ARH_HUMAN
ID ARH_HUMAN Reviewed; 308 AA.
AC Q5SW96; A2BHI5; Q6TQS9; Q8N2Y0; Q9UFI9;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Low density lipoprotein receptor adapter protein 1 {ECO:0000305};
DE AltName: Full=Autosomal recessive hypercholesterolemia protein {ECO:0000303|PubMed:11326085};
GN Name=LDLRAP1 {ECO:0000312|HGNC:HGNC:18640};
GN Synonyms=ARH {ECO:0000303|PubMed:11326085};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PRO-202, AND VARIANT FHCL4
RP HIS-202.
RX PubMed=11326085; DOI=10.1126/science.1060458;
RA Garcia C.K., Wilund K.R., Arca M., Zuliani G., Fellin R., Maioli M.,
RA Calandra S., Bertolini S., Cossu F., Grishin N., Barnes R., Cohen J.C.,
RA Hobbs H.H.;
RT "Autosomal recessive hypercholesterolemia caused by mutations in a putative
RT LDL receptor adaptor protein.";
RL Science 292:1394-1398(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PRO-202.
RX PubMed=12417523; DOI=10.1093/hmg/11.24.3019;
RA Wilund K.R., Yi M., Campagna F., Arca M., Zuliani G., Fellin R., Ho Y.K.,
RA Garcia J.V., Hobbs H.H., Cohen J.C.;
RT "Molecular mechanisms of autosomal recessive hypercholesterolemia.";
RL Hum. Mol. Genet. 11:3019-3030(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-202.
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-202.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH LDLR; CLATHRIN AND AP-2 COMPLEX, MUTAGENESIS OF PHE-165;
RP 212-LEU-LEU-213; ASP-214; GLU-216 AND ARG-266, MOTIF, AND REGION.
RX PubMed=12221107; DOI=10.1074/jbc.m208539200;
RA He G., Gupta S., Yi M., Michaely P., Hobbs H.H., Cohen J.C.;
RT "ARH is a modular adaptor protein that interacts with the LDL receptor,
RT clathrin, and AP-2.";
RL J. Biol. Chem. 277:44044-44049(2002).
RN [7]
RP CHARACTERIZATION, INTERACTION WITH CLATHRIN AND AP-2 COMPLEX, AND
RP SUBCELLULAR LOCATION.
RX PubMed=12451172; DOI=10.1073/pnas.252630799;
RA Mishra S.K., Watkins S.C., Traub L.M.;
RT "The autosomal recessive hypercholesterolemia (ARH) protein interfaces
RT directly with the clathrin-coat machinery.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16099-16104(2002).
RN [8]
RP FUNCTION, AND INTERACTION WITH AP2B1.
RX PubMed=15728179; DOI=10.1074/jbc.m501029200;
RA Mishra S.K., Keyel P.A., Edeling M.A., Dupin A.L., Owen D.J., Traub L.M.;
RT "Functional dissection of an AP-2 beta2 appendage-binding sequence within
RT the autosomal recessive hypercholesterolemia protein.";
RL J. Biol. Chem. 280:19270-19280(2005).
RN [9]
RP INTERACTION WITH AP2B1, AND MUTAGENESIS OF ASP-256.
RX PubMed=16903783; DOI=10.1371/journal.pbio.0040262;
RA Schmid E.M., Ford M.G.J., Burtey A., Praefcke G.J.K., Peak-Chew S.-Y.,
RA Mills I.G., Benmerah A., McMahon H.T.;
RT "Role of the AP2 beta-appendage hub in recruiting partners for clathrin-
RT coated vesicle assembly.";
RL PLoS Biol. 4:E262-E262(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14 AND SER-186, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 252-267 IN COMPLEX WITH AP2B1,
RP AND DOMAIN.
RX PubMed=16516836; DOI=10.1016/j.devcel.2006.01.016;
RA Edeling M.A., Mishra S.K., Keyel P.A., Steinhauser A.L., Collins B.M.,
RA Roth R., Heuser J.E., Owen D.J., Traub L.M.;
RT "Molecular switches involving the AP-2 beta2 appendage regulate endocytic
RT cargo selection and clathrin coat assembly.";
RL Dev. Cell 10:329-342(2006).
RN [15]
RP VARIANTS MET-56 AND PRO-202.
RX PubMed=20124734; DOI=10.5551/jat.2873;
RA Harada K., Miyamoto Y., Morisaki H., Ohta N., Yamanaka I., Kokubo Y.,
RA Makino H., Harada-Shiba M., Okayama A., Tomoike H., Okamura T.,
RA Tomonori O., Saito Y., Yoshimasa Y., Morisaki T.;
RT "A novel Thr56Met mutation of the autosomal recessive hypercholesterolemia
RT gene associated with hypercholesterolemia.";
RL J. Atheroscler. Thromb. 17:131-140(2010).
CC -!- FUNCTION: Adapter protein (clathrin-associated sorting protein (CLASP))
CC required for efficient endocytosis of the LDL receptor (LDLR) in
CC polarized cells such as hepatocytes and lymphocytes, but not in non-
CC polarized cells (fibroblasts). May be required for LDL binding and
CC internalization but not for receptor clustering in coated pits. May
CC facilitate the endocytosis of LDLR and LDLR-LDL complexes from coated
CC pits by stabilizing the interaction between the receptor and the
CC structural components of the pits. May also be involved in the
CC internalization of other LDLR family members. Binds to
CC phosphoinositides, which regulate clathrin bud assembly at the cell
CC surface. Required for trafficking of LRP2 to the endocytic recycling
CC compartment which is necessary for LRP2 proteolysis, releasing a tail
CC fragment which translocates to the nucleus and mediates transcriptional
CC repression (By similarity). {ECO:0000250|UniProtKB:D3ZAR1,
CC ECO:0000269|PubMed:15728179}.
CC -!- SUBUNIT: Interacts (via PID domain) with LDLR (via NPXY motif)
CC (PubMed:12221107). Binds to soluble clathrin trimers (PubMed:12221107).
CC Interacts with AP2B1; the interaction mediates the association with the
CC AP-2 complex (PubMed:12221107). Interacts with VLDLR (By similarity).
CC Interacts with LRP2 (By similarity). {ECO:0000250|UniProtKB:D3ZAR1,
CC ECO:0000250|UniProtKB:Q8C142, ECO:0000269|PubMed:12221107}.
CC -!- INTERACTION:
CC Q5SW96; Q10567-3: AP1B1; NbExp=3; IntAct=EBI-747813, EBI-11978055;
CC Q5SW96; P63010: AP2B1; NbExp=5; IntAct=EBI-747813, EBI-432924;
CC Q5SW96; P63010-2: AP2B1; NbExp=5; IntAct=EBI-747813, EBI-11529439;
CC Q5SW96; Q6ZVH7: ESPNL; NbExp=3; IntAct=EBI-747813, EBI-12831272;
CC Q5SW96; Q14192: FHL2; NbExp=3; IntAct=EBI-747813, EBI-701903;
CC Q5SW96; P31273: HOXC8; NbExp=8; IntAct=EBI-747813, EBI-1752118;
CC Q5SW96; P13378: HOXD8; NbExp=3; IntAct=EBI-747813, EBI-7098661;
CC Q5SW96; P43358: MAGEA4; NbExp=3; IntAct=EBI-747813, EBI-743122;
CC Q5SW96; Q9UPT6: MAPK8IP3; NbExp=6; IntAct=EBI-747813, EBI-717887;
CC Q5SW96; A8MTQ0: NOTO; NbExp=3; IntAct=EBI-747813, EBI-17490746;
CC Q5SW96; Q02548: PAX5; NbExp=3; IntAct=EBI-747813, EBI-296331;
CC Q5SW96; Q8NDX1-2: PSD4; NbExp=6; IntAct=EBI-747813, EBI-12215623;
CC Q5SW96; Q9H668: STN1; NbExp=12; IntAct=EBI-747813, EBI-746930;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12451172}.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in the kidney, liver, and
CC placenta, with lower levels detectable in brain, heart, muscle, colon,
CC spleen, intestine, lung, and leukocytes.
CC -!- DOMAIN: The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction
CC the AP-2 complex subunit AP2B1. {ECO:0000269|PubMed:16516836}.
CC -!- DOMAIN: The PID domain mediates interaction with the NPXY
CC internalization motif of LDLR. {ECO:0000250|UniProtKB:D3ZAR1}.
CC -!- DISEASE: Hypercholesterolemia, familial, 4 (FHCL4) [MIM:603813]: A form
CC of hypercholesterolemia, a disorder of lipoprotein metabolism
CC characterized by elevated serum low-density lipoprotein (LDL)
CC cholesterol levels, which result in excess deposition of cholesterol in
CC tissues and leads to xanthelasma, xanthomas, accelerated
CC atherosclerosis and increased risk of premature coronary heart disease.
CC FHCL4 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:11326085}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; AY389348; AAQ90407.1; -; Genomic_DNA.
DR EMBL; AL117654; CAB56030.2; -; mRNA.
DR EMBL; AL606491; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX572623; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC029770; AAH29770.2; -; mRNA.
DR CCDS; CCDS30639.1; -.
DR PIR; T17340; T17340.
DR RefSeq; NP_056442.2; NM_015627.2.
DR PDB; 2G30; X-ray; 1.60 A; P=252-267.
DR PDBsum; 2G30; -.
DR AlphaFoldDB; Q5SW96; -.
DR SMR; Q5SW96; -.
DR BioGRID; 117561; 35.
DR ELM; Q5SW96; -.
DR IntAct; Q5SW96; 22.
DR MINT; Q5SW96; -.
DR STRING; 9606.ENSP00000363458; -.
DR MoonDB; Q5SW96; Curated.
DR iPTMnet; Q5SW96; -.
DR PhosphoSitePlus; Q5SW96; -.
DR BioMuta; LDLRAP1; -.
DR DMDM; 116241254; -.
DR EPD; Q5SW96; -.
DR jPOST; Q5SW96; -.
DR MassIVE; Q5SW96; -.
DR MaxQB; Q5SW96; -.
DR PaxDb; Q5SW96; -.
DR PeptideAtlas; Q5SW96; -.
DR PRIDE; Q5SW96; -.
DR ProteomicsDB; 63967; -.
DR Antibodypedia; 30473; 567 antibodies from 35 providers.
DR DNASU; 26119; -.
DR Ensembl; ENST00000374338.5; ENSP00000363458.4; ENSG00000157978.12.
DR GeneID; 26119; -.
DR KEGG; hsa:26119; -.
DR MANE-Select; ENST00000374338.5; ENSP00000363458.4; NM_015627.3; NP_056442.2.
DR UCSC; uc001bkl.5; human.
DR CTD; 26119; -.
DR DisGeNET; 26119; -.
DR GeneCards; LDLRAP1; -.
DR HGNC; HGNC:18640; LDLRAP1.
DR HPA; ENSG00000157978; Low tissue specificity.
DR MalaCards; LDLRAP1; -.
DR MIM; 603813; phenotype.
DR MIM; 605747; gene.
DR neXtProt; NX_Q5SW96; -.
DR OpenTargets; ENSG00000157978; -.
DR Orphanet; 391665; Homozygous familial hypercholesterolemia.
DR PharmGKB; PA128394641; -.
DR VEuPathDB; HostDB:ENSG00000157978; -.
DR eggNOG; KOG3536; Eukaryota.
DR GeneTree; ENSGT00940000157118; -.
DR HOGENOM; CLU_078253_0_0_1; -.
DR InParanoid; Q5SW96; -.
DR OMA; NNSVVWE; -.
DR OrthoDB; 1531411at2759; -.
DR PhylomeDB; Q5SW96; -.
DR TreeFam; TF314159; -.
DR PathwayCommons; Q5SW96; -.
DR Reactome; R-HSA-196791; Vitamin D (calciferol) metabolism.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-HSA-8964026; Chylomicron clearance.
DR Reactome; R-HSA-8964038; LDL clearance.
DR Reactome; R-HSA-9758890; Transport of RCbl within the body.
DR SignaLink; Q5SW96; -.
DR BioGRID-ORCS; 26119; 21 hits in 1076 CRISPR screens.
DR ChiTaRS; LDLRAP1; human.
DR EvolutionaryTrace; Q5SW96; -.
DR GeneWiki; Low_density_lipoprotein_receptor_adapter_protein_1; -.
DR GenomeRNAi; 26119; -.
DR Pharos; Q5SW96; Tbio.
DR PRO; PR:Q5SW96; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5SW96; protein.
DR Bgee; ENSG00000157978; Expressed in cerebellar hemisphere and 196 other tissues.
DR Genevisible; Q5SW96; HS.
DR GO; GO:0030424; C:axon; ISS:BHF-UCL.
DR GO; GO:0009925; C:basal plasma membrane; IDA:UniProtKB.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005883; C:neurofilament; ISS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0055037; C:recycling endosome; IDA:BHF-UCL.
DR GO; GO:0001540; F:amyloid-beta binding; IPI:BHF-UCL.
DR GO; GO:0035650; F:AP-1 adaptor complex binding; IDA:UniProtKB.
DR GO; GO:0035612; F:AP-2 adaptor complex binding; IDA:UniProtKB.
DR GO; GO:0035615; F:clathrin adaptor activity; IDA:BHF-UCL.
DR GO; GO:0030276; F:clathrin binding; IDA:UniProtKB.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IPI:BHF-UCL.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:BHF-UCL.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IDA:UniProtKB.
DR GO; GO:0035591; F:signaling adaptor activity; IDA:BHF-UCL.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; IMP:UniProtKB.
DR GO; GO:0042982; P:amyloid precursor protein metabolic process; IMP:BHF-UCL.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IMP:BHF-UCL.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:BHF-UCL.
DR GO; GO:0008203; P:cholesterol metabolic process; NAS:UniProtKB.
DR GO; GO:0030301; P:cholesterol transport; NAS:UniProtKB.
DR GO; GO:0034383; P:low-density lipoprotein particle clearance; IMP:BHF-UCL.
DR GO; GO:0090205; P:positive regulation of cholesterol metabolic process; IC:BHF-UCL.
DR GO; GO:1905581; P:positive regulation of low-density lipoprotein particle clearance; IMP:BHF-UCL.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; IMP:UniProtKB.
DR GO; GO:1905602; P:positive regulation of receptor-mediated endocytosis involved in cholesterol transport; IMP:BHF-UCL.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IMP:BHF-UCL.
DR GO; GO:0031623; P:receptor internalization; IMP:BHF-UCL.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IDA:BHF-UCL.
DR GO; GO:0090118; P:receptor-mediated endocytosis involved in cholesterol transport; IMP:BHF-UCL.
DR GO; GO:0043393; P:regulation of protein binding; IMP:UniProtKB.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; IMP:BHF-UCL.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006020; PTB/PI_dom.
DR Pfam; PF14719; PID_2; 1.
DR SMART; SM00462; PTB; 1.
DR PROSITE; PS01179; PID; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Atherosclerosis; Cholesterol metabolism;
KW Cytoplasm; Disease variant; Endocytosis; Hyperlipidemia; Lipid metabolism;
KW Phosphoprotein; Reference proteome; Steroid metabolism; Sterol metabolism.
FT CHAIN 1..308
FT /note="Low density lipoprotein receptor adapter protein 1"
FT /id="PRO_0000064675"
FT DOMAIN 42..196
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT REGION 249..276
FT /note="AP-2 complex binding"
FT /evidence="ECO:0000269|PubMed:12221107"
FT MOTIF 212..216
FT /note="Clathrin box"
FT /evidence="ECO:0000269|PubMed:12221107"
FT MOTIF 257..266
FT /note="[DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif"
FT /evidence="ECO:0000269|PubMed:16516836"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 202
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C142"
FT VARIANT 56
FT /note="T -> M (probable disease-associated variant found in
FT patients with hypercholesterolemia; dbSNP:rs752849346)"
FT /evidence="ECO:0000269|PubMed:20124734"
FT /id="VAR_076925"
FT VARIANT 202
FT /note="S -> H (in FHCL4; Lebanon; requires 2 nucleotide
FT substitutions; dbSNP:rs386629678)"
FT /evidence="ECO:0000269|PubMed:11326085"
FT /id="VAR_023320"
FT VARIANT 202
FT /note="S -> P (in dbSNP:rs6687605)"
FT /evidence="ECO:0000269|PubMed:11326085,
FT ECO:0000269|PubMed:12417523, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17974005, ECO:0000269|PubMed:20124734"
FT /id="VAR_028403"
FT MUTAGEN 165
FT /note="F->A: Abolishes LDLR cytoplasmic tail binding."
FT /evidence="ECO:0000269|PubMed:12221107"
FT MUTAGEN 165
FT /note="F->V: Abolishes LDLR cytoplasmic tail binding."
FT /evidence="ECO:0000269|PubMed:12221107"
FT MUTAGEN 212..213
FT /note="LL->AA: Abolishes clathrin binding."
FT /evidence="ECO:0000269|PubMed:12221107"
FT MUTAGEN 214
FT /note="D->A: Abolishes clathrin binding."
FT /evidence="ECO:0000269|PubMed:12221107"
FT MUTAGEN 216
FT /note="E->A: Abolishes clathrin binding."
FT /evidence="ECO:0000269|PubMed:12221107"
FT MUTAGEN 256
FT /note="D->R: Abolishes interaction with AP2B1."
FT /evidence="ECO:0000269|PubMed:16903783"
FT MUTAGEN 266
FT /note="R->A: Abolishes AP-2 complex binding."
FT /evidence="ECO:0000269|PubMed:12221107"
FT HELIX 256..266
FT /evidence="ECO:0007829|PDB:2G30"
SQ SEQUENCE 308 AA; 33885 MW; DE83168CB328D2A7 CRC64;
MDALKSAGRA LIRSPSLAKQ SWGGGGRHRK LPENWTDTRE TLLEGMLFSL KYLGMTLVEQ
PKGEELSAAA IKRIVATAKA SGKKLQKVTL KVSPRGIILT DNLTNQLIEN VSIYRISYCT
ADKMHDKVFA YIAQSQHNQS LECHAFLCTK RKMAQAVTLT VAQAFKVAFE FWQVSKEEKE
KRDKASQEGG DVLGARQDCT PSLKSLVATG NLLDLEETAK APLSTVSANT TNMDEVPRPQ
ALSGSSVVWE LDDGLDEAFS RLAQSRTNPQ VLDTGLTAQD MHYAQCLSPV DWDKPDSSGT
EQDDLFSF
