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

2001-08-01 Jean-Loup Huret Affiliation

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

Identity

HGNC

ATIC

LOCATION

2q35

IMAGE

LEGEND

ATIC (2p35) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

LOCUSID

471

ALIAS

AICAR,AICARFT,HEL-S-70p,IMPCHASE,PURH

FUSION GENES

Show Gene Fusions

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

inv(2)(p23q35) --> ATIC- ALK

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) ).

Bibliography

Pubmed ID	Last Year	Title	Authors
9598063	1998	Structure and functional relationships in human pur H.	Beardsley GP et al
10702393	2000	ATIC-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
10994999	2000	Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas.	Drexler HG et al
10706887	2000	Inv(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
11380391	2001	Alk+ CD30+ lymphomas: a distinct molecular genetic subtype of non-Hodgkin's lymphoma.	Morris SW et al
8567683	1996	The 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
11090048	2000	CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features.	Stein H et al
9378707	1997	Characterization of molecularly cloned human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase.	Sugita T et al
10706082	2000	A 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 ID	Transcript ID	Uniprot
ENSG00000138363	ENST00000236959	P31939
ENSG00000138363	ENST00000236959	V9HWH7
ENSG00000138363	ENST00000413174	C9JLK0
ENSG00000138363	ENST00000426233	H7C1S2
ENSG00000138363	ENST00000427397	F2Z3E8
ENSG00000138363	ENST00000435675	P31939
ENSG00000138363	ENST00000443953	F2Z3E8
ENSG00000138363	ENST00000444305	F8WEF0

Expression (GTEx)

100

150

200

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Purine metabolism	KEGG	ko00230
One carbon pool by folate	KEGG	ko00670
Purine metabolism	KEGG	hsa00230
One carbon pool by folate	KEGG	hsa00670
Metabolic pathways	KEGG	hsa01100
Inosine monophosphate biosynthesis, PRPP + glutamine => IMP	KEGG	hsa_M00048
Inosine monophosphate biosynthesis, PRPP + glutamine => IMP	KEGG	M00048
Metabolism	REACTOME	R-HSA-1430728
Metabolism of nucleotides	REACTOME	R-HSA-15869
Purine metabolism	REACTOME	R-HSA-73847
Purine ribonucleoside monophosphate biosynthesis	REACTOME	R-HSA-73817
Antifolate resistance	KEGG	ko01523
Antifolate resistance	KEGG	hsa01523

Protein levels (Protein atlas)

Not detected

Low

Medium

High

PharmGKB

Entity ID	Name	Type	Evidence	Association	PK	PD	PMIDs
PA443434	Arthritis, Rheumatoid	Disease	ClinicalAnnotation	associated		PD	15457444, 16947783, 18322994, 20847201, 25084201, 26799664, 27217051, 27676277, 27885916, 29520081
PA450428	methotrexate	Chemical	ClinicalAnnotation	associated		PD	15457444, 16947783, 18322994, 20847201, 25084201, 26799664, 27217051, 27676277, 27885916, 29520081

References

Pubmed ID	Year	Title	Citations
19913121	2009	Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.	85
17617058	2007	Regulation of multisite phosphorylation and 14-3-3 binding of AS160 in response to IGF-1, EGF, PMA and AICAR.	64
15457444	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.	61
15457444	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.	61
17530705	2007	A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent-onset rheumatoid arthritis.	47
15114530	2004	AICA-ribosiduria: a novel, neurologically devastating inborn error of purine biosynthesis caused by mutation of ATIC.	37
17009228	2006	Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis.	34
15677700	2005	Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: results of a multicentred cross sectional observational study.	32
19161160	2009	An association study of 45 folate-related genes in spina bifida: Involvement of cubilin (CUBN) and tRNA aspartic acid methyltransferase 1 (TRDMT1).	30
16947783	2006	Relationship between genetic variants in the adenosine pathway and outcome of methotrexate treatment in patients with recent-onset rheumatoid arthritis.	27

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/atic-(5-aminoimidazole-4-carboxamide-ribonucleotide-formyltransferase-imp-cyclohydrolase)