O60547 (GMDS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
GDP-mannose 4,6 dehydratase
EC=4.2.1.47

Alternative name(s):
GDP-D-mannose dehydratase
Short name=GMD

Gene names

Name:

GMDS

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	372 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the conversion of GDP-D-mannose to GDP-4-dehydro-6-deoxy-D-mannose. HAMAP-Rule MF_00955
Catalytic activity	GDP-mannose = GDP-4-dehydro-6-deoxy-D-mannose + H2O. HAMAP-Rule MF_00955
Cofactor	NADP. Ref.7
Pathway	Nucleotide-sugar biosynthesis; GDP-L-fucose biosynthesis via de novo pathway; GDP-L-fucose from GDP-alpha-D-mannose: step 1/2. HAMAP-Rule MF_00955
Sequence similarities	Belongs to the GDP-mannose 4,6-dehydratase family.

Ontologies

Keywords
Ligand	NADP
Molecular function	Lyase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	'de novo' GDP-L-fucose biosynthetic process Inferred from direct assay Ref.1. Source: UniProtKB GDP-mannose metabolic process Inferred from direct assay Ref.1. Source: UniProtKB Notch signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytoplasm Inferred by curator Ref.1. Source: UniProtKB
Molecular_function	GDP-mannose 4,6-dehydratase activity Inferred from direct assay Ref.1. Source: UniProtKB NADP+ binding Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 372

372

GDP-mannose 4,6 dehydratase HAMAP-Rule MF_00955

PRO_0000201705

Regions

Nucleotide binding

30 – 35

6

NADP HAMAP-Rule MF_00955

Nucleotide binding

55 – 58

4

NADP HAMAP-Rule MF_00955

Nucleotide binding

86 – 87

2

NADP HAMAP-Rule MF_00955

Nucleotide binding

108 – 112

5

NADP HAMAP-Rule MF_00955

Sites

Active site

155

1

By similarity

Active site

157

1

Nucleophile By similarity

Active site

179

1

Nucleophile By similarity

Binding site

123

1

NADP

Binding site

183

1

NADP

Binding site

209

1

NADP

Binding site

214

1

NADP

Experimental info

Sequence conflict

34

1

Q → M in AAC24501. Ref.5

Sequence conflict

156

1

S → N in CAG46745. Ref.2

Secondary structure

1

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372

Helix Strand Turn

Details...

Beta strand

25 – 29

5

Turn

30 – 32

3

Helix

34 – 45

12

Beta strand

49 – 54

6

Turn

63 – 65

3

Helix

66 – 68

3

Beta strand

80 – 84

5

Helix

90 – 100

11

Beta strand

103 – 107

5

Helix

114 – 119

6

Helix

121 – 128

8

Helix

130 – 141

12

Turn

145 – 147

3

Beta strand

149 – 155

7

Helix

156 – 158

3

Beta strand

163 – 167

5

Helix

178 – 197

20

Beta strand

200 – 206

7

Helix

219 – 231

13

Beta strand

238 – 241

4

Helix

252 – 264

13

Beta strand

265 – 267

3

Beta strand

271 – 273

3

Helix

281 – 291

11

Beta strand

296 – 300

5

Helix

302 – 304

3

Beta strand

306 – 309

4

Turn

310 – 312

3

Beta strand

315 – 319

5

Helix

321 – 323

3

Helix

337 – 343

7

Helix

351 – 368

18

Sequences

	Sequence		Length	Mass (Da)
	O60547 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: B1BAC441736D4C2B	FASTA	372	41,950
	10 20 30 40 50 60 MAHAPARCPS ARGSGDGEMG KPRNVALITG ITGQDGSYLA EFLLEKGYEV HGIVRRSSSF 70 80 90 100 110 120 NTGRIEHLYK NPQAHIEGNM KLHYGDLTDS TCLVKIINEV KPTEIYNLGA QSHVKISFDL 130 140 150 160 170 180 AEYTADVDGV GTLRLLDAVK TCGLINSVKF YQASTSELYG KVQEIPQKET TPFYPRSPYG 190 200 210 220 230 240 AAKLYAYWIV VNFREAYNLF AVNGILFNHE SPRRGANFVT RKISRSVAKI YLGQLECFSL 250 260 270 280 290 300 GNLDAKRDWG HAKDYVEAMW LMLQNDEPED FVIATGEVHS VREFVEKSFL HIGKTIVWEG 310 320 330 340 350 360 KNENEVGRCK ETGKVHVTVD LKYYRPTEVD FLQGDCTKAK QKLNWKPRVA FDELVREMVH 370 ADVELMRTNP NA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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 (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"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(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: Eye.
[5]	"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(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 34-372. Tissue: Brain.
[6]	"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].
[7]	"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 (APR-2004) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 23-372 IN COMPLEX WITH NADP, COFACTOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF042377 mRNA. Translation: AAC13553.1.
CR541929 mRNA. Translation: CAG46727.1.
CR541947 mRNA. Translation: CAG46745.1.
AL033517 , AL034344, AL035693, AL137179, AL158139 Genomic DNA. Translation: CAI20018.1.
AL035693 , AL033517, AL034344, AL137179, AL158139 Genomic DNA. Translation: CAB65990.2.
AL137179 , AL033517, AL034344, AL035693, AL158139 Genomic DNA. Translation: CAI16872.1.
AL158139 , AL033517, AL034344, AL035693, AL137179 Genomic DNA. Translation: CAI22880.1.
AL034344 , AL033517, AL035693, AL137179, AL158139 Genomic DNA. Translation: CAI19400.1.
BC000117 mRNA. Translation: AAH00117.1.
AF040260 mRNA. Translation: AAC24501.1.

IPI

IPI00030207.

RefSeq

NP_001240775.1. NM_001253846.1.
NP_001491.1. NM_001500.3.

UniGene

Hs.144496.
Hs.660919.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1T2A	X-ray	1.84	A/B/C/D	23-372	[»]

ProteinModelPortal

O60547.

ModBase

Search...

Protein-protein interaction databases

IntAct

O60547. 1 interaction.

STRING

9606.ENSP00000370194.

PTM databases

PhosphoSite

O60547.

Proteomic databases

PaxDb

O60547.

PeptideAtlas

O60547.

PRIDE

O60547.

Protocols and materials databases

DNASU

2762.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000380815; ENSP00000370194; ENSG00000112699.

GeneID

2762.

KEGG

hsa:2762.

UCSC

uc003mtq.3. human.

Organism-specific databases

CTD

2762.

GeneCards

GC06M001624.

HGNC

HGNC:4369. GMDS.

HPA

HPA031528.

MIM

602884. gene.

neXtProt

NX_O60547.

PharmGKB

PA28754.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1089.

HOGENOM

HOG000168003.

HOVERGEN

HBG000727.

InParanoid

O60547.

KO

K01711.

OMA

IAYNLTD.

OrthoDB

EOG4FXR7M.

PhylomeDB

O60547.

Enzyme and pathway databases

UniPathway

UPA00128; UER00190.

Gene expression databases

ArrayExpress

O60547.

Bgee

O60547.

CleanEx

HS_GMDS.

Genevestigator

O60547.

GermOnline

ENSG00000112699. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.

HAMAP

MF_00955. GDP_Man_dehydratase.

InterPro

IPR001509. Epimerase_deHydtase.
IPR006368. GDP_Man_deHydtase.
IPR016040. NAD(P)-bd_dom.
[Graphical view]

Pfam

PF01370. Epimerase. 1 hit.
[Graphical view]

TIGRFAMs

TIGR01472. gmd. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

GMDS. human.

EvolutionaryTrace

O60547.

GenomeRNAi

2762.

NextBio

10866.

SOURCE

Search...

Entry information

Entry name

GMDS_HUMAN

Accession

Primary (citable) accession number: O60547
Secondary accession number(s): O75357 , Q5T954, Q6FH09, Q9UGZ3, Q9UJK9

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	August 1, 1998
Last modified:	May 29, 2013
This is version 121 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.