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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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	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 nucleobase biosynthetic process Traceable author statement Ref.1. 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 Ref.1. Source: ProtInc pyrophosphatase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6

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.6

Modified residue

318

1

Phosphothreonine Ref.7

Modified residue

332

1

Phosphoserine Ref.7 Ref.9

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

Turn

35 – 38

4

Helix

39 – 47

9

Beta strand

52 – 54

3

Helix

61 – 67

7

Beta strand

70 – 76

7

Helix

91 – 94

4

Beta strand

100 – 104

5

Helix

105 – 113

9

Beta strand

118 – 123

6

Beta strand

127 – 133

7

Helix

138 – 140

3

Beta strand

145 – 151

7

Beta strand

153 – 159

7

Beta strand

165 – 170

6

Beta strand

173 – 179

7

Turn

180 – 183

4

Beta strand

184 – 189

6

Beta strand

193 – 196

4

Helix

199 – 207

9

Turn

208 – 211

4

Helix

219 – 234

16

Beta strand

238 – 242

5

Helix

247 – 259

13

Helix

262 – 264

3

Beta strand

265 – 271

7

Helix

281 – 289

9

Beta strand

294 – 298

5

Helix

300 – 304

5

Helix

327 – 329

3

Helix

333 – 354

22

Beta strand

361 – 365

5

Helix

377 – 382

6

Helix

387 – 389

3

Helix

396 – 403

8

Helix

410 – 413

4

Helix

416 – 425

10

Helix

430 – 433

4

Helix

442 – 446

5

Beta strand

450 – 452

3

Helix

459 – 470

12

Helix

472 – 475

4

Helix

481 – 489

9

Helix

492 – 504

13

Beta strand

507 – 520

14

Beta strand

523 – 536

14

Helix

540 – 553

14

Beta strand

557 – 563

7

Helix

582 – 601

20

Helix

605 – 607

3

Beta strand

613 – 617

5

Helix

624 – 626

3

Beta strand

633 – 637

5

Beta strand

643 – 649

7

Turn

654 – 656

3

Helix

659 – 671

13

Beta strand

675 – 681

7

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH MLL.
[4]	"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.
[5]	"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.
[6]	"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, MASS SPECTROMETRY, CLEAVAGE OF INITIATOR METHIONINE.
[7]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"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, MASS SPECTROMETRY.
+	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.

ModBase

Search...

Protein-protein interaction databases

IntAct

P49915. 12 interactions.

STRING

9606.ENSP00000419851.

Protein family/group databases

MEROPS

C26.950.

PTM databases

PhosphoSite

P49915.

Polymorphism databases

DMDM

1708072.

2D gel databases

REPRODUCTION-2DPAGE

IPI00029079.

Proteomic databases

PaxDb

P49915.

PeptideAtlas

P49915.

PRIDE

P49915.

Protocols and materials databases

DNASU

8833.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000496455; ENSP00000419851; ENSG00000163655.
ENST00000541628; ENSP00000438199; ENSG00000163655.

GeneID

8833.

KEGG

hsa:8833.

UCSC

uc003faq.3. human.

Organism-specific databases

CTD

8833.

GeneCards

GC03P155588.

HGNC

HGNC:4378. GMPS.

HPA

HPA050682.

MIM

600358. gene.

neXtProt

NX_P49915.

PharmGKB

PA28763.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0519.

HOGENOM

HOG000223965.

HOVERGEN

HBG005929.

InParanoid

P49915.

KO

K01951.

OMA

YDYVVAL.

OrthoDB

EOG4J6RQ9.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00189; UER00296.

Gene expression databases

ArrayExpress

P49915.

Bgee

P49915.

CleanEx

HS_GMPS.

Genevestigator

P49915.

GermOnline

ENSG00000163655. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.620. 1 hit.

InterPro

IPR017926. GATASE_1.
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]

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

ChEMBL

CHEMBL5721.

ChiTaRS

GMPS. human.

DrugBank

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

EvolutionaryTrace

P49915.

GenomeRNAi

8833.

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:	May 1, 2013
This is version 138 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.