9.B.87.1.14
Low-density lipoprotein receptor-related protein 2, LRP2, of 4630 aas and 1 TMS. Also called the multiligand endocytic receptor. Acts together with CUBN to mediate endocytosis of
high-density lipoproteins and is responsible for receptor-mediated
uptake of polybasic drugs such as aprotinin, aminoglycosides and
polymyxin B. In the kidney, it mediates the tubular uptake
and clearance of leptin, and transports leptin across the blood-brain barrier through endocytosis at the choroid
plexus epithelium. Endocytosis of leptin in neuronal
cells is required for hypothalamic leptin signaling and leptin-mediated
regulation of feeding and body weight. It also mediates
endocytosis and subsequent lysosomal degradation of CST3 in kidney
proximal tubule cells, and catalyzes renal uptake of
25-hydroxyvitamin D3 in complex with the vitamin D3 transporter GC/DBP. It is also involved in the renal uptake of metallothionein-bound heavy
metals (Klassen et al. 2004).
Together with CUBN, it mediates renal reabsorption of myoglobin as well as renal uptake and subsequent lysosomal degradation
of APOM while playing a role in kidney selenium homeostasis by facilitating renal endocytosis of selenoprotein SEPP1. It similarly mediates renal uptake of the antiapoptotic protein BIRC5/survivin which
may be important for functional integrity of the kidney (Jobst-Schwan et al. 2013).
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| Accession Number: | P98164 |
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| Protein Name: | Low-density lipoprotein receptor-related protein 2 |
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| Length: | 4655 |
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| Molecular Weight: | 521958.00 |
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| Species: | Homo sapiens (Human) [9606] |
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| Number of TMSs: | 1 |
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| Location1 / Topology2 / Orientation3: |
Apical cell membrane1 / Single-pass type I membrane protein2 |
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| Substrate |
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1: MDRGPAAVAC TLLLALVACL APASGQECDS AHFRCGSGHC IPADWRCDGT KDCSDDADEI
61: GCAVVTCQQG YFKCQSEGQC IPNSWVCDQD QDCDDGSDER QDCSQSTCSS HQITCSNGQC
121: IPSEYRCDHV RDCPDGADEN DCQYPTCEQL TCDNGACYNT SQKCDWKVDC RDSSDEINCT
181: EICLHNEFSC GNGECIPRAY VCDHDNDCQD GSDEHACNYP TCGGYQFTCP SGRCIYQNWV
241: CDGEDDCKDN GDEDGCESGP HDVHKCSPRE WSCPESGRCI SIYKVCDGIL DCPGREDENN
301: TSTGKYCSMT LCSALNCQYQ CHETPYGGAC FCPPGYIINH NDSRTCVEFD DCQIWGICDQ
361: KCESRPGRHL CHCEEGYILE RGQYCKANDS FGEASIIFSN GRDLLIGDIH GRSFRILVES
421: QNRGVAVGVA FHYHLQRVFW TDTVQNKVFS VDINGLNIQE VLNVSVETPE NLAVDWVNNK
481: IYLVETKVNR IDMVNLDGSY RVTLITENLG HPRGIAVDPT VGYLFFSDWE SLSGEPKLER
541: AFMDGSNRKD LVKTKLGWPA GVTLDMISKR VYWVDSRFDY IETVTYDGIQ RKTVVHGGSL
601: IPHPFGVSLF EGQVFFTDWT KMAVLKANKF TETNPQVYYQ ASLRPYGVTV YHSLRQPYAT
661: NPCKDNNGGC EQVCVLSHRT DNDGLGFRCK CTFGFQLDTD ERHCIAVQNF LIFSSQVAIR
721: GIPFTLSTQE DVMVPVSGNP SFFVGIDFDA QDSTIFFSDM SKHMIFKQKI DGTGREILAA
781: NRVENVESLA FDWISKNLYW TDSHYKSISV MRLADKTRRT VVQYLNNPRS VVVHPFAGYL
841: FFTDWFRPAK IMRAWSDGSH LLPVINTTLG WPNGLAIDWA ASRLYWVDAY FDKIEHSTFD
901: GLDRRRLGHI EQMTHPFGLA IFGEHLFFTD WRLGAIIRVR KADGGEMTVI RSGIAYILHL
961: KSYDVNIQTG SNACNQPTHP NGDCSHFCFP VPNFQRVCGC PYGMRLASNH LTCEGDPTNE
1021: PPTEQCGLFS FPCKNGRCVP NYYLCDGVDD CHDNSDEQLC GTLNNTCSSS AFTCGHGECI
1081: PAHWRCDKRN DCVDGSDEHN CPTHAPASCL DTQYTCDNHQ CISKNWVCDT DNDCGDGSDE
1141: KNCNSTETCQ PSQFNCPNHR CIDLSFVCDG DKDCVDGSDE VGCVLNCTAS QFKCASGDKC
1201: IGVTNRCDGV FDCSDNSDEA GCPTRPPGMC HSDEFQCQED GICIPNFWEC DGHPDCLYGS
1261: DEHNACVPKT CPSSYFHCDN GNCIHRAWLC DRDNDCGDMS DEKDCPTQPF RCPSWQWQCL
1321: GHNICVNLSV VCDGIFDCPN GTDESPLCNG NSCSDFNGGC THECVQEPFG AKCLCPLGFL
1381: LANDSKTCED IDECDILGSC SQHCYNMRGS FRCSCDTGYM LESDGRTCKV TASESLLLLV
1441: ASQNKIIADS VTSQVHNIYS LVENGSYIVA VDFDSISGRI FWSDATQGKT WSAFQNGTDR
1501: RVVFDSSIIL TETIAIDWVG RNLYWTDYAL ETIEVSKIDG SHRTVLISKN LTNPRGLALD
1561: PRMNEHLLFW SDWGHHPRIE RASMDGSMRT VIVQDKIFWP CGLTIDYPNR LLYFMDSYLD
1621: YMDFCDYNGH HRRQVIASDL IIRHPYALTL FEDSVYWTDR ATRRVMRANK WHGGNQSVVM
1681: YNIQWPLGIV AVHPSKQPNS VNPCAFSRCS HLCLLSSQGP HFYSCVCPSG WSLSPDLLNC
1741: LRDDQPFLIT VRQHIIFGIS LNPEVKSNDA MVPIAGIQNG LDVEFDDAEQ YIYWVENPGE
1801: IHRVKTDGTN RTVFASISMV GPSMNLALDW ISRNLYSTNP RTQSIEVLTL HGDIRYRKTL
1861: IANDGTALGV GFPIGITVDP ARGKLYWSDQ GTDSGVPAKI ASANMDGTSV KTLFTGNLEH
1921: LECVTLDIEE QKLYWAVTGR GVIERGNVDG TDRMILVHQL SHPWGIAVHD SFLYYTDEQY
1981: EVIERVDKAT GANKIVLRDN VPNLRGLQVY HRRNAAESSN GCSNNMNACQ QICLPVPGGL
2041: FSCACATGFK LNPDNRSCSP YNSFIVVSML SAIRGFSLEL SDHSETMVPV AGQGRNALHV
2101: DVDVSSGFIY WCDFSSSVAS DNAIRRIKPD GSSLMNIVTH GIGENGVRGI AVDWVAGNLY
2161: FTNAFVSETL IEVLRINTTY RRVLLKVTVD MPRHIVVDPK NRYLFWADYG QRPKIERSFL
2221: DCTNRTVLVS EGIVTPRGLA VDRSDGYVYW VDDSLDIIAR IRINGENSEV IRYGSRYPTP
2281: YGITVFENSI IWVDRNLKKI FQASKEPENT EPPTVIRDNI NWLRDVTIFD KQVQPRSPAE
2341: VNNNPCLENN GGCSHLCFAL PGLHTPKCDC AFGTLQSDGK NCAISTENFL IFALSNSLRS
2401: LHLDPENHSP PFQTINVERT VMSLDYDSVS DRIYFTQNLA SGVGQISYAT LSSGIHTPTV
2461: IASGIGTADG IAFDWITRRI YYSDYLNQMI NSMAEDGSNR TVIARVPKPR AIVLDPCQGY
2521: LYWADWDTHA KIERATLGGN FRVPIVNSSL VMPSGLTLDY EEDLLYWVDA SLQRIERSTL
2581: TGVDREVIVN AAVHAFGLTL YGQYIYWTDL YTQRIYRANK YDGSGQIAMT TNLLSQPRGI
2641: NTVVKNQKQQ CNNPCEQFNG GCSHICAPGP NGAECQCPHE GNWYLANNRK HCIVDNGERC
2701: GASSFTCSNG RCISEEWKCD NDNDCGDGSD EMESVCALHT CSPTAFTCAN GRCVQYSYRC
2761: DYYNDCGDGS DEAGCLFRDC NATTEFMCNN RRCIPREFIC NGVDNCHDNN TSDEKNCPDR
2821: TCQSGYTKCH NSNICIPRVY LCDGDNDCGD NSDENPTYCT THTCSSSEFQ CASGRCIPQH
2881: WYCDQETDCF DASDEPASCG HSERTCLADE FKCDGGRCIP SEWICDGDND CGDMSDEDKR
2941: HQCQNQNCSD SEFLCVNDRP PDRRCIPQSW VCDGDVDCTD GYDENQNCTR RTCSENEFTC
3001: GYGLCIPKIF RCDRHNDCGD YSDERGCLYQ TCQQNQFTCQ NGRCISKTFV CDEDNDCGDG
3061: SDELMHLCHT PEPTCPPHEF KCDNGRCIEM MKLCNHLDDC LDNSDEKGCG INECHDPSIS
3121: GCDHNCTDTL TSFYCSCRPG YKLMSDKRTC VDIDECTEMP FVCSQKCENV IGSYICKCAP
3181: GYLREPDGKT CRQNSNIEPY LIFSNRYYLR NLTIDGYFYS LILEGLDNVV ALDFDRVEKR
3241: LYWIDTQRQV IERMFLNKTN KETIINHRLP AAESLAVDWV SRKLYWLDAR LDGLFVSDLN
3301: GGHRRMLAQH CVDANNTFCF DNPRGLALHP QYGYLYWADW GHRAYIGRVG MDGTNKSVII
3361: STKLEWPNGI TIDYTNDLLY WADAHLGYIE YSDLEGHHRH TVYDGALPHP FAITIFEDTI
3421: YWTDWNTRTV EKGNKYDGSN RQTLVNTTHR PFDIHVYHPY RQPIVSNPCG TNNGGCSHLC
3481: LIKPGGKGFT CECPDDFRTL QLSGSTYCMP MCSSTQFLCA NNEKCIPIWW KCDGQKDCSD
3541: GSDELALCPQ RFCRLGQFQC SDGNCTSPQT LCNAHQNCPD GSDEDRLLCE NHHCDSNEWQ
3601: CANKRCIPES WQCDTFNDCE DNSDEDSSHC ASRTCRPGQF RCANGRCIPQ AWKCDVDNDC
3661: GDHSDEPIEE CMSSAHLCDN FTEFSCKTNY RCIPKWAVCN GVDDCRDNSD EQGCEERTCH
3721: PVGDFRCKNH HCIPLRWQCD GQNDCGDNSD EENCAPRECT ESEFRCVNQQ CIPSRWICDH
3781: YNDCGDNSDE RDCEMRTCHP EYFQCTSGHC VHSELKCDGS ADCLDASDEA DCPTRFPDGA
3841: YCQATMFECK NHVCIPPYWK CDGDDDCGDG SDEELHLCLD VPCNSPNRFR CDNNRCIYSH
3901: EVCNGVDDCG DGTDETEEHC RKPTPKPCTE YEYKCGNGHC IPHDNVCDDA DDCGDWSDEL
3961: GCNKGKERTC AENICEQNCT QLNEGGFICS CTAGFETNVF DRTSCLDINE CEQFGTCPQH
4021: CRNTKGSYEC VCADGFTSMS DRPGKRCAAE GSSPLLLLPD NVRIRKYNLS SERFSEYLQD
4081: EEYIQAVDYD WDPKDIGLSV VYYTVRGEGS RFGAIKRAYI PNFESGRNNL VQEVDLKLKY
4141: VMQPDGIAVD WVGRHIYWSD VKNKRIEVAK LDGRYRKWLI STDLDQPAAI AVNPKLGLMF
4201: WTDWGKEPKI ESAWMNGEDR NILVFEDLGW PTGLSIDYLN NDRIYWSDFK EDVIETIKYD
4261: GTDRRVIAKE AMNPYSLDIF EDQLYWISKE KGEVWKQNKF GQGKKEKTLV VNPWLTQVRI
4321: FHQLRYNKSV PNLCKQICSH LCLLRPGGYS CACPQGSSFI EGSTTECDAA IELPINLPPP
4381: CRCMHGGNCY FDETDLPKCK CPSGYTGKYC EMAFSKGISP GTTAVAVLLT ILLIVVIGAL
4441: AIAGFFHYRR TGSLLPALPK LPSLSSLVKP SENGNGVTFR SGADLNMDIG VSGFGPETAI
4501: DRSMAMSEDF VMEMGKQPII FENPMYSARD SAVKVVQPIQ VTVSENVDNK NYGSPINPSE
4561: IVPETNPTSP AADGTQVTKW NLFKRKSKQT TNFENPIYAQ MENEQKESVA ATPPPSPSLP
4621: AKPKPPSRRD PTPTYSATED TFKDTANLVK EDSEV
