DPM3_HUMAN
ID DPM3_HUMAN Reviewed; 92 AA.
AC Q9P2X0; Q5SR62; Q5SR63; Q9BXN4; Q9BXN5;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Dolichol-phosphate mannosyltransferase subunit 3;
DE AltName: Full=Dolichol-phosphate mannose synthase subunit 3;
DE Short=DPM synthase subunit 3;
DE AltName: Full=Dolichyl-phosphate beta-D-mannosyltransferase subunit 3;
DE AltName: Full=Mannose-P-dolichol synthase subunit 3;
DE Short=MPD synthase subunit 3;
DE AltName: Full=Prostin-1;
GN Name=DPM3;
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] (ISOFORM 1), PROTEIN SEQUENCE OF 1-13, FUNCTION,
RP 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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=11420690; DOI=10.1038/sj.onc.1204379;
RA Manos E.J., Kim M.L., Kassis J., Chang P.Y., Wells A., Jones D.A.;
RT "Dolichol-phosphate-mannose-3 (DPM3)/prostin-1 is a novel phospholipase C-
RT gamma regulated gene negatively associated with prostate tumor invasion.";
RL Oncogene 20:2781-2790(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [6]
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., Buerckstuemmer T.,
RA 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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [8]
RP INVOLVEMENT IN MDDGC15, VARIANT MDDGC15 SER-85, CHARACTERIZATION OF VARIANT
RP MDDGC15 SER-85, AND INTERACTION WITH DPM1.
RX PubMed=19576565; DOI=10.1016/j.ajhg.2009.06.006;
RA Lefeber D.J., Schonberger J., Morava E., Guillard M., Huyben K.M.,
RA Verrijp K., Grafakou O., Evangeliou A., Preijers F.W., Manta P., Yildiz J.,
RA Grunewald S., Spilioti M., van den Elzen C., Klein D., Hess D., Ashida H.,
RA Hofsteenge J., Maeda Y., van den Heuvel L., Lammens M., Lehle L.,
RA Wevers R.A.;
RT "Deficiency of Dol-P-Man synthase subunit DPM3 bridges the congenital
RT disorders of glycosylation with the dystroglycanopathies.";
RL Am. J. Hum. Genet. 85:76-86(2009).
RN [9]
RP INVOLVEMENT IN MDDGC15, AND VARIANT MDDGC15 PRO-14.
RX PubMed=28803818; DOI=10.1016/j.nmd.2017.07.006;
RA Van den Bergh P.Y.K., Sznajer Y., Van Parys V., van Tol W., Wevers R.A.,
RA Lefeber D.J., Xu L., Lek M., MacArthur D.G., Johnson K., Phillips L.,
RA Toepf A., Straub V.;
RT "A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related
RT limb girdle muscular dystrophy.";
RL Neuromuscul. Disord. 27:1043-1046(2017).
RN [10]
RP ERRATUM OF PUBMED:28803818.
RX PubMed=29246662; DOI=10.1016/j.nmd.2017.11.012;
RA Van den Bergh P.Y.K., Sznajer Y., Van Parys V., van Tol W., Wevers R.A.,
RA Lefeber D.J., Xu L., Lek M., MacArthur D.G., Johnson K., Phillips L.,
RA Toepf A., Straub V.;
RT "Corrigendum to 'A homozygous DPM3 mutation in a patient with alpha-
RT dystroglycan-related limb girdle muscular dystrophy' [Neuromuscular
RT disorders 27/11 (2017) 1043-1046].";
RL Neuromuscul. Disord. 28:101-101(2018).
RN [11]
RP INVOLVEMENT IN MDDGB15, AND VARIANTS MDDGB15 ALA-42 AND 85-LEU--PHE-92 DEL.
RX PubMed=31469168; DOI=10.1111/cge.13634;
RA Fu J., Ma M., Song J., Pang M., Yang L., Li G., Zhang J.;
RT "Novel mutations in DPM3 cause dystroglycanopathy with central nervous
RT system involvement.";
RL Clin. Genet. 96:590-591(2019).
RN [12]
RP INVOLVEMENT IN MDDGC15, AND VARIANT MDDGC15 PRO-14.
RX PubMed=31266720; DOI=10.1016/j.nmd.2019.05.004;
RA Svahn J., Laforet P., Vial C., Streichenberger N., Romero N.,
RA Bouchet-Seraphin C., Bruneel A., Dupre T., Seta N., Menassa R.,
RA Michel-Calemard L., Stojkovic T.;
RT "Dilated cardiomyopathy and limb-girdle muscular dystrophy-
RT dystroglycanopathy due to novel pathogenic variants in the DPM3 gene.";
RL Neuromuscul. Disord. 29:497-502(2019).
CC -!- FUNCTION: Stabilizer subunit of the dolichol-phosphate mannose (DPM)
CC synthase complex; tethers catalytic subunit DPM1 to the endoplasmic
CC reticulum. {ECO:0000269|PubMed:10835346}.
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- SUBUNIT: Component of the dolichol-phosphate mannose (DPM) synthase
CC complex composed of DPM1, DPM2 and DPM3; within the complex, associates
CC with DPM1 via its C-terminal domain and with DPM2 via its N-terminal
CC portion (PubMed:10835346, PubMed:19576565). This interaction stabilizes
CC DPM1 protein (PubMed:19576565). {ECO:0000269|PubMed:10835346,
CC ECO:0000269|PubMed:19576565}.
CC -!- INTERACTION:
CC Q9P2X0; O60762: DPM1; NbExp=5; IntAct=EBI-9087337, EBI-719526;
CC Q9P2X0; O94777: DPM2; NbExp=3; IntAct=EBI-9087337, EBI-9097061;
CC Q9P2X0; Q9Z325: Dpm2; Xeno; NbExp=2; IntAct=EBI-9087337, EBI-9097185;
CC Q9P2X0-2; Q8N128-2: FAM177A1; NbExp=3; IntAct=EBI-10962476, EBI-12201693;
CC Q9P2X0-2; Q9Y5U9: IER3IP1; NbExp=3; IntAct=EBI-10962476, EBI-725665;
CC Q9P2X0-2; O75396: SEC22B; NbExp=3; IntAct=EBI-10962476, EBI-1058865;
CC Q9P2X0-2; Q9BVK8: TMEM147; NbExp=3; IntAct=EBI-10962476, EBI-348587;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Short;
CC IsoId=Q9P2X0-1; Sequence=Displayed;
CC Name=2; Synonyms=Long;
CC IsoId=Q9P2X0-2; Sequence=VSP_001308;
CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy congenital with impaired
CC intellectual development B15 (MDDGB15) [MIM:618992]: An autosomal
CC recessive, congenital muscular disorder characterized by hyperCKemia,
CC myopathic features observed on muscle biopsy, developmental delay,
CC mildly impaired intellectual development with learning difficulties,
CC epilepsy, and mild white matter abnormalities.
CC {ECO:0000269|PubMed:31469168}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy limb-girdle C15
CC (MDDGC15) [MIM:612937]: An autosomal recessive muscular dystrophy
CC associated with a disorder of glycosylation resulting in under-
CC glycosylated serum glycoproteins. MDDGC15 patients have muscle
CC weakness, increased serum creatine kinase, dystrophic changes on muscle
CC biopsy, and reduced O-mannosylation of alpha-dystroglycan.
CC {ECO:0000269|PubMed:19576565, ECO:0000269|PubMed:28803818,
CC ECO:0000269|PubMed:31266720}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the DPM3 family. {ECO:0000305}.
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DR EMBL; AB028128; BAA96291.1; -; mRNA.
DR EMBL; AF312922; AAK28487.1; -; mRNA.
DR EMBL; AF312923; AAK28486.1; -; mRNA.
DR EMBL; AL691442; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53126.1; -; Genomic_DNA.
DR EMBL; BC104202; AAI04203.1; -; mRNA.
DR EMBL; BC104203; AAI04204.1; -; mRNA.
DR CCDS; CCDS1094.1; -. [Q9P2X0-2]
DR CCDS; CCDS1095.1; -. [Q9P2X0-1]
DR RefSeq; NP_061846.2; NM_018973.3. [Q9P2X0-2]
DR RefSeq; NP_714963.1; NM_153741.1. [Q9P2X0-1]
DR RefSeq; XP_016856987.1; XM_017001498.1. [Q9P2X0-1]
DR AlphaFoldDB; Q9P2X0; -.
DR BioGRID; 119935; 17.
DR ComplexPortal; CPX-6268; Dolichol-phosphate mannosyltransferase complex.
DR CORUM; Q9P2X0; -.
DR IntAct; Q9P2X0; 15.
DR STRING; 9606.ENSP00000357384; -.
DR GlyGen; Q9P2X0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9P2X0; -.
DR PhosphoSitePlus; Q9P2X0; -.
DR SwissPalm; Q9P2X0; -.
DR BioMuta; DPM3; -.
DR DMDM; 125987822; -.
DR EPD; Q9P2X0; -.
DR jPOST; Q9P2X0; -.
DR MassIVE; Q9P2X0; -.
DR MaxQB; Q9P2X0; -.
DR PaxDb; Q9P2X0; -.
DR PeptideAtlas; Q9P2X0; -.
DR PRIDE; Q9P2X0; -.
DR ProteomicsDB; 83907; -. [Q9P2X0-1]
DR ProteomicsDB; 83908; -. [Q9P2X0-2]
DR TopDownProteomics; Q9P2X0-1; -. [Q9P2X0-1]
DR TopDownProteomics; Q9P2X0-2; -. [Q9P2X0-2]
DR Antibodypedia; 3056; 39 antibodies from 21 providers.
DR DNASU; 54344; -.
DR Ensembl; ENST00000341298.3; ENSP00000344338.3; ENSG00000179085.8. [Q9P2X0-1]
DR Ensembl; ENST00000368399.1; ENSP00000357384.1; ENSG00000179085.8. [Q9P2X0-2]
DR Ensembl; ENST00000368400.5; ENSP00000357385.5; ENSG00000179085.8. [Q9P2X0-1]
DR GeneID; 54344; -.
DR KEGG; hsa:54344; -.
DR MANE-Select; ENST00000368400.5; ENSP00000357385.5; NM_153741.2; NP_714963.1.
DR UCSC; uc001fhm.3; human. [Q9P2X0-1]
DR CTD; 54344; -.
DR DisGeNET; 54344; -.
DR GeneCards; DPM3; -.
DR GeneReviews; DPM3; -.
DR HGNC; HGNC:3007; DPM3.
DR HPA; ENSG00000179085; Low tissue specificity.
DR MalaCards; DPM3; -.
DR MIM; 605951; gene.
DR MIM; 612937; phenotype.
DR MIM; 618992; phenotype.
DR neXtProt; NX_Q9P2X0; -.
DR OpenTargets; ENSG00000179085; -.
DR Orphanet; 263494; DPM3-CDG.
DR PharmGKB; PA27465; -.
DR VEuPathDB; HostDB:ENSG00000179085; -.
DR eggNOG; KOG4841; Eukaryota.
DR GeneTree; ENSGT00390000008892; -.
DR HOGENOM; CLU_150782_0_1_1; -.
DR InParanoid; Q9P2X0; -.
DR PhylomeDB; Q9P2X0; -.
DR TreeFam; TF300274; -.
DR BioCyc; MetaCyc:ENSG00000179085-MON; -.
DR BRENDA; 2.4.1.83; 2681.
DR PathwayCommons; Q9P2X0; -.
DR Reactome; R-HSA-162699; Synthesis of dolichyl-phosphate mannose.
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; Q9P2X0; -.
DR SIGNOR; Q9P2X0; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 54344; 101 hits in 1073 CRISPR screens.
DR ChiTaRS; DPM3; human.
DR GeneWiki; DPM3; -.
DR GenomeRNAi; 54344; -.
DR Pharos; Q9P2X0; Tdark.
DR PRO; PR:Q9P2X0; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9P2X0; protein.
DR Bgee; ENSG00000179085; Expressed in mucosa of transverse colon and 202 other tissues.
DR ExpressionAtlas; Q9P2X0; baseline and differential.
DR Genevisible; Q9P2X0; HS.
DR GO; GO:0033185; C:dolichol-phosphate-mannose synthase complex; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:HGNC-UCL.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:HGNC-UCL.
DR GO; GO:0031501; C:mannosyltransferase complex; TAS:HGNC-UCL.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0008047; F:enzyme activator activity; IDA:HGNC-UCL.
DR GO; GO:0005975; P:carbohydrate metabolic process; NAS:ProtInc.
DR GO; GO:0019348; P:dolichol metabolic process; IDA:ComplexPortal.
DR GO; GO:0006506; P:GPI anchor biosynthetic process; IDA:UniProtKB.
DR GO; GO:0018406; P:protein C-linked glycosylation via 2'-alpha-mannosyl-L-tryptophan; TAS:HGNC-UCL.
DR GO; GO:0035268; P:protein mannosylation; TAS:HGNC-UCL.
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; IPR013174; DPM3.
DR PANTHER; PTHR16433; PTHR16433; 1.
DR Pfam; PF08285; DPM3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Congenital disorder of glycosylation;
KW Congenital muscular dystrophy; Direct protein sequencing; Disease variant;
KW Dystroglycanopathy; Endoplasmic reticulum; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..92
FT /note="Dolichol-phosphate mannosyltransferase subunit 3"
FT /id="PRO_0000195000"
FT TRANSMEM 8..28
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 37..57
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1
FT /note="M -> MLSVGGLRLSLVRFSFLLLRGALLPSLAVTM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11420690,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_001308"
FT VARIANT 14
FT /note="L -> P (in MDDGC15; unknown pathological
FT significance; dbSNP:rs778481307)"
FT /evidence="ECO:0000269|PubMed:28803818,
FT ECO:0000269|PubMed:31266720"
FT /id="VAR_085122"
FT VARIANT 42
FT /note="P -> A (in MDDGB15; unknown pathological
FT significance; dbSNP:rs745692004)"
FT /evidence="ECO:0000269|PubMed:31469168"
FT /id="VAR_085123"
FT VARIANT 85..92
FT /note="Missing (in MDDGB15; unknown pathological
FT significance; dbSNP:rs121908155)"
FT /evidence="ECO:0000269|PubMed:31469168"
FT /id="VAR_085124"
FT VARIANT 85
FT /note="L -> S (in MDDGC15; when transfected into DPM3-
FT deficient cells, only slightly restores dolichol-phosphate
FT mannose synthase activity contrary to wild-type DPM3;
FT reduced interaction with DPM1; dbSNP:rs121908155)"
FT /evidence="ECO:0000269|PubMed:19576565"
FT /id="VAR_062518"
FT CONFLICT 90
FT /note="L -> V (in Ref. 1; BAA96291)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 92 AA; 10094 MW; C350A6896842A877 CRC64;
MTKLAQWLWG LAILGSTWVA LTTGALGLEL PLSCQEVLWP LPAYLLVSAG CYALGTVGYR
VATFHDCEDA ARELQSQIQE ARADLARRGL RF
