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Protein

GMP synthase [glutamine-hydrolyzing]

Gene

GMPS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

GMP biosynthesis, Purine biosynthesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS08906-MONOMER.
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

HGNCiHGNC:4378. GMPS.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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.
MalaCardsiGMPS.
OpenTargetsiENSG00000163655.
PharmGKBiPA28763.

Chemistry databases

ChEMBLiCHEMBL5721.
DrugBankiDB00130. 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.

2D gel databases

REPRODUCTION-2DPAGEIPI00029079.

PTM databases

iPTMnetiP49915.
PhosphoSitePlusiP49915.
SwissPalmiP49915.

Expressioni

Gene expression databases

BgeeiENSG00000163655.
CleanExiHS_GMPS.
ExpressionAtlasiP49915. baseline and differential.
GenevisibleiP49915. HS.

Organism-specific databases

HPAiHPA046630.
HPA050682.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi114360. 46 interactors.
IntActiP49915. 23 interactors.
MINTiMINT-5004310.
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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2VPIX-ray2.40A/B25-219[»]
2VXOX-ray2.50A/B20-693[»]
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

Sequence similaritiesi

Contains 1 glutamine amidotransferase type-1 domain.PROSITE-ProRule annotation
Contains 1 GMPS ATP-PPase (ATP pyrophosphatase) domain.PROSITE-ProRule annotation

Keywords - Domaini

Glutamine amidotransferase

Phylogenomic databases

eggNOGiKOG1622. Eukaryota.
COG0518. LUCA.
COG0519. LUCA.
GeneTreeiENSGT00390000006591.
HOGENOMiHOG000223965.
HOVERGENiHBG005929.
InParanoidiP49915.
KOiK01951.
OMAiNMTTNPE.
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.
InterProiIPR029062. 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.
[Graphical view]
PfamiPF00117. GATase. 1 hit.
PF00958. GMP_synt_C. 1 hit.
PF02540. NAD_synthase. 1 hit.
[Graphical view]
SUPFAMiSSF52317. SSF52317. 1 hit.
TIGRFAMsiTIGR00888. guaA_Nterm. 1 hit.
PROSITEiPS51273. GATASE_TYPE_1. 1 hit.
PS51553. GMPS_ATP_PPASE. 1 hit.
[Graphical view]

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

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2VPIX-ray2.40A/B25-219[»]
2VXOX-ray2.50A/B20-693[»]
ProteinModelPortaliP49915.
SMRiP49915.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114360. 46 interactors.
IntActiP49915. 23 interactors.
MINTiMINT-5004310.
STRINGi9606.ENSP00000419851.

Chemistry databases

ChEMBLiCHEMBL5721.
DrugBankiDB00130. L-Glutamine.

Protein family/group databases

MEROPSiC26.950.

PTM databases

iPTMnetiP49915.
PhosphoSitePlusiP49915.
SwissPalmiP49915.

Polymorphism and mutation databases

BioMutaiGMPS.
DMDMi1708072.

2D gel databases

REPRODUCTION-2DPAGEIPI00029079.

Proteomic databases

EPDiP49915.
MaxQBiP49915.
PaxDbiP49915.
PeptideAtlasiP49915.
PRIDEiP49915.

Protocols and materials databases

DNASUi8833.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi8833.
DisGeNETi8833.
GeneCardsiGMPS.
HGNCiHGNC:4378. GMPS.
HPAiHPA046630.
HPA050682.
MalaCardsiGMPS.
MIMi600358. gene.
neXtProtiNX_P49915.
OpenTargetsiENSG00000163655.
PharmGKBiPA28763.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayiUPA00189; UER00296.
BioCyciZFISH:HS08906-MONOMER.
BRENDAi6.3.5.2. 2681.
ReactomeiR-HSA-73817. Purine ribonucleoside monophosphate biosynthesis.
SIGNORiP49915.

Miscellaneous databases

ChiTaRSiGMPS. human.
EvolutionaryTraceiP49915.
GeneWikiiGMP_synthase.
GenomeRNAii8833.
PROiP49915.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163655.
CleanExiHS_GMPS.
ExpressionAtlasiP49915. baseline and differential.
GenevisibleiP49915. HS.

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.
InterProiIPR029062. 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.
[Graphical view]
PfamiPF00117. GATase. 1 hit.
PF00958. GMP_synt_C. 1 hit.
PF02540. NAD_synthase. 1 hit.
[Graphical view]
SUPFAMiSSF52317. SSF52317. 1 hit.
TIGRFAMsiTIGR00888. guaA_Nterm. 1 hit.
PROSITEiPS51273. GATASE_TYPE_1. 1 hit.
PS51553. GMPS_ATP_PPASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGUAA_HUMAN
AccessioniPrimary (citable) accession number: P49915
Secondary accession number(s): A8K639, B4DXV7, F8W720
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 30, 2016
This is version 175 of the entry and version 1 of the sequence. [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
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.