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Protein

GMP synthase [glutamine-hydrolyzing]

Gene

GMPS

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

Functioni

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 activityi

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

Pathwayi: GMP biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes GMP from XMP (L-Gln route).
Proteins known to be involved in this subpathway in this organism are:
  1. GMP synthase [glutamine-hydrolyzing] (GMPS)
This subpathway is part of the pathway GMP biosynthesis, which is itself part of Purine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes GMP from XMP (L-Gln route), the pathway GMP biosynthesis and in Purine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei104For GATase activityPROSITE-ProRule annotation1 Publication1
Active sitei190For GATase activityPROSITE-ProRule annotation1 Publication1
Active sitei192For GATase activityPROSITE-ProRule annotation1 Publication1
Binding sitei337Substrate1
Binding sitei522Substrate1
Binding sitei610Substrate1
Binding sitei685Substrate1
Binding sitei691Substrate1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi244 – 250ATPPROSITE-ProRule annotation7

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionLigase
Biological processGMP biosynthesis, Purine biosynthesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi6.3.5.2 2681
ReactomeiR-HSA-73817 Purine ribonucleoside monophosphate biosynthesis
SIGNORiP49915
UniPathwayiUPA00189; UER00296

Protein family/group databases

MEROPSiC26.950

Names & Taxonomyi

Protein namesi
Recommended name:
GMP synthase [glutamine-hydrolyzing] (EC:6.3.5.2)
Alternative name(s):
GMP synthetase
Glutamine amidotransferase
Gene namesi
Name:GMPS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000163655.15
HGNCiHGNC:4378 GMPS
MIMi600358 gene
neXtProtiNX_P49915

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

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

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

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi8833
OpenTargetsiENSG00000163655
PharmGKBiPA28763

Chemistry databases

ChEMBLiCHEMBL5721
DrugBankiDB00142 L-Glutamic Acid
DB00130 L-Glutamine

Polymorphism and mutation databases

BioMutaiGMPS
DMDMi1708072

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001402572 – 693GMP synthase [glutamine-hydrolyzing]Add BLAST692

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei8PhosphoserineCombined sources1
Modified residuei9N6-acetyllysineCombined sources1
Modified residuei318PhosphothreonineCombined sources1
Modified residuei332PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP49915
MaxQBiP49915
PaxDbiP49915
PeptideAtlasiP49915
PRIDEiP49915
ProteomicsDBi56180

2D gel databases

REPRODUCTION-2DPAGEiIPI00029079

PTM databases

iPTMnetiP49915
PhosphoSitePlusiP49915
SwissPalmiP49915

Expressioni

Gene expression databases

BgeeiENSG00000163655
CleanExiHS_GMPS
ExpressionAtlasiP49915 baseline and differential
GenevisibleiP49915 HS

Organism-specific databases

HPAiHPA046630

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi114360, 52 interactors
IntActiP49915, 29 interactors
MINTiP49915
STRINGi9606.ENSP00000419851

Structurei

Secondary structure

1693
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi28 – 32Combined sources5
Turni35 – 38Combined sources4
Helixi39 – 47Combined sources9
Beta strandi52 – 54Combined sources3
Helixi61 – 67Combined sources7
Beta strandi70 – 76Combined sources7
Helixi91 – 94Combined sources4
Beta strandi100 – 104Combined sources5
Helixi105 – 113Combined sources9
Beta strandi118 – 123Combined sources6
Beta strandi127 – 133Combined sources7
Helixi138 – 140Combined sources3
Beta strandi145 – 151Combined sources7
Beta strandi153 – 159Combined sources7
Beta strandi165 – 170Combined sources6
Beta strandi173 – 179Combined sources7
Turni180 – 183Combined sources4
Beta strandi184 – 189Combined sources6
Beta strandi193 – 196Combined sources4
Helixi199 – 207Combined sources9
Turni208 – 211Combined sources4
Helixi219 – 234Combined sources16
Beta strandi238 – 242Combined sources5
Helixi247 – 259Combined sources13
Helixi262 – 264Combined sources3
Beta strandi265 – 271Combined sources7
Helixi281 – 289Combined sources9
Beta strandi294 – 298Combined sources5
Helixi300 – 304Combined sources5
Helixi327 – 329Combined sources3
Helixi333 – 354Combined sources22
Beta strandi361 – 365Combined sources5
Helixi377 – 382Combined sources6
Helixi387 – 389Combined sources3
Helixi396 – 403Combined sources8
Helixi410 – 413Combined sources4
Helixi416 – 425Combined sources10
Helixi430 – 433Combined sources4
Helixi442 – 446Combined sources5
Beta strandi450 – 452Combined sources3
Helixi459 – 470Combined sources12
Helixi472 – 475Combined sources4
Helixi481 – 489Combined sources9
Helixi492 – 504Combined sources13
Beta strandi507 – 520Combined sources14
Beta strandi523 – 536Combined sources14
Helixi540 – 553Combined sources14
Beta strandi557 – 563Combined sources7
Helixi582 – 601Combined sources20
Helixi605 – 607Combined sources3
Beta strandi613 – 617Combined sources5
Helixi624 – 626Combined sources3
Beta strandi633 – 637Combined sources5
Beta strandi643 – 649Combined sources7
Turni654 – 656Combined sources3
Helixi659 – 671Combined sources13
Beta strandi675 – 681Combined sources7

3D structure databases

ProteinModelPortaliP49915
SMRiP49915
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP49915

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 216Glutamine amidotransferase type-1PROSITE-ProRule annotationAdd BLAST190
Domaini217 – 435GMPS ATP-PPasePROSITE-ProRule annotationAdd BLAST219

Keywords - Domaini

Glutamine amidotransferase

Phylogenomic databases

eggNOGiKOG1622 Eukaryota
COG0518 LUCA
COG0519 LUCA
GeneTreeiENSGT00390000006591
HOGENOMiHOG000223965
HOVERGENiHBG005929
InParanoidiP49915
KOiK01951
OMAiKRKIIGH
OrthoDBiEOG091G031G
PhylomeDBiP49915
TreeFamiTF106132

Family and domain databases

CDDicd01742 GATase1_GMP_Synthase, 1 hit
cd01997 GMP_synthase_C, 1 hit
Gene3Di3.40.50.620, 1 hit
3.40.50.880, 1 hit
InterProiView protein in InterPro
IPR029062 Class_I_gatase-like
IPR017926 GATASE
IPR001674 GMP_synth_C
IPR004739 GMP_synth_GATase
IPR025777 GMPS_ATP_PPase_dom
IPR022310 NAD/GMP_synthase
IPR014729 Rossmann-like_a/b/a_fold
PfamiView protein in Pfam
PF00117 GATase, 1 hit
PF00958 GMP_synt_C, 1 hit
PF02540 NAD_synthase, 1 hit
SUPFAMiSSF52317 SSF52317, 1 hit
TIGRFAMsiTIGR00888 guaA_Nterm, 1 hit
PROSITEiView protein in PROSITE
PS51273 GATASE_TYPE_1, 1 hit
PS51553 GMPS_ATP_PPASE, 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 1 (identifier: P49915-1) [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
MALCNGDSKL ENAGGDLKDG HHHYEGAVVI LDAGAQYGKV IDRRVRELFV
60 70 80 90 100
QSEIFPLETP AFAIKEQGFR AIIISGGPNS VYAEDAPWFD PAIFTIGKPV
110 120 130 140 150
LGICYGMQMM NKVFGGTVHK KSVREDGVFN ISVDNTCSLF RGLQKEEVVL
160 170 180 190 200
LTHGDSVDKV ADGFKVVARS GNIVAGIANE SKKLYGAQFH PEVGLTENGK
210 220 230 240 250
VILKNFLYDI AGCSGTFTVQ NRELECIREI KERVGTSKVL VLLSGGVDST
260 270 280 290 300
VCTALLNRAL NQEQVIAVHI DNGFMRKRES QSVEEALKKL GIQVKVINAA
310 320 330 340 350
HSFYNGTTTL PISDEDRTPR KRISKTLNMT TSPEEKRKII GDTFVKIANE
360 370 380 390 400
VIGEMNLKPE EVFLAQGTLR PDLIESASLV ASGKAELIKT HHNDTELIRK
410 420 430 440 450
LREEGKVIEP LKDFHKDEVR ILGRELGLPE ELVSRHPFPG PGLAIRVICA
460 470 480 490 500
EEPYICKDFP ETNNILKIVA DFSASVKKPH TLLQRVKACT TEEDQEKLMQ
510 520 530 540 550
ITSLHSLNAF LLPIKTVGVQ GDCRSYSYVC GISSKDEPDW ESLIFLARLI
560 570 580 590 600
PRMCHNVNRV VYIFGPPVKE PPTDVTPTFL TTGVLSTLRQ ADFEAHNILR
610 620 630 640 650
ESGYAGKISQ MPVILTPLHF DRDPLQKQPS CQRSVVIRTF ITSDFMTGIP
660 670 680 690
ATPGNEIPVE VVLKMVTEIK KIPGISRIMY DLTSKPPGTT EWE
Length:693
Mass (Da):76,715
Last modified:October 1, 1996 - v1
Checksum:i1CDA0DD3B244728D
GO
Isoform 2 (identifier: P49915-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     10-108: Missing.

Note: No experimental confirmation available.
Show »
Length:594
Mass (Da):65,929
Checksum:i376D7F0A7E3F8C07
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti261N → D in BAG63519 (PubMed:14702039).Curated1
Sequence conflicti415H → I AA sequence (PubMed:8089153).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05393310 – 108Missing in isoform 2. 1 PublicationAdd BLAST99

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS46941.1 [P49915-1]
PIRiA54847
RefSeqiNP_003866.1, NM_003875.2 [P49915-1]
UniGeneiHs.591314

Genome annotation databases

EnsembliENST00000295920; ENSP00000295920; ENSG00000163655 [P49915-2]
ENST00000496455; ENSP00000419851; ENSG00000163655 [P49915-1]
GeneIDi8833
KEGGihsa:8833
UCSCiuc003faq.4 human [P49915-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement

Similar proteinsi

Entry informationi

Entry nameiGUAA_HUMAN
AccessioniPrimary (citable) accession number: P49915
Secondary accession number(s): A8K639, B4DXV7, F8W720
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 18, 2018
This is version 187 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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