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P49915 (GUAA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
GMP synthase [glutamine-hydrolyzing]

EC=6.3.5.2
Alternative name(s):
GMP synthetase
Glutamine amidotransferase
Gene names
Name:GMPS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length693 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in the de novo synthesis of guanine nucleotides which are not only essential for DNA and RNA synthesis, but also provide GTP, which is involved in a number of cellular processes important for cell division.

Catalytic activity

ATP + XMP + L-glutamine + H2O = AMP + diphosphate + GMP + L-glutamate.

Pathway

Purine metabolism; GMP biosynthesis; GMP from XMP (L-Gln route): step 1/1.

Subunit structure

Homodimer. Ref.14

Subcellular location

Cytoplasm.

Involvement in disease

A chromosomal aberration involving GMPS is found in acute myeloid leukemias. Translocation t(3,11)(q25,q23) with KMT2A/MLL1.

Sequence similarities

Contains 1 glutamine amidotransferase type-1 domain.

Contains 1 GMPS ATP-PPase (ATP pyrophosphatase) domain.

Ontologies

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P49915-1)

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 2 (identifier: P49915-2)

The sequence of this isoform differs from the canonical sequence as follows:
     10-108: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.8
Chain2 – 693692GMP synthase [glutamine-hydrolyzing]
PRO_0000140257

Regions

Domain27 – 216190Glutamine amidotransferase type-1
Domain217 – 435219GMPS ATP-PPase
Nucleotide binding244 – 2507ATP By similarity

Sites

Active site1041For GATase activity Ref.14
Active site1901For GATase activity Ref.14
Active site1921For GATase activity Ref.14
Binding site3371Substrate
Binding site5221Substrate
Binding site6101Substrate
Binding site6851Substrate
Binding site6911Substrate

Amino acid modifications

Modified residue21N-acetylalanine Ref.8 Ref.10
Modified residue91N6-acetyllysine Ref.10
Modified residue3181Phosphothreonine Ref.11
Modified residue3321Phosphoserine Ref.11 Ref.13

Natural variations

Alternative sequence10 – 10899Missing in isoform 2.
VSP_053933

Experimental info

Sequence conflict2611N → D in BAG63519. Ref.2
Sequence conflict4151H → I AA sequence Ref.1

Secondary structure

............................................................................................................. 693
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 1CDA0DD3B244728D

FASTA69376,715
        10         20         30         40         50         60 
MALCNGDSKL ENAGGDLKDG HHHYEGAVVI LDAGAQYGKV IDRRVRELFV QSEIFPLETP 

        70         80         90        100        110        120 
AFAIKEQGFR AIIISGGPNS VYAEDAPWFD PAIFTIGKPV LGICYGMQMM NKVFGGTVHK 

       130        140        150        160        170        180 
KSVREDGVFN ISVDNTCSLF RGLQKEEVVL LTHGDSVDKV ADGFKVVARS GNIVAGIANE 

       190        200        210        220        230        240 
SKKLYGAQFH PEVGLTENGK VILKNFLYDI AGCSGTFTVQ NRELECIREI KERVGTSKVL 

       250        260        270        280        290        300 
VLLSGGVDST VCTALLNRAL NQEQVIAVHI DNGFMRKRES QSVEEALKKL GIQVKVINAA 

       310        320        330        340        350        360 
HSFYNGTTTL PISDEDRTPR KRISKTLNMT TSPEEKRKII GDTFVKIANE VIGEMNLKPE 

       370        380        390        400        410        420 
EVFLAQGTLR PDLIESASLV ASGKAELIKT HHNDTELIRK LREEGKVIEP LKDFHKDEVR 

       430        440        450        460        470        480 
ILGRELGLPE ELVSRHPFPG PGLAIRVICA EEPYICKDFP ETNNILKIVA DFSASVKKPH 

       490        500        510        520        530        540 
TLLQRVKACT TEEDQEKLMQ ITSLHSLNAF LLPIKTVGVQ GDCRSYSYVC GISSKDEPDW 

       550        560        570        580        590        600 
ESLIFLARLI PRMCHNVNRV VYIFGPPVKE PPTDVTPTFL TTGVLSTLRQ ADFEAHNILR 

       610        620        630        640        650        660 
ESGYAGKISQ MPVILTPLHF DRDPLQKQPS CQRSVVIRTF ITSDFMTGIP ATPGNEIPVE 

       670        680        690 
VVLKMVTEIK KIPGISRIMY DLTSKPPGTT EWE 

« Hide

Isoform 2 [UniParc].

Checksum: 376D7F0A7E3F8C07
Show »

FASTA59465,929

References

« Hide 'large scale' references
[1]"Human GMP synthetase. Protein purification, cloning, and functional expression of cDNA."
Hirst M., Haliday E., Nakamura J., Lou L.
J. Biol. Chem. 269:23830-23837(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Testis.
[3]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Placenta.
[6]"t(3;11) translocation in treatment-related acute myeloid leukemia fuses MLL with the GMPS (guanosine 5-prime monophosphate synthetase) gene."
Pegram L.D., Megonigal M.D., Lange B.J., Nowell P.C., Rowley J.D., Rappaport E.F., Felix C.A.
Blood 96:4360-4362(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH KMT2A/MLL1.
[7]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[9]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[10]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2 AND LYS-9, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-318 AND SER-332, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-332, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Substrate specificity and oligomerization of human GMP synthetase."
Welin M., Lehtio L., Johansson A., Flodin S., Nyman T., Tresaugues L., Hammarstrom M., Graslund S., Nordlund P.
J. Mol. Biol. 425:4323-4333(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 20-693, SUBSTRATE-BINDING SITES, ACTIVE SITE, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U10860 mRNA. Translation: AAA60331.1.
AK291504 mRNA. Translation: BAF84193.1.
AK302148 mRNA. Translation: BAG63519.1.
AK315832 mRNA. Translation: BAF98723.1.
AC067721 Genomic DNA. No translation available.
AC104472 Genomic DNA. No translation available.
AC140753 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78741.1.
BC012178 mRNA. Translation: AAH12178.1.
CCDSCCDS46941.1.
PIRA54847.
RefSeqNP_003866.1. NM_003875.2. [P49915-1]
UniGeneHs.591314.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2VPIX-ray2.40A/B25-219[»]
2VXOX-ray2.50A/B20-693[»]
ProteinModelPortalP49915.
SMRP49915. Positions 23-693.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114360. 27 interactions.
IntActP49915. 13 interactions.
MINTMINT-5004310.
STRING9606.ENSP00000419851.

Chemistry

ChEMBLCHEMBL5721.
DrugBankDB00142. L-Glutamic Acid.
DB00130. L-Glutamine.

Protein family/group databases

MEROPSC26.950.

PTM databases

PhosphoSiteP49915.

Polymorphism databases

DMDM1708072.

2D gel databases

REPRODUCTION-2DPAGEIPI00029079.

Proteomic databases

MaxQBP49915.
PaxDbP49915.
PeptideAtlasP49915.
PRIDEP49915.

Protocols and materials databases

DNASU8833.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000295920; ENSP00000295920; ENSG00000163655.
ENST00000496455; ENSP00000419851; ENSG00000163655.
GeneID8833.
KEGGhsa:8833.
UCSCuc003faq.3. human. [P49915-1]

Organism-specific databases

CTD8833.
GeneCardsGC03P155588.
HGNCHGNC:4378. GMPS.
HPAHPA046630.
HPA050682.
MIM600358. gene.
neXtProtNX_P49915.
PharmGKBPA28763.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0519.
HOGENOMHOG000223965.
HOVERGENHBG005929.
InParanoidP49915.
KOK01951.
OMAKIYGLQF.
OrthoDBEOG7J17Z9.
PhylomeDBP49915.
TreeFamTF106132.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
UniPathwayUPA00189; UER00296.

Gene expression databases

ArrayExpressP49915.
BgeeP49915.
CleanExHS_GMPS.
GenevestigatorP49915.

Family and domain databases

Gene3D3.40.50.620. 1 hit.
3.40.50.880. 1 hit.
InterProIPR029062. Class_I_gatase-like.
IPR017926. GATASE.
IPR001674. GMP_synth_C.
IPR004739. GMP_synth_N.
IPR025777. GMPS_ATP_PPase_dom.
IPR022310. NAD/GMP_synthase.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]
PfamPF00117. GATase. 1 hit.
PF00958. GMP_synt_C. 1 hit.
PF02540. NAD_synthase. 1 hit.
[Graphical view]
SUPFAMSSF52317. SSF52317. 1 hit.
TIGRFAMsTIGR00888. guaA_Nterm. 1 hit.
PROSITEPS51273. GATASE_TYPE_1. 1 hit.
PS51553. GMPS_ATP_PPASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGMPS. human.
EvolutionaryTraceP49915.
GeneWikiGMP_synthase.
GenomeRNAi8833.
NextBio33152.
PROP49915.
SOURCESearch...

Entry information

Entry nameGUAA_HUMAN
AccessionPrimary (citable) accession number: P49915
Secondary accession number(s): A8K639, B4DXV7, F8W720
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

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

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM