AMRP_HUMAN
ID AMRP_HUMAN Reviewed; 357 AA.
AC P30533; D3DVR9; Q2M310; Q53HQ3; Q53HS6;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Alpha-2-macroglobulin receptor-associated protein {ECO:0000305};
DE Short=Alpha-2-MRAP;
DE AltName: Full=Low density lipoprotein receptor-related protein-associated protein 1;
DE Short=RAP;
DE Flags: Precursor;
GN Name=LRPAP1 {ECO:0000312|HGNC:HGNC:6701}; Synonyms=A2MRAP;
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], PROTEIN SEQUENCE OF 183-195 AND 257-272, AND
RP INTERACTION WITH LRP1.
RC TISSUE=Placenta;
RX PubMed=1712782; DOI=10.1016/s0021-9258(18)98848-4;
RA Strickland D.K., Ashcom J.D., Williams S., Battey F., Behre E., McTigue K.,
RA Battey J.F., Argraves W.S.;
RT "Primary structure of alpha 2-macroglobulin receptor-associated protein.
RT Human homologue of a Heymann nephritis antigen.";
RL J. Biol. Chem. 266:13364-13369(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT MET-311.
RX PubMed=9782079; DOI=10.1006/geno.1998.5413;
RA Van Leuven F., Thiry E., Stas L., Nelissen B.;
RT "Analysis of the human LRPAP1 gene coding for the lipoprotein receptor-
RT associated protein: identification of 22 polymorphisms and one mutation.";
RL Genomics 52:145-151(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adipose tissue;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 204-250.
RX PubMed=7789983; DOI=10.1016/0888-7543(95)80050-v;
RA Van Leuven F., Hilliker C., Serneels L., Umans L., Overbergh L.,
RA Strooper B., Fryns J.-P., Van den Berghe H.;
RT "Cloning, characterization, and chromosomal localization to 4p16 of the
RT human gene (LRPAP1) coding for the alpha 2-macroglobulin receptor-
RT associated protein and structural comparison with the murine gene coding
RT for the 44-kDa heparin-binding protein.";
RL Genomics 25:492-500(1995).
RN [8]
RP CHARACTERIZATION, AND INTERACTION WITH LRP1 AND LRP2.
RX PubMed=1400426; DOI=10.1016/s0021-9258(19)36811-5;
RA Kounnas M.Z., Argraves W.S., Strickland D.K.;
RT "The 39-kDa receptor-associated protein interacts with two members of the
RT low density lipoprotein receptor family, alpha 2-macroglobulin receptor and
RT glycoprotein 330.";
RL J. Biol. Chem. 267:21162-21166(1992).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH LRP1, MOTIF, AND
RP GLYCOSYLATION.
RX PubMed=7774585; DOI=10.1002/j.1460-2075.1995.tb07221.x;
RA Bu G., Geuze H.J., Strous G.J., Schwartz A.L.;
RT "39 kDa receptor-associated protein is an ER resident protein and molecular
RT chaperone for LDL receptor-related protein.";
RL EMBO J. 14:2269-2280(1995).
RN [10]
RP INTERACTION WITH SORL1.
RX PubMed=8940146; DOI=10.1074/jbc.271.49.31379;
RA Jacobsen L., Madsen P., Moestrup S.K., Lund A.H., Tommerup N., Nykjaer A.,
RA Sottrup-Jensen L., Gliemann J., Petersen C.M.;
RT "Molecular characterization of a novel human hybrid-type receptor that
RT binds the alpha2-macroglobulin receptor-associated protein.";
RL J. Biol. Chem. 271:31379-31383(1996).
RN [11]
RP INTERACTION WITH SORL1.
RX PubMed=11294867; DOI=10.1074/jbc.m100857200;
RA Jacobsen L., Madsen P., Jacobsen C., Nielsen M.S., Gliemann J.,
RA Petersen C.M.;
RT "Activation and functional characterization of the mosaic receptor
RT SorLA/LR11.";
RL J. Biol. Chem. 276:22788-22796(2001).
RN [12]
RP INTERACTION WITH LRP1B, AND SUBCELLULAR LOCATION.
RX PubMed=11384978; DOI=10.1074/jbc.m102727200;
RA Liu C.-X., Li Y., Obermoeller-McCormick L.M., Schwartz A.L., Bu G.;
RT "The putative tumor suppressor LRP1B, a novel member of the low density
RT lipoprotein (LDL) receptor family, exhibits both overlapping and distinct
RT properties with the LDL receptor-related protein.";
RL J. Biol. Chem. 276:28889-28896(2001).
RN [13]
RP INTERACTION WITH SORL1.
RX PubMed=12530537; DOI=10.1515/bc.2002.193;
RA Lintzel J., Franke I., Riedel I.B., Schaller H.C., Hampe W.;
RT "Characterization of the VPS10 domain of SorLA/LR11 as binding site for the
RT neuropeptide HA.";
RL Biol. Chem. 383:1727-1733(2002).
RN [14]
RP INTERACTION WITH LRP1 AND SORL1.
RX PubMed=15053742; DOI=10.1042/bj20040149;
RA Gliemann J., Hermey G., Nykjaer A., Petersen C.M., Jacobsen C.,
RA Andreasen P.A.;
RT "The mosaic receptor sorLA/LR11 binds components of the plasminogen-
RT activating system and platelet-derived growth factor-BB similarly to LRP1
RT (low-density lipoprotein receptor-related protein), but mediates slow
RT internalization of bound ligand.";
RL Biochem. J. 381:203-212(2004).
RN [15]
RP INTERACTION WITH SORL1.
RX PubMed=15364913; DOI=10.1074/jbc.m408873200;
RA Westergaard U.B., Soerensen E.S., Hermey G., Nielsen M.S., Nykjaer A.,
RA Kirkegaard K., Jacobsen C., Gliemann J., Madsen P., Petersen C.M.;
RT "Functional organization of the sortilin Vps10p domain.";
RL J. Biol. Chem. 279:50221-50229(2004).
RN [16]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-268.
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 [17]
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 [18]
RP INVOLVEMENT IN MYP23.
RX PubMed=23830514; DOI=10.1016/j.ajhg.2013.06.002;
RA Aldahmesh M.A., Khan A.O., Alkuraya H., Adly N., Anazi S., Al-Saleh A.A.,
RA Mohamed J.Y., Hijazi H., Prabakaran S., Tacke M., Al-Khrashi A., Hashem M.,
RA Reinheckel T., Assiri A., Alkuraya F.S.;
RT "Mutations in LRPAP1 are associated with severe myopia in humans.";
RL Am. J. Hum. Genet. 93:313-320(2013).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-248, AND IDENTIFICATION BY
RP 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 [20]
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).
RN [21]
RP INTERACTION WITH SORL1.
RX PubMed=26858303; DOI=10.1128/mcb.00917-15;
RA Larsen J.V., Kristensen A.M., Pallesen L.T., Bauer J., Vaegter C.B.,
RA Nielsen M.S., Madsen P., Petersen C.M.;
RT "Cytokine-like factor 1, an essential facilitator of cardiotrophin-like
RT cytokine:ciliary neurotrophic factor receptor alpha signaling and sorLA-
RT mediated turnover.";
RL Mol. Cell. Biol. 36:1272-1286(2016).
RN [22]
RP INTERACTION WITH LRP1, MUTAGENESIS OF LYS-290 AND LYS-304, AND FUNCTION.
RX PubMed=32296178; DOI=10.1038/s41586-020-2156-5;
RA Rauch J.N., Luna G., Guzman E., Challis C., Sibih Y.E., Leshuk C.,
RA Hernandez I., Wegmann S., Hyman B.T., Gradinaru V., Kampmann M.,
RA Kosik K.S.;
RT "LRP1 is a master regulator of tau uptake and spread.";
RL Nature 580:381-385(2020).
RN [23]
RP STRUCTURE BY NMR OF 51-131.
RX PubMed=9207124; DOI=10.1073/pnas.94.14.7521;
RA Nielsen P.R., Ellgaard L., Etzerodt M., Thoegersen H.C., Poulsen F.M.;
RT "The solution structure of the N-terminal domain of alpha2-macroglobulin
RT receptor-associated protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:7521-7525(1997).
RN [24]
RP STRUCTURE BY NMR OF 51-132.
RX PubMed=12766414; DOI=10.1023/a:1023534107920;
RA Wu Y., Migliorini M., Yu P., Strickland D.K., Wang Y.-X.;
RT "1H, 13C and 15N resonance assignments of domain 1 of receptor associated
RT protein.";
RL J. Biomol. NMR 26:187-188(2003).
RN [25]
RP STRUCTURE BY NMR OF 51-131 IN COMPLEX WITH LRP1.
RX PubMed=16938309; DOI=10.1016/j.jmb.2006.07.013;
RA Jensen G.A., Andersen O.M.J.J., Bonvin A.M., Bjerrum-Bohr I., Etzerodt M.,
RA Thoegersen H.C., O'Shea C., Poulsen F.M., Kragelund B.B.;
RT "Binding site structure of one LRP-RAP complex: implications for a common
RT ligand-receptor binding motif.";
RL J. Mol. Biol. 362:700-716(2006).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.26 ANGSTROMS) OF 250-357 IN COMPLEX WITH LDLR, AND
RP INTERACTION WITH LDLR.
RX PubMed=16630895; DOI=10.1016/j.molcel.2006.02.021;
RA Fisher C., Beglova N., Blacklow S.C.;
RT "Structure of an LDLR-RAP complex reveals a general mode for ligand
RT recognition by lipoprotein receptors.";
RL Mol. Cell 22:277-283(2006).
RN [27]
RP STRUCTURE BY NMR OF 240-357, INTERACTION WITH LRP1, SUBCELLULAR LOCATION,
RP GLYCOSYLATION, AND MUTAGENESIS OF HIS-283; HIS-291; HIS-293; HIS-302;
RP HIS-307 AND HIS-341.
RX PubMed=16678114; DOI=10.1016/j.molcel.2006.04.011;
RA Lee D., Walsh J.D., Mikhailenko I., Yu P., Migliorini M., Wu Y.,
RA Krueger S., Curtis J.E., Harris B., Lockett S., Blacklow S.C.,
RA Strickland D.K., Wang Y.-X.;
RT "RAP uses a histidine switch to regulate its interaction with LRP in the ER
RT and Golgi.";
RL Mol. Cell 22:423-430(2006).
CC -!- FUNCTION: Molecular chaperone for LDL receptor-related proteins that
CC may regulate their ligand binding activity along the secretory pathway.
CC {ECO:0000269|PubMed:32296178, ECO:0000269|PubMed:7774585}.
CC -!- SUBUNIT: Interacts with the LRP1/alpha-2-macroglobulin receptor heavy
CC and light chains; the interaction is transient and coincides with a
CC reduction of ligand binding by the receptor (PubMed:1712782,
CC PubMed:1400426, PubMed:7774585, PubMed:16938309, PubMed:16678114,
CC PubMed:32296178). Interacts with LRP2/glycoprotein 330
CC (PubMed:1400426). Interacts with LRP1B; binding is followed by
CC internalization and degradation (PubMed:11384978). Interacts with LDLR
CC (PubMed:16630895). Interacts with SORL1 (PubMed:8940146,
CC PubMed:11294867, PubMed:12530537, PubMed:15053742, PubMed:15364913,
CC PubMed:26858303). Interacts with LRP1; this interaction is followed by
CC rapid internalization (PubMed:15053742). {ECO:0000269|PubMed:11294867,
CC ECO:0000269|PubMed:11384978, ECO:0000269|PubMed:12530537,
CC ECO:0000269|PubMed:1400426, ECO:0000269|PubMed:15053742,
CC ECO:0000269|PubMed:15364913, ECO:0000269|PubMed:16630895,
CC ECO:0000269|PubMed:16678114, ECO:0000269|PubMed:16938309,
CC ECO:0000269|PubMed:1712782, ECO:0000269|PubMed:26858303,
CC ECO:0000269|PubMed:32296178, ECO:0000269|PubMed:7774585,
CC ECO:0000269|PubMed:8940146}.
CC -!- INTERACTION:
CC P30533; P05067: APP; NbExp=3; IntAct=EBI-715927, EBI-77613;
CC P30533; Q12797-6: ASPH; NbExp=3; IntAct=EBI-715927, EBI-12092171;
CC P30533; P01130: LDLR; NbExp=3; IntAct=EBI-715927, EBI-988319;
CC P30533; Q07954: LRP1; NbExp=4; IntAct=EBI-715927, EBI-1046087;
CC P30533; Q92673: SORL1; NbExp=4; IntAct=EBI-715927, EBI-1171329;
CC P30533; Q99523: SORT1; NbExp=5; IntAct=EBI-715927, EBI-1057058;
CC P30533; P98155: VLDLR; NbExp=5; IntAct=EBI-715927, EBI-9004309;
CC -!- SUBCELLULAR LOCATION: Rough endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:7774585}. Endoplasmic reticulum-Golgi intermediate
CC compartment lumen {ECO:0000269|PubMed:7774585}. Golgi apparatus, cis-
CC Golgi network {ECO:0000269|PubMed:7774585}. Golgi apparatus lumen
CC {ECO:0000269|PubMed:7774585}. Endosome lumen
CC {ECO:0000269|PubMed:7774585}. Cell surface
CC {ECO:0000269|PubMed:11384978}. Note=May be associated with receptors at
CC the cell surface. {ECO:0000269|PubMed:11384978}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:16678114,
CC ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:7774585}.
CC -!- DISEASE: Myopia 23, autosomal recessive (MYP23) [MIM:615431]: A
CC refractive error of the eye, in which parallel rays from a distant
CC object come to focus in front of the retina, vision being better for
CC near objects than for far. {ECO:0000269|PubMed:23830514}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the alpha-2-MRAP family. {ECO:0000305}.
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DR EMBL; M63959; AAA51553.1; -; mRNA.
DR EMBL; AF035767; AAC67373.1; -; Genomic_DNA.
DR EMBL; AF035760; AAC67373.1; JOINED; Genomic_DNA.
DR EMBL; AF035761; AAC67373.1; JOINED; Genomic_DNA.
DR EMBL; AF035762; AAC67373.1; JOINED; Genomic_DNA.
DR EMBL; AF035763; AAC67373.1; JOINED; Genomic_DNA.
DR EMBL; AF035764; AAC67373.1; JOINED; Genomic_DNA.
DR EMBL; AF035765; AAC67373.1; JOINED; Genomic_DNA.
DR EMBL; AF035766; AAC67373.1; JOINED; Genomic_DNA.
DR EMBL; AK222504; BAD96224.1; -; mRNA.
DR EMBL; AK222527; BAD96247.1; -; mRNA.
DR EMBL; AL590235; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471131; EAW82460.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82461.1; -; Genomic_DNA.
DR EMBL; BC105074; AAI05075.1; -; mRNA.
DR EMBL; BC112067; AAI12068.1; -; mRNA.
DR EMBL; U06976; AAA87889.1; -; Genomic_DNA.
DR CCDS; CCDS3371.1; -.
DR PIR; A39875; A39875.
DR RefSeq; NP_002328.1; NM_002337.3.
DR PDB; 1LRE; NMR; -; A=51-131.
DR PDB; 1NRE; NMR; -; A=51-131.
DR PDB; 1OP1; NMR; -; A=51-132.
DR PDB; 1OV2; NMR; -; A=35-133.
DR PDB; 2FCW; X-ray; 1.26 A; A=249-357.
DR PDB; 2FTU; NMR; -; A=240-357.
DR PDB; 2FYL; NMR; -; A=51-131.
DR PDB; 2P01; NMR; -; A=35-357.
DR PDB; 2P03; NMR; -; A=35-357.
DR PDBsum; 1LRE; -.
DR PDBsum; 1NRE; -.
DR PDBsum; 1OP1; -.
DR PDBsum; 1OV2; -.
DR PDBsum; 2FCW; -.
DR PDBsum; 2FTU; -.
DR PDBsum; 2FYL; -.
DR PDBsum; 2P01; -.
DR PDBsum; 2P03; -.
DR AlphaFoldDB; P30533; -.
DR BMRB; P30533; -.
DR SMR; P30533; -.
DR BioGRID; 110221; 149.
DR DIP; DIP-39355N; -.
DR IntAct; P30533; 36.
DR MINT; P30533; -.
DR STRING; 9606.ENSP00000421922; -.
DR GlyConnect; 1004; 12 N-Linked glycans (1 site).
DR GlyGen; P30533; 2 sites, 11 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; P30533; -.
DR PhosphoSitePlus; P30533; -.
DR BioMuta; LRPAP1; -.
DR DMDM; 231539; -.
DR EPD; P30533; -.
DR jPOST; P30533; -.
DR MassIVE; P30533; -.
DR MaxQB; P30533; -.
DR PaxDb; P30533; -.
DR PeptideAtlas; P30533; -.
DR PRIDE; P30533; -.
DR ProteomicsDB; 54716; -.
DR TopDownProteomics; P30533; -.
DR Antibodypedia; 1334; 500 antibodies from 32 providers.
DR DNASU; 4043; -.
DR Ensembl; ENST00000650182.1; ENSP00000497444.1; ENSG00000163956.13.
DR GeneID; 4043; -.
DR KEGG; hsa:4043; -.
DR MANE-Select; ENST00000650182.1; ENSP00000497444.1; NM_002337.4; NP_002328.1.
DR UCSC; uc003ghh.5; human.
DR CTD; 4043; -.
DR DisGeNET; 4043; -.
DR GeneCards; LRPAP1; -.
DR HGNC; HGNC:6701; LRPAP1.
DR HPA; ENSG00000163956; Low tissue specificity.
DR MalaCards; LRPAP1; -.
DR MIM; 104225; gene.
DR MIM; 615431; phenotype.
DR neXtProt; NX_P30533; -.
DR OpenTargets; ENSG00000163956; -.
DR Orphanet; 98619; Rare isolated myopia.
DR PharmGKB; PA30458; -.
DR VEuPathDB; HostDB:ENSG00000163956; -.
DR eggNOG; KOG3956; Eukaryota.
DR GeneTree; ENSGT00390000004855; -.
DR HOGENOM; CLU_064512_0_0_1; -.
DR InParanoid; P30533; -.
DR OMA; LHSKHAE; -.
DR OrthoDB; 908725at2759; -.
DR PhylomeDB; P30533; -.
DR TreeFam; TF320678; -.
DR PathwayCommons; P30533; -.
DR SignaLink; P30533; -.
DR BioGRID-ORCS; 4043; 13 hits in 1074 CRISPR screens.
DR ChiTaRS; LRPAP1; human.
DR EvolutionaryTrace; P30533; -.
DR GeneWiki; LDL-receptor-related_protein_associated_protein; -.
DR GenomeRNAi; 4043; -.
DR Pharos; P30533; Tbio.
DR PRO; PR:P30533; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P30533; protein.
DR Bgee; ENSG00000163956; Expressed in stromal cell of endometrium and 206 other tissues.
DR ExpressionAtlas; P30533; baseline and differential.
DR Genevisible; P30533; HS.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005801; C:cis-Golgi network; IDA:UniProtKB.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0031904; C:endosome lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; TAS:ParkinsonsUK-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005796; C:Golgi lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0048237; C:rough endoplasmic reticulum lumen; IDA:UniProtKB.
DR GO; GO:0001540; F:amyloid-beta binding; TAS:ARUK-UCL.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0035473; F:lipase binding; IBA:GO_Central.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IDA:UniProtKB.
DR GO; GO:0048019; F:receptor antagonist activity; IDA:BHF-UCL.
DR GO; GO:0048018; F:receptor ligand activity; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ParkinsonsUK-UCL.
DR GO; GO:0070326; F:very-low-density lipoprotein particle receptor binding; IPI:BHF-UCL.
DR GO; GO:0150093; P:amyloid-beta clearance by transcytosis; IMP:ARUK-UCL.
DR GO; GO:1900116; P:extracellular negative regulation of signal transduction; TAS:ParkinsonsUK-UCL.
DR GO; GO:1900222; P:negative regulation of amyloid-beta clearance; IGI:BHF-UCL.
DR GO; GO:0060548; P:negative regulation of cell death; IGI:ARUK-UCL.
DR GO; GO:0032091; P:negative regulation of protein binding; IDA:BHF-UCL.
DR GO; GO:0002091; P:negative regulation of receptor internalization; IGI:ARUK-UCL.
DR GO; GO:0010916; P:negative regulation of very-low-density lipoprotein particle clearance; IDA:BHF-UCL.
DR GO; GO:1900223; P:positive regulation of amyloid-beta clearance; TAS:ARUK-UCL.
DR GO; GO:0048259; P:regulation of receptor-mediated endocytosis; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IDA:UniProtKB.
DR CDD; cd14806; RAP_D1; 1.
DR CDD; cd14807; RAP_D2; 1.
DR CDD; cd14808; RAP_D3; 1.
DR Gene3D; 1.20.81.10; -; 3.
DR InterPro; IPR038003; A2-macroglobuin_RAP.
DR InterPro; IPR010483; Alpha_2_MRAP_C.
DR InterPro; IPR009066; MG_RAP_rcpt_1.
DR InterPro; IPR038001; RAP_D2.
DR InterPro; IPR037999; RAP_D3.
DR InterPro; IPR036744; RAP_sf.
DR PANTHER; PTHR16560; PTHR16560; 1.
DR Pfam; PF06401; Alpha-2-MRAP_C; 1.
DR Pfam; PF06400; Alpha-2-MRAP_N; 1.
DR SUPFAM; SSF47045; SSF47045; 3.
DR PROSITE; PS00014; ER_TARGET; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Direct protein sequencing;
KW Endoplasmic reticulum; Endosome; Glycoprotein; Golgi apparatus;
KW Heparin-binding; Phosphoprotein; Reference proteome; Signal.
FT SIGNAL 1..34
FT /evidence="ECO:0000255"
FT CHAIN 35..357
FT /note="Alpha-2-macroglobulin receptor-associated protein"
FT /id="PRO_0000020724"
FT REGION 32..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 237..353
FT /note="LDL receptor binding"
FT /evidence="ECO:0000255"
FT COILED 219..310
FT /evidence="ECO:0000255"
FT MOTIF 354..357
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000269|PubMed:7774585"
FT COMPBIAS 36..52
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99068"
FT MOD_RES 135
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55302"
FT MOD_RES 248
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 268
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT VARIANT 114
FT /note="N -> S (in dbSNP:rs2228158)"
FT /id="VAR_050660"
FT VARIANT 311
FT /note="V -> M (in dbSNP:rs1800493)"
FT /evidence="ECO:0000269|PubMed:9782079"
FT /id="VAR_011821"
FT MUTAGEN 283
FT /note="H->A: Strongly reduced interaction with LRP1; when
FT associated with A-291; A-293; A-302; A-307 and A-341."
FT /evidence="ECO:0000269|PubMed:16678114"
FT MUTAGEN 290
FT /note="K->A: Reduces competition with MAPT for binding to
FT LRP1; when associated with A-304."
FT /evidence="ECO:0000269|PubMed:32296178"
FT MUTAGEN 291
FT /note="H->A: Strongly reduced interaction with LRP1; when
FT associated with A-283; A-293; A-302; A-307 and A-341."
FT /evidence="ECO:0000269|PubMed:16678114"
FT MUTAGEN 293
FT /note="H->A: Strongly reduced interaction with LRP1; when
FT associated with A-283; A-291; A-302; A-307 and A-341."
FT /evidence="ECO:0000269|PubMed:16678114"
FT MUTAGEN 302
FT /note="H->A: Strongly reduced interaction with LRP1; when
FT associated with A-283; A-291; A-293; A-307 and A-341."
FT /evidence="ECO:0000269|PubMed:16678114"
FT MUTAGEN 304
FT /note="K->A: Reduces competition with MAPT for binding to
FT LRP1; when associated with A-290."
FT /evidence="ECO:0000269|PubMed:32296178"
FT MUTAGEN 307
FT /note="H->A: Strongly reduced interaction with LRP1; when
FT associated with A-283; A-291; A-293; A-302 and A-341."
FT /evidence="ECO:0000269|PubMed:16678114"
FT MUTAGEN 341
FT /note="H->A: Strongly reduced interaction with LRP1; when
FT associated with A-283; A-291; A-293; A-302 and A-307."
FT /evidence="ECO:0000269|PubMed:16678114"
FT CONFLICT 100
FT /note="G -> D (in Ref. 3; BAD96247)"
FT /evidence="ECO:0000305"
FT CONFLICT 183
FT /note="V -> A (in Ref. 3; BAD96224)"
FT /evidence="ECO:0000305"
FT CONFLICT 339
FT /note="K -> M (in Ref. 3; BAD96247)"
FT /evidence="ECO:0000305"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:1LRE"
FT HELIX 57..68
FT /evidence="ECO:0007829|PDB:1LRE"
FT HELIX 73..99
FT /evidence="ECO:0007829|PDB:1LRE"
FT HELIX 107..122
FT /evidence="ECO:0007829|PDB:1LRE"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:1NRE"
FT STRAND 127..130
FT /evidence="ECO:0007829|PDB:1OP1"
FT HELIX 149..161
FT /evidence="ECO:0007829|PDB:2P01"
FT HELIX 166..195
FT /evidence="ECO:0007829|PDB:2P01"
FT STRAND 208..210
FT /evidence="ECO:0007829|PDB:2P01"
FT STRAND 213..216
FT /evidence="ECO:0007829|PDB:2P01"
FT HELIX 217..243
FT /evidence="ECO:0007829|PDB:2P01"
FT STRAND 246..249
FT /evidence="ECO:0007829|PDB:2FTU"
FT HELIX 255..265
FT /evidence="ECO:0007829|PDB:2FCW"
FT HELIX 271..311
FT /evidence="ECO:0007829|PDB:2FCW"
FT TURN 314..316
FT /evidence="ECO:0007829|PDB:2FCW"
FT HELIX 317..353
FT /evidence="ECO:0007829|PDB:2FCW"
SQ SEQUENCE 357 AA; 41466 MW; D56A7DA754125CFA CRC64;
MAPRRVRSFL RGLPALLLLL LFLGPWPAAS HGGKYSREKN QPKPSPKRES GEEFRMEKLN
QLWEKAQRLH LPPVRLAELH ADLKIQERDE LAWKKLKLDG LDEDGEKEAR LIRNLNVILA
KYGLDGKKDA RQVTSNSLSG TQEDGLDDPR LEKLWHKAKT SGKFSGEELD KLWREFLHHK
EKVHEYNVLL ETLSRTEEIH ENVISPSDLS DIKGSVLHSR HTELKEKLRS INQGLDRLRR
VSHQGYSTEA EFEEPRVIDL WDLAQSANLT DKELEAFREE LKHFEAKIEK HNHYQKQLEI
AHEKLRHAES VGDGERVSRS REKHALLEGR TKELGYTVKK HLQDLSGRIS RARHNEL
