LRAD3_MOUSE
ID LRAD3_MOUSE Reviewed; 345 AA.
AC A2AR95; A2AR96; Q8CCS0; Q8CDR7;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Low-density lipoprotein receptor class A domain-containing protein 3 {ECO:0000305};
DE Flags: Precursor;
GN Name=Ldlrad3 {ECO:0000312|MGI:MGI:2138856};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Olfactory bulb, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING
RP (ISOFORM 3).
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH APP, AND TISSUE
RP SPECIFICITY.
RX PubMed=21795536; DOI=10.1523/jneurosci.5065-10.2011;
RA Ranganathan S., Noyes N.C., Migliorini M., Winkles J.A., Battey F.D.,
RA Hyman B.T., Smith E., Yepes M., Mikhailenko I., Strickland D.K.;
RT "LRAD3, a novel low-density lipoprotein receptor family member that
RT modulates amyloid precursor protein trafficking.";
RL J. Neurosci. 31:10836-10846(2011).
CC -!- FUNCTION: May influence APP processing, resulting in a decrease in
CC sAPP-alpha production and increased amyloidogenic P3 peptide production
CC (PubMed:21795536). May regulate ITCH and NEDD4 E3 ligase activity and
CC degradation (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q86YD5, ECO:0000269|PubMed:21795536}.
CC -!- SUBUNIT: Interacts with APP precursor C-terminus (PubMed:21795536).
CC Interacts directly with ITCH; this interaction promotes ITCH auto-
CC ubiquitination leading to its degradation. Interacts directly with
CC NEDD4; this interaction promotes NEDD4 auto-ubiquitination. Interacts
CC directly with NEDD4L (By similarity). {ECO:0000250|UniProtKB:Q86YD5,
CC ECO:0000269|PubMed:21795536}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21795536};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:21795536}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=A2AR95-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A2AR95-2; Sequence=VSP_027620;
CC Name=3;
CC IsoId=A2AR95-3; Sequence=VSP_027619;
CC -!- TISSUE SPECIFICITY: Expressed in the cerebral cortex and hippocampus.
CC {ECO:0000269|PubMed:21795536}.
CC -!- SIMILARITY: Belongs to the LDLR family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC27759.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK029683; BAC26562.1; -; mRNA.
DR EMBL; AK032208; BAC27759.1; ALT_INIT; mRNA.
DR EMBL; AL845300; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX322585; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX571894; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS38187.1; -. [A2AR95-1]
DR RefSeq; NP_001277713.1; NM_001290784.1.
DR RefSeq; NP_849217.2; NM_178886.3. [A2AR95-1]
DR RefSeq; XP_006499544.1; XM_006499481.3. [A2AR95-3]
DR PDB; 7N1H; EM; 4.30 A; M/N/O/P=28-66.
DR PDBsum; 7N1H; -.
DR AlphaFoldDB; A2AR95; -.
DR SMR; A2AR95; -.
DR BioGRID; 232327; 2.
DR STRING; 10090.ENSMUSP00000054134; -.
DR GlyGen; A2AR95; 1 site.
DR PhosphoSitePlus; A2AR95; -.
DR PaxDb; A2AR95; -.
DR PRIDE; A2AR95; -.
DR ProteomicsDB; 252500; -. [A2AR95-1]
DR ProteomicsDB; 252501; -. [A2AR95-2]
DR ProteomicsDB; 252502; -. [A2AR95-3]
DR Antibodypedia; 42763; 140 antibodies from 25 providers.
DR DNASU; 241576; -.
DR Ensembl; ENSMUST00000058790; ENSMUSP00000054134; ENSMUSG00000048058. [A2AR95-1]
DR Ensembl; ENSMUST00000111222; ENSMUSP00000106853; ENSMUSG00000048058. [A2AR95-3]
DR GeneID; 241576; -.
DR KEGG; mmu:241576; -.
DR UCSC; uc008lhr.2; mouse. [A2AR95-1]
DR CTD; 143458; -.
DR MGI; MGI:2138856; Ldlrad3.
DR VEuPathDB; HostDB:ENSMUSG00000048058; -.
DR eggNOG; KOG1215; Eukaryota.
DR GeneTree; ENSGT00940000160574; -.
DR HOGENOM; CLU_072228_0_0_1; -.
DR InParanoid; A2AR95; -.
DR OMA; YPSAPSM; -.
DR PhylomeDB; A2AR95; -.
DR TreeFam; TF332096; -.
DR BioGRID-ORCS; 241576; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Ldlrad3; mouse.
DR PRO; PR:A2AR95; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; A2AR95; protein.
DR Bgee; ENSMUSG00000048058; Expressed in humerus cartilage element and 214 other tissues.
DR ExpressionAtlas; A2AR95; baseline and differential.
DR Genevisible; A2AR95; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0001540; F:amyloid-beta binding; IDA:MGI.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IDA:MGI.
DR GO; GO:0070613; P:regulation of protein processing; IDA:MGI.
DR CDD; cd00112; LDLa; 3.
DR Gene3D; 4.10.400.10; -; 3.
DR InterPro; IPR036055; LDL_receptor-like_sf.
DR InterPro; IPR023415; LDLR_class-A_CS.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR Pfam; PF00057; Ldl_recept_a; 3.
DR PRINTS; PR00261; LDLRECEPTOR.
DR SMART; SM00192; LDLa; 3.
DR SUPFAM; SSF57424; SSF57424; 3.
DR PROSITE; PS01209; LDLRA_1; 3.
DR PROSITE; PS50068; LDLRA_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disulfide bond;
KW Glycoprotein; Lipoprotein; Membrane; Receptor; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..345
FT /note="Low-density lipoprotein receptor class A domain-
FT containing protein 3"
FT /id="PRO_0000299379"
FT TOPO_DOM 18..173
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 174..194
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 195..345
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 28..65
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 70..107
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 112..148
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT REGION 270..345
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 256..259
FT /note="Involved in ITCH interaction"
FT /evidence="ECO:0000250|UniProtKB:Q86YD5"
FT MOTIF 275..278
FT /note="Involved in ITCH interaction"
FT /evidence="ECO:0000250|UniProtKB:Q86YD5"
FT COMPBIAS 279..325
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 24
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..42
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 37..55
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 49..64
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 71..84
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 78..97
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 91..106
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 113..125
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 120..138
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 132..147
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT VAR_SEQ 33..65
FT /note="GNFMCSNGRCIPGAWQCDGLPDCFDKSDEKECP -> A (in isoform
FT 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_027619"
FT VAR_SEQ 305..345
FT /note="SQAASSLLSVEASSHNPEQPGSPEGSAEPRDSVPSQGTEEV -> LPRSQQP
FT PECGSQQPQPRAAWLSRGLC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027620"
SQ SEQUENCE 345 AA; 37467 MW; E3EEE9F188DC5209 CRC64;
MWLLGPLCLL LSSTAESQLL PGNNFTNECN IPGNFMCSNG RCIPGAWQCD GLPDCFDKSD
EKECPKAKSK CGPTFFPCAS GIHCIIGRFR CNGFEDCPDG SDEENCTANP LLCSTARYHC
RNGLCIDKSF ICDGQNNCQD NSDEESCESS LEPGSGQVFV TSENQLVYYP SITYAIIGSS
VIFVLVVALL ALVLHHQRKR NNLMTLPVHR LQHPVLLSRL VVLDHPHHCN VTYNVNNGVQ
YVATQAEQNA SEVGSPPSYS EALLDQRPAW YDLPPPPYSS DTESLNQADL PPYRSRSGSA
YSASSQAASS LLSVEASSHN PEQPGSPEGS AEPRDSVPSQ GTEEV
