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Reviewed, UniProtKB/Swiss-Prot Q07954 (LRP1_HUMAN)

Last modified November 25, 2008. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Prolow-density lipoprotein receptor-related protein 1
      Short name=LRP
Alternative name(s):
    Alpha-2-macroglobulin receptor
      Short name=A2MR
    Apolipoprotein E receptor
      Short name=APOER
    CD_antigen=CD91
Cleaved into the following 3 chains:
    1- Recommended name:
            Low-density lipoprotein receptor-related protein 1 85 kDa subunit
                Short name=LRP-85
    2- Recommended name:
            Low-density lipoprotein receptor-related protein 1 515 kDa subunit
                Short name=LRP-515
    3- Recommended name:
            Low-density lipoprotein receptor-related protein 1 intracellular domain
                Short name=LRPICD
Gene names
Name: LRP1
Synonyms: A2MR, APR
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length4544 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells. Required for early embryonic development. Involved in cellular lipid homeostasis. Involved in the plasma clearance of chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin), as well as the local metabolism of complexes between plasminogen activators and their endogenous inhibitors. May modulate cellular events, such as APP metabolism, kinase-dependent intracellular signaling, neuronal calcium signaling as well as neurotransmission.

Subunit structure

Heterodimer of an 85-kDa membrane-bound carboxyl subunit and a non-covalently attached 515-kDa amino-terminal subunit. Intracellular domain interacts with MAFB By similarity. Found in a complex with PID1/PCLI1, LRP1 and CUBNI. Interacts with SNX17, PID1/PCLI1, PDGF and CUBN. The intracellular domain interacts with SHC1, GULP1 and DAB1. Interacts with LRPAP1.

Subcellular location

Low-density lipoprotein receptor-related protein 1 85 kDa subunit: Cell membrane; Single-pass type I membrane protein. Membrane › coated pit.

Low-density lipoprotein receptor-related protein 1 515 kDa subunit: Cell membrane; Peripheral membrane protein; Extracellular side. Membrane › coated pit.

Low-density lipoprotein receptor-related protein 1 intracellular domain: Cytoplasm. Nucleus. Note= After cleavage, the intracellular domain (LRPICD) is detected both in the cytoplasm and in the nucleus.

Tissue specificity

Most abundant in liver, brain and lung.

Post-translational modification

Cleaved into a 85 kDa membrane-spanning subunit (LRP-85) and a 515 kDa large extracellular domain (LRP-515) that remains non-covalently associated. Gamma-secretase-dependent cleavage of LRP-85 releases the intracellular domain from the membrane.

The N-terminus is blocked.

Phosphorylated on serine and threonine residues.

Phosphorylated on tyrosine residues upon stimulation with PDGF. Tyrosine phosphorylation promotes interaction with SHC1.

Sequence similarities

Belongs to the LDLR family.

Contains 22 EGF-like domains.

Contains 31 LDL-receptor class A domains.

Contains 34 LDL-receptor class B repeats.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Chain20 – 45444525Prolow-density lipoprotein receptor-related protein 1
PRO_0000017317
Chain20 – ?39433924Low-density lipoprotein receptor-related protein 1 515 kDa subunit
PRO_0000302750
Chain?3944 – 4544601Low-density lipoprotein receptor-related protein 1 85 kDa subunit
PRO_0000302751
Chain?4441 – 4544104Low-density lipoprotein receptor-related protein 1 intracellular domain
PRO_0000302752

Regions

Topological domain20 – 44194400Extracellular Potential
Transmembrane4420 – 444425 Potential
Topological domain4445 – 4544100Cytoplasmic Potential
Domain25 – 6642LDL-receptor class A 1
Domain70 – 11041LDL-receptor class A 2
Domain111 – 14939EGF-like 1
Domain150 – 18940EGF-like 2; calcium-binding Potential
Repeat292 – 33443LDL-receptor class B 1
Repeat335 – 37844LDL-receptor class B 2
Repeat379 – 42244LDL-receptor class B 3
Domain474 – 52047EGF-like 3
Repeat571 – 61343LDL-receptor class B 4
Repeat614 – 65946LDL-receptor class B 5
Repeat660 – 71051LDL-receptor class B 6
Repeat711 – 75444LDL-receptor class B 7
Domain803 – 84341EGF-like 4
Domain852 – 89241LDL-receptor class A 3
Domain893 – 93341LDL-receptor class A 4
Domain934 – 97340LDL-receptor class A 5
Domain974 – 101340LDL-receptor class A 6
Domain1013 – 105341LDL-receptor class A 7
Domain1060 – 109940LDL-receptor class A 8
Domain1102 – 114241LDL-receptor class A 9
Domain1143 – 118240LDL-receptor class A 10
Domain1183 – 122240EGF-like 5
Domain1223 – 126240EGF-like 6
Repeat1309 – 135547LDL-receptor class B 8
Repeat1356 – 139843LDL-receptor class B 9
Repeat1399 – 144547LDL-receptor class B 10
Repeat1446 – 149045LDL-receptor class B 11
Repeat1491 – 153141LDL-receptor class B 12
Domain1536 – 157944EGF-like 7
Repeat1627 – 166943LDL-receptor class B 13
Repeat1670 – 171344LDL-receptor class B 14
Repeat1714 – 175340LDL-receptor class B 15
Repeat1754 – 179845LDL-receptor class B 16
Domain1846 – 188742EGF-like 8
Repeat1934 – 197643LDL-receptor class B 17
Repeat1977 – 201943LDL-receptor class B 18
Repeat2020 – 206344LDL-receptor class B 19
Repeat2064 – 210744LDL-receptor class B 20
Domain2155 – 219541EGF-like 9
Repeat2253 – 229442LDL-receptor class B 21
Repeat2295 – 234349LDL-receptor class B 22
Repeat2344 – 238845LDL-receptor class B 23
Repeat2389 – 243143LDL-receptor class B 24
Repeat2432 – 247342LDL-receptor class B 25
Domain2478 – 251841EGF-like 10
Domain2522 – 256342LDL-receptor class A 11
Domain2564 – 260239LDL-receptor class A 12
Domain2603 – 264139LDL-receptor class A 13
Domain2642 – 269049LDL-receptor class A 14
Domain2694 – 273239LDL-receptor class A 15
Domain2732 – 277140LDL-receptor class A 16
Domain2772 – 281443LDL-receptor class A 17
Domain2816 – 285540LDL-receptor class A 18
Domain2856 – 289944LDL-receptor class A 19
Domain2902 – 294039LDL-receptor class A 20
Domain2941 – 298141EGF-like 11
Domain2982 – 302241EGF-like 12; calcium-binding Potential
Repeat3069 – 311345LDL-receptor class B 26
Repeat3114 – 315643LDL-receptor class B 27
Repeat3157 – 320044LDL-receptor class B 28
Repeat3201 – 324343LDL-receptor class B 29
Repeat3244 – 328441LDL-receptor class B 30
Domain3290 – 333142EGF-like 13
Domain3332 – 337140LDL-receptor class A 21
Domain3372 – 341039LDL-receptor class A 22
Domain3411 – 345040LDL-receptor class A 23
Domain3451 – 349141LDL-receptor class A 24
Domain3492 – 353342LDL-receptor class A 25
Domain3534 – 357239LDL-receptor class A 26
Domain3573 – 361139LDL-receptor class A 27
Domain3611 – 364939LDL-receptor class A 28
Domain3652 – 369241LDL-receptor class A 29
Domain3693 – 373341LDL-receptor class A 30
Domain3739 – 377840LDL-receptor class A 31
Domain3781 – 382343EGF-like 14