Full text data of DPM1
DPM1
[Confidence: low (only semi-automatic identification from reviews)]
Dolichol-phosphate mannosyltransferase; 2.4.1.83 (Dolichol-phosphate mannose synthase; DPM synthase; Dolichyl-phosphate beta-D-mannosyltransferase; Mannose-P-dolichol synthase; MPD synthase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Dolichol-phosphate mannosyltransferase; 2.4.1.83 (Dolichol-phosphate mannose synthase; DPM synthase; Dolichyl-phosphate beta-D-mannosyltransferase; Mannose-P-dolichol synthase; MPD synthase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O60762
ID DPM1_HUMAN Reviewed; 260 AA.
AC O60762; O15157; Q6IB78;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-AUG-1998, sequence version 1.
DT 22-JAN-2014, entry version 131.
DE RecName: Full=Dolichol-phosphate mannosyltransferase;
DE EC=2.4.1.83;
DE AltName: Full=Dolichol-phosphate mannose synthase;
DE Short=DPM synthase;
DE AltName: Full=Dolichyl-phosphate beta-D-mannosyltransferase;
DE AltName: Full=Mannose-P-dolichol synthase;
DE Short=MPD synthase;
GN Name=DPM1;
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 [GENOMIC DNA / MRNA].
RC TISSUE=Placenta;
RX PubMed=9535917; DOI=10.1074/jbc.273.15.9249;
RA Tomita S., Inoue N., Maeda Y., Ohishi K., Takeda J., Kinoshita T.;
RT "A homologue of Saccharomyces cerevisiae Dpm1p is not sufficient for
RT synthesis of dolichol-phosphate-mannose in mammalian cells.";
RL J. Biol. Chem. 273:9249-9254(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Urinary bladder;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 8-260.
RX PubMed=9223280; DOI=10.1073/pnas.94.15.7873;
RA Colussi P.A., Taron C.H., Mack J.C., Orlean P.;
RT "Human and Saccharomyces cerevisiae dolichol phosphate mannose
RT synthases represent two classes of the enzyme, but both function in
RT Schizosaccharomyces pombe.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:7873-7878(1997).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-9, MASS SPECTROMETRY, AND CLEAVAGE OF INITIATOR
RP METHIONINE.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
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 [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-9, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP VARIANT CDG1E GLY-92.
RX PubMed=10642597; DOI=10.1172/JCI7302;
RA Kim S., Westphal V., Srikrishna G., Mehta D.P., Peterson S.,
RA Filiano J., Karnes P.S., Patterson M.C., Freeze H.H.;
RT "Dolichol phosphate mannose synthase (DPM1) mutations define
RT congenital disorder of glycosylation Ie (CDG-Ie).";
RL J. Clin. Invest. 105:191-198(2000).
RN [14]
RP VARIANT CDG1E GLY-92.
RX PubMed=10642602; DOI=10.1172/JCI8691;
RA Imbach T., Schenk B., Schollen E., Burda P., Stutz A., Gruenewald S.,
RA Bailie N.M., King M.D., Jaeken J., Matthijs G., Berger E.G., Aebi M.,
RA Hennet T.;
RT "Deficiency of dolichol-phosphate-mannose synthase-1 causes congenital
RT disorder of glycosylation type Ie.";
RL J. Clin. Invest. 105:233-239(2000).
RN [15]
RP VARIANT CDG1E PRO-248.
RX PubMed=15669674; DOI=10.1023/B:BOLI.0000042984.42433.d8;
RA Garcia-Silva M.T., Matthijs G., Schollen E., Cabrera J.C.,
RA Sanchez Del Pozo J., Herreros M.M., Simon R., Maties M.,
RA Hernandez E.M., Hennet T., Briones P.;
RT "Congenital disorder of glycosylation (CDG) type Ie. A new patient.";
RL J. Inherit. Metab. Dis. 27:591-600(2004).
CC -!- FUNCTION: Transfers mannose from GDP-mannose to dolichol
CC monophosphate to form dolichol phosphate mannose (Dol-P-Man) which
CC is the mannosyl donor in pathways leading to N-glycosylation,
CC glycosyl phosphatidylinositol membrane anchoring, and O-
CC mannosylation of proteins.
CC -!- CATALYTIC ACTIVITY: GDP-mannose + dolichyl phosphate = GDP +
CC dolichyl D-mannosyl phosphate.
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum.
CC -!- DISEASE: Congenital disorder of glycosylation 1E (CDG1E)
CC [MIM:608799]: A multisystem disorder caused by a defect in
CC glycoprotein biosynthesis and characterized by under-glycosylated
CC serum glycoproteins. Congenital disorders of glycosylation result
CC in a wide variety of clinical features, such as defects in the
CC nervous system development, psychomotor retardation, dysmorphic
CC features, hypotonia, coagulation disorders, and immunodeficiency.
CC The broad spectrum of features reflects the critical role of N-
CC glycoproteins during embryonic development, differentiation, and
CC maintenance of cell functions. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 2 family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/DPM1";
CC -!- WEB RESOURCE: Name=GGDB; Note=GlycoGene database;
CC URL="http://riodb.ibase.aist.go.jp/rcmg/ggdb/";
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DR EMBL; D86198; BAA25646.1; -; mRNA.
DR EMBL; D86202; BAA25647.1; -; Genomic_DNA.
DR EMBL; CR456926; CAG33207.1; -; mRNA.
DR EMBL; AK289569; BAF82258.1; -; mRNA.
DR EMBL; AL034553; CAB53749.1; -; Genomic_DNA.
DR EMBL; BC007073; AAH07073.1; -; mRNA.
DR EMBL; BC016322; AAH16322.1; -; mRNA.
DR EMBL; AF007875; AAC98797.1; -; mRNA.
DR RefSeq; NP_003850.1; NM_003859.1.
DR UniGene; Hs.654951; -.
DR ProteinModelPortal; O60762; -.
DR SMR; O60762; 26-120.
DR IntAct; O60762; 7.
DR STRING; 9606.ENSP00000360644; -.
DR CAZy; GT2; Glycosyltransferase Family 2.
DR PhosphoSite; O60762; -.
DR PaxDb; O60762; -.
DR PRIDE; O60762; -.
DR DNASU; 8813; -.
DR Ensembl; ENST00000371588; ENSP00000360644; ENSG00000000419.
DR GeneID; 8813; -.
DR KEGG; hsa:8813; -.
DR UCSC; uc002xvw.1; human.
DR CTD; 8813; -.
DR GeneCards; GC20M049551; -.
DR HGNC; HGNC:3005; DPM1.
DR HPA; HPA051818; -.
DR MIM; 603503; gene.
DR MIM; 608799; phenotype.
DR neXtProt; NX_O60762; -.
DR Orphanet; 79322; DPM1-CDG syndrome.
DR PharmGKB; PA27463; -.
DR eggNOG; COG0463; -.
DR HOGENOM; HOG000283250; -.
DR HOVERGEN; HBG018967; -.
DR KO; K00721; -.
DR OrthoDB; EOG7W41CN; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_17015; Metabolism of proteins.
DR UniPathway; UPA00378; -.
DR ChiTaRS; DPM1; human.
DR GeneWiki; DPM1; -.
DR GenomeRNAi; 8813; -.
DR NextBio; 33058; -.
DR PRO; PR:O60762; -.
DR ArrayExpress; O60762; -.
DR Bgee; O60762; -.
DR CleanEx; HS_DPM1; -.
DR Genevestigator; O60762; -.
DR GO; GO:0033185; C:dolichol-phosphate-mannose synthase complex; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:HGNC.
DR GO; GO:0043178; F:alcohol binding; IEA:Ensembl.
DR GO; GO:0004582; F:dolichyl-phosphate beta-D-mannosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0004169; F:dolichyl-phosphate-mannose-protein mannosyltransferase activity; IDA:HGNC.
DR GO; GO:0005537; F:mannose binding; IEA:Ensembl.
DR GO; GO:0006501; P:C-terminal protein lipidation; TAS:Reactome.
DR GO; GO:0019348; P:dolichol metabolic process; IDA:MGI.
DR GO; GO:0006488; P:dolichol-linked oligosaccharide biosynthetic process; TAS:Reactome.
DR GO; GO:0019673; P:GDP-mannose metabolic process; IEA:Ensembl.
DR GO; GO:0006506; P:GPI anchor biosynthetic process; IDA:UniProtKB.
DR GO; GO:0018279; P:protein N-linked glycosylation via asparagine; TAS:Reactome.
DR GO; GO:0035269; P:protein O-linked mannosylation; IDA:HGNC.
DR InterPro; IPR001173; Glyco_trans_2.
DR Pfam; PF00535; Glycos_transf_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Complete proteome; Congenital disorder of glycosylation;
KW Disease mutation; Endoplasmic reticulum; Glycosyltransferase;
KW Phosphoprotein; Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 260 Dolichol-phosphate mannosyltransferase.
FT /FTId=PRO_0000059170.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 9 9 Phosphoserine.
FT VARIANT 92 92 R -> G (in CDG1E).
FT /FTId=VAR_012341.
FT VARIANT 248 248 S -> P (in CDG1E).
FT /FTId=VAR_019841.
FT CONFLICT 15 15 R -> W (in Ref. 6; AAC98797).
FT CONFLICT 135 135 Q -> K (in Ref. 6; AAC98797).
FT CONFLICT 143 143 V -> A (in Ref. 6; AAC98797).
FT CONFLICT 154 154 V -> I (in Ref. 6; AAC98797).
FT CONFLICT 177 177 R -> T (in Ref. 6; AAC98797).
FT CONFLICT 191 191 R -> P (in Ref. 6; AAC98797).
SQ SEQUENCE 260 AA; 29634 MW; 9792145BFC8F0514 CRC64;
MASLEVSRSP RRSRRELEVR SPRQNKYSVL LPTYNERENL PLIVWLLVKS FSESGINYEI
IIIDDGSPDG TRDVAEQLEK IYGSDRILLR PREKKLGLGT AYIHGMKHAT GNYIIIMDAD
LSHHPKFIPE FIRKQKEGNF DIVSGTRYKG NGGVYGWDLK RKIISRGANF LTQILLRPGA
SDLTGSFRLY RKEVLEKLIE KCVSKGYVFQ MEMIVRARQL NYTIGEVPIS FVDRVYGESK
LGGNEIVSFL KGLLTLFATT
//
ID DPM1_HUMAN Reviewed; 260 AA.
AC O60762; O15157; Q6IB78;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-AUG-1998, sequence version 1.
DT 22-JAN-2014, entry version 131.
DE RecName: Full=Dolichol-phosphate mannosyltransferase;
DE EC=2.4.1.83;
DE AltName: Full=Dolichol-phosphate mannose synthase;
DE Short=DPM synthase;
DE AltName: Full=Dolichyl-phosphate beta-D-mannosyltransferase;
DE AltName: Full=Mannose-P-dolichol synthase;
DE Short=MPD synthase;
GN Name=DPM1;
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 [GENOMIC DNA / MRNA].
RC TISSUE=Placenta;
RX PubMed=9535917; DOI=10.1074/jbc.273.15.9249;
RA Tomita S., Inoue N., Maeda Y., Ohishi K., Takeda J., Kinoshita T.;
RT "A homologue of Saccharomyces cerevisiae Dpm1p is not sufficient for
RT synthesis of dolichol-phosphate-mannose in mammalian cells.";
RL J. Biol. Chem. 273:9249-9254(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Urinary bladder;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 8-260.
RX PubMed=9223280; DOI=10.1073/pnas.94.15.7873;
RA Colussi P.A., Taron C.H., Mack J.C., Orlean P.;
RT "Human and Saccharomyces cerevisiae dolichol phosphate mannose
RT synthases represent two classes of the enzyme, but both function in
RT Schizosaccharomyces pombe.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:7873-7878(1997).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-9, MASS SPECTROMETRY, AND CLEAVAGE OF INITIATOR
RP METHIONINE.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
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 [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-9, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP VARIANT CDG1E GLY-92.
RX PubMed=10642597; DOI=10.1172/JCI7302;
RA Kim S., Westphal V., Srikrishna G., Mehta D.P., Peterson S.,
RA Filiano J., Karnes P.S., Patterson M.C., Freeze H.H.;
RT "Dolichol phosphate mannose synthase (DPM1) mutations define
RT congenital disorder of glycosylation Ie (CDG-Ie).";
RL J. Clin. Invest. 105:191-198(2000).
RN [14]
RP VARIANT CDG1E GLY-92.
RX PubMed=10642602; DOI=10.1172/JCI8691;
RA Imbach T., Schenk B., Schollen E., Burda P., Stutz A., Gruenewald S.,
RA Bailie N.M., King M.D., Jaeken J., Matthijs G., Berger E.G., Aebi M.,
RA Hennet T.;
RT "Deficiency of dolichol-phosphate-mannose synthase-1 causes congenital
RT disorder of glycosylation type Ie.";
RL J. Clin. Invest. 105:233-239(2000).
RN [15]
RP VARIANT CDG1E PRO-248.
RX PubMed=15669674; DOI=10.1023/B:BOLI.0000042984.42433.d8;
RA Garcia-Silva M.T., Matthijs G., Schollen E., Cabrera J.C.,
RA Sanchez Del Pozo J., Herreros M.M., Simon R., Maties M.,
RA Hernandez E.M., Hennet T., Briones P.;
RT "Congenital disorder of glycosylation (CDG) type Ie. A new patient.";
RL J. Inherit. Metab. Dis. 27:591-600(2004).
CC -!- FUNCTION: Transfers mannose from GDP-mannose to dolichol
CC monophosphate to form dolichol phosphate mannose (Dol-P-Man) which
CC is the mannosyl donor in pathways leading to N-glycosylation,
CC glycosyl phosphatidylinositol membrane anchoring, and O-
CC mannosylation of proteins.
CC -!- CATALYTIC ACTIVITY: GDP-mannose + dolichyl phosphate = GDP +
CC dolichyl D-mannosyl phosphate.
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum.
CC -!- DISEASE: Congenital disorder of glycosylation 1E (CDG1E)
CC [MIM:608799]: A multisystem disorder caused by a defect in
CC glycoprotein biosynthesis and characterized by under-glycosylated
CC serum glycoproteins. Congenital disorders of glycosylation result
CC in a wide variety of clinical features, such as defects in the
CC nervous system development, psychomotor retardation, dysmorphic
CC features, hypotonia, coagulation disorders, and immunodeficiency.
CC The broad spectrum of features reflects the critical role of N-
CC glycoproteins during embryonic development, differentiation, and
CC maintenance of cell functions. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 2 family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/DPM1";
CC -!- WEB RESOURCE: Name=GGDB; Note=GlycoGene database;
CC URL="http://riodb.ibase.aist.go.jp/rcmg/ggdb/";
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; D86198; BAA25646.1; -; mRNA.
DR EMBL; D86202; BAA25647.1; -; Genomic_DNA.
DR EMBL; CR456926; CAG33207.1; -; mRNA.
DR EMBL; AK289569; BAF82258.1; -; mRNA.
DR EMBL; AL034553; CAB53749.1; -; Genomic_DNA.
DR EMBL; BC007073; AAH07073.1; -; mRNA.
DR EMBL; BC016322; AAH16322.1; -; mRNA.
DR EMBL; AF007875; AAC98797.1; -; mRNA.
DR RefSeq; NP_003850.1; NM_003859.1.
DR UniGene; Hs.654951; -.
DR ProteinModelPortal; O60762; -.
DR SMR; O60762; 26-120.
DR IntAct; O60762; 7.
DR STRING; 9606.ENSP00000360644; -.
DR CAZy; GT2; Glycosyltransferase Family 2.
DR PhosphoSite; O60762; -.
DR PaxDb; O60762; -.
DR PRIDE; O60762; -.
DR DNASU; 8813; -.
DR Ensembl; ENST00000371588; ENSP00000360644; ENSG00000000419.
DR GeneID; 8813; -.
DR KEGG; hsa:8813; -.
DR UCSC; uc002xvw.1; human.
DR CTD; 8813; -.
DR GeneCards; GC20M049551; -.
DR HGNC; HGNC:3005; DPM1.
DR HPA; HPA051818; -.
DR MIM; 603503; gene.
DR MIM; 608799; phenotype.
DR neXtProt; NX_O60762; -.
DR Orphanet; 79322; DPM1-CDG syndrome.
DR PharmGKB; PA27463; -.
DR eggNOG; COG0463; -.
DR HOGENOM; HOG000283250; -.
DR HOVERGEN; HBG018967; -.
DR KO; K00721; -.
DR OrthoDB; EOG7W41CN; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_17015; Metabolism of proteins.
DR UniPathway; UPA00378; -.
DR ChiTaRS; DPM1; human.
DR GeneWiki; DPM1; -.
DR GenomeRNAi; 8813; -.
DR NextBio; 33058; -.
DR PRO; PR:O60762; -.
DR ArrayExpress; O60762; -.
DR Bgee; O60762; -.
DR CleanEx; HS_DPM1; -.
DR Genevestigator; O60762; -.
DR GO; GO:0033185; C:dolichol-phosphate-mannose synthase complex; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:HGNC.
DR GO; GO:0043178; F:alcohol binding; IEA:Ensembl.
DR GO; GO:0004582; F:dolichyl-phosphate beta-D-mannosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0004169; F:dolichyl-phosphate-mannose-protein mannosyltransferase activity; IDA:HGNC.
DR GO; GO:0005537; F:mannose binding; IEA:Ensembl.
DR GO; GO:0006501; P:C-terminal protein lipidation; TAS:Reactome.
DR GO; GO:0019348; P:dolichol metabolic process; IDA:MGI.
DR GO; GO:0006488; P:dolichol-linked oligosaccharide biosynthetic process; TAS:Reactome.
DR GO; GO:0019673; P:GDP-mannose metabolic process; IEA:Ensembl.
DR GO; GO:0006506; P:GPI anchor biosynthetic process; IDA:UniProtKB.
DR GO; GO:0018279; P:protein N-linked glycosylation via asparagine; TAS:Reactome.
DR GO; GO:0035269; P:protein O-linked mannosylation; IDA:HGNC.
DR InterPro; IPR001173; Glyco_trans_2.
DR Pfam; PF00535; Glycos_transf_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Complete proteome; Congenital disorder of glycosylation;
KW Disease mutation; Endoplasmic reticulum; Glycosyltransferase;
KW Phosphoprotein; Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 260 Dolichol-phosphate mannosyltransferase.
FT /FTId=PRO_0000059170.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 9 9 Phosphoserine.
FT VARIANT 92 92 R -> G (in CDG1E).
FT /FTId=VAR_012341.
FT VARIANT 248 248 S -> P (in CDG1E).
FT /FTId=VAR_019841.
FT CONFLICT 15 15 R -> W (in Ref. 6; AAC98797).
FT CONFLICT 135 135 Q -> K (in Ref. 6; AAC98797).
FT CONFLICT 143 143 V -> A (in Ref. 6; AAC98797).
FT CONFLICT 154 154 V -> I (in Ref. 6; AAC98797).
FT CONFLICT 177 177 R -> T (in Ref. 6; AAC98797).
FT CONFLICT 191 191 R -> P (in Ref. 6; AAC98797).
SQ SEQUENCE 260 AA; 29634 MW; 9792145BFC8F0514 CRC64;
MASLEVSRSP RRSRRELEVR SPRQNKYSVL LPTYNERENL PLIVWLLVKS FSESGINYEI
IIIDDGSPDG TRDVAEQLEK IYGSDRILLR PREKKLGLGT AYIHGMKHAT GNYIIIMDAD
LSHHPKFIPE FIRKQKEGNF DIVSGTRYKG NGGVYGWDLK RKIISRGANF LTQILLRPGA
SDLTGSFRLY RKEVLEKLIE KCVSKGYVFQ MEMIVRARQL NYTIGEVPIS FVDRVYGESK
LGGNEIVSFL KGLLTLFATT
//
MIM
603503
*RECORD*
*FIELD* NO
603503
*FIELD* TI
*603503 DOLICHYL-PHOSPHATE MANNOSYLTRANSFERASE 1, CATALYTIC SUBUNIT; DPM1
;;DOLICHOL-PHOSPHATE MANNOSYLTRANSFERASE 1;;
read moreDOLICHOL-PHOSPHATE-MANNOSE SYNTHASE 1;;
MPD SYNTHASE; MPDS
*FIELD* TX
DESCRIPTION
Dolichol-phosphate-mannose synthase (EC 2.4.1.83) synthesizes
dolichol-phosphate-mannose (Dol-P-Man) from GDP-mannose and
dolichol-phosphate. Dol-P-Man serves as a donor of mannosyl residues in
major eukaryotic glycoconjugates.
CLONING
The S. cerevisiae dpm1 gene encodes a Dol-P-Man synthase that is a
transmembrane protein expressed in the endoplasmic reticulum. By
searching an EST database for homologs of yeast dpm1, Tomita et al.
(1998) identified human and mouse DPM1 cDNAs. The predicted 260-amino
acid human protein shares approximately 30% identity with yeast dpm1.
However, DPM1 lacks the C-terminal transmembrane domain found in dpm1
and does not contain a signal sequence.
Independently, Colussi et al. (1997) cloned human, rat, nematode, and S.
pombe DPM1 cDNAs. They reported that the predicted human and rat
proteins are 93% identical. Sequence analysis indicated that the human,
S. pombe, and nematode DPM1 proteins lack the hydrophobic C-terminal
domain found in S. cerevisiae dpm1. However, both human and S.
cerevisiae DPM1 complemented the lethal S. pombe dpm1+ mutation.
GENE FUNCTION
Mouse Thy1 (188230)-negative thymoma mutant cells of complementation
class E do not synthesize Dol-P-Man and consequently do not synthesize
the glycosylphosphatidylinositol (GPI) core, resulting in the defective
surface expression of GPI-anchored proteins, such as Thy1. Tomita et al.
(1998) found that expression of DPM1 in class E mutant mouse cells
completely restored surface expression of Thy1, and sequence analysis
revealed that the mutant cells have an inactivating mutation in the
murine Dpm1 gene. However, the mammalian DPM1 cDNAs did not complement
another Dol-P-Man synthesis mutant, hamster Lec15 cells, whereas yeast
dpm1 restored both class E and Lec15 cells. Tomita et al. (1998)
concluded that mammalian cells require DPM1 and an additional protein
for synthesis of Dol-P-Man. See DPM2 (603564).
Maeda et al. (2000) purified human Dol-P-Man synthase and demonstrated
that the enzyme is a protein complex with 3 subunits, DPM1, DPM2, and
DPM3 (605951). They concluded that DPM1 is stabilized by an association
with the C-terminal domain of DPM3, which is stabilized by an
association with DPM2.
MOLECULAR GENETICS
In 2 unrelated patients with congenital disorder of glycosylation Ie
(608799), Kim et al. (2000) identified mutations in the DPM1 gene
(603503.0001; 603503.0002).
In 2 sibs with CDG Ie, Imbach et al. (2000) identified compound
heterozygosity for 2 mutations in the DPM1 gene (603503.0001;
603503.0003).
*FIELD* AV
.0001
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ie
DPM1, ARG92GLY
In a patient with congenital disorder of glycosylation type Ie (CDG1E,
608799), Kim et al. (2000) identified a homozygous 274C-G transversion
in the DPM1 gene, resulting in an arg92-to-gly (R92G) substitution.
Another unrelated patient was compound heterozygous for the R92G
mutation and a 13-bp deletion (603503.0002).
In a brother and sister, Imbach et al. (2000) described features of a
congenital disorder of glycosylation due to compound heterozygosity for
the R92G mutation and a 628C deletion (603503.0003).
.0002
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ie
DPM1, 13-BP DEL
In an infant with congenital disorder of glycosylation Ie (608799), Kim
et al. (2000) found compound heterozygosity for the R92G mutation
(603503.0001) and a 13-bp deletion in exon 4 resulting in loss of
nucleotides 331-343 at the cDNA level. The predicted translated product
resulting from the deletion encodes the first 110 amino acids of the
260-amino acid protein followed by 44 random amino acids.
.0003
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ie
DPM1, 1-BP DEL, 628C
In a brother and sister with CDG Ie (608799), Imbach et al. (2000)
identified compound heterozygosity for 2 mutations in the DPM1 gene: a
1-bp deletion (628C) and R92G (603503.0001). These mutations were found
in heterozygous state in the mother and father, respectively. The
deletion resulted in the premature stop of the translation at position
640 (codon 213).
*FIELD* RF
1. Colussi, P. A.; Taron, C. H.; Mack, J. C.; Orlean, P.: Human and
Saccharomyces cerevisiae dolichol phosphate mannose synthases represent
two classes of the enzyme, but both function in Schizosaccharomyces
pombe. Proc. Nat. Acad. Sci. 94: 7873-7878, 1997.
2. Imbach, T.; Schenk, B.; Schollen, E.; Burda, P.; Stutz, A.; Grunewald,
S.; Bailie, N. M.; King, M. D.; Jaeken, J.; Matthijs, G.; Berger,
E. G.; Aebi, M.; Hennet, T.: Deficiency of dolichol-phosphate-mannose
synthase-1 causes congenital disorder of glycosylation type Ie. J.
Clin. Invest. 105: 233-239, 2000.
3. Kim, S.; Westphal, V.; Srikrishna, G.; Mehta, D. P.; Peterson,
S.; Filiano, J.; Karnes, P. S.; Patterson, M. C.; Freeze, H. H.:
Dolichol phosphate mannose synthase (DPM1) mutations define congenital
disorder of glycosylation Ie (CDG-Ie). J. Clin. Invest. 105: 191-198,
2000.
4. Maeda, Y.; Tanaka, S.; Hino, J.; Kangawa, K.; Kinoshita, T.: Human
dolichol-phosphate-mannose synthase consists of three subunits, DPM1,
DPM2 and DPM3. EMBO J. 19: 2475-2482, 2000.
5. Tomita, S.; Inoue, N.; Maeda, Y.; Ohishi, K.; Takeda, J.; Kinoshita,
T.: A homologue of Saccharomyces cerevisiae Dpm1p is not sufficient
for synthesis of dolichol-phosphate-mannose in mammalian cells. J.
Biol. Chem. 273: 9249-9254, 1998.
*FIELD* CN
Dawn Watkins-Chow - updated: 5/18/2001
Hudson H. Freeze - reviewed: 2/17/2000
Victor A. McKusick - updated: 2/10/2000
*FIELD* CD
Rebekah S. Rasooly: 2/9/1999
*FIELD* ED
joanna: 01/13/2011
carol: 7/22/2004
ckniffin: 7/13/2004
carol: 7/6/2004
carol: 3/17/2004
carol: 12/9/2003
mgross: 12/10/2002
carol: 7/3/2002
mgross: 5/21/2001
terry: 5/18/2001
carol: 3/1/2000
carol: 2/17/2000
carol: 2/16/2000
terry: 2/10/2000
jlewis: 7/22/1999
psherman: 2/24/1999
psherman: 2/19/1999
alopez: 2/9/1999
*RECORD*
*FIELD* NO
603503
*FIELD* TI
*603503 DOLICHYL-PHOSPHATE MANNOSYLTRANSFERASE 1, CATALYTIC SUBUNIT; DPM1
;;DOLICHOL-PHOSPHATE MANNOSYLTRANSFERASE 1;;
read moreDOLICHOL-PHOSPHATE-MANNOSE SYNTHASE 1;;
MPD SYNTHASE; MPDS
*FIELD* TX
DESCRIPTION
Dolichol-phosphate-mannose synthase (EC 2.4.1.83) synthesizes
dolichol-phosphate-mannose (Dol-P-Man) from GDP-mannose and
dolichol-phosphate. Dol-P-Man serves as a donor of mannosyl residues in
major eukaryotic glycoconjugates.
CLONING
The S. cerevisiae dpm1 gene encodes a Dol-P-Man synthase that is a
transmembrane protein expressed in the endoplasmic reticulum. By
searching an EST database for homologs of yeast dpm1, Tomita et al.
(1998) identified human and mouse DPM1 cDNAs. The predicted 260-amino
acid human protein shares approximately 30% identity with yeast dpm1.
However, DPM1 lacks the C-terminal transmembrane domain found in dpm1
and does not contain a signal sequence.
Independently, Colussi et al. (1997) cloned human, rat, nematode, and S.
pombe DPM1 cDNAs. They reported that the predicted human and rat
proteins are 93% identical. Sequence analysis indicated that the human,
S. pombe, and nematode DPM1 proteins lack the hydrophobic C-terminal
domain found in S. cerevisiae dpm1. However, both human and S.
cerevisiae DPM1 complemented the lethal S. pombe dpm1+ mutation.
GENE FUNCTION
Mouse Thy1 (188230)-negative thymoma mutant cells of complementation
class E do not synthesize Dol-P-Man and consequently do not synthesize
the glycosylphosphatidylinositol (GPI) core, resulting in the defective
surface expression of GPI-anchored proteins, such as Thy1. Tomita et al.
(1998) found that expression of DPM1 in class E mutant mouse cells
completely restored surface expression of Thy1, and sequence analysis
revealed that the mutant cells have an inactivating mutation in the
murine Dpm1 gene. However, the mammalian DPM1 cDNAs did not complement
another Dol-P-Man synthesis mutant, hamster Lec15 cells, whereas yeast
dpm1 restored both class E and Lec15 cells. Tomita et al. (1998)
concluded that mammalian cells require DPM1 and an additional protein
for synthesis of Dol-P-Man. See DPM2 (603564).
Maeda et al. (2000) purified human Dol-P-Man synthase and demonstrated
that the enzyme is a protein complex with 3 subunits, DPM1, DPM2, and
DPM3 (605951). They concluded that DPM1 is stabilized by an association
with the C-terminal domain of DPM3, which is stabilized by an
association with DPM2.
MOLECULAR GENETICS
In 2 unrelated patients with congenital disorder of glycosylation Ie
(608799), Kim et al. (2000) identified mutations in the DPM1 gene
(603503.0001; 603503.0002).
In 2 sibs with CDG Ie, Imbach et al. (2000) identified compound
heterozygosity for 2 mutations in the DPM1 gene (603503.0001;
603503.0003).
*FIELD* AV
.0001
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ie
DPM1, ARG92GLY
In a patient with congenital disorder of glycosylation type Ie (CDG1E,
608799), Kim et al. (2000) identified a homozygous 274C-G transversion
in the DPM1 gene, resulting in an arg92-to-gly (R92G) substitution.
Another unrelated patient was compound heterozygous for the R92G
mutation and a 13-bp deletion (603503.0002).
In a brother and sister, Imbach et al. (2000) described features of a
congenital disorder of glycosylation due to compound heterozygosity for
the R92G mutation and a 628C deletion (603503.0003).
.0002
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ie
DPM1, 13-BP DEL
In an infant with congenital disorder of glycosylation Ie (608799), Kim
et al. (2000) found compound heterozygosity for the R92G mutation
(603503.0001) and a 13-bp deletion in exon 4 resulting in loss of
nucleotides 331-343 at the cDNA level. The predicted translated product
resulting from the deletion encodes the first 110 amino acids of the
260-amino acid protein followed by 44 random amino acids.
.0003
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ie
DPM1, 1-BP DEL, 628C
In a brother and sister with CDG Ie (608799), Imbach et al. (2000)
identified compound heterozygosity for 2 mutations in the DPM1 gene: a
1-bp deletion (628C) and R92G (603503.0001). These mutations were found
in heterozygous state in the mother and father, respectively. The
deletion resulted in the premature stop of the translation at position
640 (codon 213).
*FIELD* RF
1. Colussi, P. A.; Taron, C. H.; Mack, J. C.; Orlean, P.: Human and
Saccharomyces cerevisiae dolichol phosphate mannose synthases represent
two classes of the enzyme, but both function in Schizosaccharomyces
pombe. Proc. Nat. Acad. Sci. 94: 7873-7878, 1997.
2. Imbach, T.; Schenk, B.; Schollen, E.; Burda, P.; Stutz, A.; Grunewald,
S.; Bailie, N. M.; King, M. D.; Jaeken, J.; Matthijs, G.; Berger,
E. G.; Aebi, M.; Hennet, T.: Deficiency of dolichol-phosphate-mannose
synthase-1 causes congenital disorder of glycosylation type Ie. J.
Clin. Invest. 105: 233-239, 2000.
3. Kim, S.; Westphal, V.; Srikrishna, G.; Mehta, D. P.; Peterson,
S.; Filiano, J.; Karnes, P. S.; Patterson, M. C.; Freeze, H. H.:
Dolichol phosphate mannose synthase (DPM1) mutations define congenital
disorder of glycosylation Ie (CDG-Ie). J. Clin. Invest. 105: 191-198,
2000.
4. Maeda, Y.; Tanaka, S.; Hino, J.; Kangawa, K.; Kinoshita, T.: Human
dolichol-phosphate-mannose synthase consists of three subunits, DPM1,
DPM2 and DPM3. EMBO J. 19: 2475-2482, 2000.
5. Tomita, S.; Inoue, N.; Maeda, Y.; Ohishi, K.; Takeda, J.; Kinoshita,
T.: A homologue of Saccharomyces cerevisiae Dpm1p is not sufficient
for synthesis of dolichol-phosphate-mannose in mammalian cells. J.
Biol. Chem. 273: 9249-9254, 1998.
*FIELD* CN
Dawn Watkins-Chow - updated: 5/18/2001
Hudson H. Freeze - reviewed: 2/17/2000
Victor A. McKusick - updated: 2/10/2000
*FIELD* CD
Rebekah S. Rasooly: 2/9/1999
*FIELD* ED
joanna: 01/13/2011
carol: 7/22/2004
ckniffin: 7/13/2004
carol: 7/6/2004
carol: 3/17/2004
carol: 12/9/2003
mgross: 12/10/2002
carol: 7/3/2002
mgross: 5/21/2001
terry: 5/18/2001
carol: 3/1/2000
carol: 2/17/2000
carol: 2/16/2000
terry: 2/10/2000
jlewis: 7/22/1999
psherman: 2/24/1999
psherman: 2/19/1999
alopez: 2/9/1999
MIM
608799
*RECORD*
*FIELD* NO
608799
*FIELD* TI
#608799 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ie; CDG1E
;;CDG Ie; CDGIe
*FIELD* TX
read moreA number sign (#) is used with this entry because congenital disorder of
glycosylation type Ie is caused by mutation in the DPM1 gene (603503).
DESCRIPTION
Congenital disorders of glycosylation (CDGs) are metabolic deficiencies
in glycoprotein biosynthesis that usually cause severe mental and
psychomotor retardation. Different forms of CDGs can be recognized by
altered isoelectric focusing (IEF) patterns of serum transferrin.
For a general discussion of CDGs, see CDG Ia (212065) and CDG Ib
(602579).
CLINICAL FEATURES
Kim et al. (2000) reported 2 patients with phenotypic and biochemical
features consistent with a congenital disorder of glycosylation. The
first patient was seen at age 10 months because of developmental delay,
hypotonia, seizures, and acquired microcephaly. Telangiectases on the
eyelids and hemangiomas of the occiput and sacrum were observed. The
second patient was born at 29 weeks of gestation, and the postnatal
course was complicated by hydrops, respiratory distress, apnea, patent
ductus arteriosus (see 607411), and transient hypertension. The infant
later developed generalized medically intractable seizures. At 3 years
of age, the child had no speech, was cortically blind, had strabismus,
and swallowed poorly. Both patients had similar abnormal IEF transferrin
patterns. Metabolic labeling of fibroblasts with 2-tritiated-mannose
showed that the patients produced a truncated dolichol-linked precursor
oligosaccharide with 5 mannose residues instead of the normal precursor
with 9 mannose residues. Addition of 250 microM mannose to the culture
medium corrected the size of the truncated oligosaccharide. Microsomes
from fibroblasts of these patients were approximately 95% deficient in
dolichol-phosphate-mannose synthase activity, with an apparent Km for
GDP-mannose approximately 6-fold higher than normal.
Imbach et al. (2000) reported a brother and sister with CDG Ie who had
severe developmental delay, seizures, and dysmorphic features. They were
hospitalized at ages 3 years and 19 months, respectively, after repeated
seizure episodes. Weight, length, and head circumference were normal at
birth, but microcephaly developed in early childhood. Hypertelorism,
gothic palate, small hands with dysplastic nails, and knee contractures
were observed. Notably, nipples were not inverted as is found in CDG Ia
(212065). In the girl, early childhood was complicated by recurrent
infections. Seizures began in the girl at the age of 5 weeks and in her
brother at the age of 6 months. Both children were hypotonic and showed
severe global developmental delay. There was no visual fixation, and
they were unable to interact socially. Laboratory investigations showed
hypoglycosylation on serum transferrin and cerebral spinal fluid
beta-trace protein (176803). Mannose supplementation failed to improve
the glycosylation status of DPM1-deficient fibroblasts, thus precluding
a possible therapeutic application of mannose in the patients.
MOLECULAR GENETICS
In 2 unrelated patients with CDG Ie, Kim et al. (2000) identified
mutations in the DPM1 gene: 1 patient was homozygous (603503.0001) and
the other patient was compound heterozygous (603503.0001; 603503.0002).
Defects in DPM1 defined a new glycosylation disorder, CDG Ie.
In 2 affected sibs, Imbach et al. (2000) identified compound
heterozygosity for 2 mutations in the DPM1 gene (603503.0001;
603503.0003).
*FIELD* RF
1. Imbach, T.; Schenk, B.; Schollen, E.; Burda, P.; Stutz, A.; Grunewald,
S.; Bailie, N. M.; King, M. D.; Jaeken, J.; Matthijs, G.; Berger,
E. G.; Aebi, M.; Hennet, T.: Deficiency of dolichol-phosphate-mannose
synthase-1 causes congenital disorder of glycosylation type Ie. J.
Clin. Invest. 105: 233-239, 2000.
2. Kim, S.; Westphal, V.; Srikrishna, G.; Mehta, D. P.; Peterson,
S.; Filiano, J.; Karnes, P. S.; Patterson, M. C.; Freeze, H. H.:
Dolichol phosphate mannose synthase (DPM1) mutations define congenital
disorder of glycosylation Ie (CDG-Ie). J. Clin. Invest. 105: 191-198,
2000.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Other];
Failure to thrive
HEAD AND NECK:
[Head];
Microcephaly, acquired;
Flat occiput;
[Eyes];
Hypertelorism;
Strabismus;
Downslanting palpebral fissures;
Cortical blindness;
[Nose];
Flat nasal bridge;
[Mouth];
High, narrow palate;
'Gothic' palate;
Inverted 'V-shaped' mouth
CARDIOVASCULAR:
[Vascular];
Patent ductus arteriosus
RESPIRATORY:
Respiratory distress
ABDOMEN:
[Liver];
Hepatomegaly;
[Spleen];
Splenomegaly
SKELETAL:
[Limbs];
Shortening of the arms;
Knee contractures;
Ankle contractures;
[Hands];
Small hands
SKIN, NAILS, HAIR:
[Skin];
Telangiectasia;
Hemangiomas;
[Nails];
Dysplastic nails
NEUROLOGIC:
[Central nervous system];
Global developmental delay, severe;
Hypotonia;
Seizures;
Increased deep tendon reflexes in the lower limbs;
No visual fixation;
Abnormal EEG with epileptiform changes;
MRI shows decreased myelination
HEMATOLOGY:
Antithrombin III deficiency;
Protein S deficiency;
Protein C deficiency;
Prolonged activated partial thromboplastin time (aPTT)
LABORATORY ABNORMALITIES:
Abnormal isoelectric focusing of serum transferrin (type I pattern);
Decreased tetrasialotransferrin levels;
Increased disialotransferrin and asialotransferrin levels;
Increased liver function tests;
Increased serum creatine kinase
MOLECULAR BASIS:
Caused by mutation in the catalytic subunit of the dolichyl-phosphate
mannosyltransferase 1 gene (DPM1, 603503.0001)
*FIELD* CD
Cassandra L. Kniffin: 7/13/2004
*FIELD* ED
joanna: 05/25/2012
ckniffin: 5/22/2007
ckniffin: 7/13/2004
*FIELD* CD
Cassandra L. Kniffin: 7/13/2004
*FIELD* ED
carol: 06/27/2007
carol: 6/26/2007
ckniffin: 6/21/2007
carol: 7/22/2004
ckniffin: 7/13/2004
*RECORD*
*FIELD* NO
608799
*FIELD* TI
#608799 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ie; CDG1E
;;CDG Ie; CDGIe
*FIELD* TX
read moreA number sign (#) is used with this entry because congenital disorder of
glycosylation type Ie is caused by mutation in the DPM1 gene (603503).
DESCRIPTION
Congenital disorders of glycosylation (CDGs) are metabolic deficiencies
in glycoprotein biosynthesis that usually cause severe mental and
psychomotor retardation. Different forms of CDGs can be recognized by
altered isoelectric focusing (IEF) patterns of serum transferrin.
For a general discussion of CDGs, see CDG Ia (212065) and CDG Ib
(602579).
CLINICAL FEATURES
Kim et al. (2000) reported 2 patients with phenotypic and biochemical
features consistent with a congenital disorder of glycosylation. The
first patient was seen at age 10 months because of developmental delay,
hypotonia, seizures, and acquired microcephaly. Telangiectases on the
eyelids and hemangiomas of the occiput and sacrum were observed. The
second patient was born at 29 weeks of gestation, and the postnatal
course was complicated by hydrops, respiratory distress, apnea, patent
ductus arteriosus (see 607411), and transient hypertension. The infant
later developed generalized medically intractable seizures. At 3 years
of age, the child had no speech, was cortically blind, had strabismus,
and swallowed poorly. Both patients had similar abnormal IEF transferrin
patterns. Metabolic labeling of fibroblasts with 2-tritiated-mannose
showed that the patients produced a truncated dolichol-linked precursor
oligosaccharide with 5 mannose residues instead of the normal precursor
with 9 mannose residues. Addition of 250 microM mannose to the culture
medium corrected the size of the truncated oligosaccharide. Microsomes
from fibroblasts of these patients were approximately 95% deficient in
dolichol-phosphate-mannose synthase activity, with an apparent Km for
GDP-mannose approximately 6-fold higher than normal.
Imbach et al. (2000) reported a brother and sister with CDG Ie who had
severe developmental delay, seizures, and dysmorphic features. They were
hospitalized at ages 3 years and 19 months, respectively, after repeated
seizure episodes. Weight, length, and head circumference were normal at
birth, but microcephaly developed in early childhood. Hypertelorism,
gothic palate, small hands with dysplastic nails, and knee contractures
were observed. Notably, nipples were not inverted as is found in CDG Ia
(212065). In the girl, early childhood was complicated by recurrent
infections. Seizures began in the girl at the age of 5 weeks and in her
brother at the age of 6 months. Both children were hypotonic and showed
severe global developmental delay. There was no visual fixation, and
they were unable to interact socially. Laboratory investigations showed
hypoglycosylation on serum transferrin and cerebral spinal fluid
beta-trace protein (176803). Mannose supplementation failed to improve
the glycosylation status of DPM1-deficient fibroblasts, thus precluding
a possible therapeutic application of mannose in the patients.
MOLECULAR GENETICS
In 2 unrelated patients with CDG Ie, Kim et al. (2000) identified
mutations in the DPM1 gene: 1 patient was homozygous (603503.0001) and
the other patient was compound heterozygous (603503.0001; 603503.0002).
Defects in DPM1 defined a new glycosylation disorder, CDG Ie.
In 2 affected sibs, Imbach et al. (2000) identified compound
heterozygosity for 2 mutations in the DPM1 gene (603503.0001;
603503.0003).
*FIELD* RF
1. Imbach, T.; Schenk, B.; Schollen, E.; Burda, P.; Stutz, A.; Grunewald,
S.; Bailie, N. M.; King, M. D.; Jaeken, J.; Matthijs, G.; Berger,
E. G.; Aebi, M.; Hennet, T.: Deficiency of dolichol-phosphate-mannose
synthase-1 causes congenital disorder of glycosylation type Ie. J.
Clin. Invest. 105: 233-239, 2000.
2. Kim, S.; Westphal, V.; Srikrishna, G.; Mehta, D. P.; Peterson,
S.; Filiano, J.; Karnes, P. S.; Patterson, M. C.; Freeze, H. H.:
Dolichol phosphate mannose synthase (DPM1) mutations define congenital
disorder of glycosylation Ie (CDG-Ie). J. Clin. Invest. 105: 191-198,
2000.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Other];
Failure to thrive
HEAD AND NECK:
[Head];
Microcephaly, acquired;
Flat occiput;
[Eyes];
Hypertelorism;
Strabismus;
Downslanting palpebral fissures;
Cortical blindness;
[Nose];
Flat nasal bridge;
[Mouth];
High, narrow palate;
'Gothic' palate;
Inverted 'V-shaped' mouth
CARDIOVASCULAR:
[Vascular];
Patent ductus arteriosus
RESPIRATORY:
Respiratory distress
ABDOMEN:
[Liver];
Hepatomegaly;
[Spleen];
Splenomegaly
SKELETAL:
[Limbs];
Shortening of the arms;
Knee contractures;
Ankle contractures;
[Hands];
Small hands
SKIN, NAILS, HAIR:
[Skin];
Telangiectasia;
Hemangiomas;
[Nails];
Dysplastic nails
NEUROLOGIC:
[Central nervous system];
Global developmental delay, severe;
Hypotonia;
Seizures;
Increased deep tendon reflexes in the lower limbs;
No visual fixation;
Abnormal EEG with epileptiform changes;
MRI shows decreased myelination
HEMATOLOGY:
Antithrombin III deficiency;
Protein S deficiency;
Protein C deficiency;
Prolonged activated partial thromboplastin time (aPTT)
LABORATORY ABNORMALITIES:
Abnormal isoelectric focusing of serum transferrin (type I pattern);
Decreased tetrasialotransferrin levels;
Increased disialotransferrin and asialotransferrin levels;
Increased liver function tests;
Increased serum creatine kinase
MOLECULAR BASIS:
Caused by mutation in the catalytic subunit of the dolichyl-phosphate
mannosyltransferase 1 gene (DPM1, 603503.0001)
*FIELD* CD
Cassandra L. Kniffin: 7/13/2004
*FIELD* ED
joanna: 05/25/2012
ckniffin: 5/22/2007
ckniffin: 7/13/2004
*FIELD* CD
Cassandra L. Kniffin: 7/13/2004
*FIELD* ED
carol: 06/27/2007
carol: 6/26/2007
ckniffin: 6/21/2007
carol: 7/22/2004
ckniffin: 7/13/2004