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Protein

GDP-mannose 4,6 dehydratase

Gene

GMDS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the conversion of GDP-D-mannose to GDP-4-dehydro-6-deoxy-D-mannose.

Catalytic activityi

GDP-alpha-D-mannose = GDP-4-dehydro-alpha-D-rhamnose + H2O.

Cofactori

NADP+1 Publication

Pathwayi: GDP-L-fucose biosynthesis via de novo pathway

This protein is involved in step 1 of the subpathway that synthesizes GDP-L-fucose from GDP-alpha-D-mannose.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. GDP-mannose 4,6 dehydratase (GMDS)
  2. GDP-L-fucose synthase (TSTA3)
This subpathway is part of the pathway GDP-L-fucose biosynthesis via de novo pathway, which is itself part of Nucleotide-sugar biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes GDP-L-fucose from GDP-alpha-D-mannose, the pathway GDP-L-fucose biosynthesis via de novo pathway and in Nucleotide-sugar biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei123NADP1 Publication1
Active sitei155By similarity1
Active sitei157NucleophileBy similarity1
Active sitei179NucleophileBy similarity1
Binding sitei183NADP1 Publication1
Binding sitei209NADP1 Publication1
Binding sitei214NADP1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi30 – 35NADP1 Publication6
Nucleotide bindingi55 – 58NADP1 Publication4
Nucleotide bindingi86 – 87NADP1 Publication2
Nucleotide bindingi108 – 112NADP1 Publication5

GO - Molecular functioni

  • GDP-mannose 4,6-dehydratase activity Source: UniProtKB
  • NADP+ binding Source: UniProtKB

GO - Biological processi

  • 'de novo' GDP-L-fucose biosynthetic process Source: UniProtKB
  • GDP-mannose metabolic process Source: UniProtKB
  • Notch signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Ligandi

NADP

Enzyme and pathway databases

BioCyciZFISH:HS03608-MONOMER.
BRENDAi4.2.1.47. 2681.
ReactomeiR-HSA-6787639. GDP-fucose biosynthesis.
UniPathwayiUPA00128; UER00190.

Names & Taxonomyi

Protein namesi
Recommended name:
GDP-mannose 4,6 dehydratase (EC:4.2.1.47)
Alternative name(s):
GDP-D-mannose dehydratase
Short name:
GMD
Gene namesi
Name:GMDS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:4369. GMDS.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi2762.
OpenTargetsiENSG00000112699.
PharmGKBiPA28754.

Polymorphism and mutation databases

BioMutaiGMDS.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002017052 – 372GDP-mannose 4,6 dehydrataseAdd BLAST371

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei323PhosphotyrosineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO60547.
MaxQBiO60547.
PaxDbiO60547.
PeptideAtlasiO60547.
PRIDEiO60547.

PTM databases

iPTMnetiO60547.
PhosphoSitePlusiO60547.

Expressioni

Gene expression databases

BgeeiENSG00000112699.
CleanExiHS_GMDS.
GenevisibleiO60547. HS.

Organism-specific databases

HPAiHPA031528.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-746373,EBI-746373
WDYHV1Q96HA85EBI-746373,EBI-741158

Protein-protein interaction databases

BioGridi109024. 32 interactors.
IntActiO60547. 13 interactors.
STRINGi9606.ENSP00000370194.

Structurei

Secondary structure

1372
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi25 – 29Combined sources5
Turni30 – 32Combined sources3
Helixi34 – 45Combined sources12
Beta strandi49 – 54Combined sources6
Turni63 – 65Combined sources3
Helixi66 – 68Combined sources3
Beta strandi69 – 71Combined sources3
Turni72 – 75Combined sources4
Beta strandi78 – 84Combined sources7
Helixi90 – 100Combined sources11
Beta strandi103 – 107Combined sources5
Helixi114 – 119Combined sources6
Helixi121 – 128Combined sources8
Helixi130 – 141Combined sources12
Turni145 – 147Combined sources3
Beta strandi149 – 155Combined sources7
Helixi156 – 159Combined sources4
Beta strandi163 – 167Combined sources5
Helixi178 – 197Combined sources20
Beta strandi200 – 206Combined sources7
Helixi219 – 231Combined sources13
Beta strandi238 – 241Combined sources4
Beta strandi246 – 248Combined sources3
Helixi252 – 264Combined sources13
Beta strandi265 – 267Combined sources3
Beta strandi271 – 273Combined sources3
Beta strandi278 – 280Combined sources3
Helixi281 – 290Combined sources10
Turni291 – 293Combined sources3
Beta strandi296 – 300Combined sources5
Helixi302 – 304Combined sources3
Beta strandi306 – 309Combined sources4
Turni310 – 312Combined sources3
Beta strandi315 – 319Combined sources5
Helixi321 – 323Combined sources3
Helixi337 – 343Combined sources7
Helixi351 – 368Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1T2AX-ray1.84A/B/C/D23-372[»]
5IN4X-ray1.60A/B/C/D23-372[»]
5IN5X-ray1.90A/B/C/D23-372[»]
ProteinModelPortaliO60547.
SMRiO60547.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60547.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1372. Eukaryota.
COG1089. LUCA.
GeneTreeiENSGT00440000033640.
HOGENOMiHOG000168003.
HOVERGENiHBG000727.
InParanoidiO60547.
KOiK01711.
OMAiDPHERNV.
OrthoDBiEOG091G093Z.
PhylomeDBiO60547.
TreeFamiTF300682.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
HAMAPiMF_00955. GDP_Man_dehydratase. 1 hit.
InterProiIPR006368. GDP_Man_deHydtase.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF16363. GDP_Man_Dehyd. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.
TIGRFAMsiTIGR01472. gmd. 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: O60547-1) [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
MAHAPARCPS ARGSGDGEMG KPRNVALITG ITGQDGSYLA EFLLEKGYEV
60 70 80 90 100
HGIVRRSSSF NTGRIEHLYK NPQAHIEGNM KLHYGDLTDS TCLVKIINEV
110 120 130 140 150
KPTEIYNLGA QSHVKISFDL AEYTADVDGV GTLRLLDAVK TCGLINSVKF
160 170 180 190 200
YQASTSELYG KVQEIPQKET TPFYPRSPYG AAKLYAYWIV VNFREAYNLF
210 220 230 240 250
AVNGILFNHE SPRRGANFVT RKISRSVAKI YLGQLECFSL GNLDAKRDWG
260 270 280 290 300
HAKDYVEAMW LMLQNDEPED FVIATGEVHS VREFVEKSFL HIGKTIVWEG
310 320 330 340 350
KNENEVGRCK ETGKVHVTVD LKYYRPTEVD FLQGDCTKAK QKLNWKPRVA
360 370
FDELVREMVH ADVELMRTNP NA
Length:372
Mass (Da):41,950
Last modified:August 1, 1998 - v1
Checksum:iB1BAC441736D4C2B
GO
Isoform 2 (identifier: O60547-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: MAHAPARCPSARGSGDGEMGKPRNVALITGITGQ → MCKM

Note: No experimental confirmation available.
Show »
Length:342
Mass (Da):39,054
Checksum:iED43224234CC0A7B
GO

Sequence cautioni

The sequence AAC24501 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti156S → N in CAG46745 (Ref. 3) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0473241 – 34MAHAP…GITGQ → MCKM in isoform 2. 1 PublicationAdd BLAST34

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF042377 mRNA. Translation: AAC13553.1.
AF040260 mRNA. Translation: AAC24501.1. Different initiation.
CR541929 mRNA. Translation: CAG46727.1.
CR541947 mRNA. Translation: CAG46745.1.
AL033517 Genomic DNA. No translation available.
AL034344 Genomic DNA. No translation available.
AL035693 Genomic DNA. No translation available.
AL137179 Genomic DNA. No translation available.
AL158139 Genomic DNA. No translation available.
AL354670 Genomic DNA. No translation available.
AL451141 Genomic DNA. No translation available.
AL591048 Genomic DNA. No translation available.
BC000117 mRNA. Translation: AAH00117.1.
CCDSiCCDS4474.1. [O60547-1]
CCDS58994.1. [O60547-2]
RefSeqiNP_001240775.1. NM_001253846.1. [O60547-2]
NP_001491.1. NM_001500.3. [O60547-1]
UniGeneiHs.144496.
Hs.660919.

Genome annotation databases

EnsembliENST00000380815; ENSP00000370194; ENSG00000112699. [O60547-1]
ENST00000530927; ENSP00000436726; ENSG00000112699. [O60547-2]
GeneIDi2762.
KEGGihsa:2762.
UCSCiuc003mtq.4. human. [O60547-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF042377 mRNA. Translation: AAC13553.1.
AF040260 mRNA. Translation: AAC24501.1. Different initiation.
CR541929 mRNA. Translation: CAG46727.1.
CR541947 mRNA. Translation: CAG46745.1.
AL033517 Genomic DNA. No translation available.
AL034344 Genomic DNA. No translation available.
AL035693 Genomic DNA. No translation available.
AL137179 Genomic DNA. No translation available.
AL158139 Genomic DNA. No translation available.
AL354670 Genomic DNA. No translation available.
AL451141 Genomic DNA. No translation available.
AL591048 Genomic DNA. No translation available.
BC000117 mRNA. Translation: AAH00117.1.
CCDSiCCDS4474.1. [O60547-1]
CCDS58994.1. [O60547-2]
RefSeqiNP_001240775.1. NM_001253846.1. [O60547-2]
NP_001491.1. NM_001500.3. [O60547-1]
UniGeneiHs.144496.
Hs.660919.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1T2AX-ray1.84A/B/C/D23-372[»]
5IN4X-ray1.60A/B/C/D23-372[»]
5IN5X-ray1.90A/B/C/D23-372[»]
ProteinModelPortaliO60547.
SMRiO60547.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109024. 32 interactors.
IntActiO60547. 13 interactors.
STRINGi9606.ENSP00000370194.

PTM databases

iPTMnetiO60547.
PhosphoSitePlusiO60547.

Polymorphism and mutation databases

BioMutaiGMDS.

Proteomic databases

EPDiO60547.
MaxQBiO60547.
PaxDbiO60547.
PeptideAtlasiO60547.
PRIDEiO60547.

Protocols and materials databases

DNASUi2762.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000380815; ENSP00000370194; ENSG00000112699. [O60547-1]
ENST00000530927; ENSP00000436726; ENSG00000112699. [O60547-2]
GeneIDi2762.
KEGGihsa:2762.
UCSCiuc003mtq.4. human. [O60547-1]

Organism-specific databases

CTDi2762.
DisGeNETi2762.
GeneCardsiGMDS.
HGNCiHGNC:4369. GMDS.
HPAiHPA031528.
MIMi602884. gene.
neXtProtiNX_O60547.
OpenTargetsiENSG00000112699.
PharmGKBiPA28754.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1372. Eukaryota.
COG1089. LUCA.
GeneTreeiENSGT00440000033640.
HOGENOMiHOG000168003.
HOVERGENiHBG000727.
InParanoidiO60547.
KOiK01711.
OMAiDPHERNV.
OrthoDBiEOG091G093Z.
PhylomeDBiO60547.
TreeFamiTF300682.

Enzyme and pathway databases

UniPathwayiUPA00128; UER00190.
BioCyciZFISH:HS03608-MONOMER.
BRENDAi4.2.1.47. 2681.
ReactomeiR-HSA-6787639. GDP-fucose biosynthesis.

Miscellaneous databases

ChiTaRSiGMDS. human.
EvolutionaryTraceiO60547.
GeneWikiiGMDS_(gene).
GenomeRNAii2762.
PROiO60547.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112699.
CleanExiHS_GMDS.
GenevisibleiO60547. HS.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
HAMAPiMF_00955. GDP_Man_dehydratase. 1 hit.
InterProiIPR006368. GDP_Man_deHydtase.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF16363. GDP_Man_Dehyd. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.
TIGRFAMsiTIGR01472. gmd. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiGMDS_HUMAN
AccessioniPrimary (citable) accession number: O60547
Secondary accession number(s): E9PI88
, O75357, Q5T954, Q6FH09, Q9UGZ3, Q9UJK9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: August 1, 1998
Last modified: November 30, 2016
This is version 157 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, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: 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.