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Protein

Bifunctional purine biosynthesis protein PURH

Gene

ATIC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Bifunctional enzyme that catalyzes 2 steps in purine biosynthesis.1 Publication
Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571).1 Publication

Catalytic activityi

10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide.
IMP + H2O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide.

Pathwayi: IMP biosynthesis via de novo pathway

This protein is involved in step 1 of the subpathway that synthesizes 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).
Proteins known to be involved in this subpathway in this organism are:
  1. Bifunctional purine biosynthesis protein PURH (ATIC)
This subpathway is part of the pathway IMP biosynthesis via de novo pathway, which is itself part of Purine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes 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), the pathway IMP biosynthesis via de novo pathway and in Purine metabolism.

Pathwayi: IMP biosynthesis via de novo pathway

This protein is involved in step 1 of the subpathway that synthesizes IMP from 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide.
Proteins known to be involved in this subpathway in this organism are:
  1. Bifunctional purine biosynthesis protein PURH (ATIC)
This subpathway is part of the pathway IMP biosynthesis via de novo pathway, which is itself part of Purine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes IMP from 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide, the pathway IMP biosynthesis via de novo pathway and in Purine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei137Proton acceptorSequence analysis1
Sitei266Transition state stabilizerSequence analysis1
Active sitei267Proton acceptorCurated1
Binding sitei316AICAR; via carbonyl oxygen1 Publication1
Binding sitei339AICAR1 Publication1
Binding sitei431AICAR; shared with dimeric partner1 Publication1
Binding sitei451AICAR; shared with dimeric partner1 Publication1
Binding sitei541AICAR; via carbonyl oxygen; shared with dimeric partner1 Publication1
Binding sitei588AICAR; shared with dimeric partner1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi12 – 14IMP3
Nucleotide bindingi34 – 37IMP4
Nucleotide bindingi64 – 67IMP4
Nucleotide bindingi101 – 104IMP4
Nucleotide bindingi125 – 127IMP3

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Multifunctional enzyme, Transferase
Biological processPurine biosynthesis

Enzyme and pathway databases

BioCyciMetaCyc:HS06490-MONOMER
BRENDAi2.1.2.3 2681
3.5.4.10 2681
ReactomeiR-HSA-73817 Purine ribonucleoside monophosphate biosynthesis
SABIO-RKiP31939
UniPathwayi
UPA00074;UER00133

UPA00074;UER00135

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional purine biosynthesis protein PURH
Cleaved into the following chain:
Including the following 2 domains:
Phosphoribosylaminoimidazolecarboxamide formyltransferase (EC:2.1.2.3)
Alternative name(s):
5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase
AICAR transformylase
IMP cyclohydrolase (EC:3.5.4.10)
Alternative name(s):
ATIC
IMP synthase
Inosinicase
Gene namesi
Name:ATIC
Synonyms:PURH
ORF Names:OK/SW-cl.86
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000138363.14
HGNCiHGNC:794 ATIC
MIMi601731 gene
neXtProtiNX_P31939

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

AICAR transformylase/IMP cyclohydrolase deficiency (AICAR)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurologically devastating inborn error of purine biosynthesis. Patients excrete massive amounts of AICA-riboside in the urine and accumulate AICA-ribotide and its derivatives in erythrocytes and fibroblasts. AICAR causes profound mental retardation, epilepsy, dysmorphic features and congenital blindness.
See also OMIM:608688
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019307426K → R in AICAR; loss of transformylase activity. 1 PublicationCorresponds to variant dbSNP:rs121434478EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi471
MalaCardsiATIC
MIMi608688 phenotype
OpenTargetsiENSG00000138363
Orphaneti250977 AICA-ribosiduria
PharmGKBiPA25094

Chemistry databases

ChEMBLiCHEMBL2518
DrugBankiDB03442 2-[5-Hydroxy-3-Methyl-1-(2-Methyl-4-Sulfo-Phenyl)-1h-Pyrazol-4-Ylazo]-4-Sulfo-Benzoic Acid
DB02309 5--Monophosphate-9-Beta-D-Ribofuranosyl Xanthine
DB01700 Aicar
DB01972 Guanosine-5'-Monophosphate
DB00563 Methotrexate
DB00642 Pemetrexed
DB00116 Tetrahydrofolic acid

Polymorphism and mutation databases

BioMutaiATIC
DMDMi23831360

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001921561 – 592Bifunctional purine biosynthesis protein PURHAdd BLAST592
Initiator methionineiRemoved; alternateCombined sources
ChainiPRO_00004343762 – 592Bifunctional purine biosynthesis protein PURH, N-terminally processedAdd BLAST591

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei199N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP31939
PaxDbiP31939
PeptideAtlasiP31939
PRIDEiP31939
ProteomicsDBi54805

2D gel databases

REPRODUCTION-2DPAGEiIPI00289499
UCD-2DPAGEiP31939

PTM databases

iPTMnetiP31939
PhosphoSitePlusiP31939
SwissPalmiP31939

Expressioni

Gene expression databases

BgeeiENSG00000138363 Expressed in 229 organ(s), highest expression level in adrenal gland
CleanExiHS_ATIC
ExpressionAtlasiP31939 baseline and differential
GenevisibleiP31939 HS

Organism-specific databases

HPAiCAB013462
HPA021012

Interactioni

Subunit structurei

Homodimer (PubMed:14756553, PubMed:14966129). Associates with internalized INSR complexes on Golgi/endosomal membranes. 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).3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106961, 73 interactors
IntActiP31939, 9 interactors
STRINGi9606.ENSP00000236959

Chemistry databases

BindingDBiP31939

Structurei

Secondary structure

1592
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP31939
SMRiP31939
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP31939

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 146MGS-likePROSITE-ProRule annotationAdd BLAST146

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni207 – 208AICAR binding2

Domaini

The IMP cyclohydrolase activity resides in the N-terminal region.

Sequence similaritiesi

Belongs to the PurH family.Curated

Phylogenomic databases

eggNOGiKOG2555 Eukaryota
COG0138 LUCA
GeneTreeiENSGT00390000004553
HOGENOMiHOG000230372
HOVERGENiHBG006912
InParanoidiP31939
KOiK00602
OMAiDLLFAWK
OrthoDBiEOG091G03H4
PhylomeDBiP31939
TreeFamiTF105642

Family and domain databases

Gene3Di1.10.287.440, 1 hit
3.40.140.20, 3 hits
3.40.50.1380, 1 hit
HAMAPiMF_00139 PurH, 1 hit
InterProiView protein in InterPro
IPR024051 AICAR_Tfase_dup_dom_sf
IPR024050 AICAR_Tfase_insert_dom_sf
IPR016193 Cytidine_deaminase-like
IPR011607 MGS-like_dom
IPR036914 MGS-like_dom_sf
IPR002695 PurH-like
PANTHERiPTHR11692 PTHR11692, 1 hit
PfamiView protein in Pfam
PF01808 AICARFT_IMPCHas, 1 hit
PF02142 MGS, 1 hit
PIRSFiPIRSF000414 AICARFT_IMPCHas, 1 hit
SMARTiView protein in SMART
SM00798 AICARFT_IMPCHas, 1 hit
SM00851 MGS, 1 hit
SUPFAMiSSF52335 SSF52335, 1 hit
SSF53927 SSF53927, 1 hit
TIGRFAMsiTIGR00355 purH, 1 hit
PROSITEiView protein in PROSITE
PS51855 MGS, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: P31939-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAPGQLALFS VSDKTGLVEF ARNLTALGLN LVASGGTAKA LRDAGLAVRD
60 70 80 90 100
VSELTGFPEM LGGRVKTLHP AVHAGILARN IPEDNADMAR LDFNLIRVVA
110 120 130 140 150
CNLYPFVKTV ASPGVTVEEA VEQIDIGGVT LLRAAAKNHA RVTVVCEPED
160 170 180 190 200
YVVVSTEMQS SESKDTSLET RRQLALKAFT HTAQYDEAIS DYFRKQYSKG
210 220 230 240 250
VSQMPLRYGM NPHQTPAQLY TLQPKLPITV LNGAPGFINL CDALNAWQLV
260 270 280 290 300
KELKEALGIP AAASFKHVSP AGAAVGIPLS EDEAKVCMVY DLYKTLTPIS
310 320 330 340 350
AAYARARGAD RMSSFGDFVA LSDVCDVPTA KIISREVSDG IIAPGYEEEA
360 370 380 390 400
LTILSKKKNG NYCVLQMDQS YKPDENEVRT LFGLHLSQKR NNGVVDKSLF
410 420 430 440 450
SNVVTKNKDL PESALRDLIV ATIAVKYTQS NSVCYAKNGQ VIGIGAGQQS
460 470 480 490 500
RIHCTRLAGD KANYWWLRHH PQVLSMKFKT GVKRAEISNA IDQYVTGTIG
510 520 530 540 550
EDEDLIKWKA LFEEVPELLT EAEKKEWVEK LTEVSISSDA FFPFRDNVDR
560 570 580 590
AKRSGVAYIA APSGSAADKV VIEACDELGI ILAHTNLRLF HH
Length:592
Mass (Da):64,616
Last modified:October 10, 2002 - v3
Checksum:iAD778892021F0888
GO
Isoform 2 (identifier: P31939-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: MAPGQL → MSSLS

Show »
Length:591
Mass (Da):64,524
Checksum:i372861CF93D74887
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JLK0C9JLK0_HUMAN
Bifunctional purine biosynthesis pr...
ATIC
170Annotation score:
H7C1S2H7C1S2_HUMAN
Bifunctional purine biosynthesis pr...
ATIC
231Annotation score:
F8WEF0F8WEF0_HUMAN
Bifunctional purine biosynthesis pr...
ATIC
84Annotation score:
F2Z3E8F2Z3E8_HUMAN
Bifunctional purine biosynthesis pr...
ATIC
43Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti165D → G in AAA97405 (PubMed:8567683).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019306116T → S2 PublicationsCorresponds to variant dbSNP:rs2372536Ensembl.1
Natural variantiVAR_019307426K → R in AICAR; loss of transformylase activity. 1 PublicationCorresponds to variant dbSNP:rs121434478EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0534951 – 6MAPGQL → MSSLS in isoform 2. 2 Publications6

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U37436 mRNA Translation: AAA97405.1
D82348 mRNA Translation: BAA11559.1
D89976 mRNA Translation: BAA21762.1
AB062403 mRNA Translation: BAB93490.1
AK290067 mRNA Translation: BAF82756.1
AC073284 Genomic DNA Translation: AAY24062.1
CH471063 Genomic DNA Translation: EAW70529.1
BC008879 mRNA Translation: AAH08879.1
CCDSiCCDS2398.1 [P31939-1]
PIRiJC4642
RefSeqiNP_004035.2, NM_004044.6 [P31939-1]
UniGeneiHs.90280

Genome annotation databases

EnsembliENST00000236959; ENSP00000236959; ENSG00000138363 [P31939-1]
ENST00000435675; ENSP00000415935; ENSG00000138363 [P31939-2]
GeneIDi471
KEGGihsa:471
UCSCiuc002vey.5 human [P31939-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U37436 mRNA Translation: AAA97405.1
D82348 mRNA Translation: BAA11559.1
D89976 mRNA Translation: BAA21762.1
AB062403 mRNA Translation: BAB93490.1
AK290067 mRNA Translation: BAF82756.1
AC073284 Genomic DNA Translation: AAY24062.1
CH471063 Genomic DNA Translation: EAW70529.1
BC008879 mRNA Translation: AAH08879.1
CCDSiCCDS2398.1 [P31939-1]
PIRiJC4642
RefSeqiNP_004035.2, NM_004044.6 [P31939-1]
UniGeneiHs.90280

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1P4RX-ray2.55A/B1-592[»]
1PKXX-ray1.90A/B/C/D1-592[»]
1PL0X-ray2.60A/B/C/D1-592[»]
5UY8X-ray2.39A/B/C/D2-592[»]
5UZ0X-ray1.79A/B/C/D2-592[»]
ProteinModelPortaliP31939
SMRiP31939
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106961, 73 interactors
IntActiP31939, 9 interactors
STRINGi9606.ENSP00000236959

Chemistry databases

BindingDBiP31939
ChEMBLiCHEMBL2518
DrugBankiDB03442 2-[5-Hydroxy-3-Methyl-1-(2-Methyl-4-Sulfo-Phenyl)-1h-Pyrazol-4-Ylazo]-4-Sulfo-Benzoic Acid
DB02309 5--Monophosphate-9-Beta-D-Ribofuranosyl Xanthine
DB01700 Aicar
DB01972 Guanosine-5'-Monophosphate
DB00563 Methotrexate
DB00642 Pemetrexed
DB00116 Tetrahydrofolic acid

PTM databases

iPTMnetiP31939
PhosphoSitePlusiP31939
SwissPalmiP31939

Polymorphism and mutation databases

BioMutaiATIC
DMDMi23831360

2D gel databases

REPRODUCTION-2DPAGEiIPI00289499
UCD-2DPAGEiP31939

Proteomic databases

EPDiP31939
PaxDbiP31939
PeptideAtlasiP31939
PRIDEiP31939
ProteomicsDBi54805

Protocols and materials databases

DNASUi471
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000236959; ENSP00000236959; ENSG00000138363 [P31939-1]
ENST00000435675; ENSP00000415935; ENSG00000138363 [P31939-2]
GeneIDi471
KEGGihsa:471
UCSCiuc002vey.5 human [P31939-1]

Organism-specific databases

CTDi471
DisGeNETi471
EuPathDBiHostDB:ENSG00000138363.14
GeneCardsiATIC
HGNCiHGNC:794 ATIC
HPAiCAB013462
HPA021012
MalaCardsiATIC
MIMi601731 gene
608688 phenotype
neXtProtiNX_P31939
OpenTargetsiENSG00000138363
Orphaneti250977 AICA-ribosiduria
PharmGKBiPA25094
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2555 Eukaryota
COG0138 LUCA
GeneTreeiENSGT00390000004553
HOGENOMiHOG000230372
HOVERGENiHBG006912
InParanoidiP31939
KOiK00602
OMAiDLLFAWK
OrthoDBiEOG091G03H4
PhylomeDBiP31939
TreeFamiTF105642

Enzyme and pathway databases

UniPathwayi
UPA00074;UER00133

UPA00074;UER00135

BioCyciMetaCyc:HS06490-MONOMER
BRENDAi2.1.2.3 2681
3.5.4.10 2681
ReactomeiR-HSA-73817 Purine ribonucleoside monophosphate biosynthesis
SABIO-RKiP31939

Miscellaneous databases

ChiTaRSiATIC human
EvolutionaryTraceiP31939
GeneWikiiInosine_monophosphate_synthase
GenomeRNAii471
PROiPR:P31939
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138363 Expressed in 229 organ(s), highest expression level in adrenal gland
CleanExiHS_ATIC
ExpressionAtlasiP31939 baseline and differential
GenevisibleiP31939 HS

Family and domain databases

Gene3Di1.10.287.440, 1 hit
3.40.140.20, 3 hits
3.40.50.1380, 1 hit
HAMAPiMF_00139 PurH, 1 hit
InterProiView protein in InterPro
IPR024051 AICAR_Tfase_dup_dom_sf
IPR024050 AICAR_Tfase_insert_dom_sf
IPR016193 Cytidine_deaminase-like
IPR011607 MGS-like_dom
IPR036914 MGS-like_dom_sf
IPR002695 PurH-like
PANTHERiPTHR11692 PTHR11692, 1 hit
PfamiView protein in Pfam
PF01808 AICARFT_IMPCHas, 1 hit
PF02142 MGS, 1 hit
PIRSFiPIRSF000414 AICARFT_IMPCHas, 1 hit
SMARTiView protein in SMART
SM00798 AICARFT_IMPCHas, 1 hit
SM00851 MGS, 1 hit
SUPFAMiSSF52335 SSF52335, 1 hit
SSF53927 SSF53927, 1 hit
TIGRFAMsiTIGR00355 purH, 1 hit
PROSITEiView protein in PROSITE
PS51855 MGS, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPUR9_HUMAN
AccessioniPrimary (citable) accession number: P31939
Secondary accession number(s): A8K202
, E9PBU3, Q13856, Q53S28
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: October 10, 2002
Last modified: September 12, 2018
This is version 191 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health

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