UniProt:P31939 ATIC

chain
  • chain:1-592
  • initiator methionine:1
  • chain:2-592
checksum AD778892021F0888
comment
  • FUNCTION Bifunctional enzyme that catalyzes the last two steps of purine biosynthesis (PubMed:11948179, PubMed:14756554). Acts as a transformylase that incorporates a formyl group to the AMP analog AICAR (5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide) to produce the intermediate formyl-AICAR (FAICAR) (PubMed:10985775, PubMed:11948179, PubMed:9378707). Can use both 10-formyldihydrofolate and 10-formyltetrahydrofolate as the formyl donor in this reaction (PubMed:10985775). Also catalyzes the cyclization of FAICAR to inosine monophosphate (IMP) (PubMed:11948179, PubMed:14756554). Is able to convert thio-AICAR to 6-mercaptopurine ribonucleotide, an inhibitor of purine biosynthesis used in the treatment of human leukemias (PubMed:10985775). Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571).CATALYTIC ACTIVITY (6R)-10-formyltetrahydrofolate + 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide + (6S)-5,6,7,8-tetrahydrofolateCATALYTIC ACTIVITY 10-formyldihydrofolate + 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide + 7,8-dihydrofolateCATALYTIC ACTIVITY IMP + H2O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamideCATALYTIC ACTIVITY 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-thiocarboxamide + 10-formyldihydrofolate = 6-thio-IMP + 7,8-dihydrofolate + H2OACTIVITY REGULATION AMP and XMP inhibit AICAR formyltransferase activity (PubMed:10985775). AICAR formyltransferase activity is inhibited by N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5- [(3R)-3-hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide (LSN 3213128), which acts as a tumor suppression in cancer cell lines (PubMed:29072452).BIOPHYSICOCHEMICAL PROPERTIES kcat is 3.7 sec(-1) for AICAR formyltransferase activity with (6S)-10-formyltetrahydrofolate as substrate (PubMed:10985775). kcat is 4.1 sec(-1) for AICAR formyltransferase activity with 10-formyldihydrofolate as substrate (PubMed:10985775). kcat is 2.9 sec(-1) for AICAR formyltransferase activity with (6S)-10-formyltetrahydrofolate as substrate (PubMed:11948179). kcat is 6.0 sec(-1) for FAICAR cyclization activity (PubMed:11948179). kcat is 8.6 sec(-1) for FAICAR cyclization activity (PubMed:14756554).PATHWAY Purine metabolism; IMP biosynthesis via de novo pathway; 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide (10-formyl THF route): step 1/1.PATHWAY Purine metabolism; IMP biosynthesis via de novo pathway; IMP from 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide: step 1/1.SUBUNIT Homodimer (PubMed:14756553, PubMed:14966129). Associates with internalized INSR complexes on Golgi/endosomal membranes (PubMed:25687571). Interacts with INSR; ATIC together with PRKAA2/AMPK2 and HACD3/PTPLAD1 is proposed to be part of a signaling network regulating INSR autophosphorylation and endocytosis (PubMed:25687571).SUBCELLULAR LOCATION Present in the heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas.DOMAIN The IMP cyclohydrolase activity resides in the N-terminal region.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS The de novo purine synthesis pathway includes 10 sequential steps, beginning with phosphoribosyl pyrophosphate and ending with inosine monophosphate (IMP), the first purine compound of the pathway.SIMILARITY Belongs to the PurH family.
crossReference
databaseName UniProt
dbId 62507
description
  • recommendedName: Bifunctional purine biosynthesis protein ATIC alternativeName: AICAR transformylase/inosine monophosphate cyclohydrolase shortName: ATIC domain recommendedName: Phosphoribosylaminoimidazolecarboxamide formyltransferase ecNumber evidence="4 5 14"2.1.2.3 alternativeName: fullName evidence="19"5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase shortName evidence="19"AICAR formyltransferase alternativeName: AICAR transformylase /domain domain recommendedName: fullName evidence="16"Inosine 5'-monophosphate cyclohydrolase shortName evidence="16"IMP cyclohydrolase ecNumber evidence="5 8"3.5.4.10 alternativeName: IMP synthase alternativeName: Inosinicase /domain component recommendedName: Bifunctional purine biosynthesis protein ATIC, N-terminally processed /component
displayName UniProt:P31939 ATIC
geneName
  • ATIC
  • PURH
  • OK/SW-cl.86
identifier P31939
isSequenceChanged false
keyword
  • 3D-structure
  • Acetylation
  • Alternative splicing
  • Cytoplasm
  • Direct protein sequencing
  • Disease variant
  • Epilepsy
  • Hydrolase
  • Intellectual disability
  • Multifunctional enzyme
  • Proteomics identification
  • Purine biosynthesis
  • Reference proteome
  • Transferase
modified [InstanceEdit:9963647] Weiser, Joel, 2025-08-15
moleculeType Protein
name
  • ATIC
otherIdentifier
  • 11715755_a_at
  • 16890490
  • 208758_PM_at
  • 208758_at
  • 2526766
  • 2526767
  • 2526768
  • 2526769
  • 2526770
  • 2526771
  • 2526772
  • 2526776
  • 2526777
  • 2526778
  • 2526779
  • 2526780
  • 2526781
  • 2526782
  • 2526783
  • 2526784
  • 2526785
  • 2526786
  • 2526787
  • 2526788
  • 2526793
  • 2526794
  • 2526795
  • 2526796
  • 2526797
  • 2526798
  • 2526799
  • 2526800
  • 2526801
  • 2526802
  • 2526803
  • 2526804
  • 2526805
  • 3771131
  • 38811_at
  • 471
  • 76913_at
  • 8048120
  • A_14_P101313
  • A_14_P117158
  • A_23_P68087
  • D82348_at
  • GE57324
  • GO:0003360
  • GO:0003824
  • GO:0003937
  • GO:0004643
  • GO:0005737
  • GO:0005829
  • GO:0005886
  • GO:0006139
  • GO:0006164
  • GO:0006177
  • GO:0006189
  • GO:0006575
  • GO:0016020
  • GO:0016740
  • GO:0016787
  • GO:0021549
  • GO:0021987
  • GO:0031100
  • GO:0042803
  • GO:0044208
  • GO:0045296
  • GO:0046452
  • GO:0046654
  • GO:0048856
  • GO:0055086
  • GO:0070062
  • GO:0097294
  • GO:0098761
  • GO:1901135
  • HMNXSV003041780
  • ILMN_1673991
  • PH_hs_0005040
  • TC02001260.hg
  • TC02003807.hg
  • g2317691_3p_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • PUR9_HUMAN
  • A8K202
  • E9PBU3
  • Q13856
  • Q53S28
sequenceLength 592
species [Species:48887] Homo sapiens
stId uniprot:P31939
url http://purl.uniprot.org/uniprot/P31939
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