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UniProtKB/Swiss-Prot entry P98158

[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name LRP2_RAT
Primary accession number P98158
Secondary accession numbers None
Integrated into Swiss-Prot on October 1, 1996
Sequence was last modified on October 1, 1996 (Sequence version 1)
Annotations were last modified on    July 22, 2008 (Entry version 74)
Name and origin of the protein
Protein name Low-density lipoprotein receptor-related protein 2 [Precursor]
Synonyms Megalin
Glycoprotein 330
gp330
Gene name
Name: Lrp2
From
Rattus norvegicus (Rat) [TaxID: 10116] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; Muroidea; Muridae; Murinae; Rattus.
Protein existence 1: Evidence at protein level;
References
[1]
 NUCLEOTIDE SEQUENCE [MRNA].
STRAIN=Sprague-Dawley;
TISSUE=Kidney;
PubMed=7937880 [NCBI, ExPASy, EBI, Israel, Japan]
Saito A., Pietromonaco S., Loo A.K.C., Farquhar M.G.;
"Complete cloning and sequencing of rat gp330/'megalin,' a distinctive member of the low density lipoprotein receptor gene family.";
Proc. Natl. Acad. Sci. U.S.A. 91:9725-9729(1994).
[2]
 FUNCTION IN UPTAKE OF POLYBASIC DRUGS.
PubMed=7544804 [NCBI, ExPASy, EBI, Israel, Japan]
Moestrup S.K., Cui S., Vorum H., Bregengaard C., Bjorn S.E., Norris K., Gliemann J., Christensen E.I.;
"Evidence that epithelial glycoprotein 330/megalin mediates uptake of polybasic drugs.";
J. Clin. Invest. 96:1404-1413(1995).
[3]
 TISSUE SPECIFICITY.
PubMed=7510321 [NCBI, ExPASy, EBI, Israel, Japan]
Zheng G., Bachinsky D.R., Stamenkovic I., Strickland D.K., Brown D., Andres G., McCluskey R.T.;
"Organ distribution in rats of two members of the low-density lipoprotein receptor gene family, gp330 and LRP/alpa 2MR, and the receptor-associated protein (RAP).";
J. Histochem. Cytochem. 42:531-542(1994).
Comments
  • FUNCTION: Acts together with cubilin to mediate HDL endocytosis (By similarity). Receptor-mediated uptake of polybasic drugs such as aprotinin, aminoglycosides and polymyxin B.
  • SUBUNIT: Binds plasminogen, extracellular matrix components, plasminogen activator-plasminogen activator inhibitor type I complex, apolipoprotein E-enriched beta-VLDL, lipoprotein lipase, lactoferrin, CLU/clusterin and calcium. Forms a multimeric complex together with a receptor-associated protein (RAP). Binds to ankyrin-repeat family A protein 2 (ANKRA2). Interacts with LRP2BP (By similarity).
  • SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Membrane, clathrin-coated pit. Cytoplasm. Note=Expressed in clathrin-coated pits, a soluble form is possibly derived by cleavage at the cell surface.
  • TISSUE SPECIFICITY: Epithelial cells of kidney glomerulus and proximal tubule, lung, epididymis, yolk sac, among others.
  • SIMILARITY: Belongs to the LDLR family.
  • SIMILARITY: Contains 17 EGF-like domains.
  • SIMILARITY: Contains 36 LDL-receptor class A domains.
  • SIMILARITY: Contains 37 LDL-receptor class B repeats.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
L34049; AAA51369.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR T42737; T42737.
RefSeq NP_110454.1; -.
UniGene Rn.26430
3D structure databases
PDB
2I1P; NMR; -; A=1185-1229.[ExPASy / RCSB / EBI]
PDBsum 2I1P; -.
ModBase P98158.
PTM databases
GlycoSuiteDB P98158; -.
Organism-specific databases
RGD 68407; Lrp2.
Gene expression databases
ArrayExpress P98158; -.
GermOnline ENSRNOG00000030487; Rattus norvegicus.
Family and domain databases
InterPro IPR011042; 6-blade_b-propeller_TolB-like.
IPR006210; EGF.
IPR000152; EGF-type_Asp/Asn_hydroxyl_CS.
IPR000742; EGF_3.
IPR001881; EGF_Ca_bd.
IPR013091; EGF_Ca_bd_2.
IPR013111; EGF_extracell.
IPR006209; EGF_like.
IPR013032; EGF_like_reg_CS.
IPR002172; LDL_rcpt_classA_cys-rich.
IPR000033; LDLR.
Graphical view of domain structure.
Gene3D G3DSA:2.120.10.30; 6-blade_b-propeller_TolB-like; 8.
G3DSA:4.10.400.10; LDL_rcpt_classA_cys-rich; 31.
Pfam PF00008; EGF; 5.
PF07974; EGF_2; 1.
PF07645; EGF_CA; 3.
PF00057; Ldl_recept_a; 36.
PF00058; Ldl_recept_b; 33.
Pfam graphical view of domain structure.
PRINTS PR00261; LDLRECEPTOR.
SMART SM00181; EGF; 14.
SM00179; EGF_CA; 3.
SM00192; LDLa; 36.
SM00135; LY; 36.
SMART graphical view of domain structure.
PROSITE PS00010; ASX_HYDROXYL; 4.
PS00022; EGF_1; 1.
PS01186; EGF_2; 8.
PS50026; EGF_3; 8.
PS01187; EGF_CA; 3.
PS01209; LDLRA_1; 31.
PS50068; LDLRA_2; 36.
PS51120; LDLRB; 35.
PROSITE graphical view of domain structure (profiles).
BLOCKS P98158.
Genome annotation databases
Ensembl ENSRNOG00000030487; Rattus norvegicus. [Contig view]
GeneID 29216; -.
KEGG rno:29216; -.
Phylogenomic databases
HOVERGEN P98158; -.
Other
ProtoNet P98158.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Cell membrane; Coated pit; Cytoplasm; EGF-like domain; Endocytosis; Glycoprotein; Membrane; Phosphoprotein; Receptor; Repeat; SH3-binding; Signal; Transmembrane.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom    To Length Description FTId
SIGNAL   1     25  25     Potential. 
CHAIN   26   4660  4635     Low-density lipoprotein receptor-related protein 2. PRO_0000017322
TOPO_DOM   26   4425  4400     Extracellular (Potential). 
TRANSMEM   4426   4446  21     Potential. 
TOPO_DOM   4447   4660  214     Cytoplasmic (Potential). 
DOMAIN   26     64  39     LDL-receptor class A 1. 
DOMAIN   65    105  41     LDL-receptor class A 2. 
DOMAIN   106    144  39     LDL-receptor class A 3. 
DOMAIN   145    181  37     LDL-receptor class A 4. 
DOMAIN   181    219  39     LDL-receptor class A 5. 
DOMAIN   220    258  39     LDL-receptor class A 6. 
DOMAIN   263    307  45     LDL-receptor class A 7. 
DOMAIN   308    346  39     EGF-like 1. 
DOMAIN   347    385  39     EGF-like 2. 
REPEAT   435    477  43     LDL-receptor class B 1. 
REPEAT   478    520  43     LDL-receptor class B 2. 
REPEAT   521    567  47     LDL-receptor class B 3. 
REPEAT   568    611  44     LDL-receptor class B 4. 
REPEAT   612    652  41     LDL-receptor class B 5. 
DOMAIN   658    704  47     EGF-like 3. 
REPEAT   752    794  43     LDL-receptor class B 6. 
REPEAT   795    836  42     LDL-receptor class B 7. 
REPEAT   837    880  44     LDL-receptor class B 8. 
REPEAT   881    924  44     LDL-receptor class B 9. 
DOMAIN   969   1013  45     EGF-like 4. 
DOMAIN   1023   1061  39     LDL-receptor class A 8. 
DOMAIN   1064   1103  40     LDL-receptor class A 9. 
DOMAIN   1108   1146  39     LDL-receptor class A 10. 
DOMAIN   1148   1186  39     LDL-receptor class A 11. 
DOMAIN   1186   1225  40     LDL-receptor class A 12. 
DOMAIN   1229   1269  41     LDL-receptor class A 13. 
DOMAIN   1270   1308  39     LDL-receptor class A 14. 
DOMAIN   1311   1351  41     LDL-receptor class A 15. 
DOMAIN   1350   1390  41     EGF-like 5. 
DOMAIN   1391   1430  40     EGF-like 6; calcium-binding (Potential). 
REPEAT   1479   1521  43     LDL-receptor class B 10. 
REPEAT   1522   1564  43     LDL-receptor class B 11. 
REPEAT   1567   1610  44     LDL-receptor class B 12. 
REPEAT   1611   1654  44     LDL-receptor class B 13. 
REPEAT   1655   1696  42     LDL-receptor class B 14. 
DOMAIN   1701   1742  42     EGF-like 7. 
REPEAT   1791   1833  43     LDL-receptor class B 15. 
REPEAT   1834   1883  50     LDL-receptor class B 16. 
REPEAT   1884   1931  48     LDL-receptor class B 17. 
REPEAT   1932   1972  41     LDL-receptor class B 18. 
REPEAT   1973   2014  42     LDL-receptor class B 19. 
DOMAIN   2019   2060  42     EGF-like 8. 
REPEAT   2108   2157  50     LDL-receptor class B 20. 
REPEAT   2158   2202  45     LDL-receptor class B 21. 
REPEAT   2203   2246  44     LDL-receptor class B 22. 
REPEAT   2247   2290  44     LDL-receptor class B 23. 
REPEAT   2291   2332  42     LDL-receptor class B 24. 
DOMAIN   2343   2384  42     EGF-like 9. 
REPEAT   2433   2478  46     LDL-receptor class B 25. 
REPEAT   2479   2519  41     LDL-receptor class B 26. 
REPEAT   2520   2563  44     LDL-receptor class B 27. 
REPEAT   2564   2604  41     LDL-receptor class B 28. 
REPEAT   2605   2647  43     LDL-receptor class B 29. 
DOMAIN   2652   2694  43     EGF-like 10. 
DOMAIN   2699   2739  41     LDL-receptor class A 16. 
DOMAIN   2740   2778  39     LDL-receptor class A 17. 
DOMAIN   2779   2820  42     LDL-receptor class A 18. 
DOMAIN   2821   2862  42     LDL-receptor class A 19. 
DOMAIN   2863   2903  41     LDL-receptor class A 20. 
DOMAIN   2906   2947  42     LDL-receptor class A 21. 
DOMAIN   2948   2992  45     LDL-receptor class A 22. 
DOMAIN   2993   3031  39     LDL-receptor class A 23. 
DOMAIN   3032   3072  41     LDL-receptor class A 24. 
DOMAIN   3075   3112  38     LDL-receptor class A 25. 
DOMAIN   3113   3153  41     EGF-like 11. 
DOMAIN   3154   3194  41     EGF-like 12; calcium-binding (Potential). 
REPEAT   3241   3283  43     LDL-receptor class B 30. 
REPEAT   3284   3326  43     LDL-receptor class B 31. 
REPEAT   3335   3378  44     LDL-receptor class B 32. 
REPEAT   3379   3420  42     LDL-receptor class B 33. 
REPEAT   3421   3462  42     LDL-receptor class B 34. 
DOMAIN   3467   3511  45     EGF-like 13. 
DOMAIN   3512   3552  41     LDL-receptor class A 26. 
DOMAIN   3553   3593  41     LDL-receptor class A 27. 
DOMAIN   3594   3634  41     LDL-receptor class A 28. 
DOMAIN   3635   3675  41     LDL-receptor class A 29. 
DOMAIN   3678   3718  41     LDL-receptor class A 30. 
DOMAIN   3719   3758  40     LDL-receptor class A 31. 
DOMAIN   3759   3797  39     LDL-receptor class A 32. 
DOMAIN   3798   3836  39     LDL-receptor class A 33. 
DOMAIN   3842   3882  41     LDL-receptor class A 34. 
DOMAIN   3883   3924  42     LDL-receptor class A 35. 
DOMAIN   3928   3966  39     LDL-receptor class A 36. 
DOMAIN   3968   4008  41     EGF-like 14. 
DOMAIN   4009   4050  42     EGF-like 15; calcium-binding (Potential). 
REPEAT   4156   4198  43     LDL-receptor class B 35. 
REPEAT   4199   4242  44     LDL-receptor class B 36. 
REPEAT   4244   4285  42     LDL-receptor class B 37. 
DOMAIN   4332   4370  39     EGF-like 16. 
DOMAIN   4379   4413  35     EGF-like 17. 
MOTIF   1743   1745  3     Cell attachment site (Potential). 
MOTIF   4454   4460  7     SH3-binding (Potential). 
MOTIF   4457   4463  7     SH3-binding (Potential). 
MOTIF   4522   4527  6     Endocytosis signal (Potential). 
MOTIF   4601   4606  6     Endocytosis signal (Potential). 
MOTIF   4606   4609  4     SH2-binding (Potential). 
MOTIF   4619   4625  7     SH3-binding (Potential). 
MOTIF   4624   4630  7     SH3-binding (Potential). 
MOD_RES   4464   4464        Phosphoserine (By similarity). 
MOD_RES   4472   4472        Phosphoserine (By similarity). 
CARBOHYD   159    159        N-linked (GlcNAc...) (Potential). 
CARBOHYD   178    178        N-linked (GlcNAc...) (Potential). 
CARBOHYD   259    259        N-linked (GlcNAc...) (Potential). 
CARBOHYD   299    299        N-linked (GlcNAc...) (Potential). 
CARBOHYD   340    340        N-linked (GlcNAc...) (Potential). 
CARBOHYD   462    462        N-linked (GlcNAc...) (Potential). 
CARBOHYD   657    657        N-linked (GlcNAc...) (Potential). 
CARBOHYD   865    865        N-linked (GlcNAc...) (Potential). 
CARBOHYD   1063   1063        N-linked (GlcNAc...) (Potential). 
CARBOHYD   1187   1187        N-linked (GlcNAc...) (Potential). 
CARBOHYD   1328   1328        N-linked (GlcNAc...) (Potential). 
CARBOHYD   1341   1341        N-linked (GlcNAc...) (Potential). 
CARBOHYD   1384   1384        N-linked (GlcNAc...) (Potential). 
CARBOHYD   1451   1451        N-linked (GlcNAc...) (Potential). 
CARBOHYD   1497   1497        N-linked (GlcNAc...) (Potential). 
CARBOHYD   1551   1551        N-linked (GlcNAc...) (Potential). 
CARBOHYD   1676   1676        N-linked (GlcNAc...) (Potential). 
CARBOHYD   1733   1733        N-linked (GlcNAc...) (Potential). 
CARBOHYD   1811   1811