LRC32_MOUSE
ID LRC32_MOUSE Reviewed; 663 AA.
AC G3XA59; A0A0U1RQ93;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=Transforming growth factor beta activator LRRC32 {ECO:0000305};
DE AltName: Full=Garpin {ECO:0000250|UniProtKB:Q14392};
DE AltName: Full=Glycoprotein A repetitions predominant {ECO:0000303|PubMed:25127859};
DE Short=GARP {ECO:0000303|PubMed:25127859};
DE AltName: Full=Leucine-rich repeat-containing protein 32 {ECO:0000305};
DE Flags: Precursor;
GN Name=Lrrc32 {ECO:0000312|MGI:MGI:93882};
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 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION.
RX PubMed=25127859; DOI=10.4049/jimmunol.1401102;
RA Edwards J.P., Thornton A.M., Shevach E.M.;
RT "Release of active TGF-beta1 from the latent TGF-beta1/GARP complex on T
RT regulatory cells is mediated by integrin beta8.";
RL J. Immunol. 193:2843-2849(2014).
RN [4]
RP FUNCTION, INTERACTION WITH TGFB3, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=28912269; DOI=10.1074/jbc.m117.797613;
RA Wu B.X., Li A., Lei L., Kaneko S., Wallace C., Li X., Li Z.;
RT "Glycoprotein A repetitions predominant (GARP) positively regulates
RT transforming growth factor (TGF) beta3 and is essential for mouse
RT palatogenesis.";
RL J. Biol. Chem. 292:18091-18097(2017).
CC -!- FUNCTION: Key regulator of transforming growth factor beta (TGFB1,
CC TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in
CC a latent state during storage in extracellular space (PubMed:25127859).
CC Associates specifically via disulfide bonds with the Latency-associated
CC peptide (LAP), which is the regulatory chain of TGF-beta, and regulates
CC integrin-dependent activation of TGF-beta (PubMed:25127859,
CC PubMed:28912269). Able to outcompete LTBP1 for binding to LAP
CC regulatory chain of TGF-beta (By similarity). Controls activation of
CC TGF-beta-1 (TGFB1) on the surface of activated regulatory T-cells
CC (Tregs) (PubMed:25127859). Required for epithelial fusion during palate
CC development by regulating activation of TGF-beta-3 (TGFB3)
CC (PubMed:28912269). {ECO:0000250|UniProtKB:Q14392,
CC ECO:0000269|PubMed:25127859, ECO:0000269|PubMed:28912269}.
CC -!- SUBUNIT: Interacts with TGFB1; associates via disulfide bonds with the
CC Latency-associated peptide chain (LAP) regulatory chain of TGFB1,
CC leading to regulate activation of TGF-beta-1 (By similarity). Interacts
CC with TGFB2 (By similarity). Interacts with TGFB3; associates via
CC disulfide bonds with the Latency-associated peptide chain (LAP)
CC regulatory chain of TGFB3, leading to regulate activation of TGF-beta-3
CC (PubMed:28912269). Interacts with LAPTM4B; decreases TGFB1 production
CC in regulatory T-cells (By similarity). {ECO:0000250|UniProtKB:Q14392,
CC ECO:0000269|PubMed:28912269}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q14392};
CC Single-pass type I membrane protein {ECO:0000255}. Cell surface
CC {ECO:0000250|UniProtKB:Q14392}.
CC -!- TISSUE SPECIFICITY: Present in medial edge epithelial cells at 14.5 dpc
CC (at protein level). {ECO:0000269|PubMed:28912269}.
CC -!- DISRUPTION PHENOTYPE: Lethality within 24 hours after birth
CC (PubMed:28912269). Mice display defective palatogenesis without
CC apparent abnormalities in other major organs (PubMed:28912269).
CC {ECO:0000269|PubMed:28912269}.
CC -!- SIMILARITY: Belongs to the LRRC32/LRRC33 family. {ECO:0000305}.
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DR EMBL; AC115069; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466531; EDL16346.1; -; Genomic_DNA.
DR CCDS; CCDS52319.1; -.
DR RefSeq; NP_001106850.1; NM_001113379.1.
DR RefSeq; XP_006508040.1; XM_006507977.1.
DR RefSeq; XP_006508041.1; XM_006507978.3.
DR RefSeq; XP_006508042.1; XM_006507979.2.
DR AlphaFoldDB; G3XA59; -.
DR SMR; G3XA59; -.
DR STRING; 10090.ENSMUSP00000133205; -.
DR GlyGen; G3XA59; 6 sites.
DR PhosphoSitePlus; G3XA59; -.
DR EPD; G3XA59; -.
DR MaxQB; G3XA59; -.
DR PaxDb; G3XA59; -.
DR PeptideAtlas; G3XA59; -.
DR PRIDE; G3XA59; -.
DR ProteomicsDB; 337412; -.
DR Antibodypedia; 45130; 323 antibodies from 30 providers.
DR Ensembl; ENSMUST00000165205; ENSMUSP00000133205; ENSMUSG00000090958.
DR Ensembl; ENSMUST00000205956; ENSMUSP00000145859; ENSMUSG00000090958.
DR GeneID; 434215; -.
DR KEGG; mmu:434215; -.
DR UCSC; uc012fpt.1; mouse.
DR CTD; 2615; -.
DR MGI; MGI:93882; Lrrc32.
DR VEuPathDB; HostDB:ENSMUSG00000090958; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000162288; -.
DR HOGENOM; CLU_024194_1_0_1; -.
DR InParanoid; G3XA59; -.
DR OMA; PTWNKES; -.
DR OrthoDB; 826997at2759; -.
DR PhylomeDB; G3XA59; -.
DR TreeFam; TF317167; -.
DR BioGRID-ORCS; 434215; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Lrrc32; mouse.
DR PRO; PR:G3XA59; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; G3XA59; protein.
DR Bgee; ENSMUSG00000090958; Expressed in lung and 84 other tissues.
DR ExpressionAtlas; G3XA59; baseline and differential.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0050431; F:transforming growth factor beta binding; IPI:UniProtKB.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; IDA:MGI.
DR GO; GO:0001818; P:negative regulation of cytokine production; IDA:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:MGI.
DR GO; GO:1901388; P:regulation of transforming growth factor beta activation; ISO:MGI.
DR GO; GO:1901398; P:regulation of transforming growth factor beta3 activation; IDA:UniProtKB.
DR GO; GO:0062009; P:secondary palate development; IMP:UniProtKB.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR Gene3D; 3.80.10.10; -; 4.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR Pfam; PF13855; LRR_8; 5.
DR SMART; SM00369; LRR_TYP; 14.
DR PROSITE; PS51450; LRR; 20.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Glycoprotein; Growth factor binding;
KW Leucine-rich repeat; Membrane; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..663
FT /note="Transforming growth factor beta activator LRRC32"
FT /evidence="ECO:0000255"
FT /id="PRO_0000445577"
FT TOPO_DOM 18..628
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 629..649
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 650..663
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 22..49
FT /note="LRRNT"
FT /evidence="ECO:0000255"
FT REPEAT 49..72
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 73..96
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 98..123
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT REPEAT 125..148
FT /note="LRR 4"
FT /evidence="ECO:0000255"
FT REPEAT 149..172
FT /note="LRR 5"
FT /evidence="ECO:0000255"
FT REPEAT 174..196
FT /note="LRR 6"
FT /evidence="ECO:0000255"
FT REPEAT 197..220
FT /note="LRR 7"
FT /evidence="ECO:0000255"
FT REPEAT 222..241
FT /note="LRR 8"
FT /evidence="ECO:0000255"
FT REPEAT 243..267
FT /note="LRR 9"
FT /evidence="ECO:0000255"
FT REPEAT 269..287
FT /note="LRR 10"
FT /evidence="ECO:0000255"
FT REPEAT 315..338
FT /note="LRR 11"
FT /evidence="ECO:0000255"
FT REPEAT 340..362
FT /note="LRR 12"
FT /evidence="ECO:0000255"
FT REPEAT 363..386
FT /note="LRR 13"
FT /evidence="ECO:0000255"
FT REPEAT 387..409
FT /note="LRR 14"
FT /evidence="ECO:0000255"
FT REPEAT 411..433
FT /note="LRR 15"
FT /evidence="ECO:0000255"
FT REPEAT 443..466
FT /note="LRR 16"
FT /evidence="ECO:0000255"
FT REPEAT 468..489
FT /note="LRR 17"
FT /evidence="ECO:0000255"
FT REPEAT 491..514
FT /note="LRR 18"
FT /evidence="ECO:0000255"
FT REPEAT 515..539
FT /note="LRR 19"
FT /evidence="ECO:0000255"
FT REPEAT 541..559
FT /note="LRR 20"
FT /evidence="ECO:0000255"
FT REPEAT 561..584
FT /note="LRR 21"
FT /evidence="ECO:0000255"
FT DOMAIN 572..621
FT /note="LRRCT"
FT /evidence="ECO:0000255"
FT REGION 291..311
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 272
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 305
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 346
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 546
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 212
FT /note="Interchain (with C-33 in TGFB1); in linked form"
FT /evidence="ECO:0000250|UniProtKB:Q14392"
FT DISULFID 351
FT /note="Interchain (with C-33 in TGFB1); in linked form"
FT /evidence="ECO:0000250|UniProtKB:Q14392"
SQ SEQUENCE 663 AA; 72418 MW; 90A7D5DB8EE41A73 CRC64;
MSHQILLLLA MLTLGLAISQ RREQVPCRTV NKEALCHGLG LLQVPSVLSL DIQALYLSGN
QLQSILVSPL GFYTALRHLD LSDNQISFLQ AGVFQALPYL EHLNLAHNRL ATGMALNSGG
LGRLPLLVSL DLSGNSLHGN LVERLLGETP RLRTLSLAEN SLTRLARHTF WGMPAVEQLD
LHSNVLMDIE DGAFEALPHL THLNLSRNSL TCISDFSLQQ LQVLDLSCNS IEAFQTAPEP
QAQFQLAWLD LRENKLLHFP DLAVFPRLIY LNVSNNLIQL PAGLPRGSED LHAPSEGWSA
SPLSNPSRNA STHPLSQLLN LDLSYNEIEL VPASFLEHLT SLRFLNLSRN CLRSFEARQV
DSLPCLVLLD LSHNVLEALE LGTKVLGSLQ TLLLQDNALQ ELPPYTFASL ASLQRLNLQG
NQVSPCGGPA EPGPPGCVDF SGIPTLHVLN MAGNSMGMLR AGSFLHTPLT ELDLSTNPGL
DVATGALVGL EASLEVLELQ GNGLTVLRVD LPCFLRLKRL NLAENQLSHL PAWTRAVSLE
VLDLRNNSFS LLPGNAMGGL ETSLRRLYLQ GNPLSCCGNG WLAAQLHQGR VDVDATQDLI
CRFGSQEELS LSLVRPEDCE KGGLKNVNLI LLLSFTLVSA IVLTTLATIC FLRRQKLSQQ
YKA
