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Reviewed, UniProtKB/Swiss-Prot P22102 (PUR2_HUMAN)

Last modified June 16, 2009. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Trifunctional purine biosynthetic protein adenosine-3
Including the following 3 domains:
    1- Recommended name:
            Phosphoribosylamine--glycine ligase
              EC=6.3.4.13
        Alternative name(s):
            Glycinamide ribonucleotide synthetase
              Short name=GARS
            Phosphoribosylglycinamide synthetase
    2- Recommended name:
            Phosphoribosylformylglycinamidine cyclo-ligase
              EC=6.3.3.1
        Alternative name(s):
            Phosphoribosyl-aminoimidazole synthetase
            AIR synthase
              Short name=AIRS
    3- Recommended name:
            Phosphoribosylglycinamide formyltransferase
              EC=2.1.2.2
        Alternative name(s):
            5'-phosphoribosylglycinamide transformylase
            GAR transformylase
              Short name=GART
Gene names
Name: GART
Synonyms: PGFT, PRGS
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1010 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Catalytic activity

ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N(1)-(5-phospho-D-ribosyl)glycinamide.

ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole.

10-formyltetrahydrofolate + N(1)-(5-phospho-D-ribosyl)glycinamide = tetrahydrofolate + N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide.

Pathway

Purine metabolism; IMP biosynthesis via de novo pathway; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide: step 2/5.

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

Purine metabolism; IMP biosynthesis via de novo pathway; N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide from N(1)-(5-phospho-D-ribosyl)glycinamide (10-formyl THF route): step 1/1.

Sequence similarities

In the N-terminal section; belongs to the GARS family.

In the central section; belongs to the AIR synthase family.

In the C-terminal section; belongs to the GART family.

Contains 1 ATP-grasp domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ARF6P623301EBI-356297,EBI-638181

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: P22102-1)

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.
Isoform Short (identifier: P22102-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10101010Trifunctional purine biosynthetic protein adenosine-3
PRO_0000074937

Regions

Domain111 – 318208ATP-grasp
Nucleotide binding137 – 19963ATP By similarity
Region434 – 809376AIRS
Region810 – 1010201GART
Region818 – 82035'-phosphoribosylglycinamide binding
Region896 – 899410-formyltetrahydrofolate binding
Region947 – 951510-formyltetrahydrofolate binding
Region977 – 98045'-phosphoribosylglycinamide binding

Sites

Active site9151Proton donor By similarity
Metal binding2881Manganese By similarity
Metal binding2901Manganese By similarity
Binding site871110-formyltetrahydrofolate
Binding site913110-formyltetrahydrofolate
Site9511Raises pKa of active site His By similarity

Amino acid modifications

Modified residue3481Phosphotyrosine Ref.6 Ref.7

Natural variations

Alternative sequence434 – 1010577Missing in isoform Short.
VSP_005517
Natural variant211L → F: dbSNP rs1804387.
VAR_011817
Natural variant4211V → I: dbSNP rs8788. Ref.2 Ref.4
VAR_011818
Natural variant5101D → G: dbSNP rs35927582.
VAR_051882
Natural variant6411P → A: dbSNP rs34588874.
VAR_051883
Natural variant7521D → G: dbSNP rs8971.
VAR_011819

Secondary structure

........................................................................................................................................................ 1010
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified August 1, 1991. Version 1.
Checksum: 9A4213F746EB17A2

FASTA1,010107,767
        10         20         30         40         50         60 
MAARVLIIGS GGREHTLAWK LAQSHHVKQV LVAPGNAGTA CSEKISNTAI SISDHTALAQ 

        70         80         90        100        110        120 
FCKEKKIEFV VVGPEAPLAA GIVGNLRSAG VQCFGPTAEA AQLESSKRFA KEFMDRHGIP 

       130        140        150        160        170        180 
TAQWKAFTKP EEACSFILSA DFPALVVKAS GLAAGKGVIV AKSKEEACKA VQEIMQEKAF 

       190        200        210        220        230        240 
GAAGETIVIE ELLDGEEVSC LCFTDGKTVA PMPPAQDHKR LLEGDGGPNT GGMGAYCPAP 

       250        260        270        280        290        300 
QVSNDLLLKI KDTVLQRTVD GMQQEGTPYT GILYAGIMLT KNGPKVLEFN CRFGDPECQV 

       310        320        330        340        350        360 
ILPLLKSDLY EVIQSTLDGL LCTSLPVWLE NHTALTVVMA SKGYPGDYTK GVEITGFPEA 

       370        380        390        400        410        420 
QALGLEVFHA GTALKNGKVV THGGRVLAVT AIRENLISAL EEAKKGLAAI KFEGAIYRKD 

       430        440        450        460        470        480 
VGFRAIAFLQ QPRSLTYKES GVDIAAGNML VKKIQPLAKA TSRSGCKVDL GGFAGLFDLK 

       490        500        510        520        530        540 
AAGFKDPLLA SGTDGVGTKL KIAQLCNKHD TIGQDLVAMC VNDILAQGAE PLFFLDYFSC 

       550        560        570        580        590        600 
GKLDLSVTEA VVAGIAKACG KAGCALLGGE TAEMPDMYPP GEYDLAGFAV GAMERDQKLP 

       610        620        630        640        650        660 
HLERITEGDV VVGIASSGLH SNGFSLVRKI VAKSSLQYSS PAPDGCGDQT LGDLLLTPTR 

       670        680        690        700        710        720 
IYSHSLLPVL RSGHVKAFAH ITGGGLLENI PRVLPEKLGV DLDAQTWRIP RVFSWLQQEG 

       730        740        750        760        770        780 
HLSEEEMART FNCGVGAVLV VSKEQTEQIL RDIQQHKEEA WVIGSVVARA EGSPRVKVKN 

       790        800        810        820        830        840 
LIESMQINGS VLKNGSLTNH FSFEKKKARV AVLISGTGSN LQALIDSTRE PNSSAQIDIV 

       850        860        870        880        890        900 
ISNKAAVAGL DKAERAGIPT RVINHKLYKN RVEFDSAIDL VLEEFSIDIV CLAGFMRILS 

       910        920        930        940        950        960 
GPFVQKWNGK MLNIHPSLLP SFKGSNAHEQ ALETGVTVTG CTVHFVAEDV DAGQIILQEA 

       970        980        990       1000       1010 
VPVKRGDTVA TLSERVKLAE HKIFPAALQL VASGTVQLGE NGKICWVKEE 

« Hide

Isoform Short.

Checksum: 45289299B5E9B397
Show »

FASTA43346,033

References

« Hide 'large scale' references
[1]"De novo purine nucleotide biosynthesis: cloning of human and avian cDNAs encoding the trifunctional glycinamide ribonucleotide synthetase-aminoimidazole ribonucleotide synthetase-glycinamide ribonucleotide transformylase by functional complementation in E. coli."
Aimi J., Qiu H., Williams J., Zalkin H., Dixon J.E.
Nucleic Acids Res. 18:6665-6672(1990) [PubMed: 2147474] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG), VARIANT ILE-421.
Tissue: Testis.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
Tissue: Testis.
[4]"Intronic polyadenylation in the human glycinamide ribonucleotide formyltransferase gene."
Kan J.L.C., Moran R.G.
Nucleic Acids Res. 25:3118-3123(1997) [PubMed: 9224613] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 357-432, VARIANT ILE-421.
[5]"Cloning of three human multifunctional de novo purine biosynthetic genes by functional complementation of yeast mutations."
Schild D., Brake A.J., Kiefer M.C., Young D., Barr P.J.
Proc. Natl. Acad. Sci. U.S.A. 87:2916-2920(1990) [PubMed: 2183217] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 709-1010.
[6]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-348, MASS SPECTROMETRY.
[7]"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer."
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. expand/collapse author list , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.
Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-348, MASS SPECTROMETRY.
[8]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]"Crystal structures of human GAR Tfase at low and high pH and with substrate beta-GAR."
Zhang Y., Desharnais J., Greasley S.E., Beardsley G.P., Boger D.L., Wilson I.A.
Biochemistry 41:14206-14215(2002) [PubMed: 12450384] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 808-1010 IN COMPLEX WITH SUBSTRATE.
[10]"Rational design, synthesis, evaluation, and crystal structure of a potent inhibitor of human GAR Tfase: 10-(trifluoroacetyl)-5,10-dideazaacyclic-5,6,7,8-tetrahydrofolic acid."
Zhang Y., Desharnais J., Marsilje T.H., Li C., Hedrick M.P., Gooljarsingh L.T., Tavassoli A., Benkovic S.J., Olson A.J., Boger D.L., Wilson I.A.
Biochemistry 42:6043-6056(2003) [PubMed: 12755606] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.98 ANGSTROMS) OF 808-1010 IN COMPLEX WITH FORMYLTETRAHYDROFOLATE ANALOG.
[11]"The apo and ternary complex structures of a chemotherapeutic target: human glycinamide ribonucleotide transformylase."
Dahms T.E., Sainz G., Giroux E.L., Caperelli C.A., Smith J.L.
Biochemistry 44:9841-9850(2005) [PubMed: 16026156] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) OF 808-1010 IN COMPLEX WITH SUBSTRATE ANALOGS.
+Additional computationally mapped references.

Cross-references

Sequence databases

X54199 mRNA. Translation: CAA38119.1.
AK292560 mRNA. Translation: BAF85249.1.
BC038958 mRNA. Translation: AAH38958.1.
AF008653 Genomic DNA. Translation: AAB70812.1.
M32082 mRNA. Translation: AAA60077.1.
IPIIPI00025273.
IPI00218408.
PIRAJHUPR. S12616.
RefSeqNP_000810.1.
NP_001129477.1.
NP_001129478.1.
NP_780294.1.
UniGeneHs.473648

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1MEJX-ray2.00A/B/C810-1010[»]
1MENX-ray2.23A/B/C810-1010[»]
1MEOX-ray1.72A808-1010[»]
1NJSX-ray1.98A/B808-1010[»]
1RBMX-ray2.30A/B808-1010[»]
1RBQX-ray2.10A/B/C/D808-1010[»]
1RBYX-ray2.10A/B/C/D808-1010[»]
1RBZX-ray2.10A/B808-1010[»]
1RC0X-ray2.05A/B808-1010[»]
1RC1X-ray2.25A/B808-1010[»]
1ZLXX-ray2.20A808-1010[»]
1ZLYX-ray2.07A808-1010[»]
2QK4X-ray2.45A/B1-430[»]
2V9YX-ray2.10A/B467-794[»]
ModBaseSearch...

Protein-protein interaction databases

IntActP22102. 2 interactions.

PTM databases

PhosphoSiteP22102.

Proteomic databases

PeptideAtlasP22102.
PRIDEP22102.

Genome annotation databases

EnsemblENSG00000159131. Homo sapiens. [Contig view]
GeneID2618.
KEGGhsa:2618.
NMPDRfig|9606.3.peg.20899.

Organism-specific databases

GeneCardsGC21M033798.
H-InvDBHIX0027779.
HGNCHGNC:4163. GART.
HPAHPA002119.
HPA005779.
MIM138440. gene.
PharmGKBPA28576.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP22102.
OMAP22102. GETSEMP.

Enzyme and pathway databases

BRENDA2.1.2.2. 247.
6.3.3.1. 247.
6.3.4.13. 247.
ReactomeREACT_1698. Nucleotide metabolism.

Gene expression databases

ArrayExpressP22102.
BgeeP22102.
CleanExHS_GART.
GermOnlineENSG00000159131. Homo sapiens.

Family and domain databases

InterProIPR000728. AIR_synth.
IPR010918. AIR_synth_C.
IPR011761. ATP-grasp.
IPR013815. ATP_grasp_subdomain_1.
IPR013816. ATP_grasp_subdomain_2.
IPR002376. Formyl_transf_N.
IPR000115. Gars.
IPR001555. GART_AS.
IPR013817. Pre-ATP_grasp.
IPR004733. PurM_cligase.
IPR004607. PurN_trans.
[Graphical view]
Gene3DG3DSA:3.30.1490.20. ATP_grasp_subdomain_1. 1 hit.
G3DSA:3.30.470.20. ATP_grasp_subdomain_2. 1 hit.
G3DSA:3.40.50.170. Formyl_transf_N. 1 hit.
G3DSA:3.40.50.20. Pre-ATP_grasp. 1 hit.
PfamPF00586. 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.
[Graphical view]
TIGRFAMsTIGR00877. purD. 1 hit.
TIGR00878. purM. 1 hit.
TIGR00639. PurN. 1 hit.
PROSITEPS50975. ATP_GRASP. 1 hit.
PS00184. GARS. 1 hit.
PS00373. GART. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

BindingDBP22102.
DrugBankDB00642. Pemetrexed.
NextBio10307.
SOURCESearch...

Entry information

Entry namePUR2_HUMAN
AccessionPrimary (citable) accession number: P22102
Secondary accession number(s): A8K945, O14659
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: June 16, 2009
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents