Inosine monophosphate synthase

Bifunctional purine biosynthesis protein PURH is a protein that in humans is encoded by the ATIC gene.

ATIC
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1P4R, 1PKX, 1PL0
Identifiers
Aliases	ATIC, AICAR, AICARFT, HEL-S-70p, IMPCHASE, PURH, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase
External IDs	OMIM: 601731; MGI: 1351352; HomoloGene: 2983; GeneCards: ATIC; OMA:ATIC - orthologs
Gene location (Human) Chr. Chromosome 2 (human) Band 2q35 Start 215,311,956 bp End 215,349,773 bp
Gene location (Mouse) Chr. Chromosome 1 (mouse) Band 1|1 C3 Start 71,596,309 bp End 71,618,790 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of transverse colon stromal cell of endometrium rectum anterior pituitary ventricular zone right adrenal cortex body of pancreas gonad ganglionic eminence left adrenal cortex Top expressed in hand epiblast condyle mandibular prominence maxillary prominence transitional epithelium of urinary bladder abdominal wall mesenteric lymph nodes primitive streak foot More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity protein homodimerization activity IMP cyclohydrolase activity catalytic activity phosphoribosylaminoimidazolecarboxamide formyltransferase activity hydrolase activity cadherin binding Cellular component cytosol membrane mitochondrion extracellular exosome plasma membrane Biological process purine nucleotide biosynthetic process dihydrofolate metabolic process 'de novo' IMP biosynthetic process brainstem development ribonucleotide metabolic process cerebellum development nucleoside metabolic process tetrahydrofolate biosynthetic process animal organ regeneration response to inorganic substance cerebral cortex development purine ribonucleoside monophosphate biosynthetic process metabolism nucleobase-containing compound metabolic process cellular response to interleukin-7 Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 471 108147 Ensembl ENSG00000138363 ENSMUSG00000026192 UniProt P31939 Q9CWJ9 RefSeq (mRNA) NM_004044 NM_026195 RefSeq (protein) NP_004035 NP_080471 Location (UCSC) Chr 2: 215.31 – 215.35 Mb Chr 1: 71.6 – 71.62 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

ATIC encodes an enzyme which generates inosine monophosphate from aminoimidazole carboxamide ribonucleotide (AICA ribonucleotide).

It has two functions:

• EC 2.1.2.3 - 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase

In this step, AICA ribonucleotide is formylated, with the formyl group being transferred from the cofactor 5,10-methylenetetrahydrofolate (5,10-CH₂-THF).

AICA ribonucleotide

+ 5,10-CH₂-THF

 

 

 

 

 

 

 

N-formyl AICA ribonucleotide

+ tetrahydrofolate

 

• EC 3.5.4.10 - IMP cyclohydrolase

This enzyme forms the purine ring of inosine monophosphate by dehydration and cyclisation of N-formyl AICA ribonucleotide.

N-formyl AICA ribonucleotide

 

 

H₂O

 

 

 

inosinic acid

Further reading

• Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE, Vandekerckhove J (1993). "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes". Electrophoresis. 13 (12): 960–9. doi:10.1002/elps.11501301199. PMID 1286667. S2CID 41855774.
• Yamauchi M, Seki N, Mita K, Saito T, Tsuji S, Hongo E, Morimyo M, Shiomi T, Koyama H (1996). "Isolation of human purH gene expressed in the rodent transformant cells by subtractive enrichment of 3'-untranslated region of human transcript". DNA Res. 2 (6): 269–75. doi:10.1093/dnares/2.6.269. PMID 8867801.
• Beardsley GP, Rayl EA, Gunn K, Moroson BA, Seow H, Anderson KS, Vergis J, Fleming K, Worland S (1998). "Structure and Functional Relationships in Human pur H". Purine and Pyrimidine Metabolism in Man IX. Advances in Experimental Medicine and Biology. Vol. 431. pp. 221–6. doi:10.1007/978-1-4615-5381-6_43. ISBN 978-0-306-45778-4. PMID 9598063.
• Vergis JM, Bulock KG, Fleming KG, Beardsley GP (2001). "Human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine 5'-monophosphate cyclohydrolase. A bifunctional protein requiring dimerization for transformylase activity but not for cyclohydrolase activity". J. Biol. Chem. 276 (11): 7727–33. doi:10.1074/jbc.M009940200. PMID 11096114.
• Bulock KG, Beardsley GP, Anderson KS (2002). "The kinetic mechanism of the human bifunctional enzyme ATIC (5-amino-4-imidazolecarboxamide ribonucleotide transformylase/inosine 5'-monophosphate cyclohydrolase). A surprising lack of substrate channeling". J. Biol. Chem. 277 (25): 22168–74. doi:10.1074/jbc.M111964200. PMID 11948179.
• Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Cheong CG, Wolan DW, Greasley SE, Horton PA, Beardsley GP, Wilson IA (2004). "Crystal structures of human bifunctional enzyme aminoimidazole-4-carboxamide ribonucleotide transformylase/IMP cyclohydrolase in complex with potent sulfonyl-containing antifolates". J. Biol. Chem. 279 (17): 18034–45. doi:10.1074/jbc.M313691200. PMID 14966129.
• Marie S, Heron B, Bitoun P, Timmerman T, Van Den Berghe G, Vincent MF (2004). "AICA-Ribosiduria: A Novel, Neurologically Devastating Inborn Error of Purine Biosynthesis Caused by Mutation of ATIC". Am. J. Hum. Genet. 74 (6): 1276–81. doi:10.1086/421475. PMC 1182092. PMID 15114530.
• Dervieux T, Furst D, Lein DO, Capps R, Smith K, Walsh M, Kremer J (2004). "Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis". Arthritis Rheum. 50 (9): 2766–74. doi:10.1002/art.20460. PMID 15457444.
• Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L (2007). "Large-scale mapping of human protein–protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.