P30533 (AMRP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	357 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.17
Post-translational modification	N-glycosylated. Ref.17
Involvement in disease	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 component	Cytoplasm Endoplasmic reticulum
Coding sequence diversity	Polymorphism
Domain	Coiled coil Signal
Ligand	Heparin-binding
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	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
Cellular_component	cell 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 to 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: Compara vesicle Inferred from electronic annotation. Source: Compara
Molecular_function	asialoglycoprotein 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
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 34

34

Potential

Chain

35 – 357

323

Alpha-2-macroglobulin receptor-associated protein

PRO_0000020724

Regions

Region

237 – 353

117

LDL receptor binding Potential

Coiled coil

219 – 310

92

Potential

Motif

354 – 357

4

Prevents secretion from ER Potential

Amino acid modifications

Glycosylation

268

1

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

Natural variations

Natural variant

114

1

N → S.
Corresponds to variant rs2228158 [ dbSNP | Ensembl ].

VAR_050660

Natural variant

311

1

V → M. Ref.2
Corresponds to variant rs1800493 [ dbSNP | Ensembl ].

VAR_011821

Experimental info

Mutagenesis

283

1

H → A: Strongly reduced interaction with LRP1; when associated with A-291; A-293; A-302; A-307 and A-341. Ref.17

Mutagenesis

291

1

H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-293; A-302; A-307 and A-341. Ref.17

Mutagenesis

293

1

H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-291; A-302; A-307 and A-341. Ref.17

Mutagenesis

302

1

H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-291; A-293; A-307 and A-341. Ref.17

Mutagenesis

307

1

H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-291; A-293; A-302 and A-341. Ref.17

Mutagenesis

341

1

H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-291; A-293; A-302 and A-307. Ref.17

Sequence conflict

100

1

G → D in BAD96247. Ref.3

Sequence conflict

183

1

V → A in BAD96224. Ref.3

Sequence conflict

339

1

K → M in BAD96247. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

357

Helix Strand Turn

Details...

Beta strand

53 – 56

4

Helix

57 – 68

12

Helix

73 – 99

27

Helix

107 – 122

16

Beta strand

124 – 126

3

Beta strand

127 – 130

4

Helix

149 – 161

13

Helix

166 – 195

30

Beta strand

208 – 210

3

Beta strand

213 – 216

4

Helix

217 – 243

27

Beta strand

246 – 249

4

Helix

255 – 265

11

Helix

271 – 311

41

Turn

314 – 316

3

Helix

317 – 353

37

Sequences

	Sequence		Length	Mass (Da)
	P30533 [UniParc]. Last modified April 1, 1993. Version 1. Checksum: D56A7DA754125CFA	FASTA	357	41,466
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	"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 , 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.

IPI

IPI00026848.

PIR

A39875.

RefSeq

NP_002328.1. NM_002337.3.

UniGene

Hs.40966.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LRE	NMR	-	A	51-131	[»]
1NRE	NMR	-	A	51-131	[»]
1OP1	NMR	-	A	51-132	[»]
1OV2	NMR	-	A	35-133	[»]
2FCW	X-ray	1.26	A	250-357	[»]
2FTU	NMR	-	A	240-357	[»]
2FYL	NMR	-	A	51-131	[»]
2P01	NMR	-	A	35-357	[»]
2P03	NMR	-	A	35-357	[»]

ProteinModelPortal

P30533.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-39355N.

IntAct

P30533. 7 interactions.

MINT

MINT-1382467.

STRING

9606.ENSP00000296325.

PTM databases

PhosphoSite

P30533.

Polymorphism databases

DMDM

231539.

Proteomic databases

PaxDb

P30533.

PeptideAtlas

P30533.

PRIDE

P30533.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000500728; ENSP00000421922; ENSG00000163956.

GeneID

4043.

KEGG

hsa:4043.

UCSC

uc003ghh.4. human.

Organism-specific databases

CTD

4043.

GeneCards

GC04M003508.

HGNC

HGNC:6701. LRPAP1.

HPA

CAB025518.
HPA008001.

MIM

104225. gene.

neXtProt

NX_P30533.

PharmGKB

PA30458.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG323629.

HOGENOM

HOG000033926.

HOVERGEN

HBG000197.

InParanoid

P30533.

OMA

FRMAKLN.

OrthoDB

EOG479F7K.

PhylomeDB

P30533.

Enzyme and pathway databases

Pathway_Interaction_DB

lis1pathway. Lissencephaly gene (LIS1) in neuronal migration and development.
reelinpathway. Reelin signaling pathway.
hedgehog_2pathway. Signaling events mediated by the Hedgehog family.

Gene expression databases

ArrayExpress

P30533.

Bgee

P30533.

CleanEx

HS_LRPAP1.

Genevestigator

P30533.

GermOnline

ENSG00000163956. Homo sapiens.

Family and domain databases

Gene3D

1.20.81.10. 1 hit.

InterPro

IPR010483. Alpha_2_MRAP_C.
IPR009066. MG_RAP_rcpt_1.
[Graphical view]

Pfam

PF06401. Alpha-2-MRAP_C. 1 hit.
PF06400. Alpha-2-MRAP_N. 1 hit.
[Graphical view]

SUPFAM

SSF47045. MG_RAP_rcpt_1. 3 hits.

PROSITE

PS00014. ER_TARGET. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

LRPAP1. human.

EvolutionaryTrace

P30533.

GenomeRNAi

4043.

NextBio

15830.

SOURCE

Search...

Entry information

Entry name

AMRP_HUMAN

Accession

Primary (citable) accession number: P30533
Secondary accession number(s): D3DVR9 , Q2M310, Q53HQ3, Q53HS6

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	April 1, 1993
Last modified:	May 1, 2013
This is version 130 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.