LRP8_HUMAN » Low-density lipoprotein receptor-related protein 8

LRP8_HUMAN » Low-density lipoprotein receptor-related protein 8
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
LRP8_HUMAN » Low-density lipoprotein receptor-related protein 8 » LRP-8; Apolipoprotein E receptor 2;
Hydrophobic Thickness 34.0 ± 2.0 Å
Tilt Angle 9 ± 10°
ΔGtransfer -23.3 kcal/mol
ΔGfold -20.4 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome
Topology Out
TM Segments 823-846 (821-856)
Pathways

Hemostasis (Reactome)

Signal Transduction (Reactome)

PDB 3a7q (B=42-83)
OPM none
Complexes none
Interactions

SYJ2B, Complex: SYJ2B:LRP8, PubMed

Domains

AA: 45-81, PDBID: 3A7Q, Subunit B, Seq Identity:100%, Low-density lipoprotein receptor domain class A

AA: 84-122, PDBID: 2KNX, Subunit A, Seq Identity:54%, Low-density lipoprotein receptor domain class A

AA: 125-163, PDBID: 1F5Y, Subunit A, Seq Identity:50%, Low-density lipoprotein receptor domain class A

AA: 165-201, PDBID: 2KNY, Subunit A, Seq Identity:52%, Low-density lipoprotein receptor domain class A

AA: 204-245, PDBID: 1D2L, Subunit A, Seq Identity:56%, Low-density lipoprotein receptor domain class A

AA: 257-294, PDBID: 1AJJ, Subunit A, Seq Identity:62%, Low-density lipoprotein receptor domain class A

AA: 297-333, PDBID: 1D2J, Subunit A, Seq Identity:58%, Low-density lipoprotein receptor domain class A

AA: 340-374, PDBID: 3S94, Subunit A, Seq Identity:51%, Coagulation Factor Xa inhibitory site

AA: 462-506, PDBID: 1IJQ, Subunit A, Seq Identity:47%, Low-density lipoprotein receptor repeat class B

AA: 509-549, PDBID: 1IJQ, Subunit A, Seq Identity:61%, Low-density lipoprotein receptor repeat class B

AA: 552-593, PDBID: 1IJQ, Subunit A, Seq Identity:75%, Low-density lipoprotein receptor repeat class B

AA: 596-638, PDBID: 1IJQ, Subunit A, Seq Identity:67%, Low-density lipoprotein receptor repeat class B

AA: 639-679, PDBID: 1IJQ, Subunit A, Seq Identity:69%, Low-density lipoprotein receptor repeat class B

UniProt annotation for LRP8_HUMAN » Low-density lipoprotein receptor-related protein 8
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.

SUBUNIT: Reelin associates with two or more receptor molecules. Interacts with DAB1 and JNK-interacting proteins. Interacts with SNX17 (By similarity). Interacts with PCSK9.

TISSUE SPECIFICITY: Expressed mainly in brain and placenta. Also expressed in platelets and megakaryocytic cells. Not expressed in the liver.

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).

DISEASE: Myocardial infarction 1 (MCI1) OMIM: 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.

UniProt features for LRP8_HUMAN » Low-density lipoprotein receptor-related protein 8
SIGNAL 1 32 Potential.
CHAIN 33 963 Low-density lipoprotein receptor-related protein 8.
DOMAIN 46 82 LDL-receptor class A 1.
DOMAIN 85 123 LDL-receptor class A 2.
DOMAIN 126 164 LDL-receptor class A 3.
DOMAIN 166 202 LDL-receptor class A 4.
DOMAIN 205 246 LDL-receptor class A 5.
DOMAIN 258 295 LDL-receptor class A 6.
DOMAIN 298 334 LDL-receptor class A 7.
DOMAIN 336 375 EGF-like 1.
DOMAIN 376 415 EGF-like 2; calcium-binding (Potential).
REPEAT 462 508 LDL-receptor class B 1.
REPEAT 509 551 LDL-receptor class B 2.
REPEAT 552 595 LDL-receptor class B 3.
REPEAT 596 639 LDL-receptor class B 4.
REPEAT 640 681 LDL-receptor class B 5.
REGION 740 798 Clustered O-linked oligosaccharides.
DISULFID 47 59 By similarity.
DISULFID 54 72 By similarity.
DISULFID 66 81 By similarity.
DISULFID 86 98 By similarity.
DISULFID 93 111 By similarity.
DISULFID 105 122 By similarity.
DISULFID 127 141 By similarity.
DISULFID 134 154 By similarity.
DISULFID 148 163 By similarity.
DISULFID 167 179 By similarity.
DISULFID 174 192 By similarity.
DISULFID 186 201 By similarity.
DISULFID 206 221 By similarity.
DISULFID 213 234 By similarity.
DISULFID 228 245 By similarity.
DISULFID 259 272 By similarity.
DISULFID 267 285 By similarity.
DISULFID 279 294 By similarity.
DISULFID 299 311 By similarity.
DISULFID 306 324 By similarity.
DISULFID 318 333 By similarity.
DISULFID 340 351 By similarity.
DISULFID 347 360 By similarity.
DISULFID 362 374 By similarity.
DISULFID 380 390 By similarity.
DISULFID 386 399 By similarity.
DISULFID 401 414 By similarity.
Amino Acid Sequence for LRP8_HUMAN » Low-density lipoprotein receptor-related protein 8
MGLPEPGPLR LLALLLLLLL LLLLQLQHLA AAAADPLLGG QGPAKDCEKD QFQCRNERCI PSVWRCDEDD DCLDHSDEDD CPKKTCADSD FTCDNGHCIH ERWKCDGEEE CPDGSDESEA TCTKQVCPAE KLSCGPTSHK CVPASWRCDG EKDCEGGADE AGCATLCAPH EFQCGNRSCL AAVFVCDGDD DCGDGSDERG CADPACGPRE FRCGGDGGGA CIPERWVCDR QFDCEDRSDE AAELCGRPGP GATSAPAACA TASQFACRSG ECVHLGWRCD GDRDCKDKSD EADCPLGTCR GDEFQCGDGT CVLAIKHCNQ EQDCPDGSDE AGCLQGLNEC LHNNGGCSHI CTDLKIGFEC TCPAGFQLLD QKTCGDIDEC KDPDACSQIC VNYKGYFKCE CYPGYEMDLL TKNCKAAAGK SPSLIFTNRH EVRRIDLVKR NYSRLIPMLK NVVALDVEVA TNRIYWCDLS YRKIYSAYMD KASDPKEQEV LIDEQLHSPE GLAVDWVHKH IYWTDSGNKT ISVATVDGGR RRTLFSRNLS EPRAIAVDPL RGFMYWSDWG DQAKIEKSGL NGVDRQTLVS DNIEWPNGIT LDLLSQRLYW VDSKLHQLSS IDFSGGNRKT LISSTDFLSH PFGIAVFEDK VFWTDLENEA IFSANRLNGL EISILAENLN NPHDIVIFHE LKQPRAPDAC ELSVQPNGGC EYLCLPAPQI SSHSPKYTCA CPDTMWLGPD MKRCYRAPQS TSTTTLASTM TRTVPATTRA PGTTVHRSTY QNHSTETPSL TAAVPSSVSV PRAPSISPST LSPATSNHSQ HYANEDSKMG STVTAAVIGI IVPIVVIALL CMSGYLIWRN WKRKNTKSMN FDNPVYRKTT EEEDEDELHI GRTAQIGHVY PAAISSFDRP LWAEPCLGET REPEDPAPAL KELFVLPGEP RSQLHQLPKN PLSELPVVKS KRVALSLEDD GLP