PPAT

gene
On this page

Also known as GPATPRAT

Summary

PPAT (phosphoribosyl pyrophosphate amidotransferase, HGNC:9238) is a protein-coding gene on chromosome 4q12, encoding Amidophosphoribosyltransferase (Q06203). Catalyzes the formation of phosphoribosylamine from phosphoribosylpyrophosphate (PRPP) and glutamine. It is a selective cancer dependency (DepMap: 52.1% of cell lines).

The protein encoded by this gene is a member of the purine/pyrimidine phosphoribosyltransferase family. It is a regulatory allosteric enzyme that catalyzes the first step of de novo purine nucleotide biosythetic pathway. This gene and PAICS/AIRC gene, a bifunctional enzyme catalyzing steps six and seven of this pathway, are located in close proximity on chromosome 4, and divergently transcribed from an intergenic region.

Source: NCBI Gene 5471 — RefSeq curated summary.

At a glance

  • Clinical variants (ClinVar): 39 total
  • Druggable target: yes
  • Cancer dependency (DepMap): dependent in 52.1% of screened cell lines
  • MANE Select transcript: NM_002703

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:9238
Approved symbolPPAT
Namephosphoribosyl pyrophosphate amidotransferase
Location4q12
Locus typegene with protein product
StatusApproved
AliasesGPAT, PRAT
Ensembl geneENSG00000128059
Ensembl biotypeprotein_coding
OMIM172450
Entrez5471

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000264220, ENST00000425339, ENST00000507648, ENST00000507724, ENST00000510643, ENST00000913491, ENST00000965522

RefSeq mRNA: 1 — MANE Select: NM_002703 NM_002703

CCDS: CCDS3505

Canonical transcript exons

ENST00000264220 — 11 exons

ExonStartEnd
ENSE000010325615640078456400911
ENSE000010325755640133056401481
ENSE000010746485643535056435615
ENSE000010746535639917956399400
ENSE000018957385639336256395548
ENSE000034665035640765056407716
ENSE000034815985639661956396739
ENSE000034872885640304056403185
ENSE000035937325640649556406701
ENSE000036342065640210956402181
ENSE000036541055640328956403401

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 87.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.7476 / max 156.1556, expressed in 1699 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter IDTPM avgSamples expressed
521936.34471569
521913.54461109
521920.8584512

Top tissues by expression

279 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
ventricular zoneUBERON:000305387.96gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047386.95gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099185.70gold quality
cortical plateUBERON:000534385.61gold quality
ganglionic eminenceUBERON:000402385.52gold quality
adrenal tissueUBERON:001830384.15gold quality
embryoUBERON:000092282.00gold quality
islet of LangerhansUBERON:000000679.79gold quality
stromal cell of endometriumCL:000225578.36gold quality
body of pancreasUBERON:000115078.22gold quality
calcaneal tendonUBERON:000370177.75gold quality
pancreasUBERON:000126477.59gold quality
rectumUBERON:000105277.16gold quality
right adrenal gland cortexUBERON:003582776.83gold quality
left adrenal glandUBERON:000123476.75gold quality
ovaryUBERON:000099276.43gold quality
left adrenal gland cortexUBERON:003582576.42gold quality
left ovaryUBERON:000211976.37gold quality
right adrenal glandUBERON:000123375.98gold quality
adrenal glandUBERON:000236975.97gold quality
right ovaryUBERON:000211875.70gold quality
middle temporal gyrusUBERON:000277175.54silver quality
prefrontal cortexUBERON:000045175.10gold quality
cerebellar hemisphereUBERON:000224574.61gold quality
cingulate cortexUBERON:000302774.60gold quality
right hemisphere of cerebellumUBERON:001489074.57gold quality
anterior cingulate cortexUBERON:000983574.50gold quality
cerebellar cortexUBERON:000212974.48gold quality
lymph nodeUBERON:000002974.23gold quality
secondary oocyteCL:000065574.18gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes5.36
E-GEOD-99795no148.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

124 targeting PPAT, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4795-3P100.0074.624024
HSA-MIR-5692B100.0071.322622
HSA-MIR-5692C100.0071.322622
HSA-MIR-126-5P100.0072.713180
HSA-MIR-3613-3P100.0076.367965
HSA-MIR-4668-3P100.0068.742635
HSA-MIR-548C-3P99.9974.017587
HSA-MIR-371B-5P99.9975.344759
HSA-MIR-453499.9966.581907
HSA-MIR-453199.9969.703181
HSA-MIR-4789-3P99.9970.752484
HSA-MIR-196A-1-3P99.9972.152772
HSA-MIR-511-3P99.9968.851467
HSA-MIR-373-5P99.9875.364753
HSA-MIR-616-5P99.9875.584775
HSA-MIR-1213699.9872.815713
HSA-MIR-548N99.9871.944170
HSA-MIR-60799.9773.625593
HSA-MIR-548AJ-3P99.9673.385345
HSA-MIR-548X-3P99.9673.385345
HSA-MIR-9-3P99.9670.882068
HSA-MIR-551B-5P99.9671.283493
HSA-MIR-365899.9673.874379
HSA-MIR-570-3P99.9672.414910
HSA-MIR-808299.9567.271170
HSA-MIR-23A-3P99.9574.243163
HSA-MIR-23B-3P99.9574.243163
HSA-MIR-23C99.9573.923192
HSA-MIR-548J-3P99.9472.614881
HSA-MIR-548AE-3P99.9372.664867

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 52.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

  • purine biosynthetic pathway enzymes PPAT and PAICS, as well as pyruvate kinase activity are increased in lung cancer (PMID:26140362)
  • The data indicate that amino acid/nucleotide metabolism-related genes OGDH, PPAT and PCCA acquire somatic mutations in microsatellite instability-high gastric cancers and colorectal cancers and that mutational intratumoral heterogeneity may occur in at least some of these tumors. (PMID:27468871)
  • Phosphopantetheine Adenylyltransferase: A promising drug target to combat antibiotic resistance. (PMID:33271445)
  • Species-Specific Deamidation of RIG-I Reveals Collaborative Action between Viral and Cellular Deamidases in HSV-1 Lytic Replication. (PMID:33785613)
  • SHMT2 promotes the tumorigenesis of renal cell carcinoma by regulating the m6A modification of PPAT. (PMID:35798250)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_rerioppatENSDARG00000004517
mus_musculusPpatENSMUSG00000029246
rattus_norvegicusPpatENSRNOG00000002128
drosophila_melanogasterPratFBGN0004901
drosophila_melanogasterPrat2FBGN0041194

Protein

Protein identifiers

AmidophosphoribosyltransferaseQ06203 (reviewed: Q06203)

Alternative names: Glutamine phosphoribosylpyrophosphate amidotransferase

All UniProt accessions (4): Q06203, A8K4H7, D6RCC8, D6RE15

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the formation of phosphoribosylamine from phosphoribosylpyrophosphate (PRPP) and glutamine.

Subunit / interactions. Homotetramer.

Tissue specificity. Ubiquitously expressed.

Cofactor. Binds 1 Mg(2+) ion per subunit. Binds 1 [4Fe-4S] cluster per subunit.

Pathway. Purine metabolism; IMP biosynthesis via de novo pathway; N(1)-(5-phospho-D-ribosyl)glycinamide from 5-phospho-alpha-D-ribose 1-diphosphate: step 1/2.

Similarity. In the C-terminal section; belongs to the purine/pyrimidine phosphoribosyltransferase family.

RefSeq proteins (1): NP_002694* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000836PRTase_domDomain
IPR005854PurFFamily
IPR017932GATase_2_domDomain
IPR029055Ntn_hydrolases_NHomologous_superfamily
IPR029057PRTase-likeHomologous_superfamily
IPR035584PurF_NDomain

Pfam: PF00156, PF13522

Enzyme classification (BRENDA):

  • EC 2.4.2.14 — amidophosphoribosyltransferase (BRENDA: 22 organisms, 39 substrates, 103 inhibitors, 55 Km, 3 kcat entries)
  • EC 2.7.7.3 — pantetheine-phosphate adenylyltransferase (BRENDA: 25 organisms, 18 substrates, 81 inhibitors, 22 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
L-GLUTAMINE0.1–23626
5-PHOSPHO-ALPHA-D-RIBOSE 1-DIPHOSPHATE0.031–0.8715
ATP0.1157–16
3’-DEPHOSPHO-COA0.0067–0.01474
DIPHOSPHATE0.022–0.2724
PANTETHEINE 4’-PHOSPHATE0.015–0.194
NH37.34–163
GLUTAMINE1931
MG2+0.651
NH4+161
DEPHOSPHO-COA0.0171
MG-ATP0.221
PHOSPHOPANTETHEINE0.00471

Catalyzed reactions (Rhea), 1 shown:

  • 5-phospho-beta-D-ribosylamine + L-glutamate + diphosphate = 5-phospho-alpha-D-ribose 1-diphosphate + L-glutamine + H2O (RHEA:14905)

UniProt features (13 total): binding site 7, propeptide 1, chain 1, modified residue 1, sequence conflict 1, domain 1, active site 1

Structure

Experimental structures (PDB)

3 structures.

PDBMethodResolution (Å)
9Q0NELECTRON MICROSCOPY2.8
9Q0OELECTRON MICROSCOPY2.9
9Q0MELECTRON MICROSCOPY3.1

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q06203-F186.660.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 12 (nucleophile)

Ligand- & substrate-binding residues (7): 506; 280; 327; 389; 390; 426; 503

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

IDPathway
R-HSA-73817Purine ribonucleoside monophosphate biosynthesis

MSigDB gene sets: 236 (showing top): RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, KANNAN_TP53_TARGETS_DN, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, BROWNE_HCMV_INFECTION_12HR_UP, USF_C, CAGCTG_AP4_Q5, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX

GO Biological Process (6): purine nucleotide biosynthetic process (GO:0006164), GMP biosynthetic process (GO:0006177), ‘de novo’ IMP biosynthetic process (GO:0006189), purine nucleobase biosynthetic process (GO:0009113), ‘de novo’ AMP biosynthetic process (GO:0044208), ‘de novo’ XMP biosynthetic process (GO:0097294)

GO Molecular Function (8): amidophosphoribosyltransferase activity (GO:0004044), metal ion binding (GO:0046872), 4 iron, 4 sulfur cluster binding (GO:0051539), catalytic activity (GO:0003824), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Nucleotide biosynthesis1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
purine-containing compound biosynthetic process2
purine nucleotide metabolic process1
nucleotide biosynthetic process1
purine ribonucleotide biosynthetic process1
purine ribonucleoside monophosphate biosynthetic process1
GMP metabolic process1
IMP biosynthetic process1
purine nucleobase metabolic process1
nucleobase biosynthetic process1
AMP biosynthetic process1
XMP biosynthetic process1
pentosyltransferase activity1
cation binding1
iron-sulfur cluster binding1
molecular_function1
binding1
catalytic activity1
transferase activity1
metal cluster binding1
cytoplasm1
cellular anatomical structure1

Protein interactions and networks

STRING

2548 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
PPATPAICSP22234986
PPATPFASO15067983
PPATGARTP22102978
PPATADSLP30566910
PPATCADP27708805
PPATATICP31939762
PPATGMPSP49915759
PPATPGM2Q96G03729
PPATAPRTP07741717
PPATADSS2P30520688
PPATIMPDH1P20839667
PPATIMPDH2P12268665
PPATADSS1Q8N142665
PPATMTHFD1P11586664
PPATPRPS1P09329649
PPATPRPS2P11908649

IntAct

35 interactions, top by confidence:

ABTypeScore
MMS19ERCC2psi-mi:“MI:0914”(association)0.690
PPATNUDT5psi-mi:“MI:0915”(physical association)0.640
B2MNEMP1psi-mi:“MI:0914”(association)0.640
B2MKPNA3psi-mi:“MI:0914”(association)0.530
MAD2L1PPIP5K2psi-mi:“MI:0914”(association)0.530
PPATSELENOIpsi-mi:“MI:0915”(physical association)0.370
ATXN1PPATpsi-mi:“MI:0915”(physical association)0.370
OTUB1EPM2Apsi-mi:“MI:0914”(association)0.350
CIAO2BELP1psi-mi:“MI:0914”(association)0.350
LRRK2psi-mi:“MI:0914”(association)0.350
incFPMPCBpsi-mi:“MI:0914”(association)0.350
ZDHHC5IGKV2D-24psi-mi:“MI:0914”(association)0.350
HLA-AAIPpsi-mi:“MI:0914”(association)0.350
NUDT5FLNBpsi-mi:“MI:0914”(association)0.350
CA10ENTPD5psi-mi:“MI:0914”(association)0.350
DNAJA2ENC1psi-mi:“MI:0914”(association)0.350
DNAJC30UBA6psi-mi:“MI:0914”(association)0.350
FAM167AVWA8psi-mi:“MI:0914”(association)0.350
GAB2UBA6psi-mi:“MI:0914”(association)0.350
ITM2CUBA6psi-mi:“MI:0914”(association)0.350
MRPL49UBA6psi-mi:“MI:0914”(association)0.350
PCDHGA9UBA6psi-mi:“MI:0914”(association)0.350
PEX7UBA6psi-mi:“MI:0914”(association)0.350
VENTXUBA6psi-mi:“MI:0914”(association)0.350
CFTRUBA6psi-mi:“MI:2364”(proximity)0.270

BioGRID (92): PPAT (Affinity Capture-MS), G6PD (Affinity Capture-MS), CCZ1 (Affinity Capture-MS), HDAC3 (Affinity Capture-MS), PPAT (Affinity Capture-MS), ARHGAP1 (Co-fractionation), GART (Co-fractionation), IMPDH2 (Co-fractionation), NPEPL1 (Co-fractionation), PAK1 (Co-fractionation), PPAT (Co-fractionation), PPAT (Co-fractionation), PPAT (Co-fractionation), PPAT (Co-fractionation), PRPS1 (Co-fractionation)

ESM2 similar proteins: A0A3L7I2I8, A0FKG7, A1Z6E0, A6QLT2, A8QGZ7, B0X9V1, B3MDR0, B3NRP1, B4F739, B4GBN7, B4HQ29, B4J6Q0, B4KNC5, B4LMQ3, B4MR59, B4P4K8, B4QE02, O60733, P0C2W1, P0CH38, P23727, P27986, P28173, P33121, P35433, P37287, P41216, P53041, P53042, P97570, P97819, Q06203, Q13614, Q16XV7, Q27601, Q290L5, Q5R685, Q5REB9, Q60676, Q6NZ03

Diamond homologs: A0A7T8J1U7, O26273, O26742, O29388, O57979, P00497, P04046, P0AG16, P0AG17, P28173, P35433, P35853, P41390, P43854, P52418, P52419, P65830, P65831, P77935, P99164, P9WHQ6, P9WHQ7, Q06203, Q12698, Q27601, Q50028, Q51342, Q55038, Q55621, Q57657, Q577Y1, Q5FUY5, Q5HH14, Q5HQA0, Q6GAE3, Q6GI14, Q86A85, Q8CIH9, Q8CT30, Q8CY30

SIGNOR signaling

8 interactions.

AEffectBMechanism
PPAT“down-regulates quantity”“L-glutamine zwitterion”“chemical modification”
PPAT“up-regulates activity”Purine_biosynthesis
PPAT“up-regulates quantity”5-phospho-beta-D-ribosylaminium(1-)“chemical modification”
PPAT“down-regulates quantity”“5-phospho-α-D-ribose 1-diphosphate”“chemical modification”
PPAT“up-regulates quantity”L-glutamate(1-)“chemical modification”
NFE2L2“up-regulates quantity by expression”PPAT“transcriptional regulation”
MYC“up-regulates quantity by expression”PPAT“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

39 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance25
Likely benign2
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3358 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
4:56399246:T:AD390V1.000
4:56399344:G:CF357L1.000
4:56399344:G:TF357L1.000
4:56399346:A:GF357L1.000
4:56435431:C:TG16E1.000
4:56396663:A:GL438P0.999
4:56396691:C:GG429R0.999
4:56396691:C:TG429R0.999
4:56396698:G:CC426W0.999
4:56396700:A:GC426R0.999
4:56399244:A:GS391P0.999
4:56399245:A:CD390E0.999
4:56399245:A:TD390E0.999
4:56399246:T:CD390G0.999
4:56399246:T:GD390A0.999
4:56399247:C:GD390H0.999
4:56399345:A:CF357C0.999
4:56399345:A:GF357S0.999
4:56399350:T:AR355S0.999
4:56399350:T:GR355S0.999
4:56399351:C:AR355I0.999
4:56399351:C:GR355T0.999
4:56400832:G:CS322R0.999
4:56400832:G:TS322R0.999
4:56400834:T:GS322R0.999
4:56403108:C:GR198P0.999
4:56403360:A:CS148R0.999
4:56403360:A:TS148R0.999
4:56403362:T:GS148R0.999
4:56406529:C:AG123V0.999

dbSNP variants (sampled 300 via entrez): RS10000147 (4:56394795 A>G), RS1000028114 (4:56434461 C>T), RS1000127698 (4:56414252 T>C), RS1000293847 (4:56406192 G>A), RS1000386892 (4:56420672 G>A,C), RS1000389708 (4:56413788 T>C), RS1000466178 (4:56416025 A>G,T), RS1000548492 (4:56399664 A>T), RS1000549232 (4:56434737 T>C), RS1000669384 (4:56422405 C>T), RS1000735527 (4:56420982 T>G), RS1000774872 (4:56415235 A>G), RS1001017892 (4:56426319 T>C), RS1001029821 (4:56408091 T>A), RS1001069837 (4:56426591 C>T)

Disease associations

OMIM: gene MIM:172450 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2362992 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — C44: Phosphoribosyl pyrophosphate amidotransferase

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Tetrachlorodibenzodioxindecreases expression3
sodium arseniteincreases expression, decreases expression, increases abundance2
Arsenicincreases methylation, increases abundance, increases expression2
Tretinoindecreases expression2
Cadmium Chloridedecreases reaction, increases abundance, increases palmitoylation, decreases expression2
aristolochic acid Iincreases expression, decreases expression1
TAK-243increases sumoylation1
alpha phellandrenedecreases expression1
triphenyl phosphateaffects expression1
pirinixic acidaffects binding, increases activity, increases expression1
bisphenol Adecreases expression1
cobaltous chloridedecreases expression1
2-bromopalmitatedecreases reaction, increases abundance, increases palmitoylation1
2,3-bis(3’-hydroxybenzyl)butyrolactoneaffects cotreatment, increases expression1
beta-methylcholineaffects expression1
pinosylvindecreases expression1
tamibarotenedecreases expression1
di-n-butylphosphoric acidaffects expression1
abrinedecreases expression1
jinfukangdecreases expression1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic aciddecreases expression1
Dasatinibaffects binding1
Resveratrolaffects cotreatment, increases expression1
Arsenic Trioxideincreases expression1
Acetaminophenincreases expression1
Biological Factorsdecreases expression1
Cadmiumincreases palmitoylation, decreases reaction, increases abundance1
Carbamazepineaffects expression1
Copperaffects cotreatment, increases expression1
Coumestrolaffects cotreatment, increases expression1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL4118787BindingBinding affinity to PPAT in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assayStudies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.