LRA25_HUMAN
ID LRA25_HUMAN Reviewed; 189 AA.
AC Q8N5H3; E9PB01; E9PL72; Q6PJ27;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2013, sequence version 2.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Leucine repeat adapter protein 25;
GN Name=FAM89B; Synonyms=Lrap25;
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 [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Brain;
RA Yu W., Sarginson J., Gibbs R.A.;
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 1-157 (ISOFORM 3).
RC TISSUE=Cervix, Lung, and Melanoma;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(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. Acts as an adapter
CC that mediates the specific recognition of LIMK1 by CDC42BPA and
CC CDC42BPB in the lamellipodia. LRAP25-mediated CDC42BPA/CDC42BPB
CC targeting to LIMK1 and the lamellipodium results in LIMK1 activation
CC and the subsequent phosphorylation of CFL1 which is important for
CC lamellipodial F-actin regulation. {ECO:0000250|UniProtKB:Q9QUI1}.
CC -!- SUBUNIT: Interacts with SKI. Interacts (via LRR repeat) with CDC42BPA
CC (via AGC-kinase C-terminal domain), CDC42BPB (via AGC-kinase C-terminal
CC domain) and LIMK1 (via LIM zinc-binding domains). Forms a tripartite
CC complex with CDC42BPA, CDC42BPB and LIMK1.
CC {ECO:0000250|UniProtKB:Q9QUI1}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm
CC {ECO:0000250|UniProtKB:Q9QUI1}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:Q9QUI1}. Note=Co-localizes with CDC42BPA,
CC CDC42BPB and LIMK1 in the lamellipodium.
CC {ECO:0000250|UniProtKB:Q9QUI1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=3;
CC IsoId=Q8N5H3-3; Sequence=Displayed;
CC Name=1;
CC IsoId=Q8N5H3-1; Sequence=VSP_045015;
CC Name=2;
CC IsoId=Q8N5H3-2; Sequence=VSP_045016;
CC Name=4;
CC IsoId=Q8N5H3-4; Sequence=VSP_045631, VSP_045632;
CC -!- SIMILARITY: Belongs to the FAM89 family. {ECO:0000305}.
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DR EMBL; AF052151; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AP001362; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC023991; AAH23991.1; -; mRNA.
DR EMBL; BC032373; AAH32373.1; -; mRNA.
DR EMBL; BM557093; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS44648.1; -. [Q8N5H3-4]
DR CCDS; CCDS53662.1; -. [Q8N5H3-3]
DR CCDS; CCDS8105.1; -. [Q8N5H3-1]
DR RefSeq; NP_001092254.1; NM_001098784.1. [Q8N5H3-4]
DR RefSeq; NP_001092255.1; NM_001098785.1. [Q8N5H3-3]
DR RefSeq; NP_690045.1; NM_152832.2. [Q8N5H3-1]
DR AlphaFoldDB; Q8N5H3; -.
DR SMR; Q8N5H3; -.
DR BioGRID; 117157; 8.
DR STRING; 9606.ENSP00000431459; -.
DR iPTMnet; Q8N5H3; -.
DR PhosphoSitePlus; Q8N5H3; -.
DR BioMuta; FAM89B; -.
DR DMDM; 449081271; -.
DR EPD; Q8N5H3; -.
DR jPOST; Q8N5H3; -.
DR MassIVE; Q8N5H3; -.
DR MaxQB; Q8N5H3; -.
DR PaxDb; Q8N5H3; -.
DR PeptideAtlas; Q8N5H3; -.
DR PRIDE; Q8N5H3; -.
DR ProteomicsDB; 19112; -.
DR ProteomicsDB; 21701; -.
DR ProteomicsDB; 72052; -. [Q8N5H3-3]
DR ProteomicsDB; 72053; -. [Q8N5H3-2]
DR TopDownProteomics; Q8N5H3-1; -. [Q8N5H3-1]
DR Antibodypedia; 29851; 96 antibodies from 15 providers.
DR DNASU; 23625; -.
DR Ensembl; ENST00000316409.2; ENSP00000314829.2; ENSG00000176973.8. [Q8N5H3-1]
DR Ensembl; ENST00000449319.2; ENSP00000402439.2; ENSG00000176973.8. [Q8N5H3-4]
DR Ensembl; ENST00000530349.2; ENSP00000431459.1; ENSG00000176973.8. [Q8N5H3-3]
DR GeneID; 23625; -.
DR KEGG; hsa:23625; -.
DR MANE-Select; ENST00000530349.2; ENSP00000431459.1; NM_001098785.2; NP_001092255.1.
DR UCSC; uc001oel.3; human. [Q8N5H3-3]
DR CTD; 23625; -.
DR DisGeNET; 23625; -.
DR GeneCards; FAM89B; -.
DR HGNC; HGNC:16708; FAM89B.
DR HPA; ENSG00000176973; Low tissue specificity.
DR MIM; 616128; gene.
DR neXtProt; NX_Q8N5H3; -.
DR OpenTargets; ENSG00000176973; -.
DR PharmGKB; PA142671795; -.
DR VEuPathDB; HostDB:ENSG00000176973; -.
DR eggNOG; ENOG502S05U; Eukaryota.
DR GeneTree; ENSGT00940000153370; -.
DR HOGENOM; CLU_1749030_0_0_1; -.
DR InParanoid; Q8N5H3; -.
DR OMA; EAIQECK; -.
DR OrthoDB; 1585340at2759; -.
DR PhylomeDB; Q8N5H3; -.
DR PathwayCommons; Q8N5H3; -.
DR BioGRID-ORCS; 23625; 32 hits in 1079 CRISPR screens.
DR ChiTaRS; FAM89B; human.
DR GenomeRNAi; 23625; -.
DR Pharos; Q8N5H3; Tbio.
DR PRO; PR:Q8N5H3; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q8N5H3; protein.
DR Bgee; ENSG00000176973; Expressed in cortical plate and 94 other tissues.
DR Genevisible; Q8N5H3; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0001222; F:transcription corepressor binding; ISS:UniProtKB.
DR GO; GO:0030010; P:establishment of cell polarity; ISS:UniProtKB.
DR GO; GO:0060392; P:negative regulation of SMAD protein signal transduction; ISS:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS: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; Reference proteome; Repeat.
FT CHAIN 1..189
FT /note="Leucine repeat adapter protein 25"
FT /id="PRO_0000271763"
FT REPEAT 86..114
FT /note="LRR"
FT /evidence="ECO:0000250|UniProtKB:Q566R4"
FT REGION 54..83
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 141..175
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 188
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT VAR_SEQ 51..97
FT /note="IHDELSRAARAPDGPRHAAGAANAGPAAGPRRPVNLDSALAALRKEM -> V
FT VLSTSTQRWPRCARRCCLQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045016"
FT VAR_SEQ 98..154
FT /note="VGLRQLDMSLLCQLWGLYESIQDYKHLCQDLSFCQDLSSSLHSDSSYPPDAG
FT LSDDE -> LSAGGAAAVGHVLVVPAVGPVRVNPGLQTPVPRPELLPGPVILPPFGQLL
FT PTGCGPV (in isoform 4)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_045631"
FT VAR_SEQ 98..110
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045015"
FT VAR_SEQ 155..189
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_045632"
SQ SEQUENCE 189 AA; 20147 MW; FA025D3895EAC290 CRC64;
MNGLPSAEAP GGAGCALAGL PPLPRGLSGL LNASGGSWRE LERVYSQRSR IHDELSRAAR
APDGPRHAAG AANAGPAAGP RRPVNLDSAL AALRKEMVGL RQLDMSLLCQ LWGLYESIQD
YKHLCQDLSF CQDLSSSLHS DSSYPPDAGL SDDEEPPDAS LPPDPPPLTV PQTHNARDQW
LQDAFHISL
