MPRD_HUMAN
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 03-AUG-2022, entry version 201.
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; 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.
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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_002346.1; NM_002355.3.
DR RefSeq; XP_005253433.1; XM_005253376.2.
DR PDB; 1JUQ; X-ray; 2.20 A; E/F/G/H=265-277.
DR PDBsum; 1JUQ; -.
DR AlphaFoldDB; P20645; -.
DR SMR; P20645; -.
DR BioGRID; 110251; 51.
DR ELM; P20645; -.
DR IntAct; P20645; 19.
DR MINT; P20645; -.
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; 1083; 20 N-Linked glycans (2 sites).
DR GlyGen; P20645; 7 sites, 20 N-linked glycans (2 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 EPD; P20645; -.
DR jPOST; P20645; -.
DR MassIVE; P20645; -.
DR MaxQB; P20645; -.
DR PaxDb; P20645; -.
DR PeptideAtlas; P20645; -.
DR PRIDE; P20645; -.
DR ProteomicsDB; 53769; -.
DR Antibodypedia; 11573; 266 antibodies from 31 providers.
DR DNASU; 4074; -.
DR Ensembl; ENST00000000412.8; ENSP00000000412.3; ENSG00000003056.8.
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 CTD; 4074; -.
DR DisGeNET; 4074; -.
DR GeneCards; M6PR; -.
DR HGNC; HGNC:6752; M6PR.
DR HPA; ENSG00000003056; Low tissue specificity.
DR MIM; 154540; gene.
DR neXtProt; NX_P20645; -.
DR OpenTargets; ENSG00000003056; -.
DR PharmGKB; PA30513; -.
DR VEuPathDB; HostDB:ENSG00000003056; -.
DR eggNOG; ENOG502QTJ5; Eukaryota.
DR GeneTree; ENSGT00390000002109; -.
DR HOGENOM; CLU_058440_0_0_1; -.
DR InParanoid; P20645; -.
DR OMA; CKRGVTA; -.
DR OrthoDB; 1214298at2759; -.
DR PhylomeDB; P20645; -.
DR TreeFam; TF328910; -.
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 SignaLink; P20645; -.
DR SIGNOR; P20645; -.
DR BioGRID-ORCS; 4074; 10 hits in 1078 CRISPR screens.
DR ChiTaRS; M6PR; human.
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 206 other tissues.
DR ExpressionAtlas; P20645; baseline and differential.
DR Genevisible; P20645; HS.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005770; C:late endosome; IEA:Ensembl.
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:0019904; F:protein domain specific binding; IEA:InterPro.
DR GO; GO:1905394; F:retromer complex binding; IMP:ParkinsonsUK-UCL.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; TAS:ProtInc.
DR GO; GO:0008333; P:endosome to lysosome transport; TAS:ProtInc.
DR GO; GO:0007041; P:lysosomal transport; ISS:UniProtKB.
DR GO; GO:0006622; P:protein targeting to lysosome; IBA:GO_Central.
DR GO; GO:0006898; P:receptor-mediated endocytosis; TAS:ProtInc.
DR GO; GO:0033299; P:secretion of lysosomal enzymes; IEA:Ensembl.
DR Gene3D; 2.70.130.10; -; 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 Pfam; PF02157; Man-6-P_recep; 1.
DR PRINTS; PR00715; MAN6PRECEPTR.
DR SUPFAM; SSF50911; SSF50911; 1.
DR PROSITE; PS51914; MRH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Glycoprotein; Lysosome; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Signal; Transmembrane;
KW 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
