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Protein

Trifunctional purine biosynthetic protein adenosine-3

Gene

GART

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

Functioni

Catalytic activityi

ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N1-(5-phospho-D-ribosyl)glycinamide.
ATP + 2-(formamido)-N1-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole.
10-formyltetrahydrofolate + N1-(5-phospho-D-ribosyl)glycinamide = tetrahydrofolate + N2-formyl-N1-(5-phospho-D-ribosyl)glycinamide.

Pathwayi: IMP biosynthesis via de novo pathway

This protein is involved in step 2 of the subpathway that synthesizes 5-amino-1-(5-phospho-D-ribosyl)imidazole from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Phosphoribosylformylglycinamidine synthase (PFAS)
  2. Trifunctional purine biosynthetic protein adenosine-3, Trifunctional purine biosynthetic protein adenosine-3 (GART), Trifunctional purine biosynthetic protein adenosine-3 (GART)
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-amino-1-(5-phospho-D-ribosyl)imidazole from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide, 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 2 of the subpathway that synthesizes N(1)-(5-phospho-D-ribosyl)glycinamide from 5-phospho-alpha-D-ribose 1-diphosphate.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Amidophosphoribosyltransferase (purF), Amidophosphoribosyltransferase (PPAT), Amidophosphoribosyltransferase (PPAT)
  2. Trifunctional purine biosynthetic protein adenosine-3, Trifunctional purine biosynthetic protein adenosine-3 (GART), Trifunctional purine biosynthetic protein adenosine-3 (GART)
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 N(1)-(5-phospho-D-ribosyl)glycinamide from 5-phospho-alpha-D-ribose 1-diphosphate, 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 N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide from N(1)-(5-phospho-D-ribosyl)glycinamide (10-formyl THF route).
Proteins known to be involved in this subpathway in this organism are:
  1. Trifunctional purine biosynthetic protein adenosine-3, Trifunctional purine biosynthetic protein adenosine-3 (GART), Trifunctional purine biosynthetic protein adenosine-3 (GART)
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 N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide from N(1)-(5-phospho-D-ribosyl)glycinamide (10-formyl THF route), the pathway IMP biosynthesis via de novo pathway and in Purine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi288ManganeseBy similarity1
Metal bindingi290ManganeseBy similarity1
Binding sitei87110-formyltetrahydrofolate1
Binding sitei91310-formyltetrahydrofolate1
Active sitei915Proton donorBy similarity1
Sitei951Raises pKa of active site HisBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi137 – 199ATPBy similarityAdd BLAST63

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionLigase, Multifunctional enzyme, Transferase
Biological processPurine biosynthesis
LigandATP-binding, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS08358-MONOMER
BRENDAi2.1.2.2 2681
ReactomeiR-HSA-73817 Purine ribonucleoside monophosphate biosynthesis
SIGNORiP22102
UniPathwayiUPA00074; UER00125
UPA00074; UER00126
UPA00074; UER00129

Names & Taxonomyi

Protein namesi
Recommended name:
Trifunctional purine biosynthetic protein adenosine-3
Including the following 3 domains:
Phosphoribosylamine--glycine ligase (EC:6.3.4.13)
Alternative name(s):
Glycinamide ribonucleotide synthetase
Short name:
GARS
Phosphoribosylglycinamide synthetase
Phosphoribosylformylglycinamidine cyclo-ligase (EC:6.3.3.1)
Alternative name(s):
AIR synthase
Short name:
AIRS
Phosphoribosyl-aminoimidazole synthetase
Phosphoribosylglycinamide formyltransferase (EC:2.1.2.2)
Alternative name(s):
5'-phosphoribosylglycinamide transformylase
GAR transformylase
Short name:
GART
Gene namesi
Name:GART
Synonyms:PGFT, PRGS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

EuPathDBiHostDB:ENSG00000159131.16
HGNCiHGNC:4163 GART
MIMi138440 gene
neXtProtiNX_P22102

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

Organism-specific databases

DisGeNETi2618
OpenTargetsiENSG00000159131
PharmGKBiPA28576

Chemistry databases

ChEMBLiCHEMBL3972
DrugBankiDB03546 10-CF3C(OH)2-DDACTHF
DB02236 Glycinamide Ribonucleotide
DB00642 Pemetrexed

Polymorphism and mutation databases

BioMutaiGART
DMDMi131616

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000749372 – 1010Trifunctional purine biosynthetic protein adenosine-3Add BLAST1009

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei10PhosphoserineCombined sources1
Modified residuei350N6-acetyllysineCombined sources1
Modified residuei440PhosphoserineCombined sources1
Modified residuei682PhosphothreonineCombined sources1
Modified residuei796PhosphoserineCombined sources1
Modified residuei802PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP22102
MaxQBiP22102
PaxDbiP22102
PeptideAtlasiP22102
PRIDEiP22102
ProteomicsDBi53961
53962 [P22102-2]

PTM databases

iPTMnetiP22102
PhosphoSitePlusiP22102
SwissPalmiP22102

Expressioni

Gene expression databases

BgeeiENSG00000159131
CleanExiHS_GART
ExpressionAtlasiP22102 baseline and differential
GenevisibleiP22102 HS

Organism-specific databases

HPAiHPA002119
HPA005779

Interactioni

Protein-protein interaction databases

BioGridi108888, 71 interactors
IntActiP22102, 25 interactors
MINTiP22102
STRINGi9606.ENSP00000371236

Chemistry databases

BindingDBiP22102

Structurei

Secondary structure

11010
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi2 – 9Combined sources8
Helixi12 – 21Combined sources10
Beta strandi27 – 34Combined sources8
Helixi37 – 39Combined sources3
Beta strandi40 – 47Combined sources8
Helixi55 – 65Combined sources11
Beta strandi69 – 72Combined sources4
Helixi76 – 79Combined sources4
Helixi82 – 88Combined sources7
Beta strandi93 – 95Combined sources3
Turni98 – 101Combined sources4
Helixi102 – 105Combined sources4
Helixi107 – 116Combined sources10
Beta strandi124 – 129Combined sources6
Helixi130 – 139Combined sources10
Beta strandi144 – 151Combined sources8
Beta strandi158 – 160Combined sources3
Helixi164 – 174Combined sources11
Beta strandi187 – 191Combined sources5
Beta strandi195 – 204Combined sources10
Beta strandi209 – 211Combined sources3
Beta strandi215 – 222Combined sources8
Turni223 – 225Combined sources3
Beta strandi226 – 238Combined sources13
Helixi244 – 253Combined sources10
Helixi255 – 264Combined sources10
Beta strandi271 – 280Combined sources10
Beta strandi283 – 292Combined sources10
Turni295 – 297Combined sources3
Helixi298 – 301Combined sources4
Helixi302 – 304Combined sources3
Helixi309 – 317Combined sources9
Helixi321 – 324Combined sources4
Beta strandi333 – 340Combined sources8
Turni342 – 345Combined sources4
Helixi357 – 362Combined sources6
Beta strandi366 – 375Combined sources10
Beta strandi378 – 381Combined sources4
Beta strandi383 – 395Combined sources13
Helixi396 – 409Combined sources14
Helixi423 – 428Combined sources6
Turni479 – 483Combined sources5
Beta strandi485 – 494Combined sources10
Helixi499 – 506Combined sources8
Helixi512 – 525Combined sources14
Turni526 – 528Combined sources3
Beta strandi530 – 542Combined sources13
Helixi545 – 562Combined sources18
Beta strandi565 – 573Combined sources9
Turni575 – 577Combined sources3
Beta strandi583 – 594Combined sources12
Helixi595 – 597Combined sources3
Helixi602 – 604Combined sources3
Beta strandi610 – 615Combined sources6
Beta strandi617 – 619Combined sources3
Helixi624 – 633Combined sources10
Beta strandi648 – 650Combined sources3
Helixi651 – 655Combined sources5
Helixi663 – 671Combined sources9
Beta strandi677 – 680Combined sources4
Helixi685 – 689Combined sources5
Helixi691 – 693Combined sources3
Beta strandi698 – 703Combined sources6
Helixi704 – 706Combined sources3
Helixi711 – 720Combined sources10
Helixi724 – 730Combined sources7
Beta strandi735 – 741Combined sources7
Helixi743 – 745Combined sources3
Helixi746 – 755Combined sources10
Beta strandi760 – 768Combined sources9
Beta strandi776 – 779Combined sources4
Helixi781 – 785Combined sources5
Beta strandi809 – 816Combined sources8
Helixi819 – 828Combined sources10
Beta strandi836 – 844Combined sources9
Helixi848 – 855Combined sources8
Beta strandi860 – 862Combined sources3
Helixi865 – 867Combined sources3
Beta strandi868 – 870Combined sources3
Helixi871 – 884Combined sources14
Beta strandi888 – 894Combined sources7
Helixi901 – 906Combined sources6
Turni907 – 909Combined sources3
Beta strandi910 – 917Combined sources8
Turni919 – 922Combined sources4
Helixi927 – 934Combined sources8
Beta strandi937 – 945Combined sources9
Beta strandi955 – 962Combined sources8
Helixi969 – 992Combined sources24
Beta strandi995 – 998Combined sources4
Beta strandi1002 – 1006Combined sources5

3D structure databases

ProteinModelPortaliP22102
SMRiP22102
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP22102

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini111 – 318ATP-graspAdd BLAST208

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni434 – 809AIRSAdd BLAST376
Regioni810 – 1010GARTAdd BLAST201
Regioni818 – 8205'-phosphoribosylglycinamide binding3
Regioni896 – 89910-formyltetrahydrofolate binding4
Regioni947 – 95110-formyltetrahydrofolate binding5
Regioni977 – 9805'-phosphoribosylglycinamide binding4

Sequence similaritiesi

In the N-terminal section; belongs to the GARS family.Curated
In the central section; belongs to the AIR synthase family.Curated
In the C-terminal section; belongs to the GART family.Curated

Phylogenomic databases

eggNOGiKOG0237 Eukaryota
KOG3076 Eukaryota
COG0150 LUCA
COG0151 LUCA
COG0299 LUCA
GeneTreeiENSGT00390000000292
HOVERGENiHBG008333
InParanoidiP22102
KOiK11787
OMAiLLERHNC
OrthoDBiEOG091G026D
PhylomeDBiP22102
TreeFamiTF106368

Family and domain databases

CDDicd08645 FMT_core_GART, 1 hit
cd02196 PurM, 1 hit
Gene3Di3.30.1330.10, 1 hit
3.30.1490.20, 1 hit
3.90.600.10, 1 hit
3.90.650.10, 1 hit
HAMAPiMF_00741 AIRS, 1 hit
MF_00138 GARS, 1 hit
MF_01930 PurN, 1 hit
InterProiView protein in InterPro
IPR011761 ATP-grasp
IPR013815 ATP_grasp_subdomain_1
IPR002376 Formyl_transf_N
IPR036477 Formyl_transf_N_sf
IPR004607 GART
IPR001555 GART_AS
IPR016185 PreATP-grasp_dom_sf
IPR020561 PRibGlycinamid_synth_ATP-grasp
IPR000115 PRibGlycinamide_synth
IPR020560 PRibGlycinamide_synth_C-dom
IPR037123 PRibGlycinamide_synth_C_sf
IPR020559 PRibGlycinamide_synth_CS
IPR020562 PRibGlycinamide_synth_N
IPR010918 PurM-like_C_dom
IPR036676 PurM-like_C_sf
IPR016188 PurM-like_N
IPR036921 PurM-like_N_sf
IPR004733 PurM_cligase
IPR011054 Rudment_hybrid_motif
PANTHERiPTHR10520 PTHR10520, 1 hit
PfamiView protein in Pfam
PF00586 AIRS, 1 hit
PF02769 AIRS_C, 1 hit
PF00551 Formyl_trans_N, 1 hit
PF01071 GARS_A, 1 hit
PF02843 GARS_C, 1 hit
PF02844 GARS_N, 1 hit
SMARTiView protein in SMART
SM01210 GARS_C, 1 hit
SUPFAMiSSF51246 SSF51246, 1 hit
SSF52440 SSF52440, 1 hit
SSF53328 SSF53328, 1 hit
SSF55326 SSF55326, 1 hit
SSF56042 SSF56042, 1 hit
TIGRFAMsiTIGR00877 purD, 1 hit
TIGR00878 purM, 1 hit
TIGR00639 PurN, 1 hit
PROSITEiView protein in PROSITE
PS50975 ATP_GRASP, 1 hit
PS00184 GARS, 1 hit
PS00373 GART, 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

Isoform Long (identifier: P22102-1) [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
MAARVLIIGS GGREHTLAWK LAQSHHVKQV LVAPGNAGTA CSEKISNTAI
60 70 80 90 100
SISDHTALAQ FCKEKKIEFV VVGPEAPLAA GIVGNLRSAG VQCFGPTAEA
110 120 130 140 150
AQLESSKRFA KEFMDRHGIP TAQWKAFTKP EEACSFILSA DFPALVVKAS
160 170 180 190 200
GLAAGKGVIV AKSKEEACKA VQEIMQEKAF GAAGETIVIE ELLDGEEVSC
210 220 230 240 250
LCFTDGKTVA PMPPAQDHKR LLEGDGGPNT GGMGAYCPAP QVSNDLLLKI
260 270 280 290 300
KDTVLQRTVD GMQQEGTPYT GILYAGIMLT KNGPKVLEFN CRFGDPECQV
310 320 330 340 350
ILPLLKSDLY EVIQSTLDGL LCTSLPVWLE NHTALTVVMA SKGYPGDYTK
360 370 380 390 400
GVEITGFPEA QALGLEVFHA GTALKNGKVV THGGRVLAVT AIRENLISAL
410 420 430 440 450
EEAKKGLAAI KFEGAIYRKD VGFRAIAFLQ QPRSLTYKES GVDIAAGNML
460 470 480 490 500
VKKIQPLAKA TSRSGCKVDL GGFAGLFDLK AAGFKDPLLA SGTDGVGTKL
510 520 530 540 550
KIAQLCNKHD TIGQDLVAMC VNDILAQGAE PLFFLDYFSC GKLDLSVTEA
560 570 580 590 600
VVAGIAKACG KAGCALLGGE TAEMPDMYPP GEYDLAGFAV GAMERDQKLP
610 620 630 640 650
HLERITEGDV VVGIASSGLH SNGFSLVRKI VAKSSLQYSS PAPDGCGDQT
660 670 680 690 700
LGDLLLTPTR IYSHSLLPVL RSGHVKAFAH ITGGGLLENI PRVLPEKLGV
710 720 730 740 750
DLDAQTWRIP RVFSWLQQEG HLSEEEMART FNCGVGAVLV VSKEQTEQIL
760 770 780 790 800
RDIQQHKEEA WVIGSVVARA EGSPRVKVKN LIESMQINGS VLKNGSLTNH
810 820 830 840 850
FSFEKKKARV AVLISGTGSN LQALIDSTRE PNSSAQIDIV ISNKAAVAGL
860 870 880 890 900
DKAERAGIPT RVINHKLYKN RVEFDSAIDL VLEEFSIDIV CLAGFMRILS
910 920 930 940 950
GPFVQKWNGK MLNIHPSLLP SFKGSNAHEQ ALETGVTVTG CTVHFVAEDV
960 970 980 990 1000
DAGQIILQEA VPVKRGDTVA TLSERVKLAE HKIFPAALQL VASGTVQLGE
1010
NGKICWVKEE
Length:1,010
Mass (Da):107,767
Last modified:August 1, 1991 - v1
Checksum:i9A4213F746EB17A2
GO
Isoform Short (identifier: P22102-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     434-1010: Missing.

Show »
Length:433
Mass (Da):46,033
Checksum:i45289299B5E9B397
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01181721L → F. Corresponds to variant dbSNP:rs1804387Ensembl.1
Natural variantiVAR_011818421V → I2 PublicationsCorresponds to variant dbSNP:rs8788Ensembl.1
Natural variantiVAR_051882510D → G. Corresponds to variant dbSNP:rs35927582Ensembl.1
Natural variantiVAR_051883641P → A. Corresponds to variant dbSNP:rs34588874Ensembl.1
Natural variantiVAR_011819752D → G. Corresponds to variant dbSNP:rs8971Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005517434 – 1010Missing in isoform Short. 1 PublicationAdd BLAST577

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54199 mRNA Translation: CAA38119.1
AK292560 mRNA Translation: BAF85249.1
AK292897 mRNA Translation: BAF85586.1
CH471079 Genomic DNA Translation: EAX09826.1
CH471079 Genomic DNA Translation: EAX09827.1
CH471079 Genomic DNA Translation: EAX09828.1
CH471079 Genomic DNA Translation: EAX09829.1
BC038958 mRNA Translation: AAH38958.1
BC093641 mRNA Translation: AAH93641.1
BC101565 mRNA Translation: AAI01566.1
AF008653 Genomic DNA Translation: AAB70812.1
M32082 mRNA Translation: AAA60077.1
CCDSiCCDS13627.1 [P22102-1]
CCDS13628.1 [P22102-2]
PIRiS12616 AJHUPR
RefSeqiNP_000810.1, NM_000819.4 [P22102-1]
NP_001129477.1, NM_001136005.1 [P22102-1]
NP_001129478.1, NM_001136006.1 [P22102-1]
NP_780294.1, NM_175085.2 [P22102-2]
XP_005260998.1, XM_005260941.1 [P22102-1]
XP_006724052.1, XM_006723989.1 [P22102-1]
XP_006724053.1, XM_006723990.1 [P22102-1]
XP_011527828.1, XM_011529526.1 [P22102-1]
UniGeneiHs.473648

Genome annotation databases

EnsembliENST00000361093; ENSP00000354388; ENSG00000159131 [P22102-2]
ENST00000381815; ENSP00000371236; ENSG00000159131 [P22102-1]
ENST00000381831; ENSP00000371253; ENSG00000159131 [P22102-1]
ENST00000381839; ENSP00000371261; ENSG00000159131 [P22102-1]
ENST00000571089; ENSP00000459532; ENSG00000262473
ENST00000573055; ENSP00000459391; ENSG00000262473
ENST00000575273; ENSP00000461700; ENSG00000262473
GeneIDi2618
KEGGihsa:2618
UCSCiuc002yrx.4 human [P22102-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPUR2_HUMAN
AccessioniPrimary (citable) accession number: P22102
Secondary accession number(s): A8K945
, A8KA32, D3DSF3, D3DSF4, O14659, Q52M77
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: July 18, 2018
This is version 205 of the entry and version 1 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, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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