Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Low-density lipoprotein receptor  

UniProtKB / Swiss-Prot ID :  LDLR_HUMAN

Gene Name (Synonyms) : 
LDLR  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Cell membrane; Single-pass type I membrane protein. Endomembrane system; Single-pass type I membrane protein. Membrane, clathrin-coated pit; Single-pass type I membrane protein. Note=Found distributed from the plasma membrane to intracellular compartment 

Protein Function :  Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. In case of HIV-1 infection, functions as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells. 

Transmembrane Topology (topPTM) : LDLR_HUMAN 

Protein Sequence MGPWGWKLRWTVALLLAAAGTAVGDRCERNEFQCQDGKCISYKWVCDGSAECQDGSDESQETCLSVTCKS...
Predicted Secondary Structure CCCCCEEEEEEEEEEEEECCCCCCCCCCCCCCCCCCCEEECCCCCCCCCCCCCCCCCCCCCCCCCCCCCC...
Protein Variant
LocationDescription
2G -> R (in dbSNP:rs5931). VAR_011862
27C -> W (in San Francisco). VAR_005304
46C -> S (in FH; Japanese patient). VAR_013949
47Missing (in FH; Cape Town-1; retardsreceptor transport from the endoplasmic
50A -> S (in FH; German patient). VAR_007979
52C -> Y (in Paris-4). VAR_005306
56S -> P (in FH). VAR_007980
78R -> C (in FH). VAR_005307
87W -> G (in FH; French Canadian-4). VAR_005308
89C -> Y (in FH). VAR_005309
90D -> G (in London-4). VAR_005310
90D -> N (in FH). VAR_005311
90D -> Y (in FH; Durban-1). VAR_005312
92Q -> E (in FH; Spanish patient). VAR_005313
95C -> G (in FH; Spanish patient). VAR_005314
101E -> K (in FH; Lancashire; 6% of AmericanEnglish).
105P -> S (in dbSNP:rs13306510). VAR_059375
109C -> R (in Munster-1). VAR_005316
116C -> R (in FH; Spanish patient). VAR_005317
134C -> F (in FH). VAR_062371
134C -> W (in FH). VAR_062372
139D -> H (found in a patient withhypercholesterolemia).
140E -> K (in FH; Philippines/Durban-2/Japan).
155C -> G (in Germany). VAR_005319
160C -> Y (in FH). VAR_005320
168D -> H (in FH; Sephardic/Safed; 10% ofthe Sephardic Jews).
168D -> N (in FH). VAR_005322
168D -> Y (in FH; Norwegian patient). VAR_005323
172D -> H (may contribute to familialhypercholesterolemia).
173C -> R (in Greece-1). VAR_005324
173C -> W (in FH; French Canadian patient). VAR_005325
175D -> N (in FH; Afrikaner-3; 5-10% ofAfrikaners).
175D -> Y (in FH). VAR_007981
177S -> L (in FH; Puerto Rico). VAR_005327
184C -> Y (in FH; Glasco). VAR_013951
197C -> F (in Shreveport). VAR_005328
197C -> R (in FH; British patient). VAR_005330
197C -> Y (in El Salvador-1). VAR_005329
201E -> K (found in a patient withhypercholesterolemia).
218Missing (in FH; Piscataway/Lithuania). VAR_005331
221D -> G (in FH; Padova). VAR_005332
221D -> N (in FH; German patient). VAR_007982
221D -> Y (in FH; Cologne patient). VAR_005333
222C -> Y (in FH). VAR_062373
224D -> G (in Italy-2). VAR_005335
224D -> N (in Portugal). VAR_005334
224D -> V (in FH; Cologne patient). VAR_005336
226S -> P (in Miami-1). VAR_005337
227D -> E (in FH; Afrikaner-1/Maine; 65-70%of Afrikaner Americans).
228E -> CK (in Chieti-3). VAR_005339
228E -> K (in FH; French Canadian-3/Mexico;2% of French Canadians).
228E -> Q (in Tulsa-2). VAR_005340
231C -> G (in FH; Norwegian patient). VAR_005342
240E -> K (in Charlotte). VAR_005343
248C -> F (in Bretagne-1). VAR_005344
248C -> Y (in FH; British patient). VAR_005345
253R -> W (may contribute to familialhypercholesterolemia).
254Q -> P (in FH). VAR_062374
255C -> S (found in a patient withhypercholesterolemia).
256D -> G (in Nevers). VAR_005346
261C -> F (in FH; rare mutation; stronglyreduced receptor activity).
266D -> E (in Cincinnati-1). VAR_005347
270C -> Y (in Miami-2). VAR_005348
276C -> R (in FH). VAR_062375
276C -> Y (in FH; Syrian patient). VAR_005349
277E -> K (in FH; patients from Sweden andLa Havana).
286S -> R (in Greece-2). VAR_005351
288E -> K (in FH; German patient). VAR_007983
301D -> A (in FH; Greek patient). VAR_005352
302C -> W (in FH; Iraki patient). VAR_005354
302C -> Y (in FH; Spanish patient). VAR_005353
304D -> E (in Baltimore-1). VAR_005356
304D -> N (in Denver-2). VAR_005355
306S -> L (in Amsterdam; dbSNP:rs11547917). VAR_005357
313C -> Y (in FH). VAR_005358
318C -> F (in FH; Trieste). VAR_005360
318C -> R (in FH). VAR_062376
318C -> Y (in Mexico-1; leads to a defect inthe intracellular transport of the
327H -> Y (in FH). VAR_005361
329C -> F (in FH). VAR_067196
329C -> Y (in FH; Chinese patient). VAR_005362
335G -> S (in Paris-6). VAR_005363
338C -> S (in FH; Japanese patients). VAR_005364
342D -> E (in New York-1). VAR_005365
342D -> N (in FH). VAR_005366
343G -> S (in Picardie). VAR_005367
350R -> P (in FH; British patient). VAR_005368
352C -> Y (in Mexico-2). VAR_005369
354D -> G (in Munster-2). VAR_005370
354D -> V (in Oklahoma). VAR_005371
356D -> Y (in FH). VAR_007984
357E -> K (in Paris-7). VAR_005372
358C -> Y (in FH). VAR_062377
364C -> R (in Mexico-3). VAR_005373
366Q -> R (in FH). VAR_007985
368C -> R (in FH; French Canadian patient). VAR_005374
370N -> T (in FH). VAR_062378
379C -> R (in Naples-1). VAR_005375
379C -> Y (in FH). VAR_007986
391A -> T (in dbSNP:rs11669576). VAR_024519
399A -> D (in FH). VAR_005376
401L -> H (in Pori). VAR_005377
401L -> V (in FH). VAR_007987
403F -> L (in FH; Japanese patient). VAR_008995
406R -> Q (may contribute to familialhypercholesterolemia).
408E -> K (may contribute to familialhypercholesterolemia; Algeria-1).
414L -> R (in FH; Chinese patient). VAR_005379
415D -> G (in FH). VAR_062379
416R -> Q (in FH; German patient). VAR_005380
416R -> W (in FH). VAR_005381
423I -> T (in FH; Swedish patient). VAR_005382
429V -> M (in FH; Afrikaner-2; 20-30% ofAfrikaners and 2% of FH Dutch;
431A -> T (in FH; Algeria-2;dbSNP:rs28942079).
432L -> V (in FH; German patient). VAR_007988
433D -> H (in FH; Osaka-3). VAR_005385
434T -> K (in Algeria-3). VAR_005386
441I -> M (in Rouen). VAR_005388
441I -> N (in Russia-1). VAR_005387
443W -> C (in North Platt). VAR_005389
451I -> T (in FH). VAR_062380
468V -> I (in dbSNP:rs5932). VAR_011863
471R -> G (found in a patient withhypercholesterolemia).
478G -> R (in New York-2). VAR_005390
479L -> P (in FH). VAR_062381
482D -> H (in FH). VAR_005391
483W -> R (in FH). VAR_005392
485H -> R (in Milan). VAR_005394
487Missing (in FH; Norwegian patient). VAR_005393
523V -> M (in Kuwait; dbSNP:rs28942080). VAR_005395
526P -> S (in Cincinnati-3). VAR_005396
546G -> D (in Saint Omer; retention in theER; dbSNP:rs28942081).
549G -> D (in Genoa; dbSNP:rs28941776). VAR_005398
564N -> H (in FH; French, German and Danishpatients; dbSNP:rs28942086).
564N -> S (in FH; Sicily). VAR_005400
565G -> V (in Naples-2; dbSNP:rs28942082). VAR_005401
568L -> V (in FH; Japanese patient). VAR_008996
579D -> N (in FH; Cincinnati-4; less than 2%receptor activity).
579D -> Y (in FH). VAR_062382
592G -> E (in FH; Sicily). VAR_005403
599L -> S (in London-5). VAR_005404
608P -> S (in FH). VAR_007989
633R -> C (in FH). VAR_005405
649P -> L (in FH). VAR_005406
667C -> Y (in FH; French Canadian-2; 5% ofFrench Canadians; dbSNP:rs28942083).
677C -> R (in FH; New York-3). VAR_005408
682L -> P (in Issoire). VAR_005409
685P -> L (in FH; Gujerat/Zambia/Belgian/Dutch/Sweden/Japan; dbSNP:rs28942084).
699P -> L (may contribute to familialhypercholesterolemia).
700D -> E (in FH; Spanish patient). VAR_005412
714E -> K (in FH; Japanese patient). VAR_008997
726T -> I (in Paris-9; dbSNP:rs45508991). VAR_005413
792I -> F (in Russia-2). VAR_005414
797V -> M (in FH; La Havana patient). VAR_005415
799Missing (in FH; Danish patient). VAR_005416
814R -> Q (polymorphism that may contributeto FH; dbSNP:rs5928).
820Missing (in FH). VAR_005417
826P -> S (in FH). VAR_062383
827V -> I (in New York-5). VAR_005418
828Y -> C (in FH; J.D.Bari/Syria;dbSNP:rs28942085).
844G -> D (in Turku). VAR_005420
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
156N-linked (GlcNAc...).SFQCNSSTC
CCCCCCCEE
28.36UniProtKB
Link-
272N-linked (GlcNAc...).VGCVNVTLC
CCCCCCCEE
25.73UniProtKB
Link-
397PhosphoserineKAVGSIAYL
EECCCCCCC
9.46HPRD
Link-
404PhosphothreonineYLFFTNRHE
CCCCCCCEE
24.82HPRD
Link-
517PhosphoserineRENGSKPRA
CCCCCCCCE
51.58Phosphositeplus
Link-
657N-linked (GlcNAc...).VLFHNLTQP
EEEEECCCC
37.13UniProtKB
Link-
828PhosphotyrosineDNPVYQKTT
CCCCCCCCC
12.92Phosphositeplus
Link-
845PhosphotyrosineNQDGYSYPS
CCCCEECCC
17.20HPRD
Link-
845PhosphotyrosineNQDGYSYPS
CCCCEECCC
17.20PhosphoELM
Link-
845PhosphotyrosineNQDGYSYPS
CCCCEECCC
17.20Phosphositeplus
Link-
845PhosphotyrosineNQDGYSYPS
CCCCEECCC
17.20SysPTM
Link-
845Phosphotyrosine.NQDGYSYPS
CCCCEECCC
17.20UniProtKB
Link-
846PhosphoserineQDGYSYPSR
CCCEECCCE
35.78Phosphositeplus
Link-
847PhosphotyrosineDGYSYPSRQ
CCEECCCEE
9.20HPRD
Link-
847PhosphotyrosineDGYSYPSRQ
CCEECCCEE
9.20Phosphositeplus
Link-
847Phosphotyrosine.DGYSYPSRQ
CCEECCCEE
9.20UniProtKB
Link-
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
AMRP_HUMANin vitro
in vivo
HPRD:06091HPRD7822276
APOB_HUMANin vivoHPRD:06091HPRD12031600
APOE_HUMANin vitro
in vivo
HPRD:06091HPRD12036962
GRP78_HUMANin vivoHPRD:06091HPRD10906332
PLF4_HUMANin vivoHPRD:06091HPRD11986215
DAB1_HUMANin vitro
in vivo
HPRD:06091HPRD10380922
9837937
LDLR_HUMANin vitroHPRD:06091HPRD10884290
ARH_HUMANin vitroHPRD:06091HPRD12221107
12746448
SNX17_HUMANin vitro
in vivo
HPRD:06091HPRD12169628
ONCM_HUMANENSP00000252444STRING
TGFB1_HUMANENSP00000252444STRING
APOB_HUMANENSP00000252444STRING
SNX17_HUMANENSP00000252444STRING
APOA1_HUMANENSP00000252444STRING
EGR1_HUMANENSP00000252444STRING
INS_HUMANENSP00000252444STRING
INS_HUMANENSP00000252444STRING
APOE_HUMANENSP00000252444STRING
APOC1_HUMANENSP00000252444STRING
HMDH_HUMANENSP00000252444STRING
AMRP_HUMANENSP00000252444STRING
AMRP_HUMANENSP00000252444STRING
AMRP_HUMANENSP00000252444STRING
LIPL_HUMANENSP00000252444STRING
APOA_HUMANENSP00000252444STRING
HMCS1_HUMANENSP00000252444STRING
SP1_HUMANENSP00000252444STRING
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Disease Reference
Kegg disease
H00155 Hypercholesterolemia, including: Hypercholesterolemia, autosomal dominant; Hyperlipoproteinemia, typ
OMIM disease
143890Familial hypercholesterolemia (FH)
Drug Reference
Kegg drug
D00887 Atorvastatin calcium (USAN); Lipitor (TN)
D02258 Atorvastatin calcium hydrate (JP16); Lipitor (TN)
D07474 Atorvastatin (INN); Lipitor (TN); Sortis (TN)
There are no disease associations of PTM sites.
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Related Literatures of Post-Translational Modification
N-linked Glycosylation
ReferencePubMed
"Identification and quantification of N-linked glycoproteins usinghydrazide chemistry, stable isotope labeling and mass spectrometry.";
Zhang H., Li X.-J., Martin D.B., Aebersold R.;
Nat. Biotechnol. 21:660-666(2003).
Cited for: GLYCOSYLATION AT ASN-657.
"Human plasma N-glycoproteome analysis by immunoaffinity subtraction,hydrazide chemistry, and mass spectrometry.";
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,Moore R.J., Smith R.D.;
J. Proteome Res. 4:2070-2080(2005).
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-657, AND MASSSPECTROMETRY.
"Glycoproteomics analysis of human liver tissue by combination ofmultiple enzyme digestion and hydrazide chemistry.";
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
J. Proteome Res. 8:651-661(2009).
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-657, AND MASSSPECTROMETRY.
Phosphorylation
ReferencePubMed
"Immunoaffinity profiling of tyrosine phosphorylation in cancercells.";
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,Zha X.-M., Polakiewicz R.D., Comb M.J.;
Nat. Biotechnol. 23:94-101(2005).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-845, AND MASSSPECTROMETRY.
"Multiple reaction monitoring for robust quantitative proteomicanalysis of cellular signaling networks.";
Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M.;
Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-845, AND MASSSPECTROMETRY.
"An extensive survey of tyrosine phosphorylation revealing new sitesin human mammary epithelial cells.";
Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A.,Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D.,Wiley H.S., Qian W.-J.;
J. Proteome Res. 8:3852-3861(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-845 AND TYR-847, ANDMASS SPECTROMETRY.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures