ID MPRD_HUMAN Reviewed; 277 AA. AC P20645; A8K528; D3DUV5; DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1991, sequence version 1. DT 04-NOV-2026, entry version 221. DE RecName: Full=Cation-dependent mannose-6-phosphate receptor; DE Short=CD Man-6-P receptor; DE Short=CD-MPR; DE AltName: Full=46 kDa mannose 6-phosphate receptor; DE Short=MPR 46; DE Flags: Precursor; GN Name=M6PR; Synonyms=MPR46, MPRD; 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=2441386; DOI=10.1073/pnas.84.16.5575; RA Pohlmann R., Nagel G., Schmidt B., Stein M., Lorkowski G., Krentler C., RA Cully J., Meyer H.E., Grzeschik K.H., Mersmann G., Hasilik A., RA von Figura K.; RT "Cloning of a cDNA encoding the human cation-dependent mannose 6-phosphate- RT specific receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 84:5575-5579(1987). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Leukocyte; RX PubMed=1849818; DOI=10.1111/j.1432-1033.1991.tb15877.x; RA Klier H.J., von Figura K., Pohlmann R.; RT "Isolation and analysis of the human 46-kDa mannose 6-phosphate receptor RT gene."; RL Eur. J. Biochem. 197:23-28(1991). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [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]. RC TISSUE=Muscle; 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 INTERACTION WITH GGA1 AND GGA3. RX PubMed=11387475; DOI=10.1126/science.1060750; RA Puertollano R., Aguilar R.C., Gorshkova I., Crouch R.J., Bonifacino J.S.; RT "Sorting of mannose 6-phosphate receptors mediated by the GGAs."; RL Science 292:1712-1716(2001). RN [7] RP INTERACTION WITH GGA2. RX PubMed=11886874; DOI=10.1074/jbc.m201879200; RA Doray B., Bruns K., Ghosh P., Kornfeld S.; RT "Interaction of the cation-dependent mannose 6-phosphate receptor with GGA RT proteins."; RL J. Biol. Chem. 277:18477-18482(2002). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [9] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-83 AND ASN-107. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). 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., 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 [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [12] 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). CC -!- FUNCTION: Transport of phosphorylated lysosomal enzymes from the Golgi CC complex and the cell surface to lysosomes. Lysosomal enzymes bearing CC phosphomannosyl residues bind specifically to mannose-6-phosphate CC receptors in the Golgi apparatus and the resulting receptor-ligand CC complex is transported to an acidic prelyosomal compartment where the CC low pH mediates the dissociation of the complex. CC -!- SUBUNIT: Homodimer. Binds GGA1, GGA2 and GGA3. CC -!- INTERACTION: CC P20645; P21964-2: COMT; NbExp=3; IntAct=EBI-2907262, EBI-10200977; CC P20645; Q9UNI6: DUSP12; NbExp=3; IntAct=EBI-2907262, EBI-715161; CC P20645; Q9NZ52: GGA3; NbExp=2; IntAct=EBI-2907262, EBI-447404; CC P20645; Q96F15: GIMAP5; NbExp=3; IntAct=EBI-2907262, EBI-6166686; CC P20645; Q86UP2-3: KTN1; NbExp=3; IntAct=EBI-2907262, EBI-12007212; CC P20645; Q9NZG7: NINJ2; NbExp=3; IntAct=EBI-2907262, EBI-10317425; CC P20645; Q9NRQ5: SMCO4; NbExp=3; IntAct=EBI-2907262, EBI-8640191; CC -!- SUBCELLULAR LOCATION: Lysosome membrane; Single-pass type I membrane CC protein. CC -!- DOMAIN: The extracellular domain is homologous to the repeating units CC (of approximately 147 AA) of the cation-independent mannose 6-phosphate CC receptor. CC -!- MISCELLANEOUS: This receptor has optimal binding in the presence of CC divalent cations. 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; M16985; AAA59542.1; -; mRNA. DR EMBL; X56254; CAB94715.1; -; Genomic_DNA. DR EMBL; X56255; CAB94715.1; JOINED; Genomic_DNA. DR EMBL; X56256; CAB94715.1; JOINED; Genomic_DNA. DR EMBL; X56257; CAB94715.1; JOINED; Genomic_DNA. DR EMBL; AK291143; BAF83832.1; -; mRNA. DR EMBL; CH471116; EAW88596.1; -; Genomic_DNA. DR EMBL; CH471116; EAW88597.1; -; Genomic_DNA. DR EMBL; CH471116; EAW88598.1; -; Genomic_DNA. DR EMBL; CH471116; EAW88599.1; -; Genomic_DNA. DR EMBL; BC024206; AAH24206.1; -; mRNA. DR CCDS; CCDS8598.1; -. DR PIR; S15368; A32700. DR RefSeq; NP_001401249.1; NM_001414320.1. DR RefSeq; NP_001401260.1; NM_001414331.1. DR RefSeq; NP_001401261.1; NM_001414332.1. DR RefSeq; NP_001401262.1; NM_001414333.1. DR RefSeq; NP_002346.1; NM_002355.4. DR RefSeq; XP_047284806.1; XM_047428850.1. DR RefSeq; XP_054228029.1; XM_054372054.1. DR PDB; 1JUQ; X-ray; 2.20 A; E/F/G/H=265-277. DR AlphaFoldDB; P20645; -. DR MDRepo; P20645; -. DR SMR; P20645; -. DR BioGRID; 110251; 92. DR ELM; P20645; -. DR FunCoup; P20645; 2463. DR IntAct; P20645; 43. DR STRING; 9606.ENSP00000000412; -. DR BindingDB; P20645; -. DR ChEMBL; CHEMBL5788; -. DR DrugBank; DB02755; 1-3 Sugar Ring of Pentamannosyl 6-Phosphate. DR DrugBank; DB15874; Agalsidase alfa. DR DrugBank; DB00103; Agalsidase beta. DR DrugBank; DB01272; Alglucosidase alfa. DR DrugBank; DB02900; alpha-D-mannose 6-phosphate. DR TCDB; 9.B.247.1.1; the mannose 6-phosphate receptor (m6pr) family. DR GlyConnect; P20645; 20 N-Linked glycans (2 sites). DR GlyCosmos; P20645; 6 sites, 80 glycans. DR GlyGen; P20645; 7 sites, 81 N-linked glycans (5 sites), 1 O-linked glycan (1 site). DR iPTMnet; P20645; -. DR MetOSite; P20645; -. DR PhosphoSitePlus; P20645; -. DR SwissPalm; P20645; -. DR BioMuta; M6PR; -. DR DMDM; 127293; -. DR CPTAC; CPTAC-1308; -. DR jPOST; P20645; -. DR MassIVE; P20645; -. DR PaxDb; 9606-ENSP00000000412; -. DR PeptideAtlas; P20645; -. DR ProteomicsDB; 53769; -. DR Pumba; P20645; -. DR Antibodypedia; 11573; 308 antibodies from 35 providers. DR DNASU; 4074; -. DR Ensembl; ENST00000000412.8; ENSP00000000412.3; ENSG00000003056.9. DR Ensembl; ENST00000891555.1; ENSP00000561614.1; ENSG00000003056.9. DR Ensembl; ENST00000891556.1; ENSP00000561615.1; ENSG00000003056.9. DR Ensembl; ENST00000891557.1; ENSP00000561616.1; ENSG00000003056.9. DR Ensembl; ENST00000891558.1; ENSP00000561617.1; ENSG00000003056.9. DR Ensembl; ENST00000936872.1; ENSP00000606931.1; ENSG00000003056.9. DR Ensembl; ENST00000941063.1; ENSP00000611122.1; ENSG00000003056.9. DR Ensembl; ENST00000941065.1; ENSP00000611124.1; ENSG00000003056.9. DR GeneID; 4074; -. DR KEGG; hsa:4074; -. DR MANE-Select; ENST00000000412.8; ENSP00000000412.3; NM_002355.4; NP_002346.1. DR UCSC; uc001qvf.4; human. DR AGR; HGNC:6752; -. DR ClinPGx; PA30513; -. DR CTD; 4074; -. DR DisGeNET; 4074; -. DR GeneCards; M6PR; -. DR HGNC; HGNC:6752; M6PR. DR HPA; ENSG00000003056; Low tissue specificity. DR MIM; 154540; gene. DR OpenTargets; ENSG00000003056; -. DR VEuPathDB; HostDB:ENSG00000003056; -. DR eggNOG; ENOG502QTJ5; Eukaryota. DR GeneTree; ENSGT00390000002109; -. DR HOGENOM; CLU_058440_0_0_1; -. DR InParanoid; P20645; -. DR OMA; ACPLVMK; -. DR OrthoDB; 29460at2759; -. DR PAN-GO; P20645; 4 GO annotations based on evolutionary models. DR PhylomeDB; P20645; -. DR PathwayCommons; P20645; -. DR Reactome; R-HSA-432720; Lysosome Vesicle Biogenesis. DR Reactome; R-HSA-6811440; Retrograde transport at the Trans-Golgi-Network. DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis. DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis. DR Reactome; R-HSA-9840310; Glycosphingolipid catabolism. DR SignaLink; P20645; -. DR SIGNOR; P20645; -. DR Agora; ENSG00000003056; -. DR BioGRID-ORCS; 4074; 11 hits in 1165 CRISPR screens. DR ChiTaRS; M6PR; human. DR EvolutionaryTrace; P20645; -. DR GeneWiki; Cation-dependent_mannose-6-phosphate_receptor; -. DR GenomeRNAi; 4074; -. DR Pharos; P20645; Tbio. DR PRO; PR:P20645; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P20645; protein. DR Bgee; ENSG00000003056; Expressed in monocyte and 208 other cell types or tissues. DR ExpressionAtlas; P20645; baseline and differential. DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome. DR GO; GO:0005829; C:cytosol; IEA:GOC. DR GO; GO:0005768; C:endosome; IDA:MGI. DR GO; GO:0005770; C:late endosome; IBA:GO_Central. DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central. DR GO; GO:0032588; C:trans-Golgi network membrane; TAS:Reactome. DR GO; GO:0030133; C:transport vesicle; TAS:Reactome. DR GO; GO:0038024; F:cargo receptor activity; IDA:UniProtKB. DR GO; GO:0019904; F:protein domain specific binding; IEA:InterPro. DR GO; GO:1905394; F:retromer complex binding; IMP:ParkinsonsUK-UCL. DR GO; GO:0046479; P:glycosphingolipid catabolic process; TAS:Reactome. DR GO; GO:0090160; P:Golgi to lysosome transport; IDA:UniProtKB. DR GO; GO:0007041; P:lysosomal transport; ISS:UniProtKB. DR GO; GO:0006622; P:protein targeting to lysosome; IBA:GO_Central. DR FunFam; 2.70.130.10:FF:000008; Cation-dependent mannose-6-phosphate receptor; 1. DR Gene3D; 2.70.130.10; Mannose-6-phosphate receptor binding domain; 1. DR InterPro; IPR028927; Man-6-P_rcpt. DR InterPro; IPR000296; Man-6-P_rcpt_cation_dep. DR InterPro; IPR009011; Man6P_isomerase_rcpt-bd_dom_sf. DR InterPro; IPR044865; MRH_dom. DR PANTHER; PTHR15071:SF29; CATION-DEPENDENT MANNOSE-6-PHOSPHATE RECEPTOR; 1. DR PANTHER; PTHR15071; MANNOSE-6-PHOSPHATE RECEPTOR FAMILY MEMBER; 1. DR Pfam; PF02157; Man-6-P_recep; 1. DR PRINTS; PR00715; MAN6PRECEPTR. DR SUPFAM; SSF50911; Mannose 6-phosphate receptor domain; 1. DR PROSITE; PS51914; MRH; 1. PE 1: Evidence at protein level; KW 3D-structure; Disulfide bond; Glycoprotein; Lysosome; Membrane; KW Phosphoprotein; Proteomics identification; Receptor; Reference proteome; KW Signal; Transmembrane; Transmembrane helix; Transport. FT SIGNAL 1..26 FT CHAIN 27..277 FT /note="Cation-dependent mannose-6-phosphate receptor" FT /id="PRO_0000019226" FT TOPO_DOM 27..185 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 186..210 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 211..277 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 30..181 FT /note="MRH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01262" FT REGION 256..277 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 267 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P24668" FT CARBOHYD 57 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 83 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 94 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 107 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 113 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 32..78 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01262" FT DISULFID 132..167 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01262" FT DISULFID 145..179 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01262" SQ SEQUENCE 277 AA; 30993 MW; 1093FE25DEB6C8E8 CRC64; MFPFYSCWRT GLLLLLLAVA VRESWQTEEK TCDLVGEKGK ESEKELALVK RLKPLFNKSF ESTVGQGSDT YIYIFRVCRE AGNHTSGAGL VQINKSNGKE TVVGRLNETH IFNGSNWIML IYKGGDEYDN HCGKEQRRAV VMISCNRHTL ADNFNPVSEE RGKVQDCFYL FEMDSSLACS PEISHLSVGS ILLVTFASLV AVYVVGGFLY QRLVVGAKGM EQFPHLAFWQ DLGNLVADGC DFVCRSKPRN VPAAYRGVGD DQLGEESEER DDHLLPM //