ATIC (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase)

2001-08-01   Jean-Loup Huret  

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Identity

HGNC
LOCATION
2q35
IMAGE
Atlas Image
LEGEND
ATIC (2p35) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
ALIAS
AICAR,AICARFT,HEL-S-70p,IMPCHASE,PURH
FUSION GENES

DNA/RNA

Transcription

1776 bp mRNA; transcribed in a centromeric to telomeric orientation

Proteins

Description

591 amino acids, 64 kDa; two functional domains separated by a linker region with a dimerization domain (amino acids 170 to 199): amino acids 1 to 169 encode the IMP cyclohydrolase (IMPCH) function, and amino acids 200 to 591 encode the 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFT) function; homodimer

Expression

wide

Function

bifunctional purine biosythesis:9th and 10th step of the de novo purine synthesis

Homology

belongs to the PURH family

Implicated in

Entity name
Disease
found in rare cases of ALK+ anaplasic large cell lymphoma
Cytogenetics
hidden translocation most often
Hybrid gene
5 ATIC - 3 ALK
Fusion protein
791 amino acids, 87 kDa. 229 N-term amino acid from ATIC containing the IMPCH domain and the dimerization domain fused to the 562 C-term amino acids from ALK (i.e. the entire cytoplasmic portion of ALK with the tyrosine kinase domain); cytoplasmic localisation only.
Oncogenesis
ATIC seems to provoke the dimerization of ATIC-ALK, which should lead to constitutive autophosphorylation and activation of the ALK tyrosine kinase, as for NPM1-ALK (see t(2;5)(p23;q35) ).

Article Bibliography

Pubmed IDLast YearTitleAuthors
95980631998Structure and functional relationships in human pur H.Beardsley GP et al
107023932000ATIC-ALK: A novel variant ALK gene fusion in anaplastic large cell lymphoma resulting from the recurrent cryptic chromosomal inversion, inv(2)(p23q35).Colleoni GW et al
109949992000Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas.Drexler HG et al
107068872000Inv(2)(p23q35) in anaplastic large-cell lymphoma induces constitutive anaplastic lymphoma kinase (ALK) tyrosine kinase activation by fusion to ATIC, an enzyme involved in purine nucleotide biosynthesis.Ma Z et al
113803912001Alk+ CD30+ lymphomas: a distinct molecular genetic subtype of non-Hodgkin's lymphoma.Morris SW et al
85676831996The human purH gene product, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase. Cloning, sequencing, expression, purification, kinetic analysis, and domain mapping.Rayl EA et al
110900482000CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features.Stein H et al
93787071997Characterization of molecularly cloned human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase.Sugita T et al
107060822000A new variant anaplastic lymphoma kinase (ALK)-fusion protein (ATIC-ALK) in a case of ALK-positive anaplastic large cell lymphoma.Trinei M et al

Other Information

Locus ID:

NCBI: 471
MIM: 601731
HGNC: 794
Ensembl: ENSG00000138363

Variants:

dbSNP: 471
ClinVar: 471
TCGA: ENSG00000138363
COSMIC: ATIC

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000138363ENST00000236959P31939
ENSG00000138363ENST00000236959V9HWH7
ENSG00000138363ENST00000413174C9JLK0
ENSG00000138363ENST00000426233H7C1S2
ENSG00000138363ENST00000427397F2Z3E8
ENSG00000138363ENST00000435675P31939
ENSG00000138363ENST00000443953F2Z3E8
ENSG00000138363ENST00000444305F8WEF0

Expression (GTEx)

0
50
100
150
200

Pathways

PathwaySourceExternal ID
Purine metabolismKEGGko00230
One carbon pool by folateKEGGko00670
Purine metabolismKEGGhsa00230
One carbon pool by folateKEGGhsa00670
Metabolic pathwaysKEGGhsa01100
Inosine monophosphate biosynthesis, PRPP + glutamine => IMPKEGGhsa_M00048
Inosine monophosphate biosynthesis, PRPP + glutamine => IMPKEGGM00048
MetabolismREACTOMER-HSA-1430728
Metabolism of nucleotidesREACTOMER-HSA-15869
Purine metabolismREACTOMER-HSA-73847
Purine ribonucleoside monophosphate biosynthesisREACTOMER-HSA-73817
Antifolate resistanceKEGGko01523
Antifolate resistanceKEGGhsa01523

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA443434Arthritis, RheumatoidDiseaseClinicalAnnotationassociatedPD15457444, 16947783, 18322994, 20847201, 25084201, 26799664, 27217051, 27676277, 27885916, 29520081
PA450428methotrexateChemicalClinicalAnnotationassociatedPD15457444, 16947783, 18322994, 20847201, 25084201, 26799664, 27217051, 27676277, 27885916, 29520081

References

Pubmed IDYearTitleCitations
380718322024A meta-analysis of the association between the ATIC 347 C/G polymorphism and methotrexate responsiveness and toxicity in rheumatoid arthritis.0
390019042024LncRNA ZFAS1 regulates ATIC transcription and promotes the proliferation and migration of hepatocellular carcinoma through the PI3K/AKT signaling pathway.0
380718322024A meta-analysis of the association between the ATIC 347 C/G polymorphism and methotrexate responsiveness and toxicity in rheumatoid arthritis.0
390019042024LncRNA ZFAS1 regulates ATIC transcription and promotes the proliferation and migration of hepatocellular carcinoma through the PI3K/AKT signaling pathway.0
365843302023Promoter methylation levels of RASSF1 and ATIC genes are associated with lung cancer in Iranian patients.1
365843302023Promoter methylation levels of RASSF1 and ATIC genes are associated with lung cancer in Iranian patients.1
352053742022Impact of Variants in the ATIC and ARID5B Genes on Therapeutic Failure with Imatinib in Patients with Chronic Myeloid Leukemia.2
355797722022CircATIC Contributes to Multiple Myeloma Progression via miR-324-5p-Dependent Regulation of HGF.2
352053742022Impact of Variants in the ATIC and ARID5B Genes on Therapeutic Failure with Imatinib in Patients with Chronic Myeloid Leukemia.2
355797722022CircATIC Contributes to Multiple Myeloma Progression via miR-324-5p-Dependent Regulation of HGF.2
332261932021Upregulation of ATIC in multiple myeloma tissues based on tissue microarray and gene microarrays.6
337780662021Identification and Validation of a Prognostic Model Based on Three Autophagy-Related Genes in Hepatocellular Carcinoma.3
337801522021Polymorphism of genes involved in methotrexate pathway: Predictors of response to methotrexate therapy in Indian rheumatoid arthritis patients.2
332261932021Upregulation of ATIC in multiple myeloma tissues based on tissue microarray and gene microarrays.6
337780662021Identification and Validation of a Prognostic Model Based on Three Autophagy-Related Genes in Hepatocellular Carcinoma.3

Citation

Jean-Loup Huret

ATIC (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase)

Atlas Genet Cytogenet Oncol Haematol. 2001-08-01

Online version: http://atlasgeneticsoncology.org/gene/227/meetings/js/lib/teaching-explorer/