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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	372 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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

Ontologies

Keywords
Ligand	NADP
Molecular function	Lyase
PTM	Acetylation
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

Initiator methionine

1

1

Removed

Chain

2 – 372

371

GDP-mannose 4,6 dehydratase

PRO_0000201705

Sites

Active site

155

1

By similarity

Active site

157

1

Nucleophile By similarity

Active site

179

1

Nucleophile By similarity

Binding site

183

1

NADP By similarity

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.6

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: 9525924] [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: 14574404] [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: 15489334] [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: 9603974] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 34-372. Tissue: Brain.
[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(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[7]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	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_001491.1. NM_001500.2.

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.

SMR

O60547. Positions 23-369.

ModBase

Search...

Protein-protein interaction databases

IntAct

O60547. 2 interactions.

STRING

O60547.

PTM databases

PhosphoSite

O60547.

Proteomic databases

PeptideAtlas

O60547.

PRIDE

O60547.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000380815; ENSP00000370194; ENSG00000112699.

GeneID

2762.

KEGG

hsa:2762.

UCSC

uc003mtq.1. human.

Organism-specific databases

CTD

2762.

GeneCards

GC06M001624.

H-InvDB

HIX0022484.

HGNC

HGNC:4369. GMDS.

HPA

HPA031528.

MIM

602884. gene.

neXtProt

NX_O60547.

PharmGKB

PA28754.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17652.

HOGENOM

HBG755066.

HOVERGEN

HBG000727.

InParanoid

O60547.

OMA

TQRVDHI.

OrthoDB

EOG4FXR7M.

PhylomeDB

O60547.

Gene expression databases

ArrayExpress

O60547.

Bgee

O60547.

CleanEx

HS_GMDS.

Genevestigator

O60547.

GermOnline

ENSG00000112699. Homo sapiens.

Family and domain databases

InterPro

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

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.

KO

K01711.

PANTHER

PTHR10366:SF32. GDP_mann_dehyd. 1 hit.

Pfam

PF01370. Epimerase. 1 hit.
[Graphical view]

TIGRFAMs

TIGR01472. Gmd. 1 hit.

ProtoNet

Search...

Other

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:	January 25, 2012
This is version 107 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.