LRCH1_MOUSE
ID LRCH1_MOUSE Reviewed; 709 AA.
AC P62046; E9QLJ4;
DT 21-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Leucine-rich repeat and calponin homology domain-containing protein 1;
DE AltName: Full=Calponin homology domain-containing protein 1;
GN Name=Lrch1; Synonyms=Chdc1, Kiaa1016;
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 TISSUE=Embryonic tail;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [2]
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-581, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-395; SER-518; SER-522 AND
RP THR-581, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, and Spleen;
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 [5]
RP FUNCTION, INTERACTION WITH DOCK8, AND DISRUPTION PHENOTYPE.
RX PubMed=28028151; DOI=10.1084/jem.20160068;
RA Xu X., Han L., Zhao G., Xue S., Gao Y., Xiao J., Zhang S., Chen P.,
RA Wu Z.Y., Ding J., Hu R., Wei B., Wang H.;
RT "LRCH1 interferes with DOCK8-Cdc42-induced T cell migration and ameliorates
RT experimental autoimmune encephalomyelitis.";
RL J. Exp. Med. 214:209-226(2017).
CC -!- FUNCTION: Acts as a negative regulator of GTPase CDC42 by sequestering
CC CDC42-guanine exchange factor DOCK8. Probably by preventing CDC42
CC activation, negatively regulates CD4(+) T-cell migration in response to
CC chemokine stimulation. {ECO:0000269|PubMed:28028151}.
CC -!- SUBUNIT: Interacts (via LRR repeats) with unphosphorylated DOCK8 (via
CC DHR-2 domain); the interaction prevents the association between DOCK8
CC and CDC42. {ECO:0000269|PubMed:28028151}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y2L9}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice are viable, fertile
CC and have normal CD4(+) T-cell populations in lymph nodes and spleen. In
CC an experimental autoimmune encephalomyelitis (EAE) disease model, the
CC symptoms, such as paralysis, are more severe.
CC {ECO:0000269|PubMed:28028151}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC98074.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK129264; BAC98074.1; ALT_INIT; mRNA.
DR EMBL; AC135083; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC154621; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS36976.1; -.
DR RefSeq; NP_001028611.2; NM_001033439.3.
DR AlphaFoldDB; P62046; -.
DR SMR; P62046; -.
DR BioGRID; 237704; 5.
DR STRING; 10090.ENSMUSP00000086363; -.
DR iPTMnet; P62046; -.
DR PhosphoSitePlus; P62046; -.
DR EPD; P62046; -.
DR jPOST; P62046; -.
DR MaxQB; P62046; -.
DR PaxDb; P62046; -.
DR PeptideAtlas; P62046; -.
DR PRIDE; P62046; -.
DR ProteomicsDB; 290164; -.
DR Antibodypedia; 9206; 158 antibodies from 22 providers.
DR Ensembl; ENSMUST00000088970; ENSMUSP00000086363; ENSMUSG00000068015.
DR GeneID; 380916; -.
DR KEGG; mmu:380916; -.
DR UCSC; uc007uqf.1; mouse.
DR CTD; 23143; -.
DR MGI; MGI:2443390; Lrch1.
DR VEuPathDB; HostDB:ENSMUSG00000068015; -.
DR eggNOG; KOG0532; Eukaryota.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000159528; -.
DR HOGENOM; CLU_008231_2_0_1; -.
DR InParanoid; P62046; -.
DR OMA; DFHHIRK; -.
DR OrthoDB; 378148at2759; -.
DR PhylomeDB; P62046; -.
DR TreeFam; TF318428; -.
DR BioGRID-ORCS; 380916; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Lrch1; mouse.
DR PRO; PR:P62046; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P62046; protein.
DR Bgee; ENSMUSG00000068015; Expressed in utricle of membranous labyrinth and 213 other tissues.
DR ExpressionAtlas; P62046; baseline and differential.
DR Genevisible; P62046; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:1990869; P:cellular response to chemokine; IMP:UniProtKB.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:2000405; P:negative regulation of T cell migration; IMP:UniProtKB.
DR CDD; cd00014; CH; 1.
DR Gene3D; 1.10.418.10; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR001715; CH-domain.
DR InterPro; IPR036872; CH_dom_sf.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR Pfam; PF00307; CH; 1.
DR Pfam; PF13855; LRR_8; 2.
DR SMART; SM00033; CH; 1.
DR SMART; SM00369; LRR_TYP; 5.
DR SUPFAM; SSF47576; SSF47576; 1.
DR PROSITE; PS50021; CH; 1.
DR PROSITE; PS51450; LRR; 6.
PE 1: Evidence at protein level;
KW Cytoplasm; Leucine-rich repeat; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..709
FT /note="Leucine-rich repeat and calponin homology domain-
FT containing protein 1"
FT /id="PRO_0000084479"
FT REPEAT 60..83
FT /note="LRR 1"
FT REPEAT 86..108
FT /note="LRR 2"
FT REPEAT 109..131
FT /note="LRR 3"
FT REPEAT 132..155
FT /note="LRR 4"
FT REPEAT 157..176
FT /note="LRR 5"
FT REPEAT 177..199
FT /note="LRR 6"
FT REPEAT 200..223
FT /note="LRR 7"
FT REPEAT 225..244
FT /note="LRR 8"
FT REPEAT 245..268
FT /note="LRR 9"
FT DOMAIN 589..702
FT /note="Calponin-homology (CH)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT REGION 24..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 301..390
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 504..526
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 301..317
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 330..345
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 395
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 518
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 522
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 581
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT CONFLICT 362
FT /note="T -> A (in Ref. 1; BAC98074)"
FT /evidence="ECO:0000305"
FT CONFLICT 372
FT /note="I -> V (in Ref. 1; BAC98074)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 709 AA; 79076 MW; CC45219A1D9B04CD CRC64;
MATPGSEPQA FAPALSVTAL HPHLHQHHQH HQHHQHHGGT GGTGFNLPLN RGLERALEEA
ANSGGLNLSA RKLKEFPRTT APGHDLSDTV RADLSKNRLV EVPMELCQFV SLEILNLYHN
CIRVIPEAIV NLQMLTHLNL SRNQLSALPA CLCGLPLKVL IASNNKLGSL PEEIGQLKQL
MELDVSCNEI TALPQQIGQL KSLRELNVRR NYLKVLPPEL VDLPLVKFDF SCNKVLVIPV
CFREMKQLQV LLLENNPLQS PPAQICTKGK VHIFKYLSIQ ACQIKTSDSL YLPTIERPHL
HQHVEDSKKD SDSGVGSDNG DKRLSATEPS DEDTVSLNAP MSNIVEEDQT IKEDACHRLT
PTKGEFQPKP SILGDSGISG QEREQLAGRA DARHSGLMNY IKDQAEDCEE LLRIEEDAHW
HMEELLNSSK DRELDIAMIE QLREAELLQD PNGLSADIIE RSILNLFPMD SGEASEFPDP
SLNGQLQLET SPDREVQNDL MLQSNGSQYS PNEIRENSPS VSPTANITAP FGLKPRSGSW
CPEEVQGSLQ AESSPRRPQL LSRHVFLRPQ RNLESIDPQF TIRRKMEQMR EEKELVEQLR
ESIEMRLKVT LHEDLGAALM DGVVLCHLAN HVRPRSVASI HVPSPAVPKL SMAKCRRNVE
NFLEACRKLG VPEEKLCLPH HILEEKGLVK VGTTVQALLD VTVTKALFT
