UniProtKB - P30533 (AMRP_HUMAN)
Alpha-2-macroglobulin receptor-associated protein
LRPAP1
Functioni
GO - Molecular functioni
- amyloid-beta binding Source: ARUK-UCL
- heparin binding Source: UniProtKB-KW
- lipase binding Source: GO_Central
- low-density lipoprotein particle receptor binding Source: UniProtKB
- receptor antagonist activity Source: BHF-UCL
- receptor ligand activity Source: UniProtKB
- signaling receptor binding Source: ParkinsonsUK-UCL
- very-low-density lipoprotein particle receptor binding Source: BHF-UCL
GO - Biological processi
- amyloid-beta clearance by transcytosis Source: ARUK-UCL
- extracellular negative regulation of signal transduction Source: ParkinsonsUK-UCL
- negative regulation of amyloid-beta clearance Source: BHF-UCL
- negative regulation of cell death Source: ARUK-UCL
- negative regulation of protein binding Source: BHF-UCL
- negative regulation of receptor internalization Source: ARUK-UCL
- negative regulation of very-low-density lipoprotein particle clearance Source: BHF-UCL
- positive regulation of amyloid-beta clearance Source: ARUK-UCL
- regulation of receptor-mediated endocytosis Source: UniProtKB
- signal transduction Source: UniProtKB
Keywordsi
Molecular function | Heparin-binding |
Enzyme and pathway databases
PathwayCommonsi | P30533 |
Names & Taxonomyi
Protein namesi | Recommended name: Alpha-2-macroglobulin receptor-associated proteinCuratedShort name: Alpha-2-MRAP Alternative name(s): Low density lipoprotein receptor-related protein-associated protein 1 Short name: RAP |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000163956.10 |
HGNCi | HGNC:6701, LRPAP1 |
MIMi | 104225, gene |
neXtProti | NX_P30533 |
Subcellular locationi
Endosome
- Endosome lumen 1 Publication
Endoplasmic reticulum
- Rough endoplasmic reticulum lumen 1 Publication
Golgi apparatus
- cis-Golgi network 1 Publication
- Golgi apparatus lumen 1 Publication
Other locations
- Endoplasmic reticulum-Golgi intermediate compartment lumen 1 Publication
- Cell surface 1 Publication
Note: May be associated with receptors at the cell surface.1 Publication
Endoplasmic reticulum
- endoplasmic reticulum Source: HPA
- rough endoplasmic reticulum lumen Source: UniProtKB
Endosome
- endosome Source: UniProtKB
- endosome lumen Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular region Source: ParkinsonsUK-UCL
Golgi apparatus
- cis-Golgi network Source: UniProtKB
- Golgi apparatus Source: UniProtKB
- Golgi lumen Source: UniProtKB-SubCell
Plasma Membrane
- plasma membrane Source: MGI
Other locations
- cell surface Source: UniProtKB-SubCell
- endomembrane system Source: GO_Central
- endoplasmic reticulum-Golgi intermediate compartment Source: UniProtKB
Keywords - Cellular componenti
Endoplasmic reticulum, Endosome, Golgi apparatusPathology & Biotechi
Involvement in diseasei
Myopia 23, autosomal recessive (MYP23)1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 283 | H → A: Strongly reduced interaction with LRP1; when associated with A-291; A-293; A-302; A-307 and A-341. 1 Publication | 1 | |
Mutagenesisi | 290 | K → A: Reduces competition with MAPT for binding to LRP1; when associated with A-304. 1 Publication | 1 | |
Mutagenesisi | 291 | H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-293; A-302; A-307 and A-341. 1 Publication | 1 | |
Mutagenesisi | 293 | H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-291; A-302; A-307 and A-341. 1 Publication | 1 | |
Mutagenesisi | 302 | H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-291; A-293; A-307 and A-341. 1 Publication | 1 | |
Mutagenesisi | 304 | K → A: Reduces competition with MAPT for binding to LRP1; when associated with A-290. 1 Publication | 1 | |
Mutagenesisi | 307 | H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-291; A-293; A-302 and A-341. 1 Publication | 1 | |
Mutagenesisi | 341 | H → A: Strongly reduced interaction with LRP1; when associated with A-283; A-291; A-293; A-302 and A-307. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 4043 |
MalaCardsi | LRPAP1 |
MIMi | 615431, phenotype |
OpenTargetsi | ENSG00000163956 |
Orphaneti | 98619, Rare isolated myopia |
PharmGKBi | PA30458 |
Miscellaneous databases
Pharosi | P30533, Tbio |
Polymorphism and mutation databases
BioMutai | LRPAP1 |
DMDMi | 231539 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 34 | Sequence analysisAdd BLAST | 34 | |
ChainiPRO_0000020724 | 35 – 357 | Alpha-2-macroglobulin receptor-associated proteinAdd BLAST | 323 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 50 | PhosphoserineBy similarity | 1 | |
Modified residuei | 135 | PhosphoserineBy similarity | 1 | |
Modified residuei | 248 | PhosphothreonineCombined sources | 1 | |
Glycosylationi | 268 | N-linked (GlcNAc...) asparagine1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
EPDi | P30533 |
jPOSTi | P30533 |
MassIVEi | P30533 |
MaxQBi | P30533 |
PaxDbi | P30533 |
PeptideAtlasi | P30533 |
PRIDEi | P30533 |
ProteomicsDBi | 54716 |
TopDownProteomicsi | P30533 |
PTM databases
GlyConnecti | 1004, 12 N-Linked glycans (1 site) |
GlyGeni | P30533, 1 site |
iPTMneti | P30533 |
PhosphoSitePlusi | P30533 |
Expressioni
Gene expression databases
Bgeei | ENSG00000163956, Expressed in caudate nucleus and 247 other tissues |
ExpressionAtlasi | P30533, baseline and differential |
Genevisiblei | P30533, HS |
Organism-specific databases
HPAi | ENSG00000163956, Low tissue specificity |
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, PubMed:32296178).
Interacts with LRP2/glycoprotein 330 (PubMed:1400426).
Interacts with LRP1B; binding is followed by internalization and degradation (PubMed:11384978).
Interacts with LDLR (PubMed:16630895).
Interacts with SORL1 (PubMed:8940146, PubMed:11294867, PubMed:12530537, PubMed:15053742, PubMed:15364913, PubMed:26858303).
Interacts with LRP1; this interaction is followed by rapid internalization (PubMed:15053742).
14 PublicationsBinary interactionsi
Hide detailsP30533
GO - Molecular functioni
- lipase binding Source: GO_Central
- low-density lipoprotein particle receptor binding Source: UniProtKB
- receptor antagonist activity Source: BHF-UCL
- receptor ligand activity Source: UniProtKB
- signaling receptor binding Source: ParkinsonsUK-UCL
- very-low-density lipoprotein particle receptor binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 110221, 29 interactors |
DIPi | DIP-39355N |
IntActi | P30533, 31 interactors |
MINTi | P30533 |
STRINGi | 9606.ENSP00000421922 |
Miscellaneous databases
RNActi | P30533, protein |
Structurei
Secondary structure
3D structure databases
BMRBi | P30533 |
SMRi | P30533 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P30533 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 237 – 353 | LDL receptor bindingSequence analysisAdd BLAST | 117 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 219 – 310 | Sequence analysisAdd BLAST | 92 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 354 – 357 | Prevents secretion from ER1 Publication | 4 |
Sequence similaritiesi
Keywords - Domaini
Coiled coil, SignalPhylogenomic databases
eggNOGi | KOG3956, Eukaryota |
GeneTreei | ENSGT00390000004855 |
HOGENOMi | CLU_064512_0_0_1 |
InParanoidi | P30533 |
OMAi | RVSRQGY |
OrthoDBi | 908725at2759 |
PhylomeDBi | P30533 |
TreeFami | TF320678 |
Family and domain databases
CDDi | cd14806, RAP_D1, 1 hit cd14807, RAP_D2, 1 hit cd14808, RAP_D3, 1 hit |
Gene3Di | 1.20.81.10, 3 hits |
InterProi | View protein in InterPro IPR038003, A2-macroglobuin_RAP IPR010483, Alpha_2_MRAP_C IPR009066, MG_RAP_rcpt_1 IPR038001, RAP_D2 IPR037999, RAP_D3 IPR036744, RAP_sf |
PANTHERi | PTHR16560, PTHR16560, 1 hit |
Pfami | View protein in Pfam PF06401, Alpha-2-MRAP_C, 1 hit PF06400, Alpha-2-MRAP_N, 1 hit |
SUPFAMi | SSF47045, SSF47045, 3 hits |
PROSITEi | View protein in PROSITE PS00014, ER_TARGET, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A3B3IRQ7 | A0A3B3IRQ7_HUMAN | Alpha-2-macroglobulin receptor-asso... | LRPAP1 | 279 | Annotation score: | ||
D6REW6 | D6REW6_HUMAN | Alpha-2-macroglobulin receptor-asso... | LRPAP1 | 105 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 100 | G → D in BAD96247 (Ref. 3) Curated | 1 | |
Sequence conflicti | 183 | V → A in BAD96224 (Ref. 3) Curated | 1 | |
Sequence conflicti | 339 | K → M in BAD96247 (Ref. 3) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_050660 | 114 | N → S. Corresponds to variant dbSNP:rs2228158Ensembl. | 1 | |
Natural variantiVAR_011821 | 311 | V → M1 PublicationCorresponds to variant dbSNP:rs1800493Ensembl. | 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 No translation available. 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 |
CCDSi | CCDS3371.1 |
PIRi | A39875 |
RefSeqi | NP_002328.1, NM_002337.3 |
Genome annotation databases
Ensembli | ENST00000650182; ENSP00000497444; ENSG00000163956 |
GeneIDi | 4043 |
KEGGi | hsa:4043 |
UCSCi | uc003ghh.5, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
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 No translation available. 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 |
CCDSi | CCDS3371.1 |
PIRi | A39875 |
RefSeqi | NP_002328.1, NM_002337.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB 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 | 249-357 | [»] | |
2FTU | NMR | - | A | 240-357 | [»] | |
2FYL | NMR | - | A | 51-131 | [»] | |
2P01 | NMR | - | A | 35-357 | [»] | |
2P03 | NMR | - | A | 35-357 | [»] | |
BMRBi | P30533 | |||||
SMRi | P30533 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110221, 29 interactors |
DIPi | DIP-39355N |
IntActi | P30533, 31 interactors |
MINTi | P30533 |
STRINGi | 9606.ENSP00000421922 |
PTM databases
GlyConnecti | 1004, 12 N-Linked glycans (1 site) |
GlyGeni | P30533, 1 site |
iPTMneti | P30533 |
PhosphoSitePlusi | P30533 |
Polymorphism and mutation databases
BioMutai | LRPAP1 |
DMDMi | 231539 |
Proteomic databases
EPDi | P30533 |
jPOSTi | P30533 |
MassIVEi | P30533 |
MaxQBi | P30533 |
PaxDbi | P30533 |
PeptideAtlasi | P30533 |
PRIDEi | P30533 |
ProteomicsDBi | 54716 |
TopDownProteomicsi | P30533 |
Protocols and materials databases
Antibodypediai | 1334, 484 antibodies |
Genome annotation databases
Ensembli | ENST00000650182; ENSP00000497444; ENSG00000163956 |
GeneIDi | 4043 |
KEGGi | hsa:4043 |
UCSCi | uc003ghh.5, human |
Organism-specific databases
CTDi | 4043 |
DisGeNETi | 4043 |
EuPathDBi | HostDB:ENSG00000163956.10 |
GeneCardsi | LRPAP1 |
HGNCi | HGNC:6701, LRPAP1 |
HPAi | ENSG00000163956, Low tissue specificity |
MalaCardsi | LRPAP1 |
MIMi | 104225, gene 615431, phenotype |
neXtProti | NX_P30533 |
OpenTargetsi | ENSG00000163956 |
Orphaneti | 98619, Rare isolated myopia |
PharmGKBi | PA30458 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3956, Eukaryota |
GeneTreei | ENSGT00390000004855 |
HOGENOMi | CLU_064512_0_0_1 |
InParanoidi | P30533 |
OMAi | RVSRQGY |
OrthoDBi | 908725at2759 |
PhylomeDBi | P30533 |
TreeFami | TF320678 |
Enzyme and pathway databases
PathwayCommonsi | P30533 |
Miscellaneous databases
BioGRID-ORCSi | 4043, 4 hits in 842 CRISPR screens |
ChiTaRSi | LRPAP1, human |
EvolutionaryTracei | P30533 |
GeneWikii | LDL-receptor-related_protein_associated_protein |
GenomeRNAii | 4043 |
Pharosi | P30533, Tbio |
PROi | PR:P30533 |
RNActi | P30533, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000163956, Expressed in caudate nucleus and 247 other tissues |
ExpressionAtlasi | P30533, baseline and differential |
Genevisiblei | P30533, HS |
Family and domain databases
CDDi | cd14806, RAP_D1, 1 hit cd14807, RAP_D2, 1 hit cd14808, RAP_D3, 1 hit |
Gene3Di | 1.20.81.10, 3 hits |
InterProi | View protein in InterPro IPR038003, A2-macroglobuin_RAP IPR010483, Alpha_2_MRAP_C IPR009066, MG_RAP_rcpt_1 IPR038001, RAP_D2 IPR037999, RAP_D3 IPR036744, RAP_sf |
PANTHERi | PTHR16560, PTHR16560, 1 hit |
Pfami | View protein in Pfam PF06401, Alpha-2-MRAP_C, 1 hit PF06400, Alpha-2-MRAP_N, 1 hit |
SUPFAMi | SSF47045, SSF47045, 3 hits |
PROSITEi | View protein in PROSITE PS00014, ER_TARGET, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | AMRP_HUMAN | |
Accessioni | P30533Primary (citable) accession number: P30533 Secondary accession number(s): D3DVR9 Q53HS6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 1, 1993 |
Last sequence update: | April 1, 1993 | |
Last modified: | December 2, 2020 | |
This is version 192 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations