR DrugBank; DB02309; 5-monophosphate-9-beta-D-ribofuranosyl xanthine.
DR DrugBank; DB03442; Acid yellow 54 free acid.
DR DrugBank; DB01700; AICA ribonucleotide.
DR DrugBank; DB01972; Guanosine-5'-Monophosphate.
DR DrugBank; DB00563; Methotrexate.
DR DrugBank; DB04057; N-[4-([(2-Amino-4-oxo-1,4-dihydropyrido[3,2-d]pyrimidin-6-yl)methyl]{(2E)-3-[4-carbamoyl-1-(5-O-phosphono-beta-D-ribofuranosyl)-1H-imidazol-5-yl]-2-propenoyl}amino)benzoyl]-L-glutamic acid.
DR DrugBank; DB00642; Pemetrexed.
DR DrugBank; DB00116; Tetrahydrofolic acid.
DR GlyGen; P31939; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P31939; -.
DR MetOSite; P31939; -.
DR PhosphoSitePlus; P31939; -.
DR SwissPalm; P31939; -.
DR BioMuta; ATIC; -.
DR DMDM; 23831360; -.
DR REPRODUCTION-2DPAGE; IPI00289499; -.
DR UCD-2DPAGE; P31939; -.
DR EPD; P31939; -.
DR jPOST; P31939; -.
DR MassIVE; P31939; -.
DR MaxQB; P31939; -.
DR PaxDb; P31939; -.
DR PeptideAtlas; P31939; -.
DR PRIDE; P31939; -.
DR ProteomicsDB; 19298; -.
DR ProteomicsDB; 54805; -. [P31939-1]
DR Antibodypedia; 4601; 424 antibodies from 36 providers.
DR DNASU; 471; -.
DR Ensembl; ENST00000236959.14; ENSP00000236959.9; ENSG00000138363.15. [P31939-1]
DR Ensembl; ENST00000435675.5; ENSP00000415935.1; ENSG00000138363.15. [P31939-2]
DR GeneID; 471; -.
DR KEGG; hsa:471; -.
DR MANE-Select; ENST00000236959.14; ENSP00000236959.9; NM_004044.7; NP_004035.2.
DR UCSC; uc002vey.5; human. [P31939-1]
DR CTD; 471; -.
DR DisGeNET; 471; -.
DR GeneCards; ATIC; -.
DR HGNC; HGNC:794; ATIC.
DR HPA; ENSG00000138363; Low tissue specificity.
DR MalaCards; ATIC; -.
DR MIM; 601731; gene.
DR MIM; 608688; phenotype.
DR neXtProt; NX_P31939; -.
DR OpenTargets; ENSG00000138363; -.
DR Orphanet; 250977; AICA-ribosiduria.
DR PharmGKB; PA25094; -.
DR VEuPathDB; HostDB:ENSG00000138363; -.
DR eggNOG; KOG2555; Eukaryota.
DR GeneTree; ENSGT00390000004553; -.
DR HOGENOM; CLU_016316_3_2_1; -.
DR InParanoid; P31939; -.
DR OMA; WRVAKFV; -.
DR PhylomeDB; P31939; -.
DR TreeFam; TF105642; -.
DR BioCyc; MetaCyc:HS06490-MON; -.
DR BRENDA; 2.1.2.3; 2681.
DR BRENDA; 3.5.4.10; 2681.
DR PathwayCommons; P31939; -.
DR Reactome; R-HSA-73817; Purine ribonucleoside monophosphate biosynthesis.
DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants.
DR SABIO-RK; P31939; -.
DR SignaLink; P31939; -.
DR SIGNOR; P31939; -.
DR UniPathway; UPA00074; UER00133.
DR UniPathway; UPA00074; UER00135.
DR BioGRID-ORCS; 471; 207 hits in 1088 CRISPR screens.
DR ChiTaRS; ATIC; human.
DR EvolutionaryTrace; P31939; -.
DR GeneWiki; Inosine_monophosphate_synthase; -.
DR GenomeRNAi; 471; -.
DR Pharos; P31939; Tchem.
DR PRO; PR:P31939; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P31939; protein.
DR Bgee; ENSG00000138363; Expressed in mucosa of transverse colon and 199 other tissues.
DR ExpressionAtlas; P31939; baseline and differential.
DR Genevisible; P31939; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0003937; F:IMP cyclohydrolase activity; IDA:MGI.
DR GO; GO:0004643; F:phosphoribosylaminoimidazolecarboxamide formyltransferase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0044208; P:'de novo' AMP biosynthetic process; IDA:MGI.
DR GO; GO:0006189; P:'de novo' IMP biosynthetic process; IDA:MGI.
DR GO; GO:0097294; P:'de novo' XMP biosynthetic process; IDA:MGI.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0003360; P:brainstem development; IEA:Ensembl.
DR GO; GO:0098761; P:cellular response to interleukin-7; IEA:Ensembl.
DR GO; GO:0021549; P:cerebellum development; IEA:Ensembl.
DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl.
DR GO; GO:0046452; P:dihydrofolate metabolic process; IEA:Ensembl.
DR GO; GO:0006177; P:GMP biosynthetic process; IDA:MGI.
DR GO; GO:0006139; P:nucleobase-containing compound metabolic process; TAS:ProtInc.
DR GO; GO:0009116; P:nucleoside metabolic process; IEA:Ensembl.
DR GO; GO:0010035; P:response to inorganic substance; IEA:Ensembl.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:Ensembl.
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 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing;
KW Disease variant; Epilepsy; Hydrolase; Intellectual disability;
KW Multifunctional enzyme; Purine biosynthesis; Reference proteome;
KW Transferase.
FT CHAIN 1..592
FT /note="Bifunctional purine biosynthesis protein ATIC"
FT /id="PRO_0000192156"
FT INIT_MET 1
FT /note="Removed; alternate"
FT /evidence="ECO:0007744|PubMed:22223895"
FT CHAIN 2..592
FT /note="Bifunctional purine biosynthesis protein ATIC, N-
FT terminally processed"
FT /evidence="ECO:0000269|PubMed:9378707"
FT /id="PRO_0000434376"
FT DOMAIN 2..146
FT /note="MGS-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01202"
FT REGION 2..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:0000305|PubMed:14756553"
FT ACT_SITE 267
FT /note="Proton acceptor; for AICAR formyltransferase
FT activity"
FT /evidence="ECO:0000305|PubMed:14966129"
FT BINDING 12..14
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000305|PubMed:14756553,
FT ECO:0000305|PubMed:14966129, ECO:0007744|PDB:1P4R,
FT ECO:0007744|PDB:1PKX, ECO:0007744|PDB:1PL0"
FT BINDING 34..37
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000305|PubMed:14756553,
FT ECO:0000305|PubMed:14966129, ECO:0007744|PDB:1P4R,
FT ECO:0007744|PDB:1PKX, ECO:0007744|PDB:1PL0"
FT BINDING 64..67
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000305|PubMed:14756553,
FT ECO:0000305|PubMed:14966129, ECO:0007744|PDB:1P4R,
FT ECO:0007744|PDB:1PKX, ECO:0007744|PDB:1PL0"
FT BINDING 101..102
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000305|PubMed:14756553,
FT ECO:0000305|PubMed:14966129, ECO:0007744|PDB:1P4R,
FT ECO:0007744|PDB:1PKX, ECO:0007744|PDB:1PL0"
FT BINDING 125..126
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000305|PubMed:14756553,
FT ECO:0000305|PubMed:14966129, ECO:0007744|PDB:1P4R,
FT ECO:0007744|PDB:1PKX, ECO:0007744|PDB:1PL0"
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:0000269|PubMed:14966129,
FT ECO:0007744|PDB:1P4R, ECO:0007744|PDB:1PL0"
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:0000269|PubMed:14966129,
FT ECO:0000269|PubMed:29072452, ECO:0007744|PDB:1P4R,
FT ECO:0007744|PDB:1PL0"
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:0000269|PubMed:14966129,
FT ECO:0000269|PubMed:29072452, ECO:0007744|PDB:1P4R,
FT ECO:0007744|PDB:1PL0"
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:0000269|PubMed:14966129,
FT ECO:0000269|PubMed:29072452, ECO:0007744|PDB:1P4R,
FT ECO:0007744|PDB:1PL0"
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:0000269|PubMed:14966129,
FT ECO:0000269|PubMed:29072452, ECO:0007744|PDB:1P4R,
FT ECO:0007744|PDB:1PL0"
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:0000269|PubMed:14966129,
FT ECO:0000269|PubMed:29072452, ECO:0007744|PDB:1P4R,
FT ECO:0007744|PDB:1PL0"
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:0000269|PubMed:14966129,
FT ECO:0000269|PubMed:29072452, ECO:0007744|PDB:1P4R,
FT ECO:0007744|PDB:1PL0"
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:0000269|PubMed:14966129,
FT ECO:0000269|PubMed:29072452, ECO:0007744|PDB:1P4R,
FT ECO:0007744|PDB:1PL0"
FT SITE 266
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000305|PubMed:14966129"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 199
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..6
FT /note="MAPGQL -> MSSLS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:8567683"
FT /id="VSP_053495"
FT VARIANT 116
FT /note="T -> S (in dbSNP:rs2372536)"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.7"
FT /id="VAR_019306"
FT VARIANT 426
FT /note="K -> R (in AICAR; loss of transformylase activity;
FT dbSNP:rs121434478)"
FT /evidence="ECO:0000269|PubMed:15114530"
FT /id="VAR_019307"
FT MUTAGEN 66
FT /note="K->A: Decreased affinity to FAICAR; no change in
FT FAICAR cyclization activity."
FT /evidence="ECO:0000269|PubMed:14756554"
FT MUTAGEN 104
FT /note="Y->A,F: Decreased FAICAR cyclization activity; no
FT change in affinity to FAICAR."
FT /evidence="ECO:0000269|PubMed:14756554"
FT MUTAGEN 125
FT /note="D->A,E,N: Decreased FAICAR cyclization activity; no
FT change in affinity to FAICAR."
FT /evidence="ECO:0000269|PubMed:14756554"
FT MUTAGEN 137
FT /note="K->A: Decreased affinity to FAICAR; no change in
FT FAICAR cyclization activity."
FT /evidence="ECO:0000269|PubMed:14756554"
FT MUTAGEN 137
FT /note="K->R: Decreased FAICAR cyclization activity; no
FT change in affinity to FAICAR."
FT /evidence="ECO:0000269|PubMed:14756554"
FT MUTAGEN 213
FT /note="H->A: Loss of AICAR transformylase activity."
FT /evidence="ECO:0000269|PubMed:9378707"
FT MUTAGEN 267
FT /note="H->A: Loss of AICAR transformylase activity."
FT /evidence="ECO:0000269|PubMed:9378707"
FT CONFLICT 165
FT /note="D -> G (in Ref. 1; AAA97405)"
FT /evidence="ECO:0000305"
FT STRAND 6..13
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 17..26
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 30..33
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 35..42
FT /evidence="ECO:0007829|PDB:5UZ0"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 51..55
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 70..77
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 82..91
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 96..102
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 106..110
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 117..122
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 127..137
FT /evidence="ECO:0007829|PDB:5UZ0"
FT TURN 138..141
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 148..150
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 151..160
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 161..165
FT /evidence="ECO:0007829|PDB:1P4R"
FT HELIX 168..197
FT /evidence="ECO:0007829|PDB:5UZ0"
FT TURN 200..202
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 217..220
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 222..225
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 227..233
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 237..257
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 261..266
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 269..275
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 281..286
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 290..295
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 298..308
FT /evidence="ECO:0007829|PDB:5UZ0"
FT TURN 309..316
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 317..323
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 327..334
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 338..344
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 348..355
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 358..360
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 363..367
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 375..381
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 384..389
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 397..400
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 412..426
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 433..437
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 440..445
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 451..467
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 471..474
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 484..496
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 502..509
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 512..514
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 521..528
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 534..540
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 543..545
FT /evidence="ECO:0007829|PDB:1PL0"
FT HELIX 546..552
FT /evidence="ECO:0007829|PDB:5UZ0"
FT TURN 553..555
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 556..562
FT /evidence="ECO:0007829|PDB:5UZ0"
FT HELIX 568..577
FT /evidence="ECO:0007829|PDB:5UZ0"
FT STRAND 581..586
FT /evidence="ECO:0007829|PDB:5UZ0"
SQ SEQUENCE 592 AA; 64616 MW; AD778892021F0888 CRC64;
MAPGQLALFS VSDKTGLVEF ARNLTALGLN LVASGGTAKA LRDAGLAVRD VSELTGFPEM
LGGRVKTLHP AVHAGILARN IPEDNADMAR LDFNLIRVVA CNLYPFVKTV ASPGVTVEEA
VEQIDIGGVT LLRAAAKNHA RVTVVCEPED YVVVSTEMQS SESKDTSLET RRQLALKAFT
HTAQYDEAIS DYFRKQYSKG VSQMPLRYGM NPHQTPAQLY TLQPKLPITV LNGAPGFINL
CDALNAWQLV KELKEALGIP AAASFKHVSP AGAAVGIPLS EDEAKVCMVY DLYKTLTPIS
AAYARARGAD RMSSFGDFVA LSDVCDVPTA KIISREVSDG IIAPGYEEEA LTILSKKKNG
NYCVLQMDQS YKPDENEVRT LFGLHLSQKR NNGVVDKSLF SNVVTKNKDL PESALRDLIV
ATIAVKYTQS NSVCYAKNGQ VIGIGAGQQS RIHCTRLAGD KANYWWLRHH PQVLSMKFKT
GVKRAEISNA IDQYVTGTIG EDEDLIKWKA LFEEVPELLT EAEKKEWVEK LTEVSISSDA
FFPFRDNVDR AKRSGVAYIA APSGSAADKV VIEACDELGI ILAHTNLRLF HH
