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   27-MAR-2024, entry version 179.
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/jci13419;
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; 67.
DR   IntAct; O75352; 6.
DR   STRING; 9606.ENSP00000250124; -.
DR   GlyGen; O75352; 1 site, 1 O-linked glycan (1 site).
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; 9606-ENSP00000250124; -.
DR   PeptideAtlas; O75352; -.
DR   ProteomicsDB; 49919; -. [O75352-1]
DR   ProteomicsDB; 5083; -.
DR   Pumba; O75352; -.
DR   TopDownProteomics; O75352-1; -. [O75352-1]
DR   Antibodypedia; 12103; 117 antibodies from 17 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   AGR; HGNC:7207; -.
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; LQVLYYW; -.
DR   OrthoDB; 7736at2759; -.
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; 63 hits in 1172 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 153 other cell types or tissues.
DR   ExpressionAtlas; O75352; baseline and differential.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; NAS:UniProtKB.
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   Gene3D; 1.20.1280.290; -; 1.
DR   InterPro; IPR016817; MannP-dilichol_defect-1.
DR   InterPro; IPR006603; PQ-loop_rpt.
DR   PANTHER; PTHR12226; MANNOSE-P-DOLICHOL UTILIZATION DEFECT 1 LEC35 -RELATED; 1.
DR   PANTHER; PTHR12226:SF2; MANNOSE-P-DOLICHOL UTILIZATION DEFECT 1 PROTEIN; 1.
DR   Pfam; PF04193; PQ-loop; 2.
DR   PIRSF; PIRSF023381; MannP-dilichol_defect-1p; 1.
DR   SMART; SM00679; CTNS; 2.
DR   Genevisible; O75352; HS.
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
//