Q14114 (LRP8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Low-density lipoprotein receptor-related protein 8
Short name=LRP-8

Alternative name(s):
Apolipoprotein E receptor 2

Gene names

Name:	LRP8
Synonyms:	APOER2

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	963 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	Cell surface receptor for Reelin (RELN) and apolipoprotein E (apoE)-containing ligands. LRP8 participates in transmitting the extracellular Reelin signal to intracellular signaling processes, by binding to DAB1 on its cytoplasmic tail. Reelin acts via both the VLDL receptor (VLDLR) and LRP8 to regulate DAB1 tyrosine phosphorylation and microtubule function in neurons. LRP8 has higher affinity for Reelin than VLDLR. LRP8 is thus a key component of the Reelin pathway which governs neuronal layering of the forebrain during embryonic brain development. Binds the endoplasmic reticulum resident receptor-associated protein (RAP). Binds dimers of beta 2-glycoprotein I and may be involved in the suppression of platelet aggregation in the vasculature. Highly expressed in the initial segment of the epididymis, where it affects the functional expression of clusterin and phospholipid hydroperoxide glutathione peroxidase (PHGPx), two proteins required for sperm maturation. May also function as an endocytic receptor. Ref.9 Ref.10 Ref.11
Subunit structure	Reelin associates with two or more receptor molecules. Interacts with DAB1 and JNK-interacting proteins. Interacts with SNX17 By similarity. Interacts with PCSK9. Ref.12
Subcellular location	Cell membrane; Single-pass type I membrane protein By similarity. Secreted By similarity. Note: Isoforms that contain the exon coding for a furin-type cleavage site are proteolytically processed, leading to a secreted receptor fragment By similarity.
Tissue specificity	Expressed mainly in brain and placenta. Also expressed in platelets and megakaryocytic cells. Not expressed in the liver. Ref.6 Ref.8
Domain	The cytoplasmic domain is involved in the binding of DAB1 and in the recruitment of JNK-interacting proteins. Isoforms, which lack part of the cytoplasmic domain, are unable to recruit members of the family of JNK interacting proteins (JIP) to the cytoplasmic tail By similarity.
Post-translational modification	O-glycosylated. Some alternatively spliced isoforms lack the O-linked sugar domain By similarity. Undergoes sequential, furin and gamma-secretase dependent, proteolytic processing, resulting in the extracellular release of the entire ligand-binding domain as a soluble polypeptide and in the intracellular domain (ICD) release into the cytoplasm. The gamma-secretase-dependent proteolytical processing occurs after the bulk of the extracellular domain has been shed, in a furin-dependent manner, in alternatively spliced isoforms carrying the furin cleavage site. Hypoglycosylation (mainly hypo-O-glycosylation) leads to increased extracellular cleavage, which in turn results in accelerating release of the intracellular domain (ICD) by the gamma-secretase. The resulting receptor fragment is able to inhibit Reelin signaling and in particular the Reelin-induced DAB1 phosphorylation By similarity. Tyrosine phosphorylated upon apoE binding. Ref.7 Ubiquitinated by MYLIP leading to degradation. Ref.13
Involvement in disease	Myocardial infarction 1 (MCI1) [MIM:608446]: A condition defined by the irreversible necrosis of heart muscle secondary to prolonged ischemia. Note: The disease is caused by mutations affecting the gene represented in this entry.
Miscellaneous	Natural isoforms of apoE (E2, E3, E4) have similar affinities for LRP8.
Sequence similarities	Belongs to the LDLR family. Contains 2 EGF-like domains. Contains 7 LDL-receptor class A domains. Contains 5 LDL-receptor class B repeats.
Sequence caution	The sequence CAA99509.1 differs from that shown. Reason: Frameshift at positions 430, 432 and 438.

Ontologies

Keywords
Biological process	Endocytosis
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	EGF-like domain Repeat Signal Transmembrane Transmembrane helix
Ligand	Calcium
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ammon gyrus development Inferred from sequence or structural similarity. Source: BHF-UCL blood coagulation Traceable author statement. Source: Reactome cytokine-mediated signaling pathway Non-traceable author statement Ref.3. Source: UniProtKB layer formation in cerebral cortex Inferred from electronic annotation. Source: Compara lipid metabolic process Non-traceable author statement Ref.3. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of CREB transcription factor activity Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of dendrite development Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of dendritic spine morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of protein tyrosine kinase activity Inferred from sequence or structural similarity. Source: BHF-UCL proteolysis Non-traceable author statement Ref.3. Source: UniProtKB regulation of synaptic transmission Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	caveola Inferred from direct assay PubMed 11369809. Source: BHF-UCL extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred by curator Ref.3. Source: UniProtKB
Molecular_function	apolipoprotein binding Inferred by curator Ref.1. Source: BHF-UCL calcium ion binding Inferred from electronic annotation. Source: InterPro reelin receptor activity Inferred from sequence or structural similarity. Source: BHF-UCL very-low-density lipoprotein particle receptor activity Inferred from direct assay Ref.1. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist. No differences were observed in the pattern splicing between control and Alzheimer brains.

Isoform 1 (identifier: Q14114-1)

Also known as: ApoER2 922;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q14114-2)

Also known as: ApoER2 906;

The sequence of this isoform differs from the canonical sequence as follows:
     166-295: LCAPHEFQCG...KDKSDEADCP → S
     737-812: APQSTSTTTL...PATSNHSQHY → D
     893-951: Missing.

Isoform 3 (identifier: Q14114-3)

The sequence of this isoform differs from the canonical sequence as follows:
     893-951: Missing.

Isoform 4 (identifier: Q14114-4)

Also known as: ApoER2delta4-7;

The sequence of this isoform differs from the canonical sequence as follows:
     166-166: L → W
     167-336: Missing.

Isoform 5 (identifier: Q14114-5)

The sequence of this isoform is not available.

Note: Contains an insert in the extracellular part which carries a furin cleavage site.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 32

32

Potential

Chain

33 – 963

931

Low-density lipoprotein receptor-related protein 8

PRO_0000017332

Regions

Topological domain

42 – 826

785

Extracellular Potential

Transmembrane

827 – 847

21

Helical; Potential

Topological domain

848 – 963

116

Cytoplasmic Potential

Domain

46 – 82

37

LDL-receptor class A 1

Domain

85 – 123

39

LDL-receptor class A 2

Domain

126 – 164

39

LDL-receptor class A 3

Domain

166 – 202

37

LDL-receptor class A 4

Domain

205 – 246

42

LDL-receptor class A 5

Domain

258 – 295

38

LDL-receptor class A 6

Domain

298 – 334

37

LDL-receptor class A 7

Domain

336 – 375

40

EGF-like 1

Domain

376 – 415

40

EGF-like 2; calcium-binding Potential

Repeat

462 – 508

47

LDL-receptor class B 1

Repeat

509 – 551

43

LDL-receptor class B 2

Repeat

552 – 595

44

LDL-receptor class B 3

Repeat

596 – 639

44

LDL-receptor class B 4

Repeat

640 – 681

42

LDL-receptor class B 5

Region

740 – 798

59

Clustered O-linked oligosaccharides

Amino acid modifications

Glycosylation

176

1

N-linked (GlcNAc...) Potential

Glycosylation

441

1

N-linked (GlcNAc...) Potential

Glycosylation

518

1

N-linked (GlcNAc...) Potential

Glycosylation

538

1

N-linked (GlcNAc...) Potential

Glycosylation

772

1

N-linked (GlcNAc...) Potential

Glycosylation

807

1

N-linked (GlcNAc...) Potential

Disulfide bond

47 ↔ 59

By similarity

Disulfide bond

54 ↔ 72

By similarity

Disulfide bond

66 ↔ 81

By similarity

Disulfide bond

86 ↔ 98

By similarity

Disulfide bond

93 ↔ 111

By similarity

Disulfide bond

105 ↔ 122

By similarity

Disulfide bond

127 ↔ 141

By similarity

Disulfide bond

134 ↔ 154

By similarity

Disulfide bond

148 ↔ 163

By similarity

Disulfide bond

167 ↔ 179

By similarity

Disulfide bond

174 ↔ 192

By similarity

Disulfide bond

186 ↔ 201

By similarity

Disulfide bond

206 ↔ 221

By similarity

Disulfide bond

213 ↔ 234

By similarity

Disulfide bond

228 ↔ 245

By similarity

Disulfide bond

259 ↔ 272

By similarity

Disulfide bond

267 ↔ 285

By similarity

Disulfide bond

279 ↔ 294

By similarity

Disulfide bond

299 ↔ 311

By similarity

Disulfide bond

306 ↔ 324

By similarity

Disulfide bond

318 ↔ 333

By similarity

Disulfide bond

340 ↔ 351

By similarity

Disulfide bond

347 ↔ 360

By similarity

Disulfide bond

362 ↔ 374

By similarity

Disulfide bond

380 ↔ 390

By similarity

Disulfide bond

386 ↔ 399

By similarity

Disulfide bond

401 ↔ 414

By similarity

Natural variations

Alternative sequence

166 – 295

130

LCAPH…EADCP → S in isoform 2.

VSP_010305

Alternative sequence

166

1

L → W in isoform 4.

VSP_038181

Alternative sequence

167 – 336

170

Missing in isoform 4.

VSP_010306

Alternative sequence

737 – 812

76

APQST…HSQHY → D in isoform 2.

VSP_010307

Alternative sequence

893 – 951

59

Missing in isoform 2 and isoform 3.

VSP_010308

Natural variant

25

1

Q → R. Ref.1 Ref.2 Ref.3 Ref.5
Corresponds to variant rs4926972 [ dbSNP | Ensembl ].

VAR_046974

Natural variant

46

1

D → E. Ref.1 Ref.2 Ref.3 Ref.5 Ref.14
Corresponds to variant rs3820198 [ dbSNP | Ensembl ].

VAR_018468

Natural variant

453

1

V → M.
Corresponds to variant rs5180 [ dbSNP | Ensembl ].

VAR_037624

Natural variant

466

1

W → C.
Corresponds to variant rs5181 [ dbSNP | Ensembl ].

VAR_037625

Natural variant

607

1

Q → R.
Corresponds to variant rs5172 [ dbSNP | Ensembl ].

VAR_037626

Natural variant

611

1

I → L.
Corresponds to variant rs5170 [ dbSNP | Ensembl ].

VAR_037627

Natural variant

653

1

S → T.
Corresponds to variant rs5171 [ dbSNP | Ensembl ].

VAR_037628

Natural variant

736

1

R → Q.
Corresponds to variant rs5172 [ dbSNP | Ensembl ].

VAR_059079

Natural variant

952

1

R → Q Associated with susceptibility to myocardial infarction type 1; increases activation of MAPK14 by oxidized low density lipoprotein. Ref.14 Ref.15
Corresponds to variant rs5174 [ dbSNP | Ensembl ].

VAR_018469

Experimental info

Sequence conflict

262

1

A → V in BAA09328. Ref.1

Sequence conflict

262

1

A → V in BAA21824. Ref.2

Sequence conflict

405

1

Y → C in CAA99509. Ref.3

Sequence conflict

418

1

A → G in BAA09328. Ref.1

Sequence conflict

418

1

A → G in BAA21824. Ref.2

Sequence conflict

418

1

A → G in BAA21825. Ref.2

Sequence conflict

430

1

H → Y in BAA09328. Ref.1

Sequence conflict

430

1

H → Y in BAA21824. Ref.2

Sequence conflict

430

1

H → Y in BAA21825. Ref.2

Sequence conflict

430

1

H → Y in CAA99509. Ref.3

Sequence conflict

488

1

Q → R in CAA99509. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

963

Helix Strand Turn

Details...

Beta strand

51 – 53

3

Beta strand

59 – 61

3

Helix

62 – 64

3

Beta strand

67 – 69

3

Beta strand

72 – 75

4

Turn

76 – 78

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (ApoER2 922) [UniParc]. Last modified September 22, 2009. Version 4. Checksum: B10DCF72F62DE71C	FASTA	963	105,634
	10 20 30 40 50 60 MGLPEPGPLR LLALLLLLLL LLLLQLQHLA AAAADPLLGG QGPAKDCEKD QFQCRNERCI 70 80 90 100 110 120 PSVWRCDEDD DCLDHSDEDD CPKKTCADSD FTCDNGHCIH ERWKCDGEEE CPDGSDESEA 130 140 150 160 170 180 TCTKQVCPAE KLSCGPTSHK CVPASWRCDG EKDCEGGADE AGCATLCAPH EFQCGNRSCL 190 200 210 220 230 240 AAVFVCDGDD DCGDGSDERG CADPACGPRE FRCGGDGGGA CIPERWVCDR QFDCEDRSDE 250 260 270 280 290 300 AAELCGRPGP GATSAPAACA TASQFACRSG ECVHLGWRCD GDRDCKDKSD EADCPLGTCR 310 320 330 340 350 360 GDEFQCGDGT CVLAIKHCNQ EQDCPDGSDE AGCLQGLNEC LHNNGGCSHI CTDLKIGFEC 370 380 390 400 410 420 TCPAGFQLLD QKTCGDIDEC KDPDACSQIC VNYKGYFKCE CYPGYEMDLL TKNCKAAAGK 430 440 450 460 470 480 SPSLIFTNRH EVRRIDLVKR NYSRLIPMLK NVVALDVEVA TNRIYWCDLS YRKIYSAYMD 490 500 510 520 530 540 KASDPKEQEV LIDEQLHSPE GLAVDWVHKH IYWTDSGNKT ISVATVDGGR RRTLFSRNLS 550 560 570 580 590 600 EPRAIAVDPL RGFMYWSDWG DQAKIEKSGL NGVDRQTLVS DNIEWPNGIT LDLLSQRLYW 610 620 630 640 650 660 VDSKLHQLSS IDFSGGNRKT LISSTDFLSH PFGIAVFEDK VFWTDLENEA IFSANRLNGL 670 680 690 700 710 720 EISILAENLN NPHDIVIFHE LKQPRAPDAC ELSVQPNGGC EYLCLPAPQI SSHSPKYTCA 730 740 750 760 770 780 CPDTMWLGPD MKRCYRAPQS TSTTTLASTM TRTVPATTRA PGTTVHRSTY QNHSTETPSL 790 800 810 820 830 840 TAAVPSSVSV PRAPSISPST LSPATSNHSQ HYANEDSKMG STVTAAVIGI IVPIVVIALL 850 860 870 880 890 900 CMSGYLIWRN WKRKNTKSMN FDNPVYRKTT EEEDEDELHI GRTAQIGHVY PAAISSFDRP 910 920 930 940 950 960 LWAEPCLGET REPEDPAPAL KELFVLPGEP RSQLHQLPKN PLSELPVVKS KRVALSLEDD GLP
	Isoform 2 (ApoER2 906) [UniParc]. Checksum: B996C9CAEC69C1E9	FASTA	700	77,845
	10 20 30 40 50 60 MGLPEPGPLR LLALLLLLLL LLLLQLQHLA AAAADPLLGG QGPAKDCEKD QFQCRNERCI 70 80 90 100 110 120 PSVWRCDEDD DCLDHSDEDD CPKKTCADSD FTCDNGHCIH ERWKCDGEEE CPDGSDESEA 130 140 150 160 170 180 TCTKQVCPAE KLSCGPTSHK CVPASWRCDG EKDCEGGADE AGCATSLGTC RGDEFQCGDG 190 200 210 220 230 240 TCVLAIKHCN QEQDCPDGSD EAGCLQGLNE CLHNNGGCSH ICTDLKIGFE CTCPAGFQLL 250 260 270 280 290 300 DQKTCGDIDE CKDPDACSQI CVNYKGYFKC ECYPGYEMDL LTKNCKAAAG KSPSLIFTNR 310 320 330 340 350 360 HEVRRIDLVK RNYSRLIPML KNVVALDVEV ATNRIYWCDL SYRKIYSAYM DKASDPKEQE 370 380 390 400 410 420 VLIDEQLHSP EGLAVDWVHK HIYWTDSGNK TISVATVDGG RRRTLFSRNL SEPRAIAVDP 430 440 450 460 470 480 LRGFMYWSDW GDQAKIEKSG LNGVDRQTLV SDNIEWPNGI TLDLLSQRLY WVDSKLHQLS 490 500 510 520 530 540 SIDFSGGNRK TLISSTDFLS HPFGIAVFED KVFWTDLENE AIFSANRLNG LEISILAENL 550 560 570 580 590 600 NNPHDIVIFH ELKQPRAPDA CELSVQPNGG CEYLCLPAPQ ISSHSPKYTC ACPDTMWLGP 610 620 630 640 650 660 DMKRCYRDAN EDSKMGSTVT AAVIGIIVPI VVIALLCMSG YLIWRNWKRK NTKSMNFDNP 670 680 690 700 VYRKTTEEED EDELHIGRTA QIGHVYPARV ALSLEDDGLP
	Isoform 3 [UniParc]. Checksum: 043E708314261E3C	FASTA	904	99,092
	10 20 30 40 50 60 MGLPEPGPLR LLALLLLLLL LLLLQLQHLA AAAADPLLGG QGPAKDCEKD QFQCRNERCI 70 80 90 100 110 120 PSVWRCDEDD DCLDHSDEDD CPKKTCADSD FTCDNGHCIH ERWKCDGEEE CPDGSDESEA 130 140 150 160 170 180 TCTKQVCPAE KLSCGPTSHK CVPASWRCDG EKDCEGGADE AGCATLCAPH EFQCGNRSCL 190 200 210 220 230 240 AAVFVCDGDD DCGDGSDERG CADPACGPRE FRCGGDGGGA CIPERWVCDR QFDCEDRSDE 250 260 270 280 290 300 AAELCGRPGP GATSAPAACA TASQFACRSG ECVHLGWRCD GDRDCKDKSD EADCPLGTCR 310 320 330 340 350 360 GDEFQCGDGT CVLAIKHCNQ EQDCPDGSDE AGCLQGLNEC LHNNGGCSHI CTDLKIGFEC 370 380 390 400 410 420 TCPAGFQLLD QKTCGDIDEC KDPDACSQIC VNYKGYFKCE CYPGYEMDLL TKNCKAAAGK 430 440 450 460 470 480 SPSLIFTNRH EVRRIDLVKR NYSRLIPMLK NVVALDVEVA TNRIYWCDLS YRKIYSAYMD 490 500 510 520 530 540 KASDPKEQEV LIDEQLHSPE GLAVDWVHKH IYWTDSGNKT ISVATVDGGR RRTLFSRNLS 550 560 570 580 590 600 EPRAIAVDPL RGFMYWSDWG DQAKIEKSGL NGVDRQTLVS DNIEWPNGIT LDLLSQRLYW 610 620 630 640 650 660 VDSKLHQLSS IDFSGGNRKT LISSTDFLSH PFGIAVFEDK VFWTDLENEA IFSANRLNGL 670 680 690 700 710 720 EISILAENLN NPHDIVIFHE LKQPRAPDAC ELSVQPNGGC EYLCLPAPQI SSHSPKYTCA 730 740 750 760 770 780 CPDTMWLGPD MKRCYRAPQS TSTTTLASTM TRTVPATTRA PGTTVHRSTY QNHSTETPSL 790 800 810 820 830 840 TAAVPSSVSV PRAPSISPST LSPATSNHSQ HYANEDSKMG STVTAAVIGI IVPIVVIALL 850 860 870 880 890 900 CMSGYLIWRN WKRKNTKSMN FDNPVYRKTT EEEDEDELHI GRTAQIGHVY PARVALSLED DGLP
	Isoform 4 (ApoER2delta4-7) [UniParc]. Checksum: 1A414B09D40BA1BC	FASTA	793	87,959
	10 20 30 40 50 60 MGLPEPGPLR LLALLLLLLL LLLLQLQHLA AAAADPLLGG QGPAKDCEKD QFQCRNERCI 70 80 90 100 110 120 PSVWRCDEDD DCLDHSDEDD CPKKTCADSD FTCDNGHCIH ERWKCDGEEE CPDGSDESEA 130 140 150 160 170 180 TCTKQVCPAE KLSCGPTSHK CVPASWRCDG EKDCEGGADE AGCATWLNEC LHNNGGCSHI 190 200 210 220 230 240 CTDLKIGFEC TCPAGFQLLD QKTCGDIDEC KDPDACSQIC VNYKGYFKCE CYPGYEMDLL 250 260 270 280 290 300 TKNCKAAAGK SPSLIFTNRH EVRRIDLVKR NYSRLIPMLK NVVALDVEVA TNRIYWCDLS 310 320 330 340 350 360 YRKIYSAYMD KASDPKEQEV LIDEQLHSPE GLAVDWVHKH IYWTDSGNKT ISVATVDGGR 370 380 390 400 410 420 RRTLFSRNLS EPRAIAVDPL RGFMYWSDWG DQAKIEKSGL NGVDRQTLVS DNIEWPNGIT 430 440 450 460 470 480 LDLLSQRLYW VDSKLHQLSS IDFSGGNRKT LISSTDFLSH PFGIAVFEDK VFWTDLENEA 490 500 510 520 530 540 IFSANRLNGL EISILAENLN NPHDIVIFHE LKQPRAPDAC ELSVQPNGGC EYLCLPAPQI 550 560 570 580 590 600 SSHSPKYTCA CPDTMWLGPD MKRCYRAPQS TSTTTLASTM TRTVPATTRA PGTTVHRSTY 610 620 630 640 650 660 QNHSTETPSL TAAVPSSVSV PRAPSISPST LSPATSNHSQ HYANEDSKMG STVTAAVIGI 670 680 690 700 710 720 IVPIVVIALL CMSGYLIWRN WKRKNTKSMN FDNPVYRKTT EEEDEDELHI GRTAQIGHVY 730 740 750 760 770 780 PAAISSFDRP LWAEPCLGET REPEDPAPAL KELFVLPGEP RSQLHQLPKN PLSELPVVKS 790 KRVALSLEDD GLP
	Isoform 5 (Sequence not available).		–	–

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human apolipoprotein E receptor 2. A novel lipoprotein receptor of the low density lipoprotein receptor family predominantly expressed in brain." Kim D.-H., Iijima H., Goto K., Sakai J., Ishii H., Kim H.-J., Suzuki H., Kondo H., Saeki S., Yamamoto T. J. Biol. Chem. 271:8373-8380(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS ARG-25 AND GLU-46. Tissue: Placenta.
[2]	"Exon/intron organization, chromosome localization, alternative splicing, and transcription units of the human apolipoprotein E receptor 2 gene." Kim D.-H., Magoori K., Inoue T.R., Mao C.C., Kim H.-J., Suzuki H., Fujita T., Endo Y., Saeki S., Yamamoto T.T. J. Biol. Chem. 272:8498-8504(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 4), VARIANTS ARG-25 AND GLU-46. Tissue: Peripheral blood.
[3]	"Identification of a novel exon in apolipoprotein E receptor 2 leading to alternatively spliced mRNAs found in cells of the vascular wall but not in neuronal tissue." Korschineck I., Ziegler S., Breuss J., Lang I., Lorenz M., Kaun C., Ambros P.F., Binder B.R. J. Biol. Chem. 276:13192-13197(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS ARG-25 AND GLU-46. Tissue: Umbilical vein.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 720-963 (ISOFORM 1), VARIANTS ARG-25 AND GLU-46. Tissue: Eye and Lung.
[6]	"Expression and alternate splicing of apolipoprotein E receptor 2 in brain." Clatworthy A.E., Stockinger W., Christie R.H., Schneider W.J., Nimpf J., Hyman B.T., Rebeck G.W. Neuroscience 90:903-911(1999) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[7]	"Apolipoprotein E (apoE) isoforms differentially induce nitric oxide production in endothelial cells." Sacre S.M., Stannard A.K., Owen J.S. FEBS Lett. 540:181-187(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYROSINE RESIDUES.
[8]	"Identification and characterization of LRP8 (apoER2) in human blood platelets." Riddell D.R., Vinogradov D.V., Stannard A.K., Chadwick N., Owen J.S. J. Lipid Res. 40:1925-1930(1999) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION, TISSUE SPECIFICITY.
[9]	"Differential binding of ligands to the apolipoprotein E receptor 2." Andersen O.M., Benhayon D., Curran T., Willnow T.E. Biochemistry 42:9355-9364(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A RECEPTOR FOR REELIN.
[10]	"Domains of apoE required for binding to apoE receptor 2 and to phospholipids: implications for the functions of apoE in the brain." Li X., Kypreos K., Zanni E.E., Zannis V. Biochemistry 42:10406-10417(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A RECEPTOR FOR APOE.
[11]	"Dimers of beta 2-glycoprotein I increase platelet deposition to collagen via interaction with phospholipids and the apolipoprotein E receptor 2'." Lutters B.C., Derksen R.H., Tekelenburg W.L., Lenting P.J., Arnout J., de Groot P.G. J. Biol. Chem. 278:33831-33838(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A RECEPTOR FOR BETA 2-GLYCOPROTEIN I.
[12]	"The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2." Poirier S., Mayer G., Benjannet S., Bergeron E., Marcinkiewicz J., Nassoury N., Mayer H., Nimpf J., Prat A., Seidah N.G. J. Biol. Chem. 283:2363-2372(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PCSK9.
[13]	"The E3 ubiquitin ligase IDOL induces the degradation of the low density lipoprotein receptor family members VLDLR and ApoER2." Hong C., Duit S., Jalonen P., Out R., Scheer L., Sorrentino V., Boyadjian R., Rodenburg K.W., Foley E., Korhonen L., Lindholm D., Nimpf J., van Berkel T.J., Tontonoz P., Zelcer N. J. Biol. Chem. 285:19720-19726(2010) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION.
[14]	"Low-density lipoprotein receptor-related protein 8 (apolipoprotein E receptor 2) gene polymorphisms in Alzheimer's disease." Ma S.L., Ng H.K., Baum L., Pang J.C., Chiu H.F., Woo J., Tang N.L., Lam L.C. Neurosci. Lett. 332:216-218(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GLU-46 AND GLN-952.
[15]	"An LRP8 variant is associated with familial and premature coronary artery disease and myocardial infarction." Shen G.-Q., Li L., Girelli D., Seidelmann S.B., Rao S., Fan C., Park J.E., Xi Q., Li J., Hu Y., Olivieri O., Marchant K., Barnard J., Corrocher R., Elston R., Cassano J., Henderson S., Hazen S.L. , Plow E.F., Topol E.J., Wang Q.K. Am. J. Hum. Genet. 81:780-791(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GLN-952, CHARACTERIZATION OF VARIANT GLN-952, ASSOCIATION WITH SUSCEPTIBILITY TO MYOCARDIAL INFARCTION TYPE 1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D50678 mRNA. Translation: BAA09328.1.
D86407 Genomic DNA. Translation: BAA21824.1.
D86407 Genomic DNA. Translation: BAA21825.1.
Z75190 mRNA. Translation: CAA99509.1. Frameshift.
AL606760, AL355483 Genomic DNA. Translation: CAI18908.1.
AL606760, AL355483 Genomic DNA. Translation: CAI18909.1.
AL355483, AL606760 Genomic DNA. Translation: CAI22782.1.
AL606760, AL355483 Genomic DNA. Translation: CAI18910.1.
AL355483, AL606760 Genomic DNA. Translation: CAI22780.1.
AL355483, AL606760 Genomic DNA. Translation: CAI22781.1.
BC006443 mRNA. Translation: AAH06443.1.
BC051836 mRNA. Translation: AAH51836.2.

IPI

IPI00005774.
IPI00384247.
IPI00410272.
IPI00410273.

RefSeq

NP_001018064.1. NM_001018054.2.
NP_004622.2. NM_004631.4.
NP_059992.3. NM_017522.4.
NP_150643.2. NM_033300.3.

UniGene

Hs.280387.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3A7Q	X-ray	2.60	B	42-83	[»]

ProteinModelPortal

Q14114.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48670N.

IntAct

Q14114. 1 interaction.

STRING

9606.ENSP00000303634.

PTM databases

PhosphoSite

Q14114.

Polymorphism databases

DMDM

259016389.

Proteomic databases

PaxDb

Q14114.

PRIDE

Q14114.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000306052; ENSP00000303634; ENSG00000157193.
ENST00000347547; ENSP00000334522; ENSG00000157193.
ENST00000354412; ENSP00000346391; ENSG00000157193.
ENST00000371454; ENSP00000360509; ENSG00000157193.

GeneID

7804.

KEGG

hsa:7804.

UCSC

uc001cvi.2. human.
uc001cvj.2. human.
uc001cvk.2. human.
uc001cvl.2. human.

Organism-specific databases

CTD

7804.

GeneCards

GC01M053711.

HGNC

HGNC:6700. LRP8.

MIM

602600. gene.
608446. phenotype.

neXtProt

NX_Q14114.

PharmGKB

PA30457.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG255913.

HOVERGEN

HBG006250.

InParanoid

Q14114.

OMA

EFQCSNR.

OrthoDB

EOG479F6G.

PhylomeDB

Q14114.

Enzyme and pathway databases

Pathway_Interaction_DB

lis1pathway. Lissencephaly gene (LIS1) in neuronal migration and development.
reelinpathway. Reelin signaling pathway.

Reactome

REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

Q14114.

Bgee

Q14114.

CleanEx

HS_LRP8.

Genevestigator

Q14114.

GermOnline

ENSG00000157193. Homo sapiens.

Family and domain databases

Gene3D

2.120.10.30. 1 hit.
4.10.400.10. 7 hits.

InterPro

IPR011042. 6-blade_b-propeller_TolB-like.
IPR026823. cEGF.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR009030. Growth_fac_rcpt.
IPR023415. LDLR_class-A_CS.
IPR000033. LDLR_classB_rpt.
IPR002172. LDrepeatLR_classA_rpt.
[Graphical view]

Pfam

PF12662. cEGF. 1 hit.
PF00057. Ldl_recept_a. 7 hits.
PF00058. Ldl_recept_b. 5 hits.
[Graphical view]

SMART

SM00181. EGF. 2 hits.
SM00179. EGF_CA. 1 hit.
SM00192. LDLa. 7 hits.
SM00135. LY. 5 hits.
[Graphical view]

SUPFAM

SSF57184. Grow_fac_recept. 1 hit.
SSF57424. LDL_rcpt_classA_cys-rich. 7 hits.

PROSITE

PS00010. ASX_HYDROXYL. 2 hits.
PS00022. EGF_1. False negative.
PS01186. EGF_2. 2 hits.
PS50026. EGF_3. 2 hits.
PS01187. EGF_CA. 1 hit.
PS01209. LDLRA_1. 7 hits.
PS50068. LDLRA_2. 7 hits.
PS51120. LDLRB. 5 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q14114.

GenomeRNAi

7804.

NextBio

30188.

PMAP-CutDB

B1AMT8.

SOURCE

Search...

Entry information

Entry name

LRP8_HUMAN

Accession

Primary (citable) accession number: Q14114
Secondary accession number(s): B1AMT6 , B1AMT7, B1AMT8, O14968, Q86V27, Q99876, Q9BR78

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2004
Last sequence update:	September 22, 2009
Last modified:	May 1, 2013
This is version 129 of the entry and version 4 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.