LOCUS       NP_000518                860 aa            linear   PRI 29-APR-2025
DEFINITION  low-density lipoprotein receptor isoform 1 precursor [Homo
            sapiens].
ACCESSION   NP_000518
VERSION     NP_000518.1
DBSOURCE    REFSEQ: accession NM_000527.5
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 860)
  AUTHORS   Mahsoub,N., Almenshawy,A., Taki Eldin,A.M., Abdel Hay,N.M.,
            Youssef,A.R., El-Farahaty,R.M., El-Sayed,K., Osman,A.M. and
            Elhennawy,E.S.
  TITLE     Association between Apo B, LDL-R and PCSK9 gene polymorphisms with
            coronary artery diseases in Egyptians
  JOURNAL   Mol Biol Rep 51 (1), 752 (2024)
   PUBMED   38874786
  REMARK    GeneRIF: Association between Apo B, LDL-R and PCSK9 gene
            polymorphisms with coronary artery diseases in Egyptians.
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 860)
  AUTHORS   Deng,J., Zhang,J., Meng,S., Ding,N., Hao,Y., Zeng,H. and Lin,J.
  TITLE     LDLR c.89_92dup: a novel frameshift variation in familial
            hypercholesterolemia
  JOURNAL   Lipids Health Dis 23 (1), 182 (2024)
   PUBMED   38867270
  REMARK    GeneRIF: LDLR c.89_92dup: a novel frameshift variation in familial
            hypercholesterolemia.
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 860)
  AUTHORS   Silva Rodrigues Marcal,E.D., Borges,J.B., Bastos,G.M., Crespo
            Hirata,T.D., de Oliveira,V.F., Goncalves,R.M., Faludi,A.A., Dias
            Franca,J.I., de Oliveira Silva,D.V., Malaquias,V.B., Luchessi,A.D.,
            Silbiger,V.N., Nakazone,M.A., Carmo,T.S., Silva Souza,D.R.,
            Sampaio,M.F., Crespo Hirata,R.D. and Hirata,M.H.
  TITLE     Methylation status of LDLR, PCSK9 and LDLRAP1 is associated with
            cardiovascular events in familial hypercholesterolemia
  JOURNAL   Epigenomics 16 (11-12), 809-820 (2024)
   PUBMED   38884343
  REMARK    GeneRIF: Methylation status of LDLR, PCSK9 and LDLRAP1 is
            associated with cardiovascular events in familial
            hypercholesterolemia.
REFERENCE   4  (residues 1 to 860)
  AUTHORS   Ison,H.E., Clarke,S.L. and Knowles,J.W.
  TITLE     Familial Hypercholesterolemia
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   24404629
REFERENCE   5  (residues 1 to 860)
  AUTHORS   Hobbs,H.H., Brown,M.S. and Goldstein,J.L.
  TITLE     Molecular genetics of the LDL receptor gene in familial
            hypercholesterolemia
  JOURNAL   Hum Mutat 1 (6), 445-466 (1992)
   PUBMED   1301956
  REMARK    Review article
REFERENCE   6  (residues 1 to 860)
  AUTHORS   Lindgren,V., Luskey,K.L., Russell,D.W. and Francke,U.
  TITLE     Human genes involved in cholesterol metabolism: chromosomal mapping
            of the loci for the low density lipoprotein receptor and
            3-hydroxy-3-methylglutaryl-coenzyme A reductase with cDNA probes
  JOURNAL   Proc Natl Acad Sci U S A 82 (24), 8567-8571 (1985)
   PUBMED   3866240
REFERENCE   7  (residues 1 to 860)
  AUTHORS   Sudhof,T.C., Goldstein,J.L., Brown,M.S. and Russell,D.W.
  TITLE     The LDL receptor gene: a mosaic of exons shared with different
            proteins
  JOURNAL   Science 228 (4701), 815-822 (1985)
   PUBMED   2988123
REFERENCE   8  (residues 1 to 860)
  AUTHORS   Yamamoto,T., Davis,C.G., Brown,M.S., Schneider,W.J., Casey,M.L.,
            Goldstein,J.L. and Russell,D.W.
  TITLE     The human LDL receptor: a cysteine-rich protein with multiple Alu
            sequences in its mRNA
  JOURNAL   Cell 39 (1), 27-38 (1984)
   PUBMED   6091915
REFERENCE   9  (residues 1 to 860)
  AUTHORS   Brown,M.S. and Goldstein,J.L.
  TITLE     Receptor-mediated endocytosis: insights from the lipoprotein
            receptor system
  JOURNAL   Proc Natl Acad Sci U S A 76 (7), 3330-3337 (1979)
   PUBMED   226968
  REMARK    Review article
REFERENCE   10 (residues 1 to 860)
  AUTHORS   Goldstein,J.L., Anderson,R.G. and Brown,M.S.
  TITLE     Coated pits, coated vesicles, and receptor-mediated endocytosis
  JOURNAL   Nature 279 (5715), 679-685 (1979)
   PUBMED   221835
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DC306821.1, AY114155.1,
            AC011485.6 and BM785950.1.
            
            Summary: The low density lipoprotein receptor (LDLR) gene family
            consists of cell surface proteins involved in receptor-mediated
            endocytosis of specific ligands. The encoded protein is normally
            bound at the cell membrane, where it binds low density
            lipoprotein/cholesterol and is taken into the cell. Lysosomes
            release the cholesterol, which is made available for repression of
            microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA)
            reductase, the rate-limiting step in cholesterol synthesis. At the
            same time, a reciprocal stimulation of cholesterol ester synthesis
            takes place. Mutations in this gene cause the autosomal dominant
            disorder, familial hypercholesterolemia. Alternate splicing results
            in multiple transcript variants.[provided by RefSeq, May 2022].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR11853563.16477.1, BC014514.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000558518.6/ ENSP00000454071.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..860
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19p13.2"
     Protein         1..860
                     /product="low-density lipoprotein receptor isoform 1
                     precursor"
                     /note="LDL receptor; low-density lipoprotein receptor
                     class A domain-containing protein 3"
                     /calculated_mol_wt=93096
     sig_peptide     1..21
                     /calculated_mol_wt=2299
     mat_peptide     22..860
                     /product="low-density lipoprotein receptor isoform 1"
                     /calculated_mol_wt=93096
     Region          25..58
                     /region_name="Ldl_recept_a"
                     /note="Low-density lipoprotein receptor domain class A;
                     pfam00057"
                     /db_xref="CDD:395011"
     Site            order(32,40,51..52)
                     /site_type="active"
                     /note="putative binding surface [active]"
                     /db_xref="CDD:238060"
     Site            order(44,47,51,57..58)
                     /site_type="other"
                     /note="calcium-binding site [ion binding]"
                     /db_xref="CDD:238060"
     Site            54..58
                     /site_type="other"
                     /note="D-X-S-D-E motif"
                     /db_xref="CDD:238060"
     Region          66..104
                     /region_name="Ldl_recept_a"
                     /note="Low-density lipoprotein receptor domain class A;
                     pfam00057"
                     /db_xref="CDD:395011"
     Site            order(73,83,94..95)
                     /site_type="active"
                     /note="putative binding surface [active]"
                     /db_xref="CDD:238060"
     Site            order(87,90,94,100..101)
                     /site_type="other"
                     /note="calcium-binding site [ion binding]"
                     /db_xref="CDD:238060"
     Site            97..101
                     /site_type="other"
                     /note="D-X-S-D-E motif"
                     /db_xref="CDD:238060"
     Site            97
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (P01130.1)"
     Region          107..143
                     /region_name="Ldl_recept_a"
                     /note="Low-density lipoprotein receptor domain class A;
                     pfam00057"
                     /db_xref="CDD:395011"
     Site            order(114,122,133..134)
                     /site_type="active"
                     /note="putative binding surface [active]"
                     /db_xref="CDD:238060"
     Site            order(126,129,133,139..140)
                     /site_type="other"
                     /note="calcium-binding site [ion binding]"
                     /db_xref="CDD:238060"
     Site            136..140
                     /site_type="other"
                     /note="D-X-S-D-E motif"
                     /db_xref="CDD:238060"
     Region          146..233
                     /region_name="Binding to Getah virus E1-E2 spike
                     glycoproteins. /evidence=ECO:0000269|PubMed:38245515"
                     /note="propagated from UniProtKB/Swiss-Prot (P01130.1)"
     Region          147..179
                     /region_name="Ldl_recept_a"
                     /note="Low-density lipoprotein receptor domain class A;
                     pfam00057"
                     /db_xref="CDD:395011"
     Site            order(153,161,172..173)
                     /site_type="active"
                     /note="putative binding surface [active]"
                     /db_xref="CDD:238060"
     Site            156
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:19520913; propagated from
                     UniProtKB/Swiss-Prot (P01130.1)"
     Site            order(165,168,172,178..179)
                     /site_type="other"
                     /note="calcium-binding site [ion binding]"
                     /db_xref="CDD:238060"
     Site            175..179
                     /site_type="other"
                     /note="D-X-S-D-E motif"
                     /db_xref="CDD:238060"
     Region          195..231
                     /region_name="Ldl_recept_a"
                     /note="Low-density lipoprotein receptor domain class A;
                     pfam00057"
                     /db_xref="CDD:395011"
     Site            order(202,210,221..222)
                     /site_type="active"
                     /note="putative binding surface [active]"
                     /db_xref="CDD:238060"
     Site            order(214,217,221,227..228)
                     /site_type="other"
                     /note="calcium-binding site [ion binding]"
                     /db_xref="CDD:238060"
     Site            224..228
                     /site_type="other"
                     /note="D-X-S-D-E motif"
                     /db_xref="CDD:238060"
     Region          235..270
                     /region_name="Ldl_recept_a"
                     /note="Low-density lipoprotein receptor domain class A;
                     pfam00057"
                     /db_xref="CDD:395011"
     Site            order(241,249,260..261)
                     /site_type="active"
                     /note="putative binding surface [active]"
                     /db_xref="CDD:238060"
     Site            order(253,256,260,266..267)
                     /site_type="other"
                     /note="calcium-binding site [ion binding]"
                     /db_xref="CDD:238060"
     Site            263..267
                     /site_type="other"
                     /note="D-X-S-D-E motif"
                     /db_xref="CDD:238060"
     Site            272
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:19520913; propagated from
                     UniProtKB/Swiss-Prot (P01130.1)"
     Region          278..308
                     /region_name="Ldl_recept_a"
                     /note="Low-density lipoprotein receptor domain class A;
                     pfam00057"
                     /db_xref="CDD:395011"
     Site            order(282,290,301..302)
                     /site_type="active"
                     /note="putative binding surface [active]"
                     /db_xref="CDD:238060"
     Site            order(294,297,301,307..308)
                     /site_type="other"
                     /note="calcium-binding site [ion binding]"
                     /db_xref="CDD:238060"
     Site            304..308
                     /site_type="other"
                     /note="D-X-S-D-E motif"
                     /db_xref="CDD:238060"
     Region          318..>346
                     /region_name="FXa_inhibition"
                     /note="Coagulation Factor Xa inhibitory site; pfam14670"
                     /db_xref="CDD:464251"
     Region          354..388
                     /region_name="EGF_CA"
                     /note="Calcium-binding EGF-like domain; smart00179"
                     /db_xref="CDD:214542"
     Site            order(354,357,370)
                     /site_type="other"
                     /note="Ca2+ binding site [ion binding]"
                     /db_xref="CDD:238011"
     Region          397..438
                     /region_name="LDL-receptor class B 1"
                     /note="propagated from UniProtKB/Swiss-Prot (P01130.1)"
     Region          419..457
                     /region_name="LY"
                     /note="Low-density lipoprotein-receptor YWTD domain;
                     smart00135"
                     /db_xref="CDD:214531"
     Region          439..485
                     /region_name="LDL-receptor class B 2"
                     /note="propagated from UniProtKB/Swiss-Prot (P01130.1)"
     Region          439..483
                     /region_name="Ldl_recept_b"
                     /note="Low-density lipoprotein receptor repeat class B;
                     pfam00058"
                     /db_xref="CDD:459654"
     Region          486..528
                     /region_name="LDL-receptor class B 3"
                     /note="propagated from UniProtKB/Swiss-Prot (P01130.1)"
     Region          487..526
                     /region_name="Ldl_recept_b"
                     /note="Low-density lipoprotein receptor repeat class B;
                     pfam00058"
                     /db_xref="CDD:459654"
     Site            515
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (P01130.1)"
     Region          529..572
                     /region_name="LDL-receptor class B 4"
                     /note="propagated from UniProtKB/Swiss-Prot (P01130.1)"
     Region          529..569
                     /region_name="Ldl_recept_b"
                     /note="Low-density lipoprotein receptor repeat class B;
                     pfam00058"
                     /db_xref="CDD:459654"
     Region          553..595
                     /region_name="LY"
                     /note="Low-density lipoprotein-receptor YWTD domain;
                     smart00135"
                     /db_xref="CDD:214531"
     Region          573..615
                     /region_name="LDL-receptor class B 5"
                     /note="propagated from UniProtKB/Swiss-Prot (P01130.1)"
     Region          616..658
                     /region_name="LDL-receptor class B 6"
                     /note="propagated from UniProtKB/Swiss-Prot (P01130.1)"
     Region          616..656
                     /region_name="Ldl_recept_b"
                     /note="Low-density lipoprotein receptor repeat class B;
                     pfam00058"
                     /db_xref="CDD:459654"
     Site            657
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:12754519,
                     ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218;
                     propagated from UniProtKB/Swiss-Prot (P01130.1)"
     Region          671..711
                     /region_name="FXa_inhibition"
                     /note="Coagulation Factor Xa inhibitory site; pfam14670"
                     /db_xref="CDD:464251"
     Region          721..768
                     /region_name="Clustered O-linked oligosaccharides"
                     /note="propagated from UniProtKB/Swiss-Prot (P01130.1)"
     Site            724
                     /site_type="phosphorylation"
                     /note="Phosphothreonine.
                     /evidence=ECO:0000250|UniProtKB:P35952; propagated from
                     UniProtKB/Swiss-Prot (P01130.1)"
     Region          734..755
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P01130.1)"
     Site            789..810
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (P01130.1)"
     Region          811..860
                     /region_name="Required for MYLIP-triggered down-regulation
                     of LDLR. /evidence=ECO:0000269|PubMed:19520913"
                     /note="propagated from UniProtKB/Swiss-Prot (P01130.1)"
     Region          823..828
                     /region_name="NPXY motif.
                     /evidence=ECO:0000269|PubMed:22509010"
                     /note="propagated from UniProtKB/Swiss-Prot (P01130.1)"
     CDS             1..860
                     /gene="LDLR"
                     /gene_synonym="FH; FHC; FHCL1; LDLCQ2"
                     /coded_by="NM_000527.5:87..2669"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1"
                     /db_xref="CCDS:CCDS12254.1"
                     /db_xref="GeneID:3949"
                     /db_xref="HGNC:HGNC:6547"
                     /db_xref="MIM:606945"
ORIGIN      
        1 mgpwgwklrw tvalllaaag tavgdrcern efqcqdgkci sykwvcdgsa ecqdgsdesq
       61 etclsvtcks gdfscggrvn rcipqfwrcd gqvdcdngsd eqgcppktcs qdefrchdgk
      121 cisrqfvcds drdcldgsde ascpvltcgp asfqcnsstc ipqlwacdnd pdcedgsdew
      181 pqrcrglyvf qgdsspcsaf efhclsgeci hsswrcdggp dckdksdeen cavatcrpde
      241 fqcsdgncih gsrqcdreyd ckdmsdevgc vnvtlcegpn kfkchsgeci tldkvcnmar
      301 dcrdwsdepi kecgtnecld nnggcshvcn dlkigyeclc pdgfqlvaqr rcedidecqd
      361 pdtcsqlcvn leggykcqce egfqldphtk ackavgsiay lfftnrhevr kmtldrseyt
      421 slipnlrnvv aldtevasnr iywsdlsqrm icstqldrah gvssydtvis rdiqapdgla
      481 vdwihsniyw tdsvlgtvsv adtkgvkrkt lfrengskpr aivvdpvhgf mywtdwgtpa
      541 kikkgglngv diyslvteni qwpngitldl lsgrlywvds klhsissidv nggnrktile
      601 dekrlahpfs lavfedkvfw tdiineaifs anrltgsdvn llaenllspe dmvlfhnltq
      661 prgvnwcert tlsnggcqyl clpapqinph spkftcacpd gmllardmrs clteaeaava
      721 tqetstvrlk vsstavrtqh tttrpvpdts rlpgatpglt tveivtmshq algdvagrgn
      781 ekkpssvral sivlpivllv flclgvfllw knwrlknins infdnpvyqk ttedevhich
      841 nqdgysypsr qmvsleddva
//
