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 27-MAR-2024, entry version 223. 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}; GN Synonyms=PURH {ECO:0000303|PubMed:8567683}; 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), AND DOMAIN. 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=(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: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 CC 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (with CC (6S)-10-formyltetrahydrofolate as cosubstrate) CC {ECO:0000269|PubMed:11948179}; CC KM=1.5 uM for CC 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (with CC 10-formyldihydrofolate as cosubstrate) {ECO:0000269|PubMed:10985775}; CC KM=1.9 uM for CC 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (with CC (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 CC 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide CC {ECO:0000269|PubMed:11948179}; CC KM=0.9 uM for CC 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide CC {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 CC 10-formyldihydrofolate as substrate (PubMed:10985775). kcat is 2.9 CC sec(-1) for AICAR formyltransferase activity with CC (6S)-10-formyltetrahydrofolate as substrate (PubMed:11948179). kcat CC is 6.0 sec(-1) for FAICAR cyclization activity (PubMed:11948179). CC kcat is 8.6 sec(-1) for FAICAR cyclization activity CC (PubMed:14756554). {ECO:0000269|PubMed:10985775, CC ECO:0000269|PubMed:11948179, 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 -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:P54113}. 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. {ECO:0000269|PubMed:8567683}. 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="https://atlasgeneticsoncology.org/gene/227/ATIC"; 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; 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; 147. DR IntAct; P31939; 23. 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 EPD; P31939; -. DR jPOST; P31939; -. DR MassIVE; P31939; -. DR MaxQB; P31939; -. DR PaxDb; 9606-ENSP00000236959; -. DR PeptideAtlas; P31939; -. DR ProteomicsDB; 19298; -. DR ProteomicsDB; 54805; -. [P31939-1] DR Pumba; P31939; -. DR Antibodypedia; 4601; 480 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 AGR; HGNC:794; -. 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; IKHNNPC; -. DR OrthoDB; 275312at2759; -. DR PhylomeDB; P31939; -. DR TreeFam; TF105642; -. DR BioCyc; MetaCyc:HS06490-MONOMER; -. 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; 225 hits in 1173 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 201 other cell types or tissues. DR ExpressionAtlas; P31939; baseline and differential. 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:0010035; P:response to inorganic substance; IEA:Ensembl. DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:Ensembl. DR CDD; cd01421; IMPCH; 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; 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. DR UCD-2DPAGE; P31939; -. DR Genevisible; P31939; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; KW Direct protein sequencing; Disease variant; Epilepsy; Hydrolase; KW Intellectual disability; Multifunctional enzyme; Purine biosynthesis; KW Reference proteome; 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="(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:0000269|PubMed:14966129, FT ECO:0000269|PubMed:29072452, ECO:0007744|PDB:1P4R, FT ECO:0007744|PDB:1PL0" 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: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 //