ID   AMRP_RAT                Reviewed;         360 AA.
AC   Q99068; Q4FZX8; Q642A1; Q64723;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   06-DEC-2005, sequence version 2.
DT   24-JAN-2024, entry version 153.
DE   RecName: Full=Alpha-2-macroglobulin receptor-associated protein;
DE            Short=Alpha-2-MRAP;
DE   AltName: Full=Gp330-binding 45 kDa protein;
DE   AltName: Full=Low density lipoprotein receptor-related protein-associated protein 1;
DE            Short=RAP;
DE   Flags: Precursor;
GN   Name=Lrpap1;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney, and Placenta;
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   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 4-360.
RC   STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX   PubMed=7681839; DOI=10.1016/s0021-9258(18)53080-5;
RA   Kanalas J.J., Makker S.P.;
RT   "Analysis of a 45-kDa protein that binds to the Heymann nephritis
RT   autoantigen GP330.";
RL   J. Biol. Chem. 268:8188-8192(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 38-360.
RX   PubMed=2408041; DOI=10.1073/pnas.87.5.1811;
RA   Pietromonaco S., Kerjaschki D., Binder S., Ullrich R., Farquhar M.G.;
RT   "Molecular cloning of a cDNA encoding a major pathogenic domain of the
RT   Heymann nephritis antigen gp330.";
RL   Proc. Natl. Acad. Sci. U.S.A. 87:1811-1815(1990).
RN   [4]
RP   PROTEIN SEQUENCE OF 38-51.
RX   PubMed=1718973; DOI=10.1016/s0021-9258(18)54845-6;
RA   Herz J., Goldstein J.L., Strickland D.K., Ho Y.K., Brown M.S.;
RT   "39-kDa protein modulates binding of ligands to low density lipoprotein
RT   receptor-related protein/alpha 2-macroglobulin receptor.";
RL   J. Biol. Chem. 266:21232-21238(1991).
RN   [5]
RP   INTERACTION WITH 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   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-53, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
CC   -!- FUNCTION: Molecular chaperone for LDL receptor-related proteins that
CC       may regulate their ligand binding activity along the secretory pathway.
CC       {ECO:0000250|UniProtKB:P30533}.
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:1400426). Interacts
CC       with LRP2/glycoprotein 330 (PubMed:1400426). Interacts with LRP1B;
CC       binding is followed by internalization and degradation. Interacts with
CC       LDLR (By similarity). Interacts with SORL1 (By similarity). Interacts
CC       with LRP1; this interaction is followed by rapid internalization (By
CC       similarity). {ECO:0000250|UniProtKB:P30533,
CC       ECO:0000269|PubMed:1400426}.
CC   -!- INTERACTION:
CC       Q99068; Q924X6: Lrp8; Xeno; NbExp=2; IntAct=EBI-919734, EBI-432319;
CC       Q99068; P98155: VLDLR; Xeno; NbExp=2; IntAct=EBI-919734, EBI-9004309;
CC   -!- SUBCELLULAR LOCATION: Rough endoplasmic reticulum lumen
CC       {ECO:0000250|UniProtKB:P30533}. Endoplasmic reticulum-Golgi
CC       intermediate compartment lumen {ECO:0000250|UniProtKB:P30533}. Golgi
CC       apparatus, cis-Golgi network {ECO:0000250|UniProtKB:P30533}. Golgi
CC       apparatus lumen {ECO:0000250|UniProtKB:P30533}. Endosome lumen
CC       {ECO:0000250|UniProtKB:P30533}. Cell surface
CC       {ECO:0000250|UniProtKB:P30533}. Note=May be associated with receptors
CC       at the cell surface. {ECO:0000250|UniProtKB:P30533}.
CC   -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P30533}.
CC   -!- SIMILARITY: Belongs to the alpha-2-MRAP family. {ECO:0000305}.
CC   -!- CAUTION: Was originally thought to be Heymann nephritis antigen gp330.
CC       {ECO:0000305|PubMed:2408041}.
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; BC082020; AAH82020.1; -; mRNA.
DR   EMBL; BC098947; AAH98947.1; -; mRNA.
DR   EMBL; Z11994; CAA78040.1; -; mRNA.
DR   EMBL; Z11995; CAA78041.1; -; mRNA.
DR   EMBL; M31051; AAA41269.1; -; mRNA.
DR   PIR; A46646; A46646.
DR   RefSeq; NP_001162584.1; NM_001169113.1.
DR   AlphaFoldDB; Q99068; -.
DR   SMR; Q99068; -.
DR   BioGRID; 250500; 1.
DR   IntAct; Q99068; 5.
DR   MINT; Q99068; -.
DR   STRING; 10116.ENSRNOP00000012665; -.
DR   GlyCosmos; Q99068; 1 site, No reported glycans.
DR   GlyGen; Q99068; 1 site.
DR   iPTMnet; Q99068; -.
DR   PhosphoSitePlus; Q99068; -.
DR   SwissPalm; Q99068; -.
DR   jPOST; Q99068; -.
DR   PaxDb; 10116-ENSRNOP00000012665; -.
DR   Ensembl; ENSRNOT00000012665.6; ENSRNOP00000012665.4; ENSRNOG00000009313.6.
DR   Ensembl; ENSRNOT00055028288; ENSRNOP00055022769; ENSRNOG00055016657.
DR   Ensembl; ENSRNOT00060037713; ENSRNOP00060031105; ENSRNOG00060021781.
DR   Ensembl; ENSRNOT00065054489; ENSRNOP00065044830; ENSRNOG00065031622.
DR   GeneID; 116565; -.
DR   KEGG; rno:116565; -.
DR   AGR; RGD:620700; -.
DR   CTD; 4043; -.
DR   RGD; 620700; Lrpap1.
DR   eggNOG; KOG3956; Eukaryota.
DR   GeneTree; ENSGT00390000004855; -.
DR   HOGENOM; CLU_064512_0_0_1; -.
DR   InParanoid; Q99068; -.
DR   OMA; QEFEHHQ; -.
DR   OrthoDB; 3665554at2759; -.
DR   PhylomeDB; Q99068; -.
DR   TreeFam; TF320678; -.
DR   PRO; PR:Q99068; -.
DR   Proteomes; UP000002494; Chromosome 14.
DR   Bgee; ENSRNOG00000009313; Expressed in adult mammalian kidney and 19 other cell types or tissues.
DR   GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR   GO; GO:0005801; C:cis-Golgi network; ISS:UniProtKB.
DR   GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR   GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISS:UniProtKB.
DR   GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR   GO; GO:0031904; C:endosome lumen; IEA:UniProtKB-SubCell.
DR   GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR   GO; GO:0005796; C:Golgi lumen; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR   GO; GO:0048237; C:rough endoplasmic reticulum lumen; IDA:RGD.
DR   GO; GO:0031982; C:vesicle; IDA:RGD.
DR   GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR   GO; GO:0035473; F:lipase binding; IPI:RGD.
DR   GO; GO:0050750; F:low-density lipoprotein particle receptor binding; ISS:UniProtKB.
DR   GO; GO:0048019; F:receptor antagonist activity; ISO:RGD.
DR   GO; GO:0048018; F:receptor ligand activity; ISO:RGD.
DR   GO; GO:0070326; F:very-low-density lipoprotein particle receptor binding; ISO:RGD.
DR   GO; GO:0150093; P:amyloid-beta clearance by transcytosis; ISO:RGD.
DR   GO; GO:1900222; P:negative regulation of amyloid-beta clearance; ISO:RGD.
DR   GO; GO:0002091; P:negative regulation of receptor internalization; ISO:RGD.
DR   GO; GO:0010916; P:negative regulation of very-low-density lipoprotein particle clearance; ISO:RGD.
DR   GO; GO:0048259; P:regulation of receptor-mediated endocytosis; ISS:UniProtKB.
DR   GO; GO:0007165; P:signal transduction; ISO:RGD.
DR   CDD; cd14806; RAP_D1; 1.
DR   CDD; cd14807; RAP_D2; 1.
DR   CDD; cd14808; RAP_D3; 1.
DR   Gene3D; 1.20.81.10; RAP domain; 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; ALPHA-2-MACROGLOBULIN RECEPTOR-ASSOCIATED PROTEIN; 1.
DR   PANTHER; PTHR16560:SF2; ALPHA-2-MACROGLOBULIN RECEPTOR-ASSOCIATED PROTEIN; 1.
DR   Pfam; PF06401; Alpha-2-MRAP_C; 1.
DR   Pfam; PF06400; Alpha-2-MRAP_N; 1.
DR   SUPFAM; SSF47045; RAP domain-like; 3.
DR   PROSITE; PS00014; ER_TARGET; 1.
DR   Genevisible; Q99068; RN.
PE   1: Evidence at protein level;
KW   Coiled coil; Direct protein sequencing; Endoplasmic reticulum; Endosome;
KW   Glycoprotein; Golgi apparatus; Heparin-binding; Phosphoprotein;
KW   Reference proteome; Signal.
FT   SIGNAL          1..33
FT                   /evidence="ECO:0000255"
FT   CHAIN           34..360
FT                   /note="Alpha-2-macroglobulin receptor-associated protein"
FT                   /id="PRO_0000020726"
FT   REGION          240..356
FT                   /note="LDL receptor binding"
FT                   /evidence="ECO:0000255"
FT   COILED          222..302
FT                   /evidence="ECO:0000255"
FT   MOTIF           357..360
FT                   /note="Prevents secretion from ER"
FT                   /evidence="ECO:0000250|UniProtKB:P30533"
FT   MOD_RES         53
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         138
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P55302"
FT   CARBOHYD        271
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        38..40
FT                   /note="YSR -> RSA (in Ref. 3; AAA41269)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        166..179
FT                   /note="KFSSEELDKLWREF -> ISVRLTSCARV (in Ref. 3)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        248..250
FT                   /note="GYG -> LR (in Ref. 3; AAA41269)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   360 AA;  42032 MW;  C7CF5ECCE1BCC5DC CRC64;
     MAPLRDRVST LPRLQLLVLL LLPLLLVPQP IAGHGGKYSR EKNEPEMAAK RESGEEFRME
     KLNQLWEKAK RLHLSPVRLA ELHSDLKIQE RDELNWKKLK VEGLDGDGEK EAKLVHNLNV
     ILARYGLDGR KDTQTVHSNA LNEDTQDELG DPRLEKLWHK AKTSGKFSSE ELDKLWREFL
     HYKEKIHEYN VLLDTLSRAE EGYENLLSPS DMTHIKSDTL ASKHSELKDR LRSINQGLDR
     LRKVSHQGYG PATEFEEPRV IDLWDLAQSA NFTEKELESF REELKHFEAK IEKHNHYQKQ
     LEISHQKLKH VESIGDPEHI SRNKEKYVLL EEKTKELGYK VKKHLQDLSS RVSRARHNEL
//