P49915 (GUAA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
GMP synthase [glutamine-hydrolyzing]
EC=6.3.5.2

Alternative name(s):
GMP synthetase
Glutamine amidotransferase

Gene names

Name:

GMPS

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	693 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 + xanthosine 5'-phosphate + 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 By similarity.
Subcellular location	Cytoplasm.
Involvement in disease	Note=A chromosomal aberration involving GMPS is found in acute myeloid leukemias. Translocation t(3,11)(q25,q23) with MLL.
Sequence similarities	Contains 1 glutamine amidotransferase type-1 domain. Contains 1 GMPS ATP-PPase (ATP pyrophosphatase) domain.

Ontologies

Keywords
Biological process	GMP biosynthesis Purine biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Chromosomal rearrangement
Disease	Proto-oncogene
Domain	Glutamine amidotransferase
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	glutamine metabolic process Inferred from electronic annotation. Source: UniProtKB-KW purine base biosynthetic process Traceable author statement. Source: ProtInc
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW GMP synthase (glutamine-hydrolyzing) activity Inferred from electronic annotation. Source: EC GMP synthase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 693

692

GMP synthase [glutamine-hydrolyzing]

PRO_0000140257

Regions

Domain

27 – 216

190

Glutamine amidotransferase type-1

Domain

217 – 435

219

GMPS ATP-PPase

Nucleotide binding

244 – 250

7

ATP By similarity

Sites

Active site

104

1

For GATase activity By similarity

Active site

190

1

For GATase activity By similarity

Active site

192

1

For GATase activity By similarity

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.6

Modified residue

9

1

N6-acetyllysine Ref.7

Modified residue

318

1

Phosphothreonine Ref.4

Modified residue

332

1

Phosphoserine Ref.5 Ref.6

Modified residue

416

1

N6-acetyllysine Ref.7

Experimental info

Sequence conflict

415

1

H → I AA sequence Ref.1

Secondary structure

1

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693

Helix Strand Turn

Details...

Beta strand

28 – 32

5

Helix

40 – 47

8

Beta strand

52 – 54

3

Helix

61 – 66

6

Beta strand

71 – 75

5

Helix

91 – 94

4

Helix

108 – 113

6

Beta strand

129 – 133

5

Helix

138 – 140

3

Beta strand

145 – 149

5

Beta strand

156 – 159

4

Turn

180 – 183

4

Helix

201 – 207

7

Turn

208 – 210

3

Sequences

	Sequence		Length	Mass (Da)
	P49915 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 1CDA0DD3B244728D	FASTA	693	76,715
	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

References

	« Hide 'large scale' referencesShow '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: 8089153] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]	"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]. Tissue: Placenta.
[3]	"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: 11110714] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH MLL.
[4]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-318, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[5]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-332, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[6]	"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: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-332, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[7]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-9 AND LYS-416, MASS SPECTROMETRY.
[8]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U10860 mRNA. Translation: AAA60331.1.
BC012178 mRNA. Translation: AAH12178.1.

IPI

IPI00029079.

PIR

A54847.

RefSeq

NP_003866.1. NM_003875.2.

UniGene

Hs.591314.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VPI	X-ray	2.40	A/B	25-219	[»]
2VXO	X-ray	2.50	A/B	20-693	[»]

ProteinModelPortal

P49915.

SMR

P49915. Positions 23-693.

ModBase

Search...

Protein-protein interaction databases

IntAct

P49915. 9 interactions.

STRING

P49915.

Protein family/group databases

MEROPS

C26.950.

PTM databases

PhosphoSite

P49915.

Polymorphism databases

DMDM

1708072.

2D gel databases

REPRODUCTION-2DPAGE

IPI00029079.

Proteomic databases

PeptideAtlas

P49915.

PRIDE

P49915.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000496455; ENSP00000419851; ENSG00000163655.

GeneID

8833.

KEGG

hsa:8833.

UCSC

uc003faq.1. human.

Organism-specific databases

CTD

8833.

GeneCards

GC03P155588.

H-InvDB

HIX0018176.

HGNC

HGNC:4378. GMPS.

MIM

600358. gene.

neXtProt

NX_P49915.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG18840.

HOGENOM

HBG391775.

HOVERGEN

HBG005929.

InParanoid

P49915.

OMA

DGRTYEY.

OrthoDB

EOG4J6RQ9.

PhylomeDB

P49915.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P49915.

Bgee

P49915.

CleanEx

HS_GMPS.

Genevestigator

P49915.

GermOnline

ENSG00000163655. Homo sapiens.

Family and domain databases

InterPro

IPR017926. GATASE_1.
IPR001674. GMP_synth_C.
IPR004739. GMP_synth_N.
IPR022310. NAD/GMP_synthase.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]

Gene3D

G3DSA:3.40.50.620. Rossmann-like_a/b/a_fold. 1 hit.

KO

K01951.

Pfam

PF00117. GATase. 1 hit.
PF00958. GMP_synt_C. 1 hit.
PF02540. NAD_synthase. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00888. GuaA_Nterm. 1 hit.

PROSITE

PS51273. GATASE_TYPE_1. 1 hit.
PS51553. GMPS_ATP_PPASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00142. L-Glutamic Acid.
DB00130. L-Glutamine.

NextBio

33152.

SOURCE

Search...

Entry information

Entry name

GUAA_HUMAN

Accession

Primary (citable) accession number: P49915

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	January 25, 2012
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.