Full text data of GMDS
GMDS
[Confidence: low (only semi-automatic identification from reviews)]
GDP-mannose 4,6 dehydratase; 4.2.1.47 (GDP-D-mannose dehydratase; GMD)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
GDP-mannose 4,6 dehydratase; 4.2.1.47 (GDP-D-mannose dehydratase; GMD)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O60547
ID GMDS_HUMAN Reviewed; 372 AA.
AC O60547; E9PI88; O75357; Q5T954; Q6FH09; Q9UGZ3; Q9UJK9;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-AUG-1998, sequence version 1.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=GDP-mannose 4,6 dehydratase;
DE EC=4.2.1.47;
DE AltName: Full=GDP-D-mannose dehydratase;
DE Short=GMD;
GN Name=GMDS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9525924; DOI=10.1074/jbc.273.14.8193;
RA Sullivan F.X., Kumar R., Kriz R., Stahl M., Xu G.-Y., Rouse J.,
RA Chang X.J., Boodhoo A., Potvin B., Cumming D.A.;
RT "Molecular cloning of human GDP-mannose 4,6-dehydratase and
RT reconstitution of GDP-fucose biosynthesis in vitro.";
RL J. Biol. Chem. 273:8193-8202(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9603974; DOI=10.1074/jbc.273.23.14582;
RA Ohyama C., Smith P.L., Angata K., Fukuda M.N., Lowe J.B., Fukuda M.;
RT "Molecular cloning and expression of GDP-D-mannose-4,6-dehydratase, a
RT key enzyme for fucose metabolism defective in Lec13 cells.";
RL J. Biol. Chem. 273:14582-14587(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 23-372 IN COMPLEX WITH NADP,
RP AND COFACTOR.
RA Vedadi M., Walker J.R., Sharma S., Houston S., Wasney G., Loppnau P.,
RA Oppermann U.;
RT "Crystal structure and biophysical characterization of human GDP-D-
RT mannose 4,6-dehydratase.";
RL Submitted (APR-2004) to the PDB data bank.
CC -!- FUNCTION: Catalyzes the conversion of GDP-D-mannose to GDP-4-
CC dehydro-6-deoxy-D-mannose.
CC -!- CATALYTIC ACTIVITY: GDP-alpha-D-mannose = GDP-4-dehydro-alpha-D-
CC rhamnose + H(2)O.
CC -!- COFACTOR: NADP.
CC -!- PATHWAY: Nucleotide-sugar biosynthesis; GDP-L-fucose biosynthesis
CC via de novo pathway; GDP-L-fucose from GDP-alpha-D-mannose: step
CC 1/2.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O60547-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O60547-2; Sequence=VSP_047324;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase
CC family. GDP-mannose 4,6-dehydratase subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC24501.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF042377; AAC13553.1; -; mRNA.
DR EMBL; AF040260; AAC24501.1; ALT_INIT; mRNA.
DR EMBL; CR541929; CAG46727.1; -; mRNA.
DR EMBL; CR541947; CAG46745.1; -; mRNA.
DR EMBL; AL033517; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL034344; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL035693; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL137179; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL158139; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL354670; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL451141; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL591048; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000117; AAH00117.1; -; mRNA.
DR RefSeq; NP_001240775.1; NM_001253846.1.
DR RefSeq; NP_001491.1; NM_001500.3.
DR UniGene; Hs.144496; -.
DR UniGene; Hs.660919; -.
DR PDB; 1T2A; X-ray; 1.84 A; A/B/C/D=23-372.
DR PDBsum; 1T2A; -.
DR ProteinModelPortal; O60547; -.
DR SMR; O60547; 23-369.
DR IntAct; O60547; 1.
DR STRING; 9606.ENSP00000370194; -.
DR PhosphoSite; O60547; -.
DR PaxDb; O60547; -.
DR PeptideAtlas; O60547; -.
DR PRIDE; O60547; -.
DR DNASU; 2762; -.
DR Ensembl; ENST00000380815; ENSP00000370194; ENSG00000112699.
DR Ensembl; ENST00000530927; ENSP00000436726; ENSG00000112699.
DR GeneID; 2762; -.
DR KEGG; hsa:2762; -.
DR UCSC; uc003mtq.3; human.
DR CTD; 2762; -.
DR GeneCards; GC06M001624; -.
DR HGNC; HGNC:4369; GMDS.
DR HPA; HPA031528; -.
DR MIM; 602884; gene.
DR neXtProt; NX_O60547; -.
DR PharmGKB; PA28754; -.
DR eggNOG; COG1089; -.
DR HOGENOM; HOG000168003; -.
DR HOVERGEN; HBG000727; -.
DR InParanoid; O60547; -.
DR KO; K01711; -.
DR OMA; TDCLYLG; -.
DR OrthoDB; EOG7K6PV5; -.
DR PhylomeDB; O60547; -.
DR UniPathway; UPA00128; UER00190.
DR ChiTaRS; GMDS; human.
DR EvolutionaryTrace; O60547; -.
DR GeneWiki; GMDS_(gene); -.
DR GenomeRNAi; 2762; -.
DR NextBio; 10866; -.
DR PRO; PR:O60547; -.
DR ArrayExpress; O60547; -.
DR Bgee; O60547; -.
DR CleanEx; HS_GMDS; -.
DR Genevestigator; O60547; -.
DR GO; GO:0005737; C:cytoplasm; IC:UniProtKB.
DR GO; GO:0008446; F:GDP-mannose 4,6-dehydratase activity; IDA:UniProtKB.
DR GO; GO:0070401; F:NADP+ binding; IDA:UniProtKB.
DR GO; GO:0042351; P:'de novo' GDP-L-fucose biosynthetic process; IDA:UniProtKB.
DR GO; GO:0019673; P:GDP-mannose metabolic process; IDA:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; ISS:UniProtKB.
DR Gene3D; 3.40.50.720; -; 1.
DR HAMAP; MF_00955; GDP_Man_dehydratase; 1; -.
DR InterPro; IPR001509; Epimerase_deHydtase.
DR InterPro; IPR006368; GDP_Man_deHydtase.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR Pfam; PF01370; Epimerase; 1.
DR TIGRFAMs; TIGR01472; gmd; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Lyase; NADP; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 372 GDP-mannose 4,6 dehydratase.
FT /FTId=PRO_0000201705.
FT NP_BIND 30 35 NADP.
FT NP_BIND 55 58 NADP.
FT NP_BIND 86 87 NADP.
FT NP_BIND 108 112 NADP.
FT ACT_SITE 155 155 By similarity.
FT ACT_SITE 157 157 Nucleophile (By similarity).
FT ACT_SITE 179 179 Nucleophile (By similarity).
FT BINDING 123 123 NADP.
FT BINDING 183 183 NADP.
FT BINDING 209 209 NADP.
FT BINDING 214 214 NADP.
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 1 34 MAHAPARCPSARGSGDGEMGKPRNVALITGITGQ -> MCK
FT M (in isoform 2).
FT /FTId=VSP_047324.
FT CONFLICT 156 156 S -> N (in Ref. 3; CAG46745).
FT STRAND 25 29
FT TURN 30 32
FT HELIX 34 45
FT STRAND 49 54
FT TURN 63 65
FT HELIX 66 68
FT STRAND 80 84
FT HELIX 90 100
FT STRAND 103 107
FT HELIX 114 119
FT HELIX 121 128
FT HELIX 130 141
FT TURN 145 147
FT STRAND 149 155
FT HELIX 156 158
FT STRAND 163 167
FT HELIX 178 197
FT STRAND 200 206
FT HELIX 219 231
FT STRAND 238 241
FT HELIX 252 264
FT STRAND 265 267
FT STRAND 271 273
FT HELIX 281 291
FT STRAND 296 300
FT HELIX 302 304
FT STRAND 306 309
FT TURN 310 312
FT STRAND 315 319
FT HELIX 321 323
FT HELIX 337 343
FT HELIX 351 368
SQ SEQUENCE 372 AA; 41950 MW; B1BAC441736D4C2B CRC64;
MAHAPARCPS ARGSGDGEMG KPRNVALITG ITGQDGSYLA EFLLEKGYEV HGIVRRSSSF
NTGRIEHLYK NPQAHIEGNM KLHYGDLTDS TCLVKIINEV KPTEIYNLGA QSHVKISFDL
AEYTADVDGV GTLRLLDAVK TCGLINSVKF YQASTSELYG KVQEIPQKET TPFYPRSPYG
AAKLYAYWIV VNFREAYNLF AVNGILFNHE SPRRGANFVT RKISRSVAKI YLGQLECFSL
GNLDAKRDWG HAKDYVEAMW LMLQNDEPED FVIATGEVHS VREFVEKSFL HIGKTIVWEG
KNENEVGRCK ETGKVHVTVD LKYYRPTEVD FLQGDCTKAK QKLNWKPRVA FDELVREMVH
ADVELMRTNP NA
//
ID GMDS_HUMAN Reviewed; 372 AA.
AC O60547; E9PI88; O75357; Q5T954; Q6FH09; Q9UGZ3; Q9UJK9;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-AUG-1998, sequence version 1.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=GDP-mannose 4,6 dehydratase;
DE EC=4.2.1.47;
DE AltName: Full=GDP-D-mannose dehydratase;
DE Short=GMD;
GN Name=GMDS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9525924; DOI=10.1074/jbc.273.14.8193;
RA Sullivan F.X., Kumar R., Kriz R., Stahl M., Xu G.-Y., Rouse J.,
RA Chang X.J., Boodhoo A., Potvin B., Cumming D.A.;
RT "Molecular cloning of human GDP-mannose 4,6-dehydratase and
RT reconstitution of GDP-fucose biosynthesis in vitro.";
RL J. Biol. Chem. 273:8193-8202(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9603974; DOI=10.1074/jbc.273.23.14582;
RA Ohyama C., Smith P.L., Angata K., Fukuda M.N., Lowe J.B., Fukuda M.;
RT "Molecular cloning and expression of GDP-D-mannose-4,6-dehydratase, a
RT key enzyme for fucose metabolism defective in Lec13 cells.";
RL J. Biol. Chem. 273:14582-14587(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 23-372 IN COMPLEX WITH NADP,
RP AND COFACTOR.
RA Vedadi M., Walker J.R., Sharma S., Houston S., Wasney G., Loppnau P.,
RA Oppermann U.;
RT "Crystal structure and biophysical characterization of human GDP-D-
RT mannose 4,6-dehydratase.";
RL Submitted (APR-2004) to the PDB data bank.
CC -!- FUNCTION: Catalyzes the conversion of GDP-D-mannose to GDP-4-
CC dehydro-6-deoxy-D-mannose.
CC -!- CATALYTIC ACTIVITY: GDP-alpha-D-mannose = GDP-4-dehydro-alpha-D-
CC rhamnose + H(2)O.
CC -!- COFACTOR: NADP.
CC -!- PATHWAY: Nucleotide-sugar biosynthesis; GDP-L-fucose biosynthesis
CC via de novo pathway; GDP-L-fucose from GDP-alpha-D-mannose: step
CC 1/2.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O60547-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O60547-2; Sequence=VSP_047324;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase
CC family. GDP-mannose 4,6-dehydratase subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC24501.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF042377; AAC13553.1; -; mRNA.
DR EMBL; AF040260; AAC24501.1; ALT_INIT; mRNA.
DR EMBL; CR541929; CAG46727.1; -; mRNA.
DR EMBL; CR541947; CAG46745.1; -; mRNA.
DR EMBL; AL033517; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL034344; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL035693; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL137179; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL158139; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL354670; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL451141; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL591048; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000117; AAH00117.1; -; mRNA.
DR RefSeq; NP_001240775.1; NM_001253846.1.
DR RefSeq; NP_001491.1; NM_001500.3.
DR UniGene; Hs.144496; -.
DR UniGene; Hs.660919; -.
DR PDB; 1T2A; X-ray; 1.84 A; A/B/C/D=23-372.
DR PDBsum; 1T2A; -.
DR ProteinModelPortal; O60547; -.
DR SMR; O60547; 23-369.
DR IntAct; O60547; 1.
DR STRING; 9606.ENSP00000370194; -.
DR PhosphoSite; O60547; -.
DR PaxDb; O60547; -.
DR PeptideAtlas; O60547; -.
DR PRIDE; O60547; -.
DR DNASU; 2762; -.
DR Ensembl; ENST00000380815; ENSP00000370194; ENSG00000112699.
DR Ensembl; ENST00000530927; ENSP00000436726; ENSG00000112699.
DR GeneID; 2762; -.
DR KEGG; hsa:2762; -.
DR UCSC; uc003mtq.3; human.
DR CTD; 2762; -.
DR GeneCards; GC06M001624; -.
DR HGNC; HGNC:4369; GMDS.
DR HPA; HPA031528; -.
DR MIM; 602884; gene.
DR neXtProt; NX_O60547; -.
DR PharmGKB; PA28754; -.
DR eggNOG; COG1089; -.
DR HOGENOM; HOG000168003; -.
DR HOVERGEN; HBG000727; -.
DR InParanoid; O60547; -.
DR KO; K01711; -.
DR OMA; TDCLYLG; -.
DR OrthoDB; EOG7K6PV5; -.
DR PhylomeDB; O60547; -.
DR UniPathway; UPA00128; UER00190.
DR ChiTaRS; GMDS; human.
DR EvolutionaryTrace; O60547; -.
DR GeneWiki; GMDS_(gene); -.
DR GenomeRNAi; 2762; -.
DR NextBio; 10866; -.
DR PRO; PR:O60547; -.
DR ArrayExpress; O60547; -.
DR Bgee; O60547; -.
DR CleanEx; HS_GMDS; -.
DR Genevestigator; O60547; -.
DR GO; GO:0005737; C:cytoplasm; IC:UniProtKB.
DR GO; GO:0008446; F:GDP-mannose 4,6-dehydratase activity; IDA:UniProtKB.
DR GO; GO:0070401; F:NADP+ binding; IDA:UniProtKB.
DR GO; GO:0042351; P:'de novo' GDP-L-fucose biosynthetic process; IDA:UniProtKB.
DR GO; GO:0019673; P:GDP-mannose metabolic process; IDA:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; ISS:UniProtKB.
DR Gene3D; 3.40.50.720; -; 1.
DR HAMAP; MF_00955; GDP_Man_dehydratase; 1; -.
DR InterPro; IPR001509; Epimerase_deHydtase.
DR InterPro; IPR006368; GDP_Man_deHydtase.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR Pfam; PF01370; Epimerase; 1.
DR TIGRFAMs; TIGR01472; gmd; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Lyase; NADP; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 372 GDP-mannose 4,6 dehydratase.
FT /FTId=PRO_0000201705.
FT NP_BIND 30 35 NADP.
FT NP_BIND 55 58 NADP.
FT NP_BIND 86 87 NADP.
FT NP_BIND 108 112 NADP.
FT ACT_SITE 155 155 By similarity.
FT ACT_SITE 157 157 Nucleophile (By similarity).
FT ACT_SITE 179 179 Nucleophile (By similarity).
FT BINDING 123 123 NADP.
FT BINDING 183 183 NADP.
FT BINDING 209 209 NADP.
FT BINDING 214 214 NADP.
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 1 34 MAHAPARCPSARGSGDGEMGKPRNVALITGITGQ -> MCK
FT M (in isoform 2).
FT /FTId=VSP_047324.
FT CONFLICT 156 156 S -> N (in Ref. 3; CAG46745).
FT STRAND 25 29
FT TURN 30 32
FT HELIX 34 45
FT STRAND 49 54
FT TURN 63 65
FT HELIX 66 68
FT STRAND 80 84
FT HELIX 90 100
FT STRAND 103 107
FT HELIX 114 119
FT HELIX 121 128
FT HELIX 130 141
FT TURN 145 147
FT STRAND 149 155
FT HELIX 156 158
FT STRAND 163 167
FT HELIX 178 197
FT STRAND 200 206
FT HELIX 219 231
FT STRAND 238 241
FT HELIX 252 264
FT STRAND 265 267
FT STRAND 271 273
FT HELIX 281 291
FT STRAND 296 300
FT HELIX 302 304
FT STRAND 306 309
FT TURN 310 312
FT STRAND 315 319
FT HELIX 321 323
FT HELIX 337 343
FT HELIX 351 368
SQ SEQUENCE 372 AA; 41950 MW; B1BAC441736D4C2B CRC64;
MAHAPARCPS ARGSGDGEMG KPRNVALITG ITGQDGSYLA EFLLEKGYEV HGIVRRSSSF
NTGRIEHLYK NPQAHIEGNM KLHYGDLTDS TCLVKIINEV KPTEIYNLGA QSHVKISFDL
AEYTADVDGV GTLRLLDAVK TCGLINSVKF YQASTSELYG KVQEIPQKET TPFYPRSPYG
AAKLYAYWIV VNFREAYNLF AVNGILFNHE SPRRGANFVT RKISRSVAKI YLGQLECFSL
GNLDAKRDWG HAKDYVEAMW LMLQNDEPED FVIATGEVHS VREFVEKSFL HIGKTIVWEG
KNENEVGRCK ETGKVHVTVD LKYYRPTEVD FLQGDCTKAK QKLNWKPRVA FDELVREMVH
ADVELMRTNP NA
//
MIM
602884
*RECORD*
*FIELD* NO
602884
*FIELD* TI
*602884 GDP-MANNOSE 4,6-DEHYDRATASE; GMDS
;;GMD
*FIELD* TX
DESCRIPTION
GDP-mannose 4,6-dehydratase (GMD; EC 4.2.1.47) catalyzes the conversion
read moreof GDP-mannose to GDP-4-keto-6-deoxymannose, the first step in the
synthesis of GDP-fucose from GDP-mannose, using NADP+ as a cofactor. The
second and third steps of the pathway are catalyzed by a single enzyme,
GDP-keto-6-deoxymannose 3,5-epimerase, 4-reductase, designated FX in
humans (137020).
CLONING
By BLAST searching, Sullivan et al. (1998) identified a partial mouse
cDNA with homology to E. coli GMD. Using PCR with primers based on
conserved regions of the protein, they isolated promyelocytic cell line
cDNAs encoding human GMD. The sequence of the predicted human protein is
61% identical to that of E. coli GMD. Northern blot analysis revealed
that GMD is expressed as a 1.7-kb transcript in all tissues examined.
Sullivan et al. (1998) demonstrated that human GMD cDNA complements the
defect in Lec13, a Chinese hamster ovary cell line deficient in GMD
activity. Using purified GMD and FX, the authors showed that the 2
proteins alone are sufficient to convert GDP-mannose to GDP-fucose in
vitro. Sullivan et al. (1998) suggested that mutations in one of these 2
enzymes may cause leukocyte adhesion deficiency, type II (LAD2; 266265),
since cells from 2 LAD2 patients appeared to have a specific defect in
this pathway. Ohyama et al. (1998) also isolated GMD cDNAs. By Northern
analysis, they showed that GMD mRNA is absent from Lec13 cells.
MAPPING
By fluorescence in situ hybridization, Sullivan et al. (1998) mapped the
GMDS gene to chromosome 6p25.
MOLECULAR GENETICS
In an analysis of chromosome 6p25.3 copy number variation, Aldinger et
al. (2009) examined brain imaging studies from 12 individuals with
chromosome 6pter-p24 deletion syndrome (612582). All had abnormalities
on MRI, showing classic or mild Dandy-Walker malformation, mega cisterna
magna, or cerebellar vermis hypoplasia. The phenotype data showed
consistently more severe phenotypes among individuals with large
compared to small deletions, suggesting contributions from more than 1
causative gene in the region; in addition, all 12 deletions involved the
FOXC1 gene plus at least 2 exons of the GMDS gene, implicating 1 or both
of these genes as having a previously unrecognized role in cerebellar
development.
*FIELD* RF
1. Aldinger, K. A.; Lehmann, O. J.; Hudgins, L.; Chizhikov, V. V.;
Bassuk, A. G.; Ades, L. C.; Krantz, I. D.; Dobyns, W. B.; Millen,
K. J.: FOXC1 is required for normal cerebellar development and is
a major contributor to chromosome 6p25.3 Dandy-Walker malformation. Nature
Genet. 41: 1037-1042, 2009.
2. Ohyama, C.; Smith, P. L.; Angata, K.; Fukuda, M. N.; Lowe, J. B.;
Fukuda, M.: Molecular cloning and expression of GDP-D-mannose-4,6-dehydratase,
a key enzyme for fucose metabolism defective in Lec13 cells. J. Biol.
Chem. 273: 14582-14587, 1998.
3. Sullivan, F. X.; Kumar, R.; Kriz, R.; Stahl, M.; Xu, G.-Y.; Rouse,
J.; Chang, X.; Boodhoo, A.; Potvin, B.; Cumming, D. A.: Molecular
cloning of human GDP-mannose 4,6-dehydratase and reconstitution of
GDP-fucose biosynthesis in vitro. J. Biol. Chem. 273: 8193-8202,
1998.
*FIELD* CN
Marla J. F. O'Neill - updated: 10/9/2009
*FIELD* CD
Rebekah S. Rasooly: 7/23/1998
*FIELD* ED
terry: 09/09/2010
wwang: 10/12/2009
terry: 10/9/2009
alopez: 8/25/2009
carol: 4/6/1999
alopez: 7/23/1998
*RECORD*
*FIELD* NO
602884
*FIELD* TI
*602884 GDP-MANNOSE 4,6-DEHYDRATASE; GMDS
;;GMD
*FIELD* TX
DESCRIPTION
GDP-mannose 4,6-dehydratase (GMD; EC 4.2.1.47) catalyzes the conversion
read moreof GDP-mannose to GDP-4-keto-6-deoxymannose, the first step in the
synthesis of GDP-fucose from GDP-mannose, using NADP+ as a cofactor. The
second and third steps of the pathway are catalyzed by a single enzyme,
GDP-keto-6-deoxymannose 3,5-epimerase, 4-reductase, designated FX in
humans (137020).
CLONING
By BLAST searching, Sullivan et al. (1998) identified a partial mouse
cDNA with homology to E. coli GMD. Using PCR with primers based on
conserved regions of the protein, they isolated promyelocytic cell line
cDNAs encoding human GMD. The sequence of the predicted human protein is
61% identical to that of E. coli GMD. Northern blot analysis revealed
that GMD is expressed as a 1.7-kb transcript in all tissues examined.
Sullivan et al. (1998) demonstrated that human GMD cDNA complements the
defect in Lec13, a Chinese hamster ovary cell line deficient in GMD
activity. Using purified GMD and FX, the authors showed that the 2
proteins alone are sufficient to convert GDP-mannose to GDP-fucose in
vitro. Sullivan et al. (1998) suggested that mutations in one of these 2
enzymes may cause leukocyte adhesion deficiency, type II (LAD2; 266265),
since cells from 2 LAD2 patients appeared to have a specific defect in
this pathway. Ohyama et al. (1998) also isolated GMD cDNAs. By Northern
analysis, they showed that GMD mRNA is absent from Lec13 cells.
MAPPING
By fluorescence in situ hybridization, Sullivan et al. (1998) mapped the
GMDS gene to chromosome 6p25.
MOLECULAR GENETICS
In an analysis of chromosome 6p25.3 copy number variation, Aldinger et
al. (2009) examined brain imaging studies from 12 individuals with
chromosome 6pter-p24 deletion syndrome (612582). All had abnormalities
on MRI, showing classic or mild Dandy-Walker malformation, mega cisterna
magna, or cerebellar vermis hypoplasia. The phenotype data showed
consistently more severe phenotypes among individuals with large
compared to small deletions, suggesting contributions from more than 1
causative gene in the region; in addition, all 12 deletions involved the
FOXC1 gene plus at least 2 exons of the GMDS gene, implicating 1 or both
of these genes as having a previously unrecognized role in cerebellar
development.
*FIELD* RF
1. Aldinger, K. A.; Lehmann, O. J.; Hudgins, L.; Chizhikov, V. V.;
Bassuk, A. G.; Ades, L. C.; Krantz, I. D.; Dobyns, W. B.; Millen,
K. J.: FOXC1 is required for normal cerebellar development and is
a major contributor to chromosome 6p25.3 Dandy-Walker malformation. Nature
Genet. 41: 1037-1042, 2009.
2. Ohyama, C.; Smith, P. L.; Angata, K.; Fukuda, M. N.; Lowe, J. B.;
Fukuda, M.: Molecular cloning and expression of GDP-D-mannose-4,6-dehydratase,
a key enzyme for fucose metabolism defective in Lec13 cells. J. Biol.
Chem. 273: 14582-14587, 1998.
3. Sullivan, F. X.; Kumar, R.; Kriz, R.; Stahl, M.; Xu, G.-Y.; Rouse,
J.; Chang, X.; Boodhoo, A.; Potvin, B.; Cumming, D. A.: Molecular
cloning of human GDP-mannose 4,6-dehydratase and reconstitution of
GDP-fucose biosynthesis in vitro. J. Biol. Chem. 273: 8193-8202,
1998.
*FIELD* CN
Marla J. F. O'Neill - updated: 10/9/2009
*FIELD* CD
Rebekah S. Rasooly: 7/23/1998
*FIELD* ED
terry: 09/09/2010
wwang: 10/12/2009
terry: 10/9/2009
alopez: 8/25/2009
carol: 4/6/1999
alopez: 7/23/1998