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Protein

Alpha-2-macroglobulin receptor-associated protein

Gene

LRPAP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Molecular chaperone for LDL receptor-related proteins that may regulate their ligand binding activity along the secretory pathway.1 Publication

GO - Molecular functioni

  • heparin binding Source: UniProtKB-KW
  • low-density lipoprotein particle receptor binding Source: UniProtKB
  • receptor antagonist activity Source: BHF-UCL
  • receptor binding Source: ParkinsonsUK-UCL
  • very-low-density lipoprotein particle receptor binding Source: BHF-UCL

GO - Biological processi

  • extracellular negative regulation of signal transduction Source: ParkinsonsUK-UCL
  • negative regulation of beta-amyloid clearance Source: BHF-UCL
  • negative regulation of protein binding Source: BHF-UCL
  • negative regulation of very-low-density lipoprotein particle clearance Source: BHF-UCL
  • receptor-mediated endocytosis Source: GOC
  • regulation of receptor-mediated endocytosis Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

Heparin-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000163956-MONOMER.

Names & Taxonomyi

Protein namesi
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 namesi
Name:LRPAP1
Synonyms:A2MRAP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:6701. LRPAP1.

Subcellular locationi

  • Rough endoplasmic reticulum lumen 1 Publication
  • Endoplasmic reticulum-Golgi intermediate compartment lumen 1 Publication
  • Golgi apparatuscis-Golgi network 1 Publication
  • Golgi apparatus lumen 1 Publication
  • Endosome lumen 1 Publication
  • Cell surface 1 Publication

  • Note: May be associated with receptors at the cell surface.1 Publication

GO - Cellular componenti

  • cell surface Source: UniProtKB-SubCell
  • cis-Golgi network Source: UniProtKB
  • endoplasmic reticulum Source: HPA
  • endoplasmic reticulum-Golgi intermediate compartment Source: UniProtKB
  • endosome Source: UniProtKB
  • extracellular region Source: ParkinsonsUK-UCL
  • Golgi apparatus Source: UniProtKB
  • plasma membrane Source: MGI
  • rough endoplasmic reticulum lumen Source: UniProtKB
  • vesicle Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Endosome, Golgi apparatus

Pathology & Biotechi

Involvement in diseasei

Myopia 23, autosomal recessive (MYP23)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:615431

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi283H → A: Strongly reduced interaction with LRP1; when associated with A-291; A-293; A-302; A-307 and A-341. 1 Publication1
Mutagenesisi291H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-293; A-302; A-307 and A-341. 1 Publication1
Mutagenesisi293H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-291; A-302; A-307 and A-341. 1 Publication1
Mutagenesisi302H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-291; A-293; A-307 and A-341. 1 Publication1
Mutagenesisi307H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-291; A-293; A-302 and A-341. 1 Publication1
Mutagenesisi341H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-291; A-293; A-302 and A-307. 1 Publication1

Organism-specific databases

DisGeNETi4043.
MalaCardsiLRPAP1.
MIMi615431. phenotype.
OpenTargetsiENSG00000163956.
Orphaneti98619. Rare isolated myopia.
PharmGKBiPA30458.

Polymorphism and mutation databases

BioMutaiLRPAP1.
DMDMi231539.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 34Sequence analysisAdd BLAST34
ChainiPRO_000002072435 – 357Alpha-2-macroglobulin receptor-associated proteinAdd BLAST323

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei50PhosphoserineBy similarity1
Modified residuei135PhosphoserineBy similarity1
Modified residuei248PhosphothreonineCombined sources1
Glycosylationi268N-linked (GlcNAc...)1 Publication1

Post-translational modificationi

N-glycosylated.3 Publications

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP30533.
MaxQBiP30533.
PaxDbiP30533.
PeptideAtlasiP30533.
PRIDEiP30533.
TopDownProteomicsiP30533.

PTM databases

iPTMnetiP30533.
PhosphoSitePlusiP30533.

Expressioni

Gene expression databases

BgeeiENSG00000163956.
CleanExiHS_LRPAP1.
ExpressionAtlasiP30533. baseline and differential.
GenevisibleiP30533. HS.

Organism-specific databases

HPAiCAB025518.
HPA008001.

Interactioni

Subunit structurei

Interacts with the LRP1/alpha-2-macroglobulin receptor heavy and light chains; the interaction is transient and coincides with a reduction of ligand binding by the receptor (PubMed:1712782, PubMed:1400426, PubMed:7774585, PubMed:16938309, PubMed:16678114). Interacts with LRP2/glycoprotein 330 (PubMed:1400426). Interacts with LRP1B; binding is followed by internalization and degradation (PubMed:11384978). Interacts with LDLR (PubMed:16630895).7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
VLDLRP981554EBI-715927,EBI-9004309

GO - Molecular functioni

  • low-density lipoprotein particle receptor binding Source: UniProtKB
  • receptor antagonist activity Source: BHF-UCL
  • receptor binding Source: ParkinsonsUK-UCL
  • very-low-density lipoprotein particle receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi110221. 21 interactors.
DIPiDIP-39355N.
IntActiP30533. 15 interactors.
MINTiMINT-1382467.
STRINGi9606.ENSP00000421922.

Structurei

Secondary structure

1357
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi53 – 56Combined sources4
Helixi57 – 68Combined sources12
Helixi73 – 99Combined sources27
Helixi107 – 122Combined sources16
Beta strandi124 – 126Combined sources3
Beta strandi127 – 130Combined sources4
Helixi149 – 161Combined sources13
Helixi166 – 195Combined sources30
Beta strandi208 – 210Combined sources3
Beta strandi213 – 216Combined sources4
Helixi217 – 243Combined sources27
Beta strandi246 – 249Combined sources4
Helixi255 – 265Combined sources11
Helixi271 – 311Combined sources41
Turni314 – 316Combined sources3
Helixi317 – 353Combined sources37

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LRENMR-A51-131[»]
1NRENMR-A51-131[»]
1OP1NMR-A51-132[»]
1OV2NMR-A35-133[»]
2FCWX-ray1.26A249-357[»]
2FTUNMR-A240-357[»]
2FYLNMR-A51-131[»]
2P01NMR-A35-357[»]
2P03NMR-A35-357[»]
ProteinModelPortaliP30533.
SMRiP30533.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP30533.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni237 – 353LDL receptor bindingSequence analysisAdd BLAST117

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili219 – 310Sequence analysisAdd BLAST92

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi354 – 357Prevents secretion from ER1 Publication4

Sequence similaritiesi

Belongs to the alpha-2-MRAP family.Curated

Keywords - Domaini

Coiled coil, Signal

Phylogenomic databases

eggNOGiKOG3956. Eukaryota.
ENOG410YJFP. LUCA.
GeneTreeiENSGT00390000004855.
HOGENOMiHOG000033926.
HOVERGENiHBG000197.
InParanoidiP30533.
OMAiNQVWEKA.
OrthoDBiEOG091G0EO4.
PhylomeDBiP30533.
TreeFamiTF320678.

Family and domain databases

Gene3Di1.20.81.10. 1 hit.
InterProiIPR010483. Alpha_2_MRAP_C.
IPR009066. MG_RAP_rcpt_1.
[Graphical view]
PfamiPF06401. Alpha-2-MRAP_C. 1 hit.
PF06400. Alpha-2-MRAP_N. 1 hit.
[Graphical view]
SUPFAMiSSF47045. SSF47045. 3 hits.
PROSITEiPS00014. ER_TARGET. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P30533-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPRRVRSFL RGLPALLLLL LFLGPWPAAS HGGKYSREKN QPKPSPKRES
60 70 80 90 100
GEEFRMEKLN QLWEKAQRLH LPPVRLAELH ADLKIQERDE LAWKKLKLDG
110 120 130 140 150
LDEDGEKEAR LIRNLNVILA KYGLDGKKDA RQVTSNSLSG TQEDGLDDPR
160 170 180 190 200
LEKLWHKAKT SGKFSGEELD KLWREFLHHK EKVHEYNVLL ETLSRTEEIH
210 220 230 240 250
ENVISPSDLS DIKGSVLHSR HTELKEKLRS INQGLDRLRR VSHQGYSTEA
260 270 280 290 300
EFEEPRVIDL WDLAQSANLT DKELEAFREE LKHFEAKIEK HNHYQKQLEI
310 320 330 340 350
AHEKLRHAES VGDGERVSRS REKHALLEGR TKELGYTVKK HLQDLSGRIS

RARHNEL
Length:357
Mass (Da):41,466
Last modified:April 1, 1993 - v1
Checksum:iD56A7DA754125CFA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti100G → D in BAD96247 (Ref. 3) Curated1
Sequence conflicti183V → A in BAD96224 (Ref. 3) Curated1
Sequence conflicti339K → M in BAD96247 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050660114N → S.Corresponds to variant rs2228158dbSNPEnsembl.1
Natural variantiVAR_011821311V → M.1 PublicationCorresponds to variant rs1800493dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3371.1.
PIRiA39875.
RefSeqiNP_002328.1. NM_002337.3.
UniGeneiHs.40966.

Genome annotation databases

EnsembliENST00000500728; ENSP00000421922; ENSG00000163956.
GeneIDi4043.
KEGGihsa:4043.
UCSCiuc003ghh.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3371.1.
PIRiA39875.
RefSeqiNP_002328.1. NM_002337.3.
UniGeneiHs.40966.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LRENMR-A51-131[»]
1NRENMR-A51-131[»]
1OP1NMR-A51-132[»]
1OV2NMR-A35-133[»]
2FCWX-ray1.26A249-357[»]
2FTUNMR-A240-357[»]
2FYLNMR-A51-131[»]
2P01NMR-A35-357[»]
2P03NMR-A35-357[»]
ProteinModelPortaliP30533.
SMRiP30533.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110221. 21 interactors.
DIPiDIP-39355N.
IntActiP30533. 15 interactors.
MINTiMINT-1382467.
STRINGi9606.ENSP00000421922.

PTM databases

iPTMnetiP30533.
PhosphoSitePlusiP30533.

Polymorphism and mutation databases

BioMutaiLRPAP1.
DMDMi231539.

Proteomic databases

EPDiP30533.
MaxQBiP30533.
PaxDbiP30533.
PeptideAtlasiP30533.
PRIDEiP30533.
TopDownProteomicsiP30533.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000500728; ENSP00000421922; ENSG00000163956.
GeneIDi4043.
KEGGihsa:4043.
UCSCiuc003ghh.5. human.

Organism-specific databases

CTDi4043.
DisGeNETi4043.
GeneCardsiLRPAP1.
HGNCiHGNC:6701. LRPAP1.
HPAiCAB025518.
HPA008001.
MalaCardsiLRPAP1.
MIMi104225. gene.
615431. phenotype.
neXtProtiNX_P30533.
OpenTargetsiENSG00000163956.
Orphaneti98619. Rare isolated myopia.
PharmGKBiPA30458.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3956. Eukaryota.
ENOG410YJFP. LUCA.
GeneTreeiENSGT00390000004855.
HOGENOMiHOG000033926.
HOVERGENiHBG000197.
InParanoidiP30533.
OMAiNQVWEKA.
OrthoDBiEOG091G0EO4.
PhylomeDBiP30533.
TreeFamiTF320678.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000163956-MONOMER.

Miscellaneous databases

ChiTaRSiLRPAP1. human.
EvolutionaryTraceiP30533.
GeneWikiiLDL-receptor-related_protein_associated_protein.
GenomeRNAii4043.
PROiP30533.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163956.
CleanExiHS_LRPAP1.
ExpressionAtlasiP30533. baseline and differential.
GenevisibleiP30533. HS.

Family and domain databases

Gene3Di1.20.81.10. 1 hit.
InterProiIPR010483. Alpha_2_MRAP_C.
IPR009066. MG_RAP_rcpt_1.
[Graphical view]
PfamiPF06401. Alpha-2-MRAP_C. 1 hit.
PF06400. Alpha-2-MRAP_N. 1 hit.
[Graphical view]
SUPFAMiSSF47045. SSF47045. 3 hits.
PROSITEiPS00014. ER_TARGET. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAMRP_HUMAN
AccessioniPrimary (citable) accession number: P30533
Secondary accession number(s): D3DVR9
, Q2M310, Q53HQ3, Q53HS6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: November 30, 2016
This is version 162 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.