LRCH1_HUMAN
ID LRCH1_HUMAN Reviewed; 728 AA.
AC Q9Y2L9; B7ZLL5; F8W6F0; Q17R43; Q2KHR1; Q5TBU9; Q7Z5F6; Q7Z5F7;
DT 22-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Leucine-rich repeat and calponin homology domain-containing protein 1;
DE AltName: Full=Calponin homology domain-containing protein 1;
DE AltName: Full=Neuronal protein 81;
DE Short=NP81;
GN Name=LRCH1; Synonyms=CHDC1, KIAA1016;
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] (ISOFORMS 1 AND 2), AND VARIANT
RP PRO-234.
RA Guo J.H., Yu L.;
RT "Cloning and characterizing of human NP81 (neuronal protein) gene.";
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-234.
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANT
RP PRO-234.
RC TISSUE=Brain, and Lung;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-568, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-532; SER-536 AND THR-568, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-370, 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).
RN [9]
RP FUNCTION, INTERACTION WITH DOCK8, AND SUBCELLULAR LOCATION.
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.
CC {ECO:0000269|PubMed:28028151}.
CC -!- SUBUNIT: Interacts (via LRR repeats) with unphosphorylated DOCK8 (via
CC DHR-2 domain); the interaction prevents the interaction between DOCK8
CC and CDC42. {ECO:0000269|PubMed:28028151}.
CC -!- INTERACTION:
CC Q9Y2L9; Q8NF50: DOCK8; NbExp=3; IntAct=EBI-2797324, EBI-2548605;
CC Q9Y2L9; Q8NF50-2: DOCK8; NbExp=5; IntAct=EBI-2797324, EBI-10174653;
CC Q9Y2L9-3; Q9Y6G1: TMEM14A; NbExp=3; IntAct=EBI-12082218, EBI-2800360;
CC Q9Y2L9-3; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-12082218, EBI-8638294;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:28028151}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=b, NP81b;
CC IsoId=Q9Y2L9-1; Sequence=Displayed;
CC Name=2; Synonyms=a, NP81a;
CC IsoId=Q9Y2L9-2; Sequence=VSP_010635, VSP_010636;
CC Name=3;
CC IsoId=Q9Y2L9-3; Sequence=VSP_044474;
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA76860.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY050631; AAK95567.1; -; mRNA.
DR EMBL; AY050632; AAK95568.1; -; mRNA.
DR EMBL; AB023233; BAA76860.1; ALT_INIT; mRNA.
DR EMBL; AL136958; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL138704; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359880; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC112937; AAI12938.1; -; mRNA.
DR EMBL; BC117472; AAI17473.1; -; mRNA.
DR EMBL; BC143883; AAI43884.1; -; mRNA.
DR CCDS; CCDS31972.1; -. [Q9Y2L9-1]
DR CCDS; CCDS53865.1; -. [Q9Y2L9-3]
DR CCDS; CCDS53866.1; -. [Q9Y2L9-2]
DR RefSeq; NP_001157683.1; NM_001164211.1. [Q9Y2L9-3]
DR RefSeq; NP_001157685.1; NM_001164213.1. [Q9Y2L9-2]
DR RefSeq; NP_055931.1; NM_015116.2. [Q9Y2L9-1]
DR AlphaFoldDB; Q9Y2L9; -.
DR SMR; Q9Y2L9; -.
DR BioGRID; 116760; 50.
DR IntAct; Q9Y2L9; 17.
DR MINT; Q9Y2L9; -.
DR STRING; 9606.ENSP00000374447; -.
DR iPTMnet; Q9Y2L9; -.
DR PhosphoSitePlus; Q9Y2L9; -.
DR BioMuta; LRCH1; -.
DR DMDM; 296439310; -.
DR EPD; Q9Y2L9; -.
DR jPOST; Q9Y2L9; -.
DR MassIVE; Q9Y2L9; -.
DR MaxQB; Q9Y2L9; -.
DR PaxDb; Q9Y2L9; -.
DR PeptideAtlas; Q9Y2L9; -.
DR PRIDE; Q9Y2L9; -.
DR ProteomicsDB; 29771; -.
DR ProteomicsDB; 85839; -. [Q9Y2L9-1]
DR ProteomicsDB; 85840; -. [Q9Y2L9-2]
DR Antibodypedia; 9206; 158 antibodies from 22 providers.
DR DNASU; 23143; -.
DR Ensembl; ENST00000311191.10; ENSP00000308493.5; ENSG00000136141.15. [Q9Y2L9-2]
DR Ensembl; ENST00000389797.8; ENSP00000374447.3; ENSG00000136141.15. [Q9Y2L9-3]
DR Ensembl; ENST00000389798.7; ENSP00000374448.3; ENSG00000136141.15. [Q9Y2L9-1]
DR GeneID; 23143; -.
DR KEGG; hsa:23143; -.
DR MANE-Select; ENST00000389797.8; ENSP00000374447.3; NM_001164211.2; NP_001157683.2. [Q9Y2L9-3]
DR UCSC; uc001vbj.4; human. [Q9Y2L9-1]
DR CTD; 23143; -.
DR DisGeNET; 23143; -.
DR GeneCards; LRCH1; -.
DR HGNC; HGNC:20309; LRCH1.
DR HPA; ENSG00000136141; Low tissue specificity.
DR MIM; 610368; gene.
DR neXtProt; NX_Q9Y2L9; -.
DR OpenTargets; ENSG00000136141; -.
DR PharmGKB; PA134898200; -.
DR VEuPathDB; HostDB:ENSG00000136141; -.
DR eggNOG; KOG0532; Eukaryota.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000159528; -.
DR HOGENOM; CLU_008231_2_0_1; -.
DR InParanoid; Q9Y2L9; -.
DR OMA; DFHHIRK; -.
DR OrthoDB; 378148at2759; -.
DR PhylomeDB; Q9Y2L9; -.
DR TreeFam; TF318428; -.
DR PathwayCommons; Q9Y2L9; -.
DR SignaLink; Q9Y2L9; -.
DR BioGRID-ORCS; 23143; 10 hits in 1076 CRISPR screens.
DR ChiTaRS; LRCH1; human.
DR GenomeRNAi; 23143; -.
DR Pharos; Q9Y2L9; Tbio.
DR PRO; PR:Q9Y2L9; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q9Y2L9; protein.
DR Bgee; ENSG00000136141; Expressed in cerebellar cortex and 162 other tissues.
DR ExpressionAtlas; Q9Y2L9; baseline and differential.
DR Genevisible; Q9Y2L9; HS.
DR GO; GO:0005737; C:cytoplasm; IMP:UniProtKB.
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 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 Alternative splicing; Cytoplasm; Leucine-rich repeat; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..728
FT /note="Leucine-rich repeat and calponin homology domain-
FT containing protein 1"
FT /id="PRO_0000084478"
FT REPEAT 98..119
FT /note="LRR 1"
FT REPEAT 121..143
FT /note="LRR 2"
FT REPEAT 144..166
FT /note="LRR 3"
FT REPEAT 167..187
FT /note="LRR 4"
FT REPEAT 189..210
FT /note="LRR 5"
FT REPEAT 212..234
FT /note="LRR 6"
FT REPEAT 235..255
FT /note="LRR 7"
FT REPEAT 257..278
FT /note="LRR 8"
FT REPEAT 283..304
FT /note="LRR 9"
FT DOMAIN 576..692
FT /note="Calponin-homology (CH)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT REGION 24..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 311..348
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 377..398
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 516..547
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 311..327
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 516..546
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 370
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 409
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62046"
FT MOD_RES 532
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 536
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 568
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 551
FT /note="S -> SDPALILPPISFNTLTQAQTWDSSSYSVPSEGDSDN (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044474"
FT VAR_SEQ 661..696
FT /note="ADLCSPCDILQLDFRHIRKTVDTLLALGEKAPPPTS -> EKLCLPHHILEE
FT KGLVKVGITIQALLDITVTKALFT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.1"
FT /id="VSP_010635"
FT VAR_SEQ 697..728
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.1"
FT /id="VSP_010636"
FT VARIANT 234
FT /note="S -> P (in dbSNP:rs842381)"
FT /evidence="ECO:0000269|PubMed:10231032,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.1"
FT /id="VAR_051133"
FT VARIANT 486
FT /note="A -> S (in dbSNP:rs11617392)"
FT /id="VAR_051134"
FT CONFLICT 326
FT /note="G -> V (in Ref. 5; AAI43884)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 728 AA; 80875 MW; D4E29414E466DBF8 CRC64;
MATPGSEPQP FVPALSVATL HPLHHPHHHH HHHQHHGGTG APGGAGGGGG GSGGFNLPLN
RGLERALEEA ANSGGLNLSA RKLKEFPRTA APGHDLSDTV QADLSKNRLV EVPMELCHFV
SLEILNLYHN CIRVIPEAIV NLQMLTYLNL SRNQLSALPA CLCGLPLKVL IASNNKLGSL
PEEIGQLKQL MELDVSCNEI TALPQQIGQL KSLRELNVRR NYLKVLPQEL VDLSLVKFDF
SCNKVLVIPI CFREMKQLQV LLLENNPLQS PPAQICTKGK VHIFKYLSIQ ACQIKTADSL
YLHTMERPHL HQHVEDGKKD SDSGVGSDNG DKRLSATEPS DEDTVSLNVP MSNIMEEEQI
IKEDSCHRLS PVKGEFHQEF QPEPSLLGDS TNSGEERDQF TDRADGLHSE FMNYKARAED
CEELLRIEED VHWQTEGIIS SSKDQDMDIA MIEQLREAVD LLQDPNGLST DITERSVLNL
YPMGSAEALE LQDSALNGQI QLETSPVCEV QSDLTLQSNG SQYSPNEIRE NSPAVSPTTN
STAPFGLKPR SVFLRPQRNL ESIDPQFTIR RKMEQMREEK ELVEQLRESI EMRLKVSLHE
DLGAALMDGV VLCHLVNHIR PRSVASIHVP SPAVPKLSMA KCRRNVENFL EACRKLGVPE
ADLCSPCDIL QLDFRHIRKT VDTLLALGEK APPPTSALRS RDLIGFCLVH ILFIVLVYIT
YHWNALSA
