AMRP_RAT
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 03-AUG-2022, entry version 146.
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}.
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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 GlyGen; Q99068; 1 site.
DR iPTMnet; Q99068; -.
DR PhosphoSitePlus; Q99068; -.
DR SwissPalm; Q99068; -.
DR jPOST; Q99068; -.
DR PaxDb; Q99068; -.
DR PRIDE; Q99068; -.
DR Ensembl; ENSRNOT00000012665; ENSRNOP00000012665; ENSRNOG00000009313.
DR GeneID; 116565; -.
DR KEGG; rno:116565; -.
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; LHSKHAE; -.
DR OrthoDB; 908725at2759; -.
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 tissues.
DR Genevisible; Q99068; RN.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005801; C:cis-Golgi network; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
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:0005791; C:rough endoplasmic reticulum; IDA: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:0060548; P:negative regulation of cell death; ISO:RGD.
DR GO; GO:0032091; P:negative regulation of protein binding; 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; -; 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 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
