LOCUS       NP_002327               1613 aa            linear   PRI 28-APR-2025
DEFINITION  low-density lipoprotein receptor-related protein 6 isoform b
            precursor [Homo sapiens].
ACCESSION   NP_002327
VERSION     NP_002327.2
DBSOURCE    REFSEQ: accession NM_002336.3
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 1613)
  AUTHORS   Zhong,S., Guo,Q., Chen,X., Luo,X., Long,Y., Chong,T., Ye,M., He,H.,
            Lu,A., Ao,K., Yin,M., Xu,A., Li,X., Hao,Y. and Guo,X.
  TITLE     The inhibition of YTHDF3/m6A/LRP6 reprograms fatty acid metabolism
            and suppresses lymph node metastasis in cervical cancer
  JOURNAL   Int J Biol Sci 20 (3), 916-936 (2024)
   PUBMED   38250152
  REMARK    GeneRIF: The inhibition of YTHDF3/m[6]A/LRP6 reprograms fatty acid
            metabolism and suppresses lymph node metastasis in cervical cancer.
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 1613)
  AUTHORS   Li,J., Liu,Z., Ren,Y., Shao,H. and Li,S.
  TITLE     LRP5-/6 gene polymorphisms and its association with risk of
            abnormal bone mass in postmenopausal women
  JOURNAL   J Orthop Surg Res 18 (1), 369 (2023)
   PUBMED   37202775
  REMARK    GeneRIF: LRP5-/6 gene polymorphisms and its association with risk
            of abnormal bone mass in postmenopausal women.
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 1613)
  AUTHORS   Hao,H., Liu,Q., Chen,J. and Zhou,H.
  TITLE     Overexpression of circRNAs LRP6 in gestational diabetes mellitus
            predicts foetal malformation and intrauterine death
  JOURNAL   Endocrinol Diabetes Nutr (Engl Ed) 70 (2), 124-129 (2023)
   PUBMED   36925229
  REMARK    GeneRIF: Overexpression of circRNAs LRP6 in gestational diabetes
            mellitus predicts foetal malformation and intrauterine death.
REFERENCE   4  (residues 1 to 1613)
  AUTHORS   Wang,J., Yang,H., Ma,X., Liu,J., Li,L., Chen,L. and Wei,F.
  TITLE     LRP6/filamentous-actin signaling facilitates osteogenic commitment
            in mechanically induced periodontal ligament stem cells
  JOURNAL   Cell Mol Biol Lett 28 (1), 7 (2023)
   PUBMED   36694134
  REMARK    GeneRIF: LRP6/filamentous-actin signaling facilitates osteogenic
            commitment in mechanically induced periodontal ligament stem cells.
            Publication Status: Online-Only
REFERENCE   5  (residues 1 to 1613)
  AUTHORS   Jones,M.E., Buchler,J., Dufor,T., Palomer,E., Teo,S.,
            Martin-Flores,N., Boroviak,K., Metzakopian,E., Gibb,A. and
            Salinas,P.C.
  TITLE     A genetic variant of the Wnt receptor LRP6 accelerates synapse
            degeneration during aging and in Alzheimer's disease
  JOURNAL   Sci Adv 9 (2), eabo7421 (2023)
   PUBMED   36638182
  REMARK    GeneRIF: A genetic variant of the Wnt receptor LRP6 accelerates
            synapse degeneration during aging and in Alzheimer's disease.
REFERENCE   6  (residues 1 to 1613)
  AUTHORS   Bafico,A., Liu,G., Yaniv,A., Gazit,A. and Aaronson,S.A.
  TITLE     Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1
            interaction with LRP6/Arrow
  JOURNAL   Nat Cell Biol 3 (7), 683-686 (2001)
   PUBMED   11433302
REFERENCE   7  (residues 1 to 1613)
  AUTHORS   Mao,B., Wu,W., Li,Y., Hoppe,D., Stannek,P., Glinka,A. and Niehrs,C.
  TITLE     LDL-receptor-related protein 6 is a receptor for Dickkopf proteins
  JOURNAL   Nature 411 (6835), 321-325 (2001)
   PUBMED   11357136
REFERENCE   8  (residues 1 to 1613)
  AUTHORS   Tamai,K., Semenov,M., Kato,Y., Spokony,R., Liu,C., Katsuyama,Y.,
            Hess,F., Saint-Jeannet,J.P. and He,X.
  TITLE     LDL-receptor-related proteins in Wnt signal transduction
  JOURNAL   Nature 407 (6803), 530-535 (2000)
   PUBMED   11029007
REFERENCE   9  (residues 1 to 1613)
  AUTHORS   Baens,M., Wlodarska,I., Corveleyn,A., Hoornaert,I., Hagemeijer,A.
            and Marynen,P.
  TITLE     A physical, transcript, and deletion map of chromosome region
            12p12.3 flanked by ETV6 and CDKN1B: hypermethylation of the LRP6
            CpG island in two leukemia patients with hemizygous del(12p)
  JOURNAL   Genomics 56 (1), 40-50 (1999)
   PUBMED   10036184
REFERENCE   10 (residues 1 to 1613)
  AUTHORS   Brown,S.D., Twells,R.C., Hey,P.J., Cox,R.D., Levy,E.R.,
            Soderman,A.R., Metzker,M.L., Caskey,C.T., Todd,J.A. and Hess,J.F.
  TITLE     Isolation and characterization of LRP6, a novel member of the low
            density lipoprotein receptor gene family
  JOURNAL   Biochem Biophys Res Commun 248 (3), 879-888 (1998)
   PUBMED   9704021
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC007621.34, BP229563.1,
            AF074264.1, BC126405.1, AC007537.3 and AA126261.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 8, 2007 this sequence version replaced NP_002327.1.
            
            Summary: This gene encodes a member of the low density lipoprotein
            (LDL) receptor gene family. LDL receptors are transmembrane cell
            surface proteins involved in receptor-mediated endocytosis of
            lipoprotein and protein ligands. The protein encoded by this gene
            functions as a receptor or, with Frizzled, a co-receptor for Wnt
            and thereby transmits the canonical Wnt/beta-catenin signaling
            cascade. Through its interaction with the Wnt/beta-catenin
            signaling cascade this gene plays a role in the regulation of cell
            differentiation, proliferation, and migration and the development
            of many cancer types. This protein undergoes gamma-secretase
            dependent RIP- (regulated intramembrane proteolysis) processing but
            the precise locations of the cleavage sites have not been
            determined.[provided by RefSeq, Dec 2009].
            
            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 :: SRR14038197.2563509.1, AF074264.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000261349.9/ ENSP00000261349.4
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..1613
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12p13.2"
     Protein         1..1613
                     /product="low-density lipoprotein receptor-related protein
                     6 isoform b precursor"
                     /note="low-density lipoprotein receptor-related protein 6;
                     LRP-6"
                     /calculated_mol_wt=180299
     Region          1..204
                     /region_name="YncE"
                     /note="DNA-binding beta-propeller fold protein YncE
                     [General function prediction only]; COG3391"
                     /db_xref="CDD:442618"
     mat_peptide     20..1613
                     /product="low-density lipoprotein receptor-related protein
                     6 isoform b"
                     /calculated_mol_wt=178425
     Region          20..275
                     /region_name="Beta-propeller 1"
                     /note="propagated from UniProtKB/Swiss-Prot (O75581.2)"
     Site            42
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (O75581.2)"
     Site            81
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (O75581.2)"
     Region          89..127
                     /region_name="LY"
                     /note="Low-density lipoprotein-receptor YWTD domain;
                     smart00135"
                     /db_xref="CDD:214531"
     Region          150..191
                     /region_name="Ldl_recept_b"
                     /note="Low-density lipoprotein receptor repeat class B;
                     pfam00058"
                     /db_xref="CDD:459654"
     Region          175..216
                     /region_name="LY"
                     /note="Low-density lipoprotein-receptor YWTD domain;
                     smart00135"
                     /db_xref="CDD:214531"
     Region          217..251
                     /region_name="LY"
                     /note="Low-density lipoprotein-receptor YWTD domain;
                     smart00135"
                     /db_xref="CDD:214531"
     Region          237..276
                     /region_name="LDL-receptor class B 5"
                     /note="propagated from UniProtKB/Swiss-Prot (O75581.2)"
     Site            281
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (O75581.2)"
     Region          286..323
                     /region_name="FXa_inhibition"
                     /note="Coagulation Factor Xa inhibitory site; pfam14670"
                     /db_xref="CDD:464251"
     Region          328..589
                     /region_name="Beta-propeller 2"
                     /note="propagated from UniProtKB/Swiss-Prot (O75581.2)"
     Region          353..393
                     /region_name="LY"
                     /note="Low-density lipoprotein-receptor YWTD domain;
                     smart00135"
                     /db_xref="CDD:214531"
     Region          397..437
                     /region_name="LY"
                     /note="Low-density lipoprotein-receptor YWTD domain;
                     smart00135"
                     /db_xref="CDD:214531"
     Site            433
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (O75581.2)"
     Region          458..499
                     /region_name="Ldl_recept_b"
                     /note="Low-density lipoprotein receptor repeat class B;
                     pfam00058"
                     /db_xref="CDD:459654"
     Region          483..524
                     /region_name="LY"
                     /note="Low-density lipoprotein-receptor YWTD domain;
                     smart00135"
                     /db_xref="CDD:214531"
     Site            486
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (O75581.2)"
     Region          525..558
                     /region_name="LY"
                     /note="Low-density lipoprotein-receptor YWTD domain;
                     smart00135"
                     /db_xref="CDD:214531"
     Region          592..627
                     /region_name="FXa_inhibition"
                     /note="Coagulation Factor Xa inhibitory site; pfam14670"
                     /db_xref="CDD:464251"
     Region          631..890
                     /region_name="Beta-propeller 3"
                     /note="propagated from UniProtKB/Swiss-Prot (O75581.2)"
     Region          <654..813
                     /region_name="YncE"
                     /note="DNA-binding beta-propeller fold protein YncE
                     [General function prediction only]; COG3391"
                     /db_xref="CDD:442618"
     Site            692
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:22000856; propagated from
                     UniProtKB/Swiss-Prot (O75581.2)"
     Region          697..739
                     /region_name="LY"
                     /note="Low-density lipoprotein-receptor YWTD domain;
                     smart00135"
                     /db_xref="CDD:214531"
     Region          827..866
                     /region_name="LY"
                     /note="Low-density lipoprotein-receptor YWTD domain;
                     smart00135"
                     /db_xref="CDD:214531"
     Site            859
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:22000856; propagated from
                     UniProtKB/Swiss-Prot (O75581.2)"
     Site            865
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:22000856; propagated from
                     UniProtKB/Swiss-Prot (O75581.2)"
     Region          893..929
                     /region_name="FXa_inhibition"
                     /note="Coagulation Factor Xa inhibitory site; pfam14670"
                     /db_xref="CDD:464251"
     Site            926
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:22000856; propagated from
                     UniProtKB/Swiss-Prot (O75581.2)"
     Region          933..1202
                     /region_name="Beta-propeller 4"
                     /note="propagated from UniProtKB/Swiss-Prot (O75581.2)"
     Region          958..998
                     /region_name="LY"
                     /note="Low-density lipoprotein-receptor YWTD domain;
                     smart00135"
                     /db_xref="CDD:214531"
     Region          <968..1075
                     /region_name="YncE"
                     /note="DNA-binding beta-propeller fold protein YncE
                     [General function prediction only]; COG3391"
                     /db_xref="CDD:442618"
     Site            1039
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:22000856; propagated from
                     UniProtKB/Swiss-Prot (O75581.2)"
     Region          1094..1136
                     /region_name="LY"
                     /note="Low-density lipoprotein-receptor YWTD domain;
                     smart00135"
                     /db_xref="CDD:214531"
     Region          1207..1243
                     /region_name="FXa_inhibition"
                     /note="Coagulation Factor Xa inhibitory site; pfam14670"
                     /db_xref="CDD:464251"
     Region          1249..1285
                     /region_name="LDLa"
                     /note="Low Density Lipoprotein Receptor Class A domain, a
                     cysteine-rich repeat that plays a central role in
                     mammalian cholesterol metabolism; the receptor protein
                     binds LDL and transports it into cells by endocytosis; 7
                     successive cysteine-rich repeats of about...; cd00112"
                     /db_xref="CDD:238060"
     Site            order(1254,1264,1275..1276)
                     /site_type="active"
                     /note="putative binding surface [active]"
                     /db_xref="CDD:238060"
     Site            order(1268,1271,1275,1281..1282)
                     /site_type="other"
                     /note="calcium-binding site [ion binding]"
                     /db_xref="CDD:238060"
     Site            1278..1282
                     /site_type="other"
                     /note="D-X-S-D-E motif"
                     /db_xref="CDD:238060"
     Region          1288..1322
                     /region_name="LDLa"
                     /note="Low Density Lipoprotein Receptor Class A domain, a
                     cysteine-rich repeat that plays a central role in
                     mammalian cholesterol metabolism; the receptor protein
                     binds LDL and transports it into cells by endocytosis; 7
                     successive cysteine-rich repeats of about...; cd00112"
                     /db_xref="CDD:238060"
     Site            order(1293,1301,1312..1313)
                     /site_type="active"
                     /note="putative binding surface [active]"
                     /db_xref="CDD:238060"
     Site            order(1305,1308,1312,1318..1319)
                     /site_type="other"
                     /note="calcium-binding site [ion binding]"
                     /db_xref="CDD:238060"
     Site            1315..1319
                     /site_type="other"
                     /note="D-X-S-D-E motif"
                     /db_xref="CDD:238060"
     Region          1326..1360
                     /region_name="LDLa"
                     /note="Low Density Lipoprotein Receptor Class A domain, a
                     cysteine-rich repeat that plays a central role in
                     mammalian cholesterol metabolism; the receptor protein
                     binds LDL and transports it into cells by endocytosis; 7
                     successive cysteine-rich repeats of about...; cd00112"
                     /db_xref="CDD:238060"
     Site            order(1331,1339,1350..1351)
                     /site_type="active"
                     /note="putative binding surface [active]"
                     /db_xref="CDD:238060"
     Site            order(1343,1346,1350,1356..1357)
                     /site_type="other"
                     /note="calcium-binding site [ion binding]"
                     /db_xref="CDD:238060"
     Site            1353..1357
                     /site_type="other"
                     /note="D-X-S-D-E motif"
                     /db_xref="CDD:238060"
     Site            1371..1393
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (O75581.2)"
     Site            1420
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by CK1.
                     /evidence=ECO:0000269|PubMed:16513652; propagated from
                     UniProtKB/Swiss-Prot (O75581.2)"
     Site            1430
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by CK1.
                     /evidence=ECO:0000269|PubMed:16513652; propagated from
                     UniProtKB/Swiss-Prot (O75581.2)"
     Site            1479
                     /site_type="phosphorylation"
                     /note="Phosphothreonine.
                     /evidence=ECO:0000269|PubMed:17569865; propagated from
                     UniProtKB/Swiss-Prot (O75581.2)"
     Region          1487..1493
                     /region_name="PPPSP motif A"
                     /note="propagated from UniProtKB/Swiss-Prot (O75581.2)"
     Site            1490
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by CDK14, GRK5 and GRK6.
                     /evidence=ECO:0000269|PubMed:16341017,
                     ECO:0000269|PubMed:17698587, ECO:0000269|PubMed:18762581,
                     ECO:0000269|PubMed:19801552, ECO:0000269|PubMed:20059949,
                     ECO:0000269|PubMed:25331957, ECO:0000269|PubMed:27821587,
                     ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (O75581.2)"
     Site            1493
                     /site_type="phosphorylation"
                     /note="Phosphothreonine, by CK1.
                     /evidence=ECO:0000269|PubMed:16341017; propagated from
                     UniProtKB/Swiss-Prot (O75581.2)"
     Region          1527..1534
                     /region_name="PPPSP motif B"
                     /note="propagated from UniProtKB/Swiss-Prot (O75581.2)"
     Region          1556..1613
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (O75581.2)"
     Region          1568..1575
                     /region_name="PPPSP motif C"
                     /note="propagated from UniProtKB/Swiss-Prot (O75581.2)"
     Region          1588..1593
                     /region_name="PPPSP motif D"
                     /note="propagated from UniProtKB/Swiss-Prot (O75581.2)"
     Region          1603..1610
                     /region_name="PPPSP motif E"
                     /note="propagated from UniProtKB/Swiss-Prot (O75581.2)"
     CDS             1..1613
                     /gene="LRP6"
                     /gene_synonym="ADCAD2; STHAG7"
                     /coded_by="NM_002336.3:310..5151"
                     /note="isoform b precursor is encoded by transcript
                     variant 1"
                     /db_xref="CCDS:CCDS8647.1"
                     /db_xref="GeneID:4040"
                     /db_xref="HGNC:HGNC:6698"
                     /db_xref="MIM:603507"
ORIGIN      
        1 mgavlrslla csfcvllraa plllyanrrd lrlvdatngk enativvggl edaaavdfvf
       61 shgliywsdv seeaikrtef nktesvqnvv vsgllspdgl acdwlgekly wtdsetnrie
      121 vsnldgslrk vlfwqeldqp raialdpssg fmywtdwgev pkieragmdg ssrfiiinse
      181 iywpngltld yeeqklywad aklnfihksn ldgtnrqavv kgslphpfal tlfedilywt
      241 dwsthsilac nkytgeglre ihsdifspmd ihafsqqrqp natnpcgidn ggcshlclms
      301 pvkpfyqcac ptgvklleng ktckdgatel lllarrtdlr risldtpdft divlqledir
      361 haiaidydpv egyiywtdde vrairrsfid gsgsqfvvta qiahpdgiav dwvarnlywt
      421 dtgtdrievt rlngtmrkil isedleepra ivldpmvgym ywtdwgeipk ieraaldgsd
      481 rvvlvntslg wpnglaldyd egkiywgdak tdkievmntd gtgrrvlved kiphifgftl
      541 lgdyvywtdw qrrsiervhk rsaereviid qlpdlmglka tnvhrvigsn pcaeenggcs
      601 hlclyrpqgl rcacpigfel isdmktcivp eafllfsrra dirrisletn nnnvaipltg
      661 vkeasaldfd vtdnriywtd islktisraf mngsalehvv efgldypegm avdwlgknly
      721 wadtgtnrie vskldgqhrq vlvwkdldsp ralaldpaeg fmywtewggk pkidraamdg
      781 serttlvpnv grangltidy akrrlywtdl dtnliessnm lglnreviad dlphpfgltq
      841 yqdyiywtdw srrsierank tsgqnrtiiq ghldyvmdil vfhssrqsgw necassnghc
      901 shlclavpvg gfvcgcpahy slnadnrtcs apttfllfsq ksainrmvid eqqspdiilp
      961 ihslrnvrai dydpldkqly widsrqnmir kaqedgsqgf tvvvssvpsq nleiqpydls
     1021 idiysryiyw tceatnvinv trldgrsvgv vlkgeqdrpr avvvnpekgy myftnlqers
     1081 pkieraaldg terevlffsg lskpialald srlgklfwad sdlrriessd lsganrivle
     1141 dsnilqpvgl tvfenwlywi dkqqqmieki dmtgregrtk vqariaqlsd ihavkelnlq
     1201 eyrqhpcaqd nggcshiclv kgdgttrcsc pmhlvllqde lscgepptcs pqqftcftge
     1261 idcipvawrc dgftecedhs delncpvcse sqfqcasgqc idgalrcngd ancqdksdek
     1321 ncevlclidq frcangqcig khkkcdhnvd csdksdeldc ypteepapqa tntvgsvigv
     1381 ivtifvsgtv yficqrmlcp rmkgdgetmt ndyvvhgpas vplgyvphps slsgslpgms
     1441 rgksmissls imggssgppy drahvtgass ssssstkgty fpailnppps patershytm
     1501 efgyssnsps thrsysyrpy syrhfapptt pcstdvcdsd yapsrrmtsv atakgytsdl
     1561 nydsepvppp ptprsqylsa eenyescpps pytersyshh lyppppspct dss
//
