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Cation-dependent mannose-6-phosphate receptor (CD Man-6-P receptor) (CD-MPR) (46 kDa mannose 6-phosphate receptor) (MPR 46)

 MPRD_HUMAN              Reviewed;         277 AA.
P20645; A8K528; D3DUV5;
01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
01-FEB-1991, sequence version 1.
27-SEP-2017, entry version 170.
RecName: Full=Cation-dependent mannose-6-phosphate receptor;
Short=CD Man-6-P receptor;
Short=CD-MPR;
AltName: Full=46 kDa mannose 6-phosphate receptor;
Short=MPR 46;
Flags: Precursor;
Name=M6PR; Synonyms=MPR46, MPRD;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=2441386; DOI=10.1073/pnas.84.16.5575;
Pohlmann R., Nagel G., Schmidt B., Stein M., Lorkowski G.,
Krentler C., Cully J., Meyer H.E., Grzeschik K.H., Mersmann G.,
Hasilik A., von Figura K.;
"Cloning of a cDNA encoding the human cation-dependent mannose 6-
phosphate-specific receptor.";
Proc. Natl. Acad. Sci. U.S.A. 84:5575-5579(1987).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
TISSUE=Leukocyte;
PubMed=1849818; DOI=10.1111/j.1432-1033.1991.tb15877.x;
Klier H.J., von Figura K., Pohlmann R.;
"Isolation and analysis of the human 46-kDa mannose 6-phosphate
receptor gene.";
Eur. J. Biochem. 197:23-28(1991).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Muscle;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
INTERACTION WITH GGA1 AND GGA3.
PubMed=11387475; DOI=10.1126/science.1060750;
Puertollano R., Aguilar R.C., Gorshkova I., Crouch R.J.,
Bonifacino J.S.;
"Sorting of mannose 6-phosphate receptors mediated by the GGAs.";
Science 292:1712-1716(2001).
[7]
INTERACTION WITH GGA2.
PubMed=11886874; DOI=10.1074/jbc.M201879200;
Doray B., Bruns K., Ghosh P., Kornfeld S.;
"Interaction of the cation-dependent mannose 6-phosphate receptor with
GGA proteins.";
J. Biol. Chem. 277:18477-18482(2002).
[8]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18669648; DOI=10.1073/pnas.0805139105;
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[9]
GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-83 AND ASN-107.
TISSUE=Liver;
PubMed=19159218; DOI=10.1021/pr8008012;
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
"Glycoproteomics analysis of human liver tissue by combination of
multiple enzyme digestion and hydrazide chemistry.";
J. Proteome Res. 8:651-661(2009).
[10]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21269460; DOI=10.1186/1752-0509-5-17;
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
"Initial characterization of the human central proteome.";
BMC Syst. Biol. 5:17-17(2011).
[11]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Liver;
PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
Wang L., Ye M., Zou H.;
"An enzyme assisted RP-RPLC approach for in-depth analysis of human
liver phosphoproteome.";
J. Proteomics 96:253-262(2014).
[12]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=25944712; DOI=10.1002/pmic.201400617;
Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M.,
Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
"N-terminome analysis of the human mitochondrial proteome.";
Proteomics 15:2519-2524(2015).
-!- FUNCTION: Transport of phosphorylated lysosomal enzymes from the
Golgi complex and the cell surface to lysosomes. Lysosomal enzymes
bearing phosphomannosyl residues bind specifically to mannose-6-
phosphate receptors in the Golgi apparatus and the resulting
receptor-ligand complex is transported to an acidic prelyosomal
compartment where the low pH mediates the dissociation of the
complex.
-!- SUBUNIT: Homodimer. Binds GGA1, GGA2 and GGA3.
-!- SUBCELLULAR LOCATION: Lysosome membrane; Single-pass type I
membrane protein.
-!- DOMAIN: The extracellular domain is homologous to the repeating
units (of approximately 147 AA) of the cation-independent mannose
6-phosphate receptor.
-!- MISCELLANEOUS: This receptor has optimal binding in the presence
of divalent cations.
-----------------------------------------------------------------------
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EMBL; M16985; AAA59542.1; -; mRNA.
EMBL; X56254; CAB94715.1; -; Genomic_DNA.
EMBL; X56255; CAB94715.1; JOINED; Genomic_DNA.
EMBL; X56256; CAB94715.1; JOINED; Genomic_DNA.
EMBL; X56257; CAB94715.1; JOINED; Genomic_DNA.
EMBL; AK291143; BAF83832.1; -; mRNA.
EMBL; CH471116; EAW88596.1; -; Genomic_DNA.
EMBL; CH471116; EAW88597.1; -; Genomic_DNA.
EMBL; CH471116; EAW88598.1; -; Genomic_DNA.
EMBL; CH471116; EAW88599.1; -; Genomic_DNA.
EMBL; BC024206; AAH24206.1; -; mRNA.
CCDS; CCDS8598.1; -.
PIR; S15368; A32700.
RefSeq; NP_002346.1; NM_002355.3.
RefSeq; XP_005253433.1; XM_005253376.2.
UniGene; Hs.134084; -.
UniGene; Hs.744902; -.
PDB; 1JUQ; X-ray; 2.20 A; E/F/G/H=265-277.
PDBsum; 1JUQ; -.
ProteinModelPortal; P20645; -.
SMR; P20645; -.
BioGrid; 110251; 26.
ELM; P20645; -.
IntAct; P20645; 7.
MINT; MINT-4999970; -.
STRING; 9606.ENSP00000000412; -.
BindingDB; P20645; -.
ChEMBL; CHEMBL5788; -.
DrugBank; DB02755; 1-3 Sugar Ring of Pentamannosyl 6-Phosphate.
DrugBank; DB01272; Alglucosidase alfa.
DrugBank; DB02900; alpha-D-mannose 6-phosphate.
iPTMnet; P20645; -.
PhosphoSitePlus; P20645; -.
SwissPalm; P20645; -.
BioMuta; M6PR; -.
DMDM; 127293; -.
EPD; P20645; -.
MaxQB; P20645; -.
PaxDb; P20645; -.
PeptideAtlas; P20645; -.
PRIDE; P20645; -.
DNASU; 4074; -.
Ensembl; ENST00000000412; ENSP00000000412; ENSG00000003056.
GeneID; 4074; -.
KEGG; hsa:4074; -.
UCSC; uc001qvf.4; human.
CTD; 4074; -.
DisGeNET; 4074; -.
EuPathDB; HostDB:ENSG00000003056.7; -.
GeneCards; M6PR; -.
HGNC; HGNC:6752; M6PR.
HPA; CAB034464; -.
HPA; HPA040445; -.
MIM; 154540; gene.
neXtProt; NX_P20645; -.
OpenTargets; ENSG00000003056; -.
PharmGKB; PA30513; -.
eggNOG; ENOG410IK0D; Eukaryota.
eggNOG; ENOG4111GED; LUCA.
GeneTree; ENSGT00390000002109; -.
HOGENOM; HOG000013085; -.
HOVERGEN; HBG006395; -.
InParanoid; P20645; -.
KO; K10089; -.
OMA; SDWIMLI; -.
OrthoDB; EOG091G0WP5; -.
PhylomeDB; P20645; -.
TreeFam; TF328910; -.
Reactome; R-HSA-432720; Lysosome Vesicle Biogenesis.
Reactome; R-HSA-6811440; Retrograde transport at the Trans-Golgi-Network.
Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
SIGNOR; P20645; -.
GeneWiki; Cation-dependent_mannose-6-phosphate_receptor; -.
GenomeRNAi; 4074; -.
PRO; PR:P20645; -.
Proteomes; UP000005640; Chromosome 12.
Bgee; ENSG00000003056; -.
CleanEx; HS_M6PR; -.
ExpressionAtlas; P20645; baseline and differential.
Genevisible; P20645; HS.
GO; GO:0030665; C:clathrin-coated vesicle membrane; TAS:Reactome.
GO; GO:0005768; C:endosome; IDA:MGI.
GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
GO; GO:0005770; C:late endosome; IEA:Ensembl.
GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
GO; GO:0016020; C:membrane; IDA:UniProtKB.
GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
GO; GO:0032588; C:trans-Golgi network membrane; TAS:Reactome.
GO; GO:0030133; C:transport vesicle; TAS:Reactome.
GO; GO:0005537; F:mannose binding; IEA:InterPro.
GO; GO:0015578; F:mannose transmembrane transporter activity; IEA:InterPro.
GO; GO:1905394; F:retromer complex binding; IMP:ParkinsonsUK-UCL.
GO; GO:0004888; F:transmembrane signaling receptor activity; TAS:ProtInc.
GO; GO:0008333; P:endosome to lysosome transport; TAS:ProtInc.
GO; GO:0061024; P:membrane organization; TAS:Reactome.
GO; GO:0006898; P:receptor-mediated endocytosis; TAS:ProtInc.
GO; GO:0033299; P:secretion of lysosomal enzymes; IEA:Ensembl.
Gene3D; 2.70.130.10; -; 1.
InterPro; IPR028927; Man-6-P_rcpt.
InterPro; IPR000296; Man-6-P_rcpt_cation_dep.
InterPro; IPR009011; Man6P_isomerase_rcpt-bd_dom.
PANTHER; PTHR15071:SF11; PTHR15071:SF11; 1.
Pfam; PF02157; Man-6-P_recep; 1.
PRINTS; PR00715; MAN6PRECEPTR.
SUPFAM; SSF50911; SSF50911; 1.
1: Evidence at protein level;
3D-structure; Complete proteome; Glycoprotein; Lysosome; Membrane;
Phosphoprotein; Receptor; Reference proteome; Signal; Transmembrane;
Transmembrane helix; Transport.
SIGNAL 1 26
CHAIN 27 277 Cation-dependent mannose-6-phosphate
receptor.
/FTId=PRO_0000019226.
TOPO_DOM 27 185 Lumenal. {ECO:0000255}.
TRANSMEM 186 210 Helical. {ECO:0000255}.
TOPO_DOM 211 277 Cytoplasmic. {ECO:0000255}.
MOD_RES 267 267 Phosphoserine.
{ECO:0000250|UniProtKB:P24668}.
CARBOHYD 57 57 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 83 83 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:19159218}.
CARBOHYD 94 94 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 107 107 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:19159218}.
CARBOHYD 113 113 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
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


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