LRA25_MOUSE
ID LRA25_MOUSE Reviewed; 189 AA.
AC Q9QUI1; Q8K2S5; Q9JHD8; Q9JL54;
DT 06-FEB-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Leucine repeat adapter protein 25 {ECO:0000303|PubMed:25107909};
DE AltName: Full=C184L ORF2 protein {ECO:0000303|PubMed:10512749};
DE AltName: Full=C184M protein {ECO:0000303|PubMed:10512749};
DE AltName: Full=MMTV receptor {ECO:0000303|PubMed:9525630};
GN Name=Fam89b {ECO:0000312|MGI:MGI:106595};
GN Synonyms=C184m {ECO:0000303|PubMed:10512749},
GN Lrap25 {ECO:0000303|PubMed:25107909}, Mtvr2 {ECO:0000303|PubMed:9525630};
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 [MRNA] (ISOFORM 1), DEVELOPMENTAL STAGE, AND TISSUE
RP SPECIFICITY.
RC STRAIN=ICR; TISSUE=Forebrain;
RX PubMed=10512749; DOI=10.1006/bbrc.1999.1462;
RA Sakuma-Takagi M., Tohyama Y., Kasama-Yoshida H., Sakagami H., Kondo H.,
RA Kurihara T.;
RT "Novel related cDNAs (C184L, C184M, and C184S) from developing mouse brain
RT encoding two apparently unrelated proteins.";
RL Biochem. Biophys. Res. Commun. 263:737-742(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION (MICROBIAL INFECTION),
RP TISSUE SPECIFICITY, INTERACTION WITH MMTV ENV (MICROBIAL INFECTION), AND
RP SUBCELLULAR LOCATION (ISOFORM 2).
RC STRAIN=Swiss Webster;
RX PubMed=9525630; DOI=10.1128/jvi.72.4.3066-3071.1998;
RA Golovkina T.V., Dzuris J., van den Hoogen B., Jaffe A.B., Wright P.C.,
RA Cofer S.M., Ross S.R.;
RT "A novel membrane protein is a mouse mammary tumor virus receptor.";
RL J. Virol. 72:3066-3071(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Swiss Webster;
RA Golovkina T.V., Dzuris J., van den Hoogen B., Ross S.R.;
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Czech II; TISSUE=Mammary tumor;
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 FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SKI.
RX PubMed=12646588; DOI=10.1074/jbc.m210855200;
RA Kokura K., Kim H., Shinagawa T., Khan M.M., Nomura T., Ishii S.;
RT "The Ski-binding protein C184M negatively regulates tumor growth factor-
RT beta signaling by sequestering the Smad proteins in the cytoplasm.";
RL J. Biol. Chem. 278:20133-20139(2003).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, and Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP FUNCTION, INTERACTION WITH CDC42BPA; CDC42BPB AND LIMK1, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Brain;
RX PubMed=25107909; DOI=10.1074/jbc.m114.588079;
RA Lee I.C., Leung T., Tan I.;
RT "Adaptor protein LRAP25 mediates myotonic dystrophy kinase-related Cdc42-
RT binding kinase (MRCK) regulation of LIMK1 protein in lamellipodial F-actin
RT dynamics.";
RL J. Biol. Chem. 289:26989-27003(2014).
CC -!- FUNCTION: Negatively regulates TGF-beta-induced signaling; in
CC cooperation with SKI prevents the translocation of SMAD2 from the
CC nucleus to the cytoplasm in response to TGF-beta (PubMed:12646588).
CC Acts as an adapter that mediates the specific recognition of LIMK1 by
CC CDC42BPA and CDC42BPB in the lamellipodia. LRAP25-mediated
CC CDC42BPA/CDC42BPB targeting to LIMK1 and the lamellipodium results in
CC LIMK1 activation and the subsequent phosphorylation of CFL1 which is
CC important for lamellipodial F-actin regulation (PubMed:25107909).
CC {ECO:0000269|PubMed:12646588, ECO:0000269|PubMed:25107909}.
CC -!- FUNCTION: [Isoform 2]: (Microbial infection) May be a receptor for
CC mouse mammary tumor virus (MMTV). {ECO:0000269|PubMed:9525630}.
CC -!- SUBUNIT: Interacts with SKI (PubMed:12646588). Interacts (via LRR
CC repeat) with CDC42BPA (via AGC-kinase C-terminal domain), CDC42BPB (via
CC AGC-kinase C-terminal domain) and LIMK1 (via LIM zinc-binding domains).
CC Forms a tripartite complex with CDC42BPA, CDC42BPB and LIMK1
CC (PubMed:25107909). {ECO:0000269|PubMed:12646588,
CC ECO:0000269|PubMed:25107909}.
CC -!- SUBUNIT: [Isoform 2]: (Microbial infection) Interacts with mouse
CC mammary tumor virus (MMTV) envelope glycoprotein gp70.
CC {ECO:0000269|PubMed:9525630}.
CC -!- INTERACTION:
CC Q9QUI1; P12755: SKI; Xeno; NbExp=6; IntAct=EBI-6503100, EBI-347281;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm
CC {ECO:0000269|PubMed:12646588}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:25107909}. Note=Co-localizes with CDC42BPA,
CC CDC42BPB and LIMK1 in the lamellipodium. {ECO:0000269|PubMed:25107909}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell surface
CC {ECO:0000269|PubMed:9525630}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=MMTV receptor variant 2;
CC IsoId=Q9QUI1-1; Sequence=Displayed;
CC Name=2; Synonyms=MMTV receptor variant 1;
CC IsoId=Q9QUI1-2; Sequence=VSP_045017;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in the early postnatal
CC brain. {ECO:0000269|PubMed:10512749, ECO:0000269|PubMed:9525630}.
CC -!- DEVELOPMENTAL STAGE: Expressed in forebrain at 16 dpc.
CC {ECO:0000269|PubMed:10512749}.
CC -!- SIMILARITY: Belongs to the FAM89 family. {ECO:0000305}.
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DR EMBL; AB012726; BAA87047.1; -; mRNA.
DR EMBL; AB012727; BAA87049.1; -; mRNA.
DR EMBL; AF212920; AAF32282.1; -; mRNA.
DR EMBL; AF212921; AAF32283.1; -; mRNA.
DR EMBL; AC134563; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC030163; AAH30163.1; -; mRNA.
DR CCDS; CCDS37890.1; -. [Q9QUI1-1]
DR CCDS; CCDS50361.1; -. [Q9QUI1-2]
DR PIR; JC7107; JC7107.
DR RefSeq; NP_852117.2; NM_181452.2. [Q9QUI1-1]
DR AlphaFoldDB; Q9QUI1; -.
DR SMR; Q9QUI1; -.
DR IntAct; Q9QUI1; 2.
DR STRING; 10090.ENSMUSP00000097538; -.
DR iPTMnet; Q9QUI1; -.
DR PhosphoSitePlus; Q9QUI1; -.
DR MaxQB; Q9QUI1; -.
DR PaxDb; Q9QUI1; -.
DR PRIDE; Q9QUI1; -.
DR ProteomicsDB; 252498; -. [Q9QUI1-1]
DR ProteomicsDB; 252499; -. [Q9QUI1-2]
DR Antibodypedia; 29851; 96 antibodies from 15 providers.
DR DNASU; 17826; -.
DR Ensembl; ENSMUST00000099955; ENSMUSP00000097538; ENSMUSG00000024939. [Q9QUI1-1]
DR Ensembl; ENSMUST00000161368; ENSMUSP00000124294; ENSMUSG00000024939. [Q9QUI1-2]
DR GeneID; 17826; -.
DR KEGG; mmu:17826; -.
DR UCSC; uc008gez.1; mouse. [Q9QUI1-1]
DR CTD; 23625; -.
DR MGI; MGI:106595; Fam89b.
DR VEuPathDB; HostDB:ENSMUSG00000024939; -.
DR eggNOG; ENOG502S05U; Eukaryota.
DR GeneTree; ENSGT00940000153370; -.
DR HOGENOM; CLU_128818_0_0_1; -.
DR InParanoid; Q9QUI1; -.
DR OMA; EAIQECK; -.
DR PhylomeDB; Q9QUI1; -.
DR BioGRID-ORCS; 17826; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Fam89b; mouse.
DR PRO; PR:Q9QUI1; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9QUI1; protein.
DR Bgee; ENSMUSG00000024939; Expressed in ganglionic eminence and 85 other tissues.
DR ExpressionAtlas; Q9QUI1; baseline.
DR Genevisible; Q9QUI1; MM.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0001222; F:transcription corepressor binding; IDA:UniProtKB.
DR GO; GO:0030010; P:establishment of cell polarity; IMP:UniProtKB.
DR GO; GO:0060392; P:negative regulation of SMAD protein signal transduction; IDA:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
DR InterPro; IPR039499; LURA1/LRA25.
DR Pfam; PF14854; LURAP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Cytoplasm; Leucine-rich repeat;
KW Phosphoprotein; Receptor; Reference proteome; Repeat.
FT CHAIN 1..189
FT /note="Leucine repeat adapter protein 25"
FT /id="PRO_0000420996"
FT REPEAT 86..114
FT /note="LRR"
FT /evidence="ECO:0000250|UniProtKB:Q566R4"
FT REGION 54..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 136..175
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 188
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N5H3"
FT VAR_SEQ 98..110
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9525630"
FT /id="VSP_045017"
FT CONFLICT 61
FT /note="A -> V (in Ref. 5; AAH30163)"
FT /evidence="ECO:0000305"
FT CONFLICT 127
FT /note="D -> H (in Ref. 2; AAF32283 and 3; AAF32282)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 189 AA; 20140 MW; C3771501EB726E01 CRC64;
MNGLPATEAP GGAGCALAGL PPLPRGLSGL LNASGGSWRE LERVYSQRSR IHDELSRAAR
APDGPRHAAG SANSGSAAGP RRPVNLDSAL AALRKEMVGL RQLDMSLLCQ LWGLYESIQD
YKHLCQDLSL CQDLSSSLHS DSSYPPDAGL SDDEEPPDAS LPPDPPPLTV PQTHNARDQW
LQDAFQISL
