9.B.87.1.34
Cubilin (CUBN, IFCR) of 3623 aas and one N-terminal TMS plus several C-terminal potential TMSs (residues 2950 - 3 623). It is an endocytic receptor which plays a role in lipoprotein, vitamin and iron metabolism by facilitating their uptake (Kozyraki et al. 1998, Fyfe et al. 2004). It acts together with LRP2 to mediate endocytosis of high-density
lipoproteins, GC, hemoglobin, ALB, TF and SCGB1A1, and it acts together with
AMN to mediate endocytosis of the CBLIF-cobalamin complex. Reabsorption of albumin, maturation of vitamin D in the kidney and nutrient delivery during embryonic development are probable functions. Cubilin is an atypical receptor, peripherally associated to the plasma membrane. The transmembrane proteins amnionless (AMN) and Lrp2/Megalin are molecular partners contributing to plasma membrane transport and internalization of cubilin (Kozyraki et al. 2022). ABCB6, ABCG2, FECH and CPOX are expressed in meningioma tissue (Spille et al. 2023). Cubilin binds
to ALB, MB, Kappa and lambda-light chains, hemoglobin, SCGB1A1,
APOA1, high density lipoprotein, and the CBLIF-cobalamin complex.
Ligand binding requires calcium. Cubilin serves
as a transporter in several absorptive epithelia, including
intestine, renal proximal tubules and embryonic yolk sac cells. A short
gluten peptide leverages the TG2/LRP-1 pathway; this pathway can be used
to endocytose and degrade representative secreted, cell surface, and
transmembrane proteins, notably streptavidin, the vitamin B12 receptor,
cubilin, and integrin alpha(v)beta(5). Optimization of these
prototypical molecules could generate pharmacologically relevant LYTAC
agents (Loppinet et al. 2023).
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| Accession Number: | O60494 |
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| Protein Name: | Cubilin |
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| Length: | 3623 |
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| Molecular Weight: | 398736.00 |
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| Species: | Homo sapiens (Human) [9606] |
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| Location1 / Topology2 / Orientation3: |
Apical cell membrane1 / Peripheral membrane protein2 |
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| Substrate |
iron atom, lipoprotein, cyanocob(III)alamin |
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1: MMNMSLPFLW SLLTLLIFAE VNGEAGELEL QRQKRSINLQ QPRMATERGN LVFLTGSAQN
61: IEFRTGSLGK IKLNDEDLSE CLHQIQKNKE DIIELKGSAI GLPQNISSQI YQLNSKLVDL
121: ERKFQGLQQT VDKKVCSSNP CQNGGTCLNL HDSFFCICPP QWKGPLCSAD VNECEIYSGT
181: PLSCQNGGTC VNTMGSYSCH CPPETYGPQC ASKYDDCEGG SVARCVHGIC EDLMREQAGE
241: PKYSCVCDAG WMFSPNSPAC TLDRDECSFQ PGPCSTLVQC FNTQGSFYCG ACPTGWQGNG
301: YICEDINECE INNGGCSVAP PVECVNTPGS SHCQACPPGY QGDGRVCTLT DICSVSNGGC
361: HPDASCSSTL GSLPLCTCLP GYTGNGYGPN GCVQLSNICL SHPCLNGQCI DTVSGYFCKC
421: DSGWTGVNCT ENINECLSNP CLNGGTCVDG VDSFSCECTR LWTGALCQVP QQVCGESLSG
481: INGSFSYRSP DVGYVHDVNC FWVIKTEMGK VLRITFTFFR LESMDNCPHE FLQVYDGDSS
541: SAFQLGRFCG SSLPHELLSS DNALYFHLYS EHLRNGRGFT VRWETQQPEC GGILTGPYGS
601: IKSPGYPGNY PPGRDCVWIV VTSPDLLVTF TFGTLSLEHH DDCNKDYLEI RDGPLYQDPL
661: LGKFCTTFSV PPLQTTGPFA RIHFHSDSQI SDQGFHITYL TSPSDLRCGG NYTDPEGELF
721: LPELSGPFTH TRQCVYMMKQ PQGEQIQINF THVELQCQSD SSQNYIEVRD GETLLGKVCG
781: NGTISHIKSI TNSVWIRFKI DASVEKASFR AVYQVACGDE LTGEGVIRSP FFPNVYPGER
841: TCRWTIHQPQ SQVILLNFTV FEIGSSAHCE TDYVEIGSSS ILGSPENKKY CGTDIPSFIT
901: SVYNFLYVTF VKSSSTENHG FMAKFSAEDL ACGEILTEST GTIQSPGHPN VYPHGINCTW
961: HILVQPNHLI HLMFETFHLE FHYNCTNDYL EVYDTDSETS LGRYCGKSIP PSLTSSGNSL
1021: MLVFVTDSDL AYEGFLINYE AISAATACLQ DYTDDLGTFT SPNFPNNYPN NWECIYRITV
1081: RTGQLIAVHF TNFSLEEAIG NYYTDFLEIR DGGYEKSPLL GIFYGSNLPP TIISHSNKLW
1141: LKFKSDQIDT RSGFSAYWDG SSTGCGGNLT TSSGTFISPN YPMPYYHSSE CYWWLKSSHG
1201: SAFELEFKDF HLEHHPNCTL DYLAVYDGPS SNSHLLTQLC GDEKPPLIRS SGDSMFIKLR
1261: TDEGQQGRGF KAEYRQTCEN VVIVNQTYGI LESIGYPNPY SENQHCNWTI RATTGNTVNY
1321: TFLAFDLEHH INCSTDYLEL YDGPRQMGRY CGVDLPPPGS TTSSKLQVLL LTDGVGRREK
1381: GFQMQWFVYG CGGELSGATG SFSSPGFPNR YPPNKECIWY IRTDPGSSIQ LTIHDFDVEY
1441: HSRCNFDVLE IYGGPDFHSP RIAQLCTQRS PENPMQVSST GNELAIRFKT DLSINGRGFN
1501: ASWQAVTGGC GGIFQAPSGE IHSPNYPSPY RSNTDCSWVI RVDRNHRVLL NFTDFDLEPQ
1561: DSCIMAYDGL SSTMSRLART CGREQLANPI VSSGNSLFLR FQSGPSRQNR GFRAQFRQAC
1621: GGHILTSSFD TVSSPRFPAN YPNNQNCSWI IQAQPPLNHI TLSFTHFELE RSTTCARDFV
1681: EILDGGHEDA PLRGRYCGTD MPHPITSFSS ALTLRFVSDS SISAGGFHTT VTASVSACGG
1741: TFYMAEGIFN SPGYPDIYPP NVECVWNIVS SPGNRLQLSF ISFQLEDSQD CSRDFVEIRE
1801: GNATGHLVGR YCGNSFPLNY SSIVGHTLWV RFISDGSGSG TGFQATFMKI FGNDNIVGTH
1861: GKVASPFWPE NYPHNSNYQW TVNVNASHVV HGRILEMDIE EIQNCYYDKL RIYDGPSIHA
1921: RLIGAYCGTQ TESFSSTGNS LTFHFYSDSS ISGKGFLLEW FAVDAPDGVL PTIAPGACGG
1981: FLRTGDAPVF LFSPGWPDSY SNRVDCTWLI QAPDSTVELN ILSLDIESHR TCAYDSLVIR
2041: DGDNNLAQQL AVLCGREIPG PIRSTGEYMF IRFTSDSSVT RAGFNASFHK SCGGYLHADR
2101: GIITSPKYPE TYPSNLNCSW HVLVQSGLTI AVHFEQPFQI PNGDSSCNQG DYLVLRNGPD
2161: ICSPPLGPPG GNGHFCGSHA SSTLFTSDNQ MFVQFISDHS NEGQGFKIKY EAKSLACGGN
2221: VYIHDADSAG YVTSPNHPHN YPPHADCIWI LAAPPETRIQ LQFEDRFDIE VTPNCTSNYL
2281: ELRDGVDSDA PILSKFCGTS LPSSQWSSGE VMYLRFRSDN SPTHVGFKAK YSIAQCGGRV
2341: PGQSGVVESI GHPTLPYRDN LFCEWHLQGL SGHYLTISFE DFNLQNSSGC EKDFVEIWDN
2401: HTSGNILGRY CGNTIPDSID TSSNTAVVRF VTDGSVTASG FRLRFESSME ECGGDLQGSI
2461: GTFTSPNYPN PNPHGRICEW RITAPEGRRI TLMFNNLRLA THPSCNNEHV IVFNGIRSNS
2521: PQLEKLCSSV NVSNEIKSSG NTMKVIFFTD GSRPYGGFTA SYTSSEDAVC GGSLPNTPEG
2581: NFTSPGYDGV RNYSRNLNCE WTLSNPNQGN SSISIHFEDF YLESHQDCQF DVLEFRVGDA
2641: DGPLMWRLCG PSKPTLPLVI PYSQVWIHFV TNERVEHIGF HAKYSFTDCG GIQIGDSGVI
2701: TSPNYPNAYD SLTHCSSLLE APQGHTITLT FSDFDIEPHT TCAWDSVTVR NGGSPESPII
2761: GQYCGNSNPR TIQSGSNQLV VTFNSDHSLQ GGGFYATWNT QTLGCGGIFH SDNGTIRSPH
2821: WPQNFPENSR CSWTAITHKS KHLEISFDNN FLIPSGDGQC QNSFVKVWAG TEEVDKALLA
2881: TGCGNVAPGP VITPSNTFTA VFQSQEAPAQ GFSASFVSRC GSNFTGPSGY IISPNYPKQY
2941: DNNMNCTYVI EANPLSVVLL TFVSFHLEAR SAVTGSCVND GVHIIRGYSV MSTPFATVCG
3001: DEMPAPLTIA GPVLLNFYSN EQITDFGFKF SYRIISCGGV FNFSSGIITS PAYSYADYPN
3061: DMHCLYTITV SDDKVIELKF SDFDVVPSTS CSHDYLAIYD GANTSDPLLG KFCGSKRPPN
3121: VKSSNNSMLL VFKTDSFQTA KGWKMSFRQT LGPQQGCGGY LTGSNNTFAS PDSDSNGMYD
3181: KNLNCVWIII APVNKVIHLT FNTFALEAAS TRQRCLYDYV KLYDGDSENA NLAGTFCGST
3241: VPAPFISSGN FLTVQFISDL TLEREGFNAT YTIMDMPCGG TYNATWTPQN ISSPNSSDPD
3301: VPFSICTWVI DSPPHQQVKI TVWALQLTSQ DCTQNYLQLQ DSPQGHGNSR FQFCGRNASA
3361: VPVFYSSMST AMVIFKSGVV NRNSRMSFTY QIADCNRDYH KAFGNLRSPG WPDNYDNDKD
3421: CTVTLTAPQN HTISLFFHSL GIENSVECRN DFLEVRNGSN SNSPLLGKYC GTLLPNPVFS
3481: QNNELYLRFK SDSVTSDRGY EIIWTSSPSG CGGTLYGDRG SFTSPGYPGT YPNNTYCEWV
3541: LVAPAGRLVT INFYFISIDD PGDCVQNYLT LYDGPNASSP SSGPYCGGDT SIAPFVASSN
3601: QVFIKFHADY ARRPSAFRLT WDS