DPM2_HUMAN
ID DPM2_HUMAN Reviewed; 84 AA.
AC O94777; Q5XKK9; Q6FGH3;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Dolichol phosphate-mannose biosynthesis regulatory protein {ECO:0000305};
DE AltName: Full=Dolichol-phosphate mannose synthase subunit 2;
DE Short=DPM synthase subunit 2;
GN Name=DPM2 {ECO:0000312|HGNC:HGNC:3006}; ORFNames=My026;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9724629; DOI=10.1093/emboj/17.17.4920;
RA Maeda Y., Tomita S., Watanabe R., Ohishi K., Kinoshita T.;
RT "DPM2 regulates biosynthesis of dolichol phosphate-mannose in mammalian
RT cells: correct subcellular localization and stabilization of DPM1, and
RT binding of dolichol phosphate.";
RL EMBO J. 17:4920-4929(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Fetal brain;
RA Mao Y.M., Xie Y., Ying K.;
RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-76.
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-76.
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-76.
RC TISSUE=Pancreas;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 2-31, AND SUBUNIT.
RX PubMed=10835346; DOI=10.1093/emboj/19.11.2475;
RA Maeda Y., Tanaka S., Hino J., Kangawa K., Kinoshita T.;
RT "Human dolichol-phosphate-mannose synthase consists of three subunits,
RT DPM1, DPM2 and DPM3.";
RL EMBO J. 19:2475-2482(2000).
RN [9]
RP FUNCTION, AND INTERACTION WITH PIGA; PIGC AND PIGQ.
RX PubMed=10944123; DOI=10.1093/emboj/19.16.4402;
RA Watanabe R., Murakami Y., Marmor M.D., Inoue N., Maeda Y., Hino J.,
RA Kangawa K., Julius M., Kinoshita T.;
RT "Initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-
RT P and is regulated by DPM2.";
RL EMBO J. 19:4402-4411(2000).
RN [10]
RP FUNCTION, AND COMPONENT OF GPI-GNT COMPLEX.
RX PubMed=16162815; DOI=10.1091/mbc.e05-08-0743;
RA Murakami Y., Siripanyaphinyo U., Hong Y., Tashima Y., Maeda Y.,
RA Kinoshita T.;
RT "The initial enzyme for glycosylphosphatidylinositol biosynthesis requires
RT PIG-Y, a seventh component.";
RL Mol. Biol. Cell 16:5236-5246(2005).
RN [11]
RP VARIANT CDG1U CYS-23.
RX PubMed=23109149; DOI=10.1002/ana.23632;
RA Barone R., Aiello C., Race V., Morava E., Foulquier F., Riemersma M.,
RA Passarelli C., Concolino D., Carella M., Santorelli F., Vleugels W.,
RA Mercuri E., Garozzo D., Sturiale L., Messina S., Jaeken J., Fiumara A.,
RA Wevers R.A., Bertini E., Matthijs G., Lefeber D.J.;
RT "DPM2-CDG: a muscular dystrophy-dystroglycanopathy syndrome with severe
RT epilepsy.";
RL Ann. Neurol. 72:550-558(2012).
CC -!- FUNCTION: Regulates the biosynthesis of dolichol phosphate-mannose
CC (PubMed:10835346). Regulatory subunit of the dolichol-phosphate mannose
CC (DPM) synthase complex; essential for the ER localization and stable
CC expression of DPM1 (PubMed:10835346). Part of the
CC glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT)
CC complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-
CC acetylglucosamine to phosphatidylinositol and participates in the first
CC step of GPI biosynthesis (PubMed:16162815). May act by regulating the
CC GPI-GNT complex (PubMed:10944123). {ECO:0000269|PubMed:10835346,
CC ECO:0000269|PubMed:10944123, ECO:0000269|PubMed:16162815}.
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000269|PubMed:10835346}.
CC -!- SUBUNIT: Component of the dolichol-phosphate mannose (DPM) synthase
CC complex composed of DPM1, DPM2 and DPM3; in the complex interacts
CC directly with DPM3 (PubMed:10835346). Component of the
CC glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT)
CC complex composed at least by PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY and
CC DPM2 (PubMed:16162815). Interacts with PIGA, PIGC and PIGQ
CC (PubMed:10944123). {ECO:0000269|PubMed:10835346,
CC ECO:0000269|PubMed:10944123, ECO:0000269|PubMed:16162815}.
CC -!- INTERACTION:
CC O94777; Q9P2X0: DPM3; NbExp=3; IntAct=EBI-9097061, EBI-9087337;
CC O94777; P37287: PIGA; NbExp=4; IntAct=EBI-9097061, EBI-26643054;
CC O94777; Q92535: PIGC; NbExp=2; IntAct=EBI-9097061, EBI-721918;
CC O94777; Q9BRB3: PIGQ; NbExp=2; IntAct=EBI-9097061, EBI-2339260;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein.
CC -!- DISEASE: Congenital disorder of glycosylation 1U (CDG1U) [MIM:615042]:
CC A form of congenital disorder of glycosylation, a multisystem disorder
CC caused by a defect in glycoprotein biosynthesis and characterized by
CC under-glycosylated serum glycoproteins. Congenital disorders of
CC glycosylation result in a wide variety of clinical features, such as
CC defects in the nervous system development, psychomotor retardation,
CC dysmorphic features, hypotonia, coagulation disorders, and
CC immunodeficiency. The broad spectrum of features reflects the critical
CC role of N-glycoproteins during embryonic development, differentiation,
CC and maintenance of cell functions. Some CDG1U patients have dystrophic
CC changes seen on muscle biopsy and reduced O-mannosyl glycans on alpha-
CC dystroglycan. {ECO:0000269|PubMed:23109149}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the DPM2 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB013361; BAA33974.1; -; mRNA.
DR EMBL; AF061729; AAG43140.1; -; mRNA.
DR EMBL; CR542134; CAG46931.1; -; mRNA.
DR EMBL; AB451329; BAG70143.1; -; mRNA.
DR EMBL; AB451473; BAG70287.1; -; mRNA.
DR EMBL; AL157935; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471090; EAW87730.1; -; Genomic_DNA.
DR EMBL; BC015233; AAH15233.1; -; mRNA.
DR EMBL; BC107863; AAI07864.1; -; mRNA.
DR CCDS; CCDS6886.1; -.
DR RefSeq; NP_003854.1; NM_003863.3.
DR AlphaFoldDB; O94777; -.
DR SMR; O94777; -.
DR BioGRID; 114345; 60.
DR ComplexPortal; CPX-6268; Dolichol-phosphate mannosyltransferase complex.
DR ComplexPortal; CPX-6502; Glycosylphosphatidylinositol-N-acetylglucosaminyltransferase complex.
DR CORUM; O94777; -.
DR IntAct; O94777; 8.
DR STRING; 9606.ENSP00000322181; -.
DR BioMuta; DPM2; -.
DR MassIVE; O94777; -.
DR PaxDb; O94777; -.
DR PeptideAtlas; O94777; -.
DR PRIDE; O94777; -.
DR TopDownProteomics; O94777; -.
DR Antibodypedia; 44831; 43 antibodies from 16 providers.
DR DNASU; 8818; -.
DR Ensembl; ENST00000314392.13; ENSP00000322181.8; ENSG00000136908.18.
DR GeneID; 8818; -.
DR KEGG; hsa:8818; -.
DR MANE-Select; ENST00000314392.13; ENSP00000322181.8; NM_003863.4; NP_003854.1.
DR UCSC; uc004bsv.3; human.
DR CTD; 8818; -.
DR DisGeNET; 8818; -.
DR GeneCards; DPM2; -.
DR GeneReviews; DPM2; -.
DR HGNC; HGNC:3006; DPM2.
DR HPA; ENSG00000136908; Low tissue specificity.
DR MalaCards; DPM2; -.
DR MIM; 603564; gene.
DR MIM; 615042; phenotype.
DR neXtProt; NX_O94777; -.
DR OpenTargets; ENSG00000136908; -.
DR Orphanet; 329178; Congenital muscular dystrophy with intellectual disability and severe epilepsy.
DR PharmGKB; PA27464; -.
DR VEuPathDB; HostDB:ENSG00000136908; -.
DR eggNOG; KOG3488; Eukaryota.
DR GeneTree; ENSGT00390000001098; -.
DR HOGENOM; CLU_150144_2_1_1; -.
DR InParanoid; O94777; -.
DR OMA; YVMLKSQ; -.
DR OrthoDB; 1605216at2759; -.
DR PhylomeDB; O94777; -.
DR TreeFam; TF300257; -.
DR BioCyc; MetaCyc:ENSG00000136908-MON; -.
DR PathwayCommons; O94777; -.
DR Reactome; R-HSA-162699; Synthesis of dolichyl-phosphate mannose.
DR Reactome; R-HSA-162710; Synthesis of glycosylphosphatidylinositol (GPI).
DR Reactome; R-HSA-4717374; Defective DPM1 causes DPM1-CDG.
DR Reactome; R-HSA-4719360; Defective DPM3 causes DPM3-CDG.
DR Reactome; R-HSA-4719377; Defective DPM2 causes DPM2-CDG.
DR SignaLink; O94777; -.
DR SIGNOR; O94777; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 8818; 173 hits in 1076 CRISPR screens.
DR ChiTaRS; DPM2; human.
DR GeneWiki; DPM2; -.
DR GenomeRNAi; 8818; -.
DR Pharos; O94777; Tdark.
DR PRO; PR:O94777; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; O94777; protein.
DR Bgee; ENSG00000136908; Expressed in body of pancreas and 180 other tissues.
DR ExpressionAtlas; O94777; baseline and differential.
DR Genevisible; O94777; HS.
DR GO; GO:0033185; C:dolichol-phosphate-mannose synthase complex; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:ComplexPortal.
DR GO; GO:0000506; C:glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex; IDA:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IEA:InterPro.
DR GO; GO:0008047; F:enzyme activator activity; IDA:HGNC-UCL.
DR GO; GO:0030234; F:enzyme regulator activity; IBA:GO_Central.
DR GO; GO:0019348; P:dolichol metabolic process; IDA:ComplexPortal.
DR GO; GO:0006506; P:GPI anchor biosynthetic process; IDA:UniProtKB.
DR GO; GO:0035269; P:protein O-linked mannosylation; TAS:HGNC-UCL.
DR GO; GO:0031647; P:regulation of protein stability; IPI:UniProtKB.
DR InterPro; IPR009914; DPM2.
DR PANTHER; PTHR15039; PTHR15039; 1.
DR Pfam; PF07297; DPM2; 1.
PE 1: Evidence at protein level;
KW Congenital disorder of glycosylation; Congenital muscular dystrophy;
KW Direct protein sequencing; Disease variant; Dystroglycanopathy;
KW Endoplasmic reticulum; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:10835346"
FT CHAIN 2..84
FT /note="Dolichol phosphate-mannose biosynthesis regulatory
FT protein"
FT /id="PRO_0000220873"
FT TRANSMEM 11..31
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 49..69
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VARIANT 23
FT /note="Y -> C (in CDG1U; dbSNP:rs397514503)"
FT /evidence="ECO:0000269|PubMed:23109149"
FT /id="VAR_069745"
FT VARIANT 76
FT /note="T -> S (in dbSNP:rs7997)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:19054851, ECO:0000269|Ref.6"
FT /id="VAR_033895"
SQ SEQUENCE 84 AA; 9312 MW; 0247A0843A711EE9 CRC64;
MATGTDQVVG LGLVAVSLII FTYYTAWVIL LPFIDSQHVI HKYFLPRAYA VAIPLAAGLL
LLLFVGLFIS YVMLKTKRVT KKAQ
