ATIC

Protein identityUniProt · HPA

UniProt accession

P31939

Gene

ATIC

Ensembl

ENSG00000138363

Chromosome

2

Canonical length

592 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Plasma membrane,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a bifunctional protein that catalyzes the last two steps of the de novo purine biosynthetic pathway. The N-terminal domain has phosphoribosylaminoimidazolecarboxamide formyltransferase activity, and the C-terminal domain has IMP cyclohydrolase activity. A mutation in this gene results in AICA-ribosiduria. [provided by RefSeq, Sep 2009]

Canonical amino-acid sequenceUniProt

592 residues, UniProt reviewed canonical sequence.

>P31939|ATIC
     1  MAPGQLALFS VSDKTGLVEF ARNLTALGLN LVASGGTAKA LRDAGLAVRD VSELTGFPEM
    61  LGGRVKTLHP AVHAGILARN IPEDNADMAR LDFNLIRVVA CNLYPFVKTV ASPGVTVEEA
   121  VEQIDIGGVT LLRAAAKNHA RVTVVCEPED YVVVSTEMQS SESKDTSLET RRQLALKAFT
   181  HTAQYDEAIS DYFRKQYSKG VSQMPLRYGM NPHQTPAQLY TLQPKLPITV LNGAPGFINL
   241  CDALNAWQLV KELKEALGIP AAASFKHVSP AGAAVGIPLS EDEAKVCMVY DLYKTLTPIS
   301  AAYARARGAD RMSSFGDFVA LSDVCDVPTA KIISREVSDG IIAPGYEEEA LTILSKKKNG
   361  NYCVLQMDQS YKPDENEVRT LFGLHLSQKR NNGVVDKSLF SNVVTKNKDL PESALRDLIV
   421  ATIAVKYTQS NSVCYAKNGQ VIGIGAGQQS RIHCTRLAGD KANYWWLRHH PQVLSMKFKT
   481  GVKRAEISNA IDQYVTGTIG EDEDLIKWKA LFEEVPELLT EAEKKEWVEK LTEVSISSDA
   541  FFPFRDNVDR AKRSGVAYIA APSGSAADKV VIEACDELGI ILAHTNLRLF HH

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ATIC can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

49 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ATIC.

Disease | AllUniProt

Conditions ATIC is implicated in, by any mechanism.

• AICA-ribosuria due to ATIC deficiency (AICAR) MIM:608688

Disease | GeneticClinVar

9 pathogenic / likely-pathogenic of 197 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• AICA-ribosiduria

Disease | ImmuneIEDB

Conditions an epitope on ATIC was assayed in.

• melanoma T cell
• skin melanoma T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.25

gnomAD pLI

0

gnomAD missense Z

-0.48

DepMap mean gene effect

-0.35

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• 'de novo' AMP biosynthetic process
• 'de novo' IMP biosynthetic process
• 'de novo' XMP biosynthetic process
• animal organ regeneration
• brainstem development
• cellular response to interleukin-7
• cerebellum development
• cerebral cortex development
• dihydrofolate metabolic process
• GMP biosynthetic process
• nucleobase-containing compound metabolic process
• tetrahydrofolate biosynthetic process

Molecular functions

• cadherin binding
• protein homodimerization activity
• IMP cyclohydrolase activity
• phosphoribosylaminoimidazolecarboxamide formyltransferase activity

Cellular components

• cytosol
• extracellular exosome
• membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Methylglyoxal synthase-like domain
• Cytidine deaminase-like
• Methylglyoxal synthase-like domain superfamily
• MGS-like domain
• Bifunctional purine biosynthesis protein PurH-like
• AICAR transformylase, insert domain superfamily
• AICAR transformylase, duplicated domain superfamily
• AICARFT/IMPCHase bienzyme

KeywordsUniProt

• Acetylation
• Cytoplasm
• Epilepsy
• Hydrolase
• Intellectual disability
• Multifunctional enzyme
• Purine biosynthesis
• Transferase

InteractionsUniProt · HPA

Protein binding partners of ATIC in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• INSR