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9.B.87.1.1
Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).  Aminoglycosides (AGs) can cause deafness through the irreversible loss of cochlear sensory hair cells (HCs). Systemically administered Texas Red-labeled gentamicin (GTTR) enters the cochlea via the stria vascularis and then HCs selectively. GTTR uptake into HCs was completely abolished in transmembrane channel-like protein 1 (TMC1) knockout mice, indicating mechanotransducer channel-dependent AG uptake. Blockage of megalin, the candidate AG transporter in the stria vascularis, by binding competitor cilastatin prevented GTTR accumulation in HCs. Furthermore, cilastatin treatment markedly reduced AG-induced HC degeneration and hearing loss in vivo (Kim and Ricci 2022).

Accession Number:A2ARV4
Protein Name:Megalin
Length:4660
Molecular Weight:519208.00
Species:Mus musculus (Mouse) [10090]
Number of TMSs:2
Location1 / Topology2 / Orientation3: Membrane1 / Single-pass type I membrane protein2
Substrate

Cross database links:

RefSeq: NP_001074557.1   
Entrez Gene ID: 14725   
Pfam: PF07645    PF00057    PF00058   
KEGG: mmu:14725   

Gene Ontology

GO:0005905 C:coated pit
GO:0030139 C:endocytic vesicle
GO:0005783 C:endoplasmic reticulum
GO:0005794 C:Golgi apparatus
GO:0016021 C:integral to membrane
GO:0005509 F:calcium ion binding
GO:0004872 F:receptor activity
GO:0017124 F:SH3 domain binding
GO:0008283 P:cell proliferation
GO:0030900 P:forebrain development
GO:0006766 P:vitamin metabolic process

References (5)

[1] “Lineage-specific biology revealed by a finished genome assembly of the mouse.”  Church D.M.et.al.   19468303
[2] “The transcriptional landscape of the mammalian genome.”  Carninci P.et.al.   16141072
[3] “Megalin acts in concert with cubilin to mediate endocytosis of high density lipoproteins.”  Hammad S.M.et.al.   10766831
[4] “Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry.”  Dai J.et.al.   17203969
[5] “Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins.”  Wollscheid B.et.al.   19349973

External Searches:

Analyze:

Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
FASTA formatted sequence 
1:	MERGAAAAAW MLLLAIAACL APVSGQECGS GNFRCDNGYC IPASWRCDGT RDCLDDTDEI 
61:	GCPPRSCGSG FFLCPAEGTC IPSSWVCDQD KDCSDGADEQ QNCPGTTCSS QQLTCSNGQC 
121:	VPIEYRCDHV SDCPDGSDER NCYYPTCDQL TCANGACYNT SQKCDHKVDC RDSSDEANCT 
181:	TLCSQKEFQC GSGECILRAY VCDHDNDCED NSDEHNCNYD TCGGHQFTCS NGQCINQNWV 
241:	CDGDDDCQDS GDEDGCESNQ RHHTCYPREW ACPGSGRCIS MDKVCDGVPD CPEGEDENNA 
301:	TSGRYCGTGL CSILNCEYQC HQTPYGGECF CPPGHIINSN DSRTCIDFDD CQIWGICDQK 
361:	CESRQGRHQC LCEEGYILER GQHCKSNDSF SAASIIFSNG RDLLVGDLHG RNFRILAESK 
421:	NRGIVMGVDF HYQKHRVFWT DPMQAKVFST DINGLNTQEI LNVSIDAPEN LAVDWINNKL 
481:	YLVETRVNRI DVVNLEGNQR VTLITENLGH PRGIALDPTV GYLFFSDWGS LSGQPKVERA 
541:	FMDGSNRKDL VTTKLGWPAG ITLDLVSKRV YWVDSRYDYI ETVTYDGIQR KTVARGGSLV 
601:	PHPFGISLFE EHVFFTDWTK MAVMKANKFT DTNPQVYHQS SLTPFGVTVY HALRQPNATN 
661:	PCGNNNGGCA QICVLSHRTD NGGLGYRCKC EFGFELDADE HHCVAVKNFL LFSSQTAVRG 
721:	IPFTLSTQED VMVPVTGSPS FFVGIDFDAQ HSTIFYSDLS KNIIYQQKID GTGKEVITAN 
781:	RLQNVECLSF DWISRNLYWT DGGSKSVTVM KLADKSRRQI ISNLNNPRSI VVHPAAGYMF 
841:	LSDWFRPAKI MRAWSDGSHL MPIVNTSLGW PNGLAIDWST SRLYWVDAFF DKIEHSNLDG 
901:	LDRKRLGHVD QMTHPFGLTV FKDNVFLTDW RLGAIIRVRK SDGGDMTVVR RGISSIMHVK 
961:	AYDADLQTGT NYCSQTTHPN GDCSHFCFPV PNFQRVCGCP YGMKLQRDQM TCEGDPAREP 
1021:	PTQQCGSSSF PCNNGKCVPS IFRCDGVDDC HDNSDEHQCG ALNNTCSSSA FTCVHGGQCI 
1081:	PGQWRCDKQN DCLDGSDEQN CPTRSPSSTC PPTSFTCDNH MCIPKEWVCD TDNDCSDGSD 
1141:	EKNCQASGTC HPTQFRCPDH RCISPLYVCD GDKDCVDGSD EAGCVLNCTS SQFKCADGSS 
1201:	CINSRYRCDG VYDCKDNSDE AGCPTRPPGM CHPDEFQCQG DGTCIPNTWE CDGHPDCIQG 
1261:	SDEHNGCVPK TCSPSHFLCD NGNCIYNSWV CDGDNDCRDM SDEKDCPTQP FHCPSSQWQC 
1321:	PGYSICVNLS ALCDGVFDCP NGTDESPLCN QDSCLHFNGG CTHRCIQGPF GATCVCPIGY 
1381:	QLANDTKTCE DVNECDIPGF CSQHCVNMRG SFRCACDPEY TLESDGRTCK VTASENLLLV 
1441:	VASRDKIIMD NITAHTHNIY SLVQDVSFVV ALDFDSVTGR VFWSDLLEGK TWSAFQNGTD 
1501:	KRVVHDSGLS LTEMIAVDWI GRNIYWTDYT LETIEVSKID GSHRTVLISK NVTKPRGLAL 
1561:	DPRMGDNVMF WSDWGHHPRI ERASMDGTMR TVIVQEKIYW PCGLSIDYPN RLIYFMDAYL 
1621:	DYIEFCDYDG QNRRQVIASD LVLHHPHALT LFEDSVFWTD RGTHQVMQAN KWHGRNQSVV 
1681:	MYSVPQPLGI IAIHPSRQPS SPNPCASATC SHLCLLSAQE PRHYSCACPS GWNLSDDSVN 
1741:	CVRGDQPFLI SVRENVIFGI SLDPEVKSND AMVPISGIQH GYDVEFDDSE QFIYWVENPG 
1801:	EIHRVKTDGS NRTAFAPLSL LGSSLGLALD WVSRNIYYTT PASRSIEVLT LRGDTRYGKT 
1861:	LITNDGTPLG VGFPVGIAVD PARGKLYWSD HGTDSGVPAK IASANMDGTS LKILFTGNME 
1921:	HLEVVTLDIQ EQKLYWAVTS RGVIERGNVD GTERMILVHH LAHPWGLVVH GSFLYYSDEQ 
1981:	YEVIERVDKS SGSNKVVFRD NIPYLRGLRV YHHRNAADSS NGCSNNPNAC QQICLPVPGG 
2041:	MFSCACASGF KLSPDGRSCS PYNSFIVVSM LPAVRGFSLE LSDHSEAMVP VAGQGRNVLH 
2101:	ADVDVANGFI YWCDFSSSVR SSNGIRRIKP NGSNFTNIVT YGIGANGIRG VAVDWVAGNL 
2161:	YFTNAFVYET LIEVIRINTT YRRVLLKVSV DMPRHIVVDP KHRYLFWADY GQKPKIERSF 
2221:	LDCTNRTVLV SEGIVTPRGL AVDHDTGYIY WVDDSLDIIA RIHRDGGESQ VVRYGSRYPT 
2281:	PYGITVFGES IIWVDRNLRK VFQASKQPGN TDPPTVIRDS INLLRDVTIF DEHVQPLSPA 
2341:	ELNNNPCLQS NGGCSHFCFA LPELPTPKCG CAFGTLEDDG KNCATSREDF LIYSLNNSLR 
2401:	SLHFDPQDHN LPFQAISVEG MAIALDYDRR NNRIFFTQKL NPIRGQISYV NLYSGASSPT 
2461:	ILLSNIGVTD GIAFDWINRR IYYSDFSNQT INSMAEDGSN RAVIARVSKP RAIVLDPCRG 
2521:	YMYWTDWGTN AKIERATLGG NFRVPIVNTS LVWPNGLTLD LETDLLYWAD ASLQKIERST 
2581:	LTGSNREVVI STAFHSFGLT VYGQYIYWTD FYTKKIYRAN KYDGSDLIAM TTRLPTQPSG 
2641:	ISTVVKTQQQ QCSNPCDQFN GGCSHICAPG PNGAECQCPH EGSWYLANDN KYCVVDTGAR 
2701:	CNQFQFTCLN GRCISQDWKC DNDNDCGDGS DELPTVCAFH TCRSTAFTCA NGRCVPYHYR 
2761:	CDFYNDCGDN SDEAGCLFRS CNSTTEFTCS NGRCIPLSYV CNGINNCHDN DTSDEKNCPP 
2821:	ITCQPDFAKC QTTNICVPRA FLCDGDNDCG DGSDENPIYC ASHTCRSNEF QCVSPHRCIP 
2881:	SYWFCDGEAD CVDSSDEPDT CGHSLNSCSA NQFHCDNGRC ISSSWVCDGD NDCGDMSDED 
2941:	QRHHCELQNC SSTEFTCINS RPPNRRCIPQ HWVCDGDADC ADALDELQNC TMRACSTGEF 
3001:	SCANGRCIRQ SFRCDRRNDC GDYSDERGCS YPPCRDDQFT CQNGQCITKL YVCDEDNDCG 
3061:	DGSDEQEHLC HTPEPTCPPH QFRCDNGHCI EMGTVCNHVD DCSDNSDEKG CGINECQDSS 
3121:	ISHCDHNCTD TITSFYCSCL PGYKLMSDKR TCVDIDECKE TPQLCSQKCE NVIGSYICKC 
3181:	APGYIREPDG KSCRQNSNIE PYLVFSNRYY IRNLTIDGTS YSLILQGLGN VVALDFDRVE 
3241:	ERLYWIDAEK QIIERMFLNK TNQETIISHR LRRAESLAVD WVSRKLYWLD AILDCLFVSD 
3301:	LEGRQRKMLA QHCVDANNTF CFENPRGIVL HPQRGYVYWA DWGDHAYIAR IGMDGTNKTV 
3361:	IISTKIEWPN AITIDYTNDL LYWADAHLGY IEFSDLEGHH RHTVYDGTLP HPFALTIFED 
3421:	TVFWTDWNTR TVEKGNKYDG SGRVVLVNTT HKPFDIHVLH PYRQPIMSNP CATNNGGCSH 
3481:	LCLIKAGGRG FTCECPDDFQ TVQLRDRTLC MPMCSSTQFL CGNNEKCIPI WWKCDGQKDC 
3541:	SDGSDESDLC PHRFCRLGQF QCRDGNCTSP QALCNARQDC ADGSDEDRVL CEHHRCEANE 
3601:	WQCANKRCIP EYWQCDSVDD CLDNSDEDPS HCASRTCRPG QFKCNNGRCI PQSWKCDVDN 
3661:	DCGDYSDEPI HECMTAAYNC DNHTEFSCKT NYRCIPQWAV CNGFDDCRDN SDEQGCESVP 
3721:	CHPSGDFRCG NHHCIPLRWK CDGIDDCGDN SDEESCVPRE CTESEFRCAD QQCIPSRWVC 
3781:	DQENDCGDNS DERDCEMKTC HPEHFQCTSG HCVPKALACD GRADCLDASD ESACPTRFPN 
3841:	GTYCPAAMFE CKNHVCIQSF WICDGENDCV DGSDEEIHLC FNVPCESPQR FRCDNSRCIY 
3901:	GHQLCNGVDD CGDGSDEKEE HCRKPTHKPC TDTEYKCSNG NCVSQHYVCD NVDDCGDLSD 
3961:	ETGCNLGENR TCAEKICEQN CTQLSNGGFI CSCRPGFKPS TLDKNSCQDI NECEEFGICP 
4021:	QSCRNSKGSY ECFCVDGFKS MSTHYGERCA ADGSPPLLLL PENVRIRKYN ISSEKFSEYL 
4081:	EEEEHIQAID YDWDPEGIGL SVVYYTVLSQ GSQFGAIKRA YLPDFESGSN NPVREVDLGL 
4141:	KYLMQPDGLA VDWVGRHIYW SDAKSQRIEV ATLDGRYRKW LITTQLDQPA AIAVNPKLGL 
4201:	MFWTDQGKQP KIESAWMNGE HRSVLASANL GWPNGLSIDY LNGDRIYWSD SKEDVIESIK 
4261:	YDGTDRRLII NDAMKPFSLD IFEDQLYWVA KEKGEVWRQN KFGKGNKEKL LVVNPWLTQV 
4321:	RIFHQLRYNQ SVSNPCKQVC SHLCLLRPGG YSCACPQGSD FVTGSTVECD AASELPITMP 
4381:	SPCRCMHGGS CYFDENDLPK CKCSSGYSGE YCEIGLSRGI PPGTTMALLL TFAMVIIVGA 
4441:	LVLVGFFHYR KTGSLLPSLP KLPSLSSLAK PSENGNGVTF RSGADVNMDI GVSPFGPETI 
4501:	IDRSMAMNEQ FVMEVGKQPV IFENPMYAAK DSTSKVGLAV QGPSVSSQVT VPENVENQNY 
4561:	GRSIDPSEIV PEPKPASPGA DETQGTKWNI FKRKPKQTTN FENPIYAEMD TEQKEAVAVA 
4621:	PPPSPSLPAK ASKRSSTPGY TATEDTFKDT ANLVKEDSDV