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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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei123 – 1231NADP1 Publication
Active sitei155 – 1551By similarity
Active sitei157 – 1571NucleophileBy similarity
Active sitei179 – 1791NucleophileBy similarity
Binding sitei183 – 1831NADP1 Publication
Binding sitei209 – 2091NADP1 Publication
Binding sitei214 – 2141NADP1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi30 – 356NADP1 Publication
Nucleotide bindingi55 – 584NADP1 Publication
Nucleotide bindingi86 – 872NADP1 Publication
Nucleotide bindingi108 – 1125NADP1 Publication

GO - Molecular functioni

  1. GDP-mannose 4,6-dehydratase activity Source: UniProtKB
  2. NADP+ binding Source: UniProtKB

GO - Biological processi

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

Keywords - Molecular functioni

Lyase

Keywords - Ligandi

NADP

Enzyme and pathway databases

BRENDAi4.2.1.47. 2681.
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
ProteomesiUP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:4369. GMDS.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. extracellular vesicular exosome Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA28754.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 372371GDP-mannose 4,6 dehydratasePRO_0000201705Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiO60547.
PaxDbiO60547.
PeptideAtlasiO60547.
PRIDEiO60547.

PTM databases

PhosphoSiteiO60547.

Expressioni

Gene expression databases

BgeeiO60547.
CleanExiHS_GMDS.
GenevestigatoriO60547.

Organism-specific databases

HPAiHPA031528.
HPA052970.

Interactioni

Protein-protein interaction databases

BioGridi109024. 15 interactions.
IntActiO60547. 1 interaction.
STRINGi9606.ENSP00000370194.

Structurei

Secondary structure

1
372
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi25 – 295Combined sources
Turni30 – 323Combined sources
Helixi34 – 4512Combined sources
Beta strandi49 – 546Combined sources
Turni63 – 653Combined sources
Helixi66 – 683Combined sources
Beta strandi80 – 845Combined sources
Helixi90 – 10011Combined sources
Beta strandi103 – 1075Combined sources
Helixi114 – 1196Combined sources
Helixi121 – 1288Combined sources
Helixi130 – 14112Combined sources
Turni145 – 1473Combined sources
Beta strandi149 – 1557Combined sources
Helixi156 – 1583Combined sources
Beta strandi163 – 1675Combined sources
Helixi178 – 19720Combined sources
Beta strandi200 – 2067Combined sources
Helixi219 – 23113Combined sources
Beta strandi238 – 2414Combined sources
Helixi252 – 26413Combined sources
Beta strandi265 – 2673Combined sources
Beta strandi271 – 2733Combined sources
Helixi281 – 29111Combined sources
Beta strandi296 – 3005Combined sources
Helixi302 – 3043Combined sources
Beta strandi306 – 3094Combined sources
Turni310 – 3123Combined sources
Beta strandi315 – 3195Combined sources
Helixi321 – 3233Combined sources
Helixi337 – 3437Combined sources
Helixi351 – 36818Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1T2AX-ray1.84A/B/C/D23-372[»]
ProteinModelPortaliO60547.
SMRiO60547. Positions 23-369.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60547.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG1089.
GeneTreeiENSGT00440000033640.
HOGENOMiHOG000168003.
HOVERGENiHBG000727.
InParanoidiO60547.
KOiK01711.
OMAiTDCLYLG.
OrthoDBiEOG7K6PV5.
PhylomeDBiO60547.
TreeFamiTF300682.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
HAMAPiMF_00955. GDP_Man_dehydratase.
InterProiIPR001509. Epimerase_deHydtase_N.
IPR006368. GDP_Man_deHydtase.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF01370. Epimerase. 1 hit.
[Graphical view]
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:July 31, 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 AAC24501.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti156 – 1561S → N in CAG46745 (Ref. 3) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 3434MAHAP…GITGQ → MCKM in isoform 2. 1 PublicationVSP_047324Add
BLAST

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.3. 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
EntryMethodResolution (Å)ChainPositionsPDBsum
1T2AX-ray1.84A/B/C/D23-372[»]
ProteinModelPortaliO60547.
SMRiO60547. Positions 23-369.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109024. 15 interactions.
IntActiO60547. 1 interaction.
STRINGi9606.ENSP00000370194.

PTM databases

PhosphoSiteiO60547.

Proteomic databases

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.3. human. [O60547-1]

Organism-specific databases

CTDi2762.
GeneCardsiGC06M001624.
HGNCiHGNC:4369. GMDS.
HPAiHPA031528.
HPA052970.
MIMi602884. gene.
neXtProtiNX_O60547.
PharmGKBiPA28754.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG1089.
GeneTreeiENSGT00440000033640.
HOGENOMiHOG000168003.
HOVERGENiHBG000727.
InParanoidiO60547.
KOiK01711.
OMAiTDCLYLG.
OrthoDBiEOG7K6PV5.
PhylomeDBiO60547.
TreeFamiTF300682.

Enzyme and pathway databases

UniPathwayiUPA00128; UER00190.
BRENDAi4.2.1.47. 2681.

Miscellaneous databases

ChiTaRSiGMDS. human.
EvolutionaryTraceiO60547.
GeneWikiiGMDS_(gene).
GenomeRNAii2762.
NextBioi10866.
PROiO60547.
SOURCEiSearch...

Gene expression databases

BgeeiO60547.
CleanExiHS_GMDS.
GenevestigatoriO60547.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
HAMAPiMF_00955. GDP_Man_dehydratase.
InterProiIPR001509. Epimerase_deHydtase_N.
IPR006368. GDP_Man_deHydtase.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF01370. Epimerase. 1 hit.
[Graphical view]
TIGRFAMsiTIGR01472. gmd. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of human GDP-mannose 4,6-dehydratase and reconstitution of GDP-fucose biosynthesis in vitro."
    Sullivan F.X., Kumar R., Kriz R., Stahl M., Xu G.-Y., Rouse J., Chang X.J., Boodhoo A., Potvin B., Cumming D.A.
    J. Biol. Chem. 273:8193-8202(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "Molecular cloning and expression of GDP-D-mannose-4,6-dehydratase, a key enzyme for fucose metabolism defective in Lec13 cells."
    Ohyama C., Smith P.L., Angata K., Fukuda M.N., Lowe J.B., Fukuda M.
    J. Biol. Chem. 273:14582-14587(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Tissue: Brain.
  3. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
    Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  4. "The DNA sequence and analysis of human chromosome 6."
    Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
    , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
    Nature 425:805-811(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Eye.
  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(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
  7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  8. "Crystal structure and biophysical characterization of human GDP-D-mannose 4,6-dehydratase."
    Vedadi M., Walker J.R., Sharma S., Houston S., Wasney G., Loppnau P., Oppermann U.
    Submitted (MAR-2004) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 23-372 IN COMPLEX WITH NADP, COFACTOR.

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: November 30, 2000
Last sequence update: July 31, 1998
Last modified: March 31, 2015
This is version 138 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

External Data

Dasty 3

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 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.