LRAD4_MOUSE
ID LRAD4_MOUSE Reviewed; 306 AA.
AC Q8BWJ4;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Low-density lipoprotein receptor class A domain-containing protein 4;
GN Name=Ldlrad4; Synonyms=D18Ertd653e;
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].
RC STRAIN=C57BL/6J; TISSUE=Heart;
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 FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=24627487; DOI=10.1074/jbc.m114.558981;
RA Nakano N., Maeyama K., Sakata N., Itoh F., Akatsu R., Nakata M., Katsu Y.,
RA Ikeno S., Togawa Y., Vo Nguyen T.T., Watanabe Y., Kato M., Itoh S.;
RT "C18 ORF1, a novel negative regulator of transforming growth factor-beta
RT signaling.";
RL J. Biol. Chem. 289:12680-12692(2014).
CC -!- FUNCTION: Functions as a negative regulator of TGF-beta signaling and
CC thereby probably plays a role in cell proliferation, differentiation,
CC apoptosis, motility, extracellular matrix production and
CC immunosuppression. In the canonical TGF-beta pathway, ZFYVE9/SARA
CC recruits the intracellular signal transducer and transcriptional
CC modulators SMAD2 and SMAD3 to the TGF-beta receptor. Phosphorylated by
CC the receptor, SMAD2 and SMAD3 then form a heteromeric complex with
CC SMAD4 that translocates to the nucleus to regulate transcription.
CC Through interaction with SMAD2 and SMAD3, LDLRAD4 may compete with
CC ZFYVE9 and SMAD4 and prevent propagation of the intracellular signal.
CC {ECO:0000269|PubMed:24627487}.
CC -!- SUBUNIT: Interacts with PMEPA1. Interacts (via the SMAD interaction
CC motif) with SMAD2 and SMAD3 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Early endosome membrane {ECO:0000250}; Single-
CC pass membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected in all tissues tested.
CC {ECO:0000269|PubMed:24627487}.
CC -!- DOMAIN: The SMAD interaction motif is required for interaction with
CC SMAD2 and SMAD3 and the negative regulation of TGF-beta signaling.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the PMEPA1 family. {ECO:0000305}.
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DR EMBL; AK052338; BAC34943.1; -; mRNA.
DR CCDS; CCDS29325.1; -.
DR RefSeq; NP_766219.2; NM_172631.3.
DR RefSeq; XP_006526148.1; XM_006526085.3.
DR RefSeq; XP_006526149.1; XM_006526086.3.
DR RefSeq; XP_006526150.1; XM_006526087.3.
DR RefSeq; XP_006526151.1; XM_006526088.3.
DR RefSeq; XP_006526152.1; XM_006526089.3.
DR AlphaFoldDB; Q8BWJ4; -.
DR STRING; 10090.ENSMUSP00000068471; -.
DR PhosphoSitePlus; Q8BWJ4; -.
DR PaxDb; Q8BWJ4; -.
DR PRIDE; Q8BWJ4; -.
DR ProteomicsDB; 287260; -.
DR Antibodypedia; 21959; 71 antibodies from 10 providers.
DR Ensembl; ENSMUST00000063775; ENSMUSP00000068471; ENSMUSG00000024544.
DR GeneID; 52662; -.
DR KEGG; mmu:52662; -.
DR UCSC; uc008fng.1; mouse.
DR CTD; 753; -.
DR MGI; MGI:1277150; Ldlrad4.
DR VEuPathDB; HostDB:ENSMUSG00000024544; -.
DR eggNOG; ENOG502QRYK; Eukaryota.
DR GeneTree; ENSGT00390000000724; -.
DR HOGENOM; CLU_074371_0_1_1; -.
DR InParanoid; Q8BWJ4; -.
DR OMA; GASEIMC; -.
DR OrthoDB; 1189277at2759; -.
DR PhylomeDB; Q8BWJ4; -.
DR TreeFam; TF331681; -.
DR BioGRID-ORCS; 52662; 0 hits in 70 CRISPR screens.
DR ChiTaRS; Ldlrad4; mouse.
DR PRO; PR:Q8BWJ4; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q8BWJ4; protein.
DR Bgee; ENSMUSG00000024544; Expressed in ascending aorta and 176 other tissues.
DR ExpressionAtlas; Q8BWJ4; baseline and differential.
DR Genevisible; Q8BWJ4; MM.
DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0070412; F:R-SMAD binding; ISO:MGI.
DR GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0060394; P:negative regulation of pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0010991; P:negative regulation of SMAD protein complex assembly; ISS:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IMP:UniProtKB.
DR CDD; cd00112; LDLa; 1.
DR Gene3D; 4.10.400.10; -; 1.
DR InterPro; IPR036055; LDL_receptor-like_sf.
DR InterPro; IPR023415; LDLR_class-A_CS.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR InterPro; IPR043445; TMEPAI/LRAD4.
DR PANTHER; PTHR16514; PTHR16514; 1.
DR Pfam; PF00057; Ldl_recept_a; 1.
DR SMART; SM00192; LDLa; 1.
DR SUPFAM; SSF57424; SSF57424; 1.
DR PROSITE; PS01209; LDLRA_1; 1.
DR PROSITE; PS50068; LDLRA_2; 1.
PE 2: Evidence at transcript level;
KW Disulfide bond; Endosome; Membrane; Reference proteome;
KW Signal transduction inhibitor; Transmembrane; Transmembrane helix.
FT CHAIN 1..306
FT /note="Low-density lipoprotein receptor class A domain-
FT containing protein 4"
FT /id="PRO_0000185445"
FT TOPO_DOM 1..64
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 65..85
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 86..306
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 11..48
FT /note="LDL-receptor class A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT REGION 100..127
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 268..306
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 180..183
FT /note="PPxY motif 1"
FT MOTIF 208..211
FT /note="SMAD interaction motif (SIM)"
FT MOTIF 252..255
FT /note="PPxY motif 2"
FT COMPBIAS 100..126
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 268..291
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 19..38
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 32..47
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
SQ SEQUENCE 306 AA; 33857 MW; 043C2260AEE8729F CRC64;
MPEAGFQATN AFTECKFTCT SGKCLYLGSL VCNQQNDCGD NSDEENCLLV TEHPPPGIFN
SELEFAQILI IVVVVTVMVV VVVCLLNHYK VSTRSFINRP NQSQRQEDGL QPEGSLWPSD
SSVQRPGASE IMCAPRGRDR FTTPSFIQRD PFSRFQPTYP YVQHEIDLPP TISLSDGEEP
PPYQGPCTLQ LRDPEQQMEL NRESVRAPPN RTVFDSDLID ISMYNGGPCP PSSHSGISAA
TCSSNGRMEG PPPTYSEVMG HYPGTSFFHH QHSNTHRGSR PQFQPNNSEG TIVPIKGKDR
KPGDLV
