MPU1_HUMAN
ID MPU1_HUMAN Reviewed; 247 AA.
AC O75352; B3KQP1; B4DT74; Q9BUU8;
DT 08-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Mannose-P-dolichol utilization defect 1 protein;
DE AltName: Full=Suppressor of Lec15 and Lec35 glycosylation mutation homolog;
DE Short=SL15;
GN Name=MPDU1;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Umbilical cord blood;
RX PubMed=9653160; DOI=10.1073/pnas.95.14.8175;
RA Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H.,
RA He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H.,
RA Wang Y.-X., Chen S.-J., Chen Z.;
RT "Identification of genes expressed in human CD34(+) hematopoietic
RT stem/progenitor cells by expressed sequence tags and efficient full-length
RT cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Pericardium;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 1), AND VARIANT THR-229.
RC TISSUE=Lung;
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 ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT 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., 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 [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
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., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [10]
RP VARIANT CDG1F SER-74.
RX PubMed=11733556; DOI=10.1172/jci13635;
RA Kranz C., Denecke J., Lehrman M.A., Ray S., Kienz P., Kreissel G., Sagi D.,
RA Peter-Katalinic J., Freeze H.H., Schmid T., Jackowski-Dohrmann S.,
RA Harms E., Marquardt T.;
RT "A mutation in the human MPDU1 gene causes congenital disorder of
RT glycosylation type If (CDG-If).";
RL J. Clin. Invest. 108:1613-1619(2001).
RN [11]
RP VARIANTS CDG1F GLU-73 AND PRO-119.
RX PubMed=11733564; DOI=10.1172/jci200113419;
RA Schenk B., Imbach T., Frank C.G., Grubenmann C.E., Raymond G.V.,
RA Hurvitz H., Raas-Rotschild A., Luder A.S., Jaeken J., Berger E.G.,
RA Matthijs G., Hennet T., Aebi M.;
RT "MPDU1 mutations underlie a novel human congenital disorder of
RT glycosylation, designated type If.";
RL J. Clin. Invest. 108:1687-1695(2001).
RN [12]
RP ERRATUM OF PUBMED:11733564.
RA Schenk B., Imbach T., Frank C.G., Grubenmann C.E., Raymond G.V.,
RA Hurvitz H., Korn-Lubetzki I., Revel-Vik S., Raas-Rotschild A., Luder A.S.,
RA Jaeken J., Berger E.G., Matthijs G., Hennet T., Aebi M.;
RL J. Clin. Invest. 111:925-925(2001).
CC -!- FUNCTION: Required for normal utilization of mannose-dolichol phosphate
CC (Dol-P-Man) in the synthesis of N-linked and O-linked oligosaccharides
CC and GPI anchors. {ECO:0000250}.
CC -!- INTERACTION:
CC O75352; Q9NQG1: MANBAL; NbExp=3; IntAct=EBI-1046501, EBI-3867271;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75352-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75352-2; Sequence=VSP_056349, VSP_056350;
CC -!- DISEASE: Congenital disorder of glycosylation 1F (CDG1F) [MIM:609180]:
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. {ECO:0000269|PubMed:11733556,
CC ECO:0000269|PubMed:11733564}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the MPDU1 (TC 2.A.43.3) family. {ECO:0000305}.
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DR EMBL; AF038961; AAC39875.1; -; mRNA.
DR EMBL; AK075299; BAG52103.1; -; mRNA.
DR EMBL; AK300083; BAG61886.1; -; mRNA.
DR EMBL; AC016876; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FJ695203; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90161.1; -; Genomic_DNA.
DR EMBL; BC001898; AAH01898.1; -; mRNA.
DR CCDS; CCDS11115.1; -. [O75352-1]
DR RefSeq; NP_001317002.1; NM_001330073.1.
DR RefSeq; NP_004861.2; NM_004870.3. [O75352-1]
DR AlphaFoldDB; O75352; -.
DR BioGRID; 114902; 62.
DR IntAct; O75352; 5.
DR STRING; 9606.ENSP00000250124; -.
DR iPTMnet; O75352; -.
DR PhosphoSitePlus; O75352; -.
DR SwissPalm; O75352; -.
DR BioMuta; MPDU1; -.
DR EPD; O75352; -.
DR jPOST; O75352; -.
DR MassIVE; O75352; -.
DR MaxQB; O75352; -.
DR PaxDb; O75352; -.
DR PeptideAtlas; O75352; -.
DR PRIDE; O75352; -.
DR ProteomicsDB; 49919; -. [O75352-1]
DR ProteomicsDB; 5083; -.
DR TopDownProteomics; O75352-1; -. [O75352-1]
DR Antibodypedia; 12103; 102 antibodies from 16 providers.
DR DNASU; 9526; -.
DR Ensembl; ENST00000250124.11; ENSP00000250124.6; ENSG00000129255.16. [O75352-1]
DR Ensembl; ENST00000423172.6; ENSP00000414071.2; ENSG00000129255.16. [O75352-2]
DR GeneID; 9526; -.
DR KEGG; hsa:9526; -.
DR MANE-Select; ENST00000250124.11; ENSP00000250124.6; NM_004870.4; NP_004861.2.
DR UCSC; uc002ghw.4; human. [O75352-1]
DR CTD; 9526; -.
DR DisGeNET; 9526; -.
DR GeneCards; MPDU1; -.
DR HGNC; HGNC:7207; MPDU1.
DR HPA; ENSG00000129255; Low tissue specificity.
DR MalaCards; MPDU1; -.
DR MIM; 604041; gene.
DR MIM; 609180; phenotype.
DR neXtProt; NX_O75352; -.
DR OpenTargets; ENSG00000129255; -.
DR Orphanet; 79323; MPDU1-CDG.
DR PharmGKB; PA30913; -.
DR VEuPathDB; HostDB:ENSG00000129255; -.
DR eggNOG; KOG3211; Eukaryota.
DR GeneTree; ENSGT00940000153916; -.
DR HOGENOM; CLU_053568_2_0_1; -.
DR InParanoid; O75352; -.
DR OMA; VIMMFAG; -.
DR OrthoDB; 895743at2759; -.
DR PhylomeDB; O75352; -.
DR TreeFam; TF324895; -.
DR PathwayCommons; O75352; -.
DR Reactome; R-HSA-446193; Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein.
DR Reactome; R-HSA-4687000; Defective MPDU1 causes CDG-1f.
DR SignaLink; O75352; -.
DR BioGRID-ORCS; 9526; 56 hits in 1086 CRISPR screens.
DR ChiTaRS; MPDU1; human.
DR GeneWiki; MPDU1; -.
DR GenomeRNAi; 9526; -.
DR Pharos; O75352; Tbio.
DR PRO; PR:O75352; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O75352; protein.
DR Bgee; ENSG00000129255; Expressed in rectum and 151 other tissues.
DR ExpressionAtlas; O75352; baseline and differential.
DR Genevisible; O75352; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; NAS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0006488; P:dolichol-linked oligosaccharide biosynthetic process; TAS:UniProtKB.
DR GO; GO:0009312; P:oligosaccharide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006457; P:protein folding; NAS:UniProtKB.
DR InterPro; IPR016817; MannP-dilichol_defect-1.
DR InterPro; IPR006603; PQ-loop_rpt.
DR PANTHER; PTHR12226; PTHR12226; 1.
DR Pfam; PF04193; PQ-loop; 2.
DR PIRSF; PIRSF023381; MannP-dilichol_defect-1p; 1.
DR SMART; SM00679; CTNS; 2.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Congenital disorder of glycosylation;
KW Disease variant; Membrane; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378, ECO:0007744|PubMed:25944712"
FT CHAIN 2..247
FT /note="Mannose-P-dolichol utilization defect 1 protein"
FT /id="PRO_0000221034"
FT TRANSMEM 37..57
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 74..94
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 100..120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 128..145
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 151..171
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 185..205
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 213..233
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 39..105
FT /note="PQ-loop 1"
FT DOMAIN 159..216
FT /note="PQ-loop 2"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378, ECO:0007744|PubMed:25944712"
FT VAR_SEQ 101..186
FT /note="SSWGEALFLMLQTITICFLVMHYRGQTVKGVAFLACYGLVLLVLLSPLTPLT
FT VVTLLQASNVPAVVVGRLLQAATNYHNGHTGQLS -> RCRFPRLLRPGPAGASLTSDA
FT LDCSHPAPGLQCACCGGGEASPGSHQLPQRAHRPALSHHSLPAVWGLPGPNLHFHSGVS
FT IPFSQL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056349"
FT VAR_SEQ 187..247
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056350"
FT VARIANT 73
FT /note="G -> E (in CDG1F; dbSNP:rs104894586)"
FT /evidence="ECO:0000269|PubMed:11733564"
FT /id="VAR_021388"
FT VARIANT 74
FT /note="L -> S (in CDG1F; dbSNP:rs104894589)"
FT /evidence="ECO:0000269|PubMed:11733556"
FT /id="VAR_021389"
FT VARIANT 119
FT /note="L -> P (in CDG1F; dbSNP:rs104894587)"
FT /evidence="ECO:0000269|PubMed:11733564"
FT /id="VAR_021390"
FT VARIANT 225
FT /note="G -> S (in dbSNP:rs16956808)"
FT /id="VAR_047757"
FT VARIANT 229
FT /note="A -> T (in dbSNP:rs10852891)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_047758"
FT CONFLICT 66
FT /note="L -> R (in Ref. 1; AAC39875)"
FT /evidence="ECO:0000305"
FT CONFLICT 181
FT /note="H -> Y (in Ref. 1; AAC39875)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 247 AA; 26638 MW; 8C840B26F06DFD9B CRC64;
MAAEADGPLK RLLVPILLPE KCYDQLFVQW DLLHVPCLKI LLSKGLGLGI VAGSLLVKLP
QVFKILGAKS AEGLSLQSVM LELVALTGTM VYSITNNFPF SSWGEALFLM LQTITICFLV
MHYRGQTVKG VAFLACYGLV LLVLLSPLTP LTVVTLLQAS NVPAVVVGRL LQAATNYHNG
HTGQLSAITV FLLFGGSLAR IFTSIQETGD PLMAGTFVVS SLCNGLIAAQ LLFYWNAKPP
HKQKKAQ
