LRC33_RAT
ID LRC33_RAT Reviewed; 692 AA.
AC Q5BK65;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Transforming growth factor beta activator LRRC33 {ECO:0000305};
DE AltName: Full=Leucine-rich repeat-containing protein 33^ {ECO:0000305};
DE AltName: Full=Negative regulator of reactive oxygen species {ECO:0000250|UniProtKB:Q8BMT4};
DE Flags: Precursor;
GN Name=Nrros {ECO:0000312|RGD:1310771};
GN Synonyms=Lrrc33 {ECO:0000312|RGD:1310771};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
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).
CC -!- FUNCTION: Key regulator of transforming growth factor beta-1 (TGFB1)
CC specifically required for microglia function in the nervous system.
CC Required for activation of latent TGF-beta-1 in macrophages and
CC microglia: associates specifically via disulfide bonds with the
CC Latency-associated peptide (LAP), which is the regulatory chain of
CC TGFB1, and regulates integrin-dependent activation of TGF-beta-1. TGF-
CC beta-1 activation mediated by LRRC33/NRROS is highly localized: there
CC is little spreading of TGF-beta-1 activated from one microglial cell to
CC neighboring microglia, suggesting the existence of localized and
CC selective activation of TGF-beta-1 by LRRC33/NRROS. Indirectly plays a
CC role in Toll-like receptor (TLR) signaling: ability to inhibit TLR-
CC mediated NF-kappa-B activation and cytokine production is probably a
CC consequence of its role in TGF-beta-1 signaling.
CC {ECO:0000250|UniProtKB:Q8BMT4}.
CC -!- SUBUNIT: Interacts (via LRR repeats) with TLR2, TLR3, TLR4, TLR9 and
CC probably other Toll-like receptors (By similarity). Interacts with
CC CYBB/NOX2; the interaction is direct. Interacts with TGFB1; associates
CC via disulfide bonds with the Latency-associated peptide chain (LAP)
CC regulatory chain of TGFB1, leading to regulate activation of TGF-beta-1
CC (By similarity). {ECO:0000250|UniProtKB:Q86YC3,
CC ECO:0000250|UniProtKB:Q8BMT4}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8BMT4};
CC Single-pass type I membrane protein {ECO:0000255}. Endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:Q8BMT4}; Single-pass type I
CC membrane protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the LRRC32/LRRC33 family. {ECO:0000305}.
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DR EMBL; BC091190; AAH91190.1; -; mRNA.
DR RefSeq; NP_001020166.1; NM_001024995.1.
DR RefSeq; XP_006248510.1; XM_006248448.3.
DR AlphaFoldDB; Q5BK65; -.
DR SMR; Q5BK65; -.
DR STRING; 10116.ENSRNOP00000048680; -.
DR GlyGen; Q5BK65; 9 sites.
DR PaxDb; Q5BK65; -.
DR PRIDE; Q5BK65; -.
DR Ensembl; ENSRNOT00000050364; ENSRNOP00000048680; ENSRNOG00000001752.
DR GeneID; 303875; -.
DR KEGG; rno:303875; -.
DR UCSC; RGD:1310771; rat.
DR CTD; 375387; -.
DR RGD; 1310771; Nrros.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000157975; -.
DR HOGENOM; CLU_024194_0_0_1; -.
DR InParanoid; Q5BK65; -.
DR OMA; CLTDFHM; -.
DR OrthoDB; 826997at2759; -.
DR PhylomeDB; Q5BK65; -.
DR PRO; PR:Q5BK65; -.
DR Proteomes; UP000002494; Chromosome 11.
DR Bgee; ENSRNOG00000001752; Expressed in spleen and 19 other tissues.
DR Genevisible; Q5BK65; RN.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:GOC.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0050431; F:transforming growth factor beta binding; ISO:RGD.
DR GO; GO:0006955; P:immune response; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR GO; GO:0014005; P:microglia development; ISS:UniProtKB.
DR GO; GO:0035583; P:sequestering of TGFbeta in extracellular matrix; ISS:UniProtKB.
DR GO; GO:0006801; P:superoxide metabolic process; ISS:UniProtKB.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0036364; P:transforming growth factor beta1 activation; ISS:UniProtKB.
DR Gene3D; 3.80.10.10; -; 3.
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; 4.
DR SMART; SM00369; LRR_TYP; 11.
DR PROSITE; PS51450; LRR; 16.
PE 2: Evidence at transcript level;
KW Cell membrane; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW Growth factor binding; Leucine-rich repeat; Membrane; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..692
FT /note="Transforming growth factor beta activator LRRC33"
FT /id="PRO_0000042662"
FT TOPO_DOM 25..650
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 651..671
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 672..692
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 29..56
FT /note="LRRNT"
FT /evidence="ECO:0000255"
FT REPEAT 58..79
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 82..103
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 106..127
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT REPEAT 133..155
FT /note="LRR 4"
FT /evidence="ECO:0000255"
FT REPEAT 158..179
FT /note="LRR 5"
FT /evidence="ECO:0000255"
FT REPEAT 182..203
FT /note="LRR 6"
FT /evidence="ECO:0000255"
FT REPEAT 206..227
FT /note="LRR 7"
FT /evidence="ECO:0000255"
FT REPEAT 228..239
FT /note="LRR 8"
FT /evidence="ECO:0000255"
FT REPEAT 251..272
FT /note="LRR 9"
FT /evidence="ECO:0000255"
FT REPEAT 273..294
FT /note="LRR 10"
FT /evidence="ECO:0000255"
FT REPEAT 329..350
FT /note="LRR 11"
FT /evidence="ECO:0000255"
FT REPEAT 353..374
FT /note="LRR 12"
FT /evidence="ECO:0000255"
FT REPEAT 377..398
FT /note="LRR 13"
FT /evidence="ECO:0000255"
FT REPEAT 403..424
FT /note="LRR 14"
FT /evidence="ECO:0000255"
FT REPEAT 427..448
FT /note="LRR 15"
FT /evidence="ECO:0000255"
FT REPEAT 463..484
FT /note="LRR 16"
FT /evidence="ECO:0000255"
FT REPEAT 486..507
FT /note="LRR 17"
FT /evidence="ECO:0000255"
FT REPEAT 512..533
FT /note="LRR 18"
FT /evidence="ECO:0000255"
FT REPEAT 537..558
FT /note="LRR 19"
FT /evidence="ECO:0000255"
FT REPEAT 559..580
FT /note="LRR 20"
FT /evidence="ECO:0000255"
FT REPEAT 585..605
FT /note="LRR 21"
FT /evidence="ECO:0000255"
FT DOMAIN 606..643
FT /note="LRRCT"
FT /evidence="ECO:0000255"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 155
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 232
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 292
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 312
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 408
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 500
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 622
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 219
FT /note="Interchain (with C-? in TGFB1); in linked form"
FT /evidence="ECO:0000250|UniProtKB:Q8BMT4"
FT DISULFID 363
FT /note="Interchain (with C-? in TGFB1); in linked form"
FT /evidence="ECO:0000250|UniProtKB:Q8BMT4"
SQ SEQUENCE 692 AA; 77070 MW; 96F66867E9DFCC6F CRC64;
MEFLPLWLCL GFHFLIVEWR SGRGTATAAS QGGCKVVDRV ADCRSLNLAS VPSGLPAHSR
MLVLDANPLR VLWNHSLQAY PRLEDLSLHS CHLDRISHWA FHEQGHLQNL VLADNRLSEN
YKESATALHT LLRLRRLDLS GNSLTEDMAA LMLQNLSSLE VVSLARNTLM RLDDSVFEGL
ERLVELDLQR NYIFEIEGGA FDGLTELRRL NLAYNNLPCI VDFSLTQLRF LNVSYNILEW
FLAAREEAAF ELEILDLSHN QLLFFPLLPQ CGKLHTLLLQ DNSMGFYREL YNTSSPQEMV
AQFLLVDGNV TNITTVSLWE EFSSSDLSAL RFLDMSQNQL RHLPDGFLKK TPSLSHLNLN
QNCLTKLHIR EHEPPGALTE LDLSRNQLAE LHLAPGLTGS LKNLRVFNLS SNQLLGVPTG
LFHSASSITT LDMSHNQISL CPQTVPLDWE EPSSCVDFRN MASLRSLSLD GCGLKALQDC
PFQGTSLTHL DLSSNWGILN GSVSPLSAVA PTLQVLSLRN VGLGSGAAEM DFSGFGNLRE
LDLSGNSLTS FPKFKGSSAL QTLDLRRNSL TALPQRVVSE QPLRGLQTIY LSQNPYDCCG
VEGWGALQHF KTIADLSMVT CNLSSKIIRV VELPEGIPQD CKWGQVDTGL FYLVLILPSC
LTLLVASTVI FLTFKKPLLQ VIKSRCHWSS IY
