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P30533 (AMRP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alpha-2-macroglobulin receptor-associated protein

Short name=Alpha-2-MRAP
Alternative name(s):
Low density lipoprotein receptor-related protein-associated protein 1
Short name=RAP
Gene names
Name:LRPAP1
Synonyms:A2MRAP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length357 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Interacts with LRP1/alpha-2-macroglobulin receptor and glycoprotein 330.

Subunit structure

Present on cell surface forming a complex with the alpha-2-macroglobulin receptor heavy and light chains. Binds LRP1B; binding is followed by internalization and degradation.

Subcellular location

Endoplasmic reticulum. Cytoplasm. Cell surface. Note: Intracellular and associated with cell surface receptors. Found in the endoplasmic reticulum. Ref.9 Ref.18

Post-translational modification

N-glycosylated. Ref.18

Involvement in disease

Myopia 23, autosomal recessive (MYP23) [MIM:615431]: A refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13

In complex with the alpha-2-MR or gp330, it may have some role in the pathogenesis of membrane glomerular nephritis.

Sequence similarities

Belongs to the alpha-2-MRAP family.

Ontologies

Keywords
   Cellular componentCytoplasm
Endoplasmic reticulum
   Coding sequence diversityPolymorphism
   DomainCoiled coil
Signal
   LigandHeparin-binding
   PTMGlycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processextracellular negative regulation of signal transduction

Inferred from direct assay PubMed 8083232. Source: GOC

negative regulation of beta-amyloid clearance

Inferred from genetic interaction PubMed 19098903. Source: BHF-UCL

negative regulation of protein binding

Inferred from direct assay PubMed 8083232. Source: BHF-UCL

negative regulation of very-low-density lipoprotein particle clearance

Inferred from direct assay PubMed 8083232. Source: BHF-UCL

protein folding

Traceable author statement PubMed 8654360. Source: ProtInc

receptor-mediated endocytosis

Traceable author statement PubMed 2229028. Source: GOC

vesicle-mediated transport

Traceable author statement PubMed 8654360. Source: ProtInc

   Cellular_componentcell surface

Inferred from electronic annotation. Source: UniProtKB-SubCell

endoplasmic reticulum

Inferred from direct assay. Source: HPA

extracellular region

Inferred from direct assay PubMed 8083232. Source: GOC

integral component of membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Inferred from direct assay PubMed 16263759. Source: MGI

rough endoplasmic reticulum lumen

Inferred from electronic annotation. Source: Ensembl

vesicle

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionasialoglycoprotein receptor activity

Traceable author statement PubMed 2229028. Source: ProtInc

heparin binding

Traceable author statement Ref.1. Source: ProtInc

low-density lipoprotein particle receptor binding

Inferred from direct assay PubMed 16263759. Source: MGI

receptor antagonist activity

Inferred from direct assay PubMed 8083232. Source: BHF-UCL

unfolded protein binding

Traceable author statement PubMed 8654360. Source: ProtInc

very-low-density lipoprotein particle receptor binding

Inferred from physical interaction PubMed 8083232. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

VLDLRP981554EBI-715927,EBI-9004309

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3434 Potential
Chain35 – 357323Alpha-2-macroglobulin receptor-associated protein
PRO_0000020724

Regions

Region237 – 353117LDL receptor binding Potential
Coiled coil219 – 31092 Potential
Motif354 – 3574Prevents secretion from ER Potential

Amino acid modifications

Glycosylation2681N-linked (GlcNAc...) Ref.11

Natural variations

Natural variant1141N → S.
Corresponds to variant rs2228158 [ dbSNP | Ensembl ].
VAR_050660
Natural variant3111V → M. Ref.2
Corresponds to variant rs1800493 [ dbSNP | Ensembl ].
VAR_011821

Experimental info

Mutagenesis2831H → A: Strongly reduced interaction with LRP1; when associated with A-291; A-293; A-302; A-307 and A-341. Ref.18
Mutagenesis2911H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-293; A-302; A-307 and A-341. Ref.18
Mutagenesis2931H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-291; A-302; A-307 and A-341. Ref.18
Mutagenesis3021H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-291; A-293; A-307 and A-341. Ref.18
Mutagenesis3071H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-291; A-293; A-302 and A-341. Ref.18
Mutagenesis3411H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-291; A-293; A-302 and A-307. Ref.18
Sequence conflict1001G → D in BAD96247. Ref.3
Sequence conflict1831V → A in BAD96224. Ref.3
Sequence conflict3391K → M in BAD96247. Ref.3

Secondary structure

............................. 357
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P30533 [UniParc].

Last modified April 1, 1993. Version 1.
Checksum: D56A7DA754125CFA

FASTA35741,466
        10         20         30         40         50         60 
MAPRRVRSFL RGLPALLLLL LFLGPWPAAS HGGKYSREKN QPKPSPKRES GEEFRMEKLN 

        70         80         90        100        110        120 
QLWEKAQRLH LPPVRLAELH ADLKIQERDE LAWKKLKLDG LDEDGEKEAR LIRNLNVILA 

       130        140        150        160        170        180 
KYGLDGKKDA RQVTSNSLSG TQEDGLDDPR LEKLWHKAKT SGKFSGEELD KLWREFLHHK 

       190        200        210        220        230        240 
EKVHEYNVLL ETLSRTEEIH ENVISPSDLS DIKGSVLHSR HTELKEKLRS INQGLDRLRR 

       250        260        270        280        290        300 
VSHQGYSTEA EFEEPRVIDL WDLAQSANLT DKELEAFREE LKHFEAKIEK HNHYQKQLEI 

       310        320        330        340        350 
AHEKLRHAES VGDGERVSRS REKHALLEGR TKELGYTVKK HLQDLSGRIS RARHNEL 

« Hide

References

« Hide 'large scale' references
[1]"Primary structure of alpha 2-macroglobulin receptor-associated protein. Human homologue of a Heymann nephritis antigen."
Strickland D.K., Ashcom J.D., Williams S., Battey F., Behre E., McTigue K., Battey J.F., Argraves W.S.
J. Biol. Chem. 266:13364-13369(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 183-195 AND 257-272.
Tissue: Placenta.
[2]"Analysis of the human LRPAP1 gene coding for the lipoprotein receptor-associated protein: identification of 22 polymorphisms and one mutation."
Van Leuven F., Thiry E., Stas L., Nelissen B.
Genomics 52:145-151(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT MET-311.
[3]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Adipose tissue.
[4]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]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. expand/collapse author list , 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
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[7]"Cloning, characterization, and chromosomal localization to 4p16 of the human gene (LRPAP1) coding for the alpha 2-macroglobulin receptor-associated protein and structural comparison with the murine gene coding for the 44-kDa heparin-binding protein."
Van Leuven F., Hilliker C., Serneels L., Umans L., Overbergh L., Strooper B., Fryns J.-P., Van den Berghe H.
Genomics 25:492-500(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 204-250.
[8]"The 39-kDa receptor-associated protein interacts with two members of the low density lipoprotein receptor family, alpha 2-macroglobulin receptor and glycoprotein 330."
Kounnas M.Z., Argraves W.S., Strickland D.K.
J. Biol. Chem. 267:21162-21166(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[9]"39 kDa receptor-associated protein is an ER resident protein and molecular chaperone for LDL receptor-related protein."
Bu G., Geuze H.J., Strous G.J., Schwartz A.L.
EMBO J. 14:2269-2280(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH LRP1.
[10]"The putative tumor suppressor LRP1B, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein."
Liu C.-X., Li Y., Obermoeller-McCormick L.M., Schwartz A.L., Bu G.
J. Biol. Chem. 276:28889-28896(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LRP1B.
[11]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-268.
Tissue: Liver.
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Mutations in LRPAP1 are associated with severe myopia in humans."
Aldahmesh M.A., Khan A.O., Alkuraya H., Adly N., Anazi S., Al-Saleh A.A., Mohamed J.Y., Hijazi H., Prabakaran S., Tacke M., Al-Khrashi A., Hashem M., Reinheckel T., Assiri A., Alkuraya F.S.
Am. J. Hum. Genet. 93:313-320(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN MYP23.
[14]"The solution structure of the N-terminal domain of alpha2-macroglobulin receptor-associated protein."
Nielsen P.R., Ellgaard L., Etzerodt M., Thoegersen H.C., Poulsen F.M.
Proc. Natl. Acad. Sci. U.S.A. 94:7521-7525(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 51-131.
[15]"1H, 13C and 15N resonance assignments of domain 1 of receptor associated protein."
Wu Y., Migliorini M., Yu P., Strickland D.K., Wang Y.-X.
J. Biomol. NMR 26:187-188(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 51-132.
[16]"Binding site structure of one LRP-RAP complex: implications for a common ligand-receptor binding motif."
Jensen G.A., Andersen O.M.J.J., Bonvin A.M., Bjerrum-Bohr I., Etzerodt M., Thoegersen H.C., O'Shea C., Poulsen F.M., Kragelund B.B.
J. Mol. Biol. 362:700-716(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 51-131 IN COMPLEX WITH LRP1.
[17]"Structure of an LDLR-RAP complex reveals a general mode for ligand recognition by lipoprotein receptors."
Fisher C., Beglova N., Blacklow S.C.
Mol. Cell 22:277-283(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.26 ANGSTROMS) OF 250-357 IN COMPLEX WITH LDLR.
[18]"RAP uses a histidine switch to regulate its interaction with LRP in the ER and Golgi."
Lee D., Walsh J.D., Mikhailenko I., Yu P., Migliorini M., Wu Y., Krueger S., Curtis J.E., Harris B., Lockett S., Blacklow S.C., Strickland D.K., Wang Y.-X.
Mol. Cell 22:423-430(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 240-357, INTERACTION WITH LRP1, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF HIS-283; HIS-291; HIS-293; HIS-302; HIS-307 AND HIS-341.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M63959 mRNA. Translation: AAA51553.1.
AF035767 expand/collapse EMBL AC list , AF035760, AF035761, AF035762, AF035763, AF035764, AF035765, AF035766 Genomic DNA. Translation: AAC67373.1.
AK222504 mRNA. Translation: BAD96224.1.
AK222527 mRNA. Translation: BAD96247.1.
AL590235 Genomic DNA. Translation: CAM21451.1.
CH471131 Genomic DNA. Translation: EAW82460.1.
CH471131 Genomic DNA. Translation: EAW82461.1.
BC105074 mRNA. Translation: AAI05075.1.
BC112067 mRNA. Translation: AAI12068.1.
U06976 Genomic DNA. Translation: AAA87889.1.
PIRA39875.
RefSeqNP_002328.1. NM_002337.3.
UniGeneHs.40966.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LRENMR-A51-131[»]
1NRENMR-A51-131[»]
1OP1NMR-A51-132[»]
1OV2NMR-A35-133[»]
2FCWX-ray1.26A250-357[»]
2FTUNMR-A240-357[»]
2FYLNMR-A51-131[»]
2P01NMR-A35-357[»]
2P03NMR-A35-357[»]
ProteinModelPortalP30533.
SMRP30533. Positions 35-357.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110221. 20 interactions.
DIPDIP-39355N.
IntActP30533. 13 interactions.
MINTMINT-1382467.
STRING9606.ENSP00000296325.

PTM databases

PhosphoSiteP30533.

Polymorphism databases

DMDM231539.

Proteomic databases

PaxDbP30533.
PeptideAtlasP30533.
PRIDEP30533.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000500728; ENSP00000421922; ENSG00000163956.
GeneID4043.
KEGGhsa:4043.
UCSCuc003ghh.4. human.

Organism-specific databases

CTD4043.
GeneCardsGC04M003508.
HGNCHGNC:6701. LRPAP1.
HPACAB025518.
HPA008001.
MIM104225. gene.
615431. phenotype.
neXtProtNX_P30533.
Orphanet98619. Rare isolated myopia.
PharmGKBPA30458.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG323629.
HOGENOMHOG000033926.
HOVERGENHBG000197.
InParanoidP30533.
OMAFRMAKLN.
OrthoDBEOG7P5T15.
PhylomeDBP30533.
TreeFamTF320678.

Gene expression databases

ArrayExpressP30533.
BgeeP30533.
CleanExHS_LRPAP1.
GenevestigatorP30533.

Family and domain databases

Gene3D1.20.81.10. 1 hit.
InterProIPR010483. Alpha_2_MRAP_C.
IPR009066. MG_RAP_rcpt_1.
[Graphical view]
PfamPF06401. Alpha-2-MRAP_C. 1 hit.
PF06400. Alpha-2-MRAP_N. 1 hit.
[Graphical view]
SUPFAMSSF47045. SSF47045. 3 hits.
PROSITEPS00014. ER_TARGET. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSLRPAP1. human.
EvolutionaryTraceP30533.
GeneWikiLDL-receptor-related_protein_associated_protein.
GenomeRNAi4043.
NextBio15830.
PROP30533.
SOURCESearch...

Entry information

Entry nameAMRP_HUMAN
AccessionPrimary (citable) accession number: P30533
Secondary accession number(s): D3DVR9 expand/collapse secondary AC list , Q2M310, Q53HQ3, Q53HS6
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: April 16, 2014
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM