LRC33_BOVIN
ID LRC33_BOVIN Reviewed; 692 AA.
AC Q3ZBI5; Q5BIS4;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 1.
DT 25-MAY-2022, entry version 91.
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:0000250|UniProtKB:Q8BMT4};
GN Synonyms=LRRC33 {ECO:0000250|UniProtKB:Q8BMT4};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Pancreas;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
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; BT021150; AAX31332.1; -; mRNA.
DR EMBL; BC103278; AAI03279.1; -; mRNA.
DR RefSeq; NP_001029563.1; NM_001034391.1.
DR AlphaFoldDB; Q3ZBI5; -.
DR SMR; Q3ZBI5; -.
DR STRING; 9913.ENSBTAP00000012650; -.
DR PaxDb; Q3ZBI5; -.
DR PRIDE; Q3ZBI5; -.
DR GeneID; 510688; -.
DR KEGG; bta:510688; -.
DR CTD; 375387; -.
DR eggNOG; KOG0619; Eukaryota.
DR InParanoid; Q3ZBI5; -.
DR OrthoDB; 826997at2759; -.
DR Proteomes; UP000009136; Unplaced.
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:0019838; F:growth factor binding; IEA:UniProtKB-KW.
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; -; 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; 3.
DR SMART; SM00369; LRR_TYP; 13.
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..19
FT /evidence="ECO:0000255"
FT CHAIN 20..692
FT /note="Transforming growth factor beta activator LRRC33"
FT /id="PRO_0000042659"
FT TOPO_DOM 29..648
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 649..669
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 670..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..248
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..447
FT /note="LRR 15"
FT /evidence="ECO:0000255"
FT REPEAT 463..484
FT /note="LRR 16"
FT /evidence="ECO:0000255"
FT REPEAT 486..495
FT /note="LRR 17"
FT /evidence="ECO:0000255"
FT REPEAT 512..534
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"
FT CONFLICT 410
FT /note="S -> N (in Ref. 1; AAX31332)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 692 AA; 76520 MW; 692AA9BEC5117B94 CRC64;
MELLPLWLCL GFHFLTVEWR HRSGMVTAAS QGGCELLDGV ADCRGRNLAS VPSDLPPSSR
TLLLDANPLR TLGNNSLQRY PFLESLSLHD CYLERIGHVA FQEQARLRSL ALPDNALSES
YKETAAALHG LRGLRMLDLS GNSLTEDMAA LMLQNLSSLE SVSLARNIIM RLDESVFEGL
GHLRELDLQR NYIFEIEGGA FDGLTQLRHL NLAYNNLPCL VDFSLTQLRS LNVSYNVLEW
FLASGGEAAF ELETLDLSHN QLLFFPLLPQ CSKLHTLLLR DNNMGFYRDL YNTSSPQEMV
AQFLLVDGNV TNITTVNLWE EFASSDLSSL RFLDMSQNQF QYLPDGFLKK MPSLSHLNLK
QNCLVTLHIR EHEPPGALVE LDLSQNQLSE LHLAPGLPGC LRSLQSFNLS SNQLLGVPAG
LFANARNLAT VDMSHNQISL CPLPASLDPG GTPGCVDFRN VASLQSLSLE DCGLEALQDC
SFQGTALTHL DLSGNWGVLN GSIAPLWDVA PTLQVLSLRN VGLTSSFTEL DFSAFENLRS
LDLSGNALTS FPRFGGSLAL QTLDLRRNLL TALPQRAVSE QLAGSLRTIY LSQNPYDCCG
VEDWGALQRL HIVADLAMVT CNLSSKVIRL TELPAGVPQV CKWERVDMGL LYLVLILPSC
LTLLVACTIT FLTFRKPLLQ VIKSRCHWSS IY
