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Negative regulator of reactive oxygen species (Leucine-rich repeat-containing protein 33)

 NRROS_MOUSE             Reviewed;         693 AA.
Q8BMT4; Q3TIA8; Q8BTT4; Q8BUI7; Q8BY16; Q8R063;
25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
25-OCT-2005, sequence version 2.
12-SEP-2018, entry version 142.
RecName: Full=Negative regulator of reactive oxygen species;
AltName: Full=Leucine-rich repeat-containing protein 33;
Flags: Precursor;
Name=Nrros; Synonyms=Lrrc33;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
STRAIN=C57BL/6J, and DBA/2J; TISSUE=Embryo, and Placenta;
PubMed=16141072; DOI=10.1126/science.1112014;
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
Hayashizaki Y.;
"The transcriptional landscape of the mammalian genome.";
Science 309:1559-1563(2005).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
STRAIN=FVB/N; TISSUE=Salivary gland;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION,
INTERACTION WITH CYBB, AND DISRUPTION PHENOTYPE.
PubMed=24739962; DOI=10.1038/nature13152;
Noubade R., Wong K., Ota N., Rutz S., Eidenschenk C., Valdez P.A.,
Ding J., Peng I., Sebrell A., Caplazi P., Devoss J., Soriano R.H.,
Sai T., Lu R., Modrusan Z., Hackney J., Ouyang W.;
"NRROS negatively regulates reactive oxygen species during host
defence and autoimmunity.";
Nature 509:235-239(2014).
-!- FUNCTION: Negative regulator of reactive oxygen species (ROS) that
limits ROS production by phagocytes during inflammatory response,
thereby playing a role during host defense. Acts via direct
interaction with CYBB/NOX2 monomer that impairs interaction
between CYBB/NOX2 and CYBA/p22-phox and formation of a stable NOX2
complex. May play a critical role in desensitizing TLR signaling
through inhibition of Toll-like receptor-mediated NF-kappa-B
activation and cytokine production. {ECO:0000269|PubMed:24739962}.
-!- SUBUNIT: Interacts (via LRR repeats) with TLR2, TLR3, TLR4, TLR9
and probably other Toll-like receptors (By similarity). Interacts
with CYBB/NOX2; the interaction is direct. {ECO:0000250,
ECO:0000269|PubMed:24739962}.
-!- INTERACTION:
Q61093:Cybb; NbExp=4; IntAct=EBI-16102695, EBI-6654585;
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass
type I membrane protein {ECO:0000269|PubMed:24739962}. Endoplasmic
reticulum membrane {ECO:0000269|PubMed:24739962}; Single-pass type
I membrane protein {ECO:0000269|PubMed:24739962}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Name=1;
IsoId=Q8BMT4-1; Sequence=Displayed;
Name=2;
IsoId=Q8BMT4-2; Sequence=VSP_016019;
Name=3;
IsoId=Q8BMT4-3; Sequence=VSP_016020;
-!- TISSUE SPECIFICITY: Preferentially expressed in immune organs such
as lymph nodes, thymus and spleen. Among leukocytes, expressed at
higher level in myeloid cell such as macrophages, neutrophils and
dendritic cells. {ECO:0000269|PubMed:24739962}.
-!- INDUCTION: Down-regulated by IFN-gamma, LPS or TNF-alpha in bone
marrow-derived macrophages (BMDMs). {ECO:0000269|PubMed:24739962}.
-!- DISRUPTION PHENOTYPE: Phagocytes display increased reactive oxygen
species (ROS) production and bactericidal ability. Mice are viable
at six-weeks of age and immune organs and leukocyte subsets are
not affected. However, significantly increased ROS production is
observed in primary bone marrow-derived macrophages (BMDMs) upon
zymosan stimulation. {ECO:0000269|PubMed:24739962}.
-!- SEQUENCE CAUTION:
Sequence=AAH27411.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
Sequence=BAC25907.1; Type=Frameshift; Positions=660; Evidence={ECO:0000305};
Sequence=BAC31275.1; Type=Frameshift; Positions=5; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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-----------------------------------------------------------------------
EMBL; AK028367; BAC25907.1; ALT_FRAME; mRNA.
EMBL; AK042502; BAC31275.1; ALT_FRAME; mRNA.
EMBL; AK084858; BAC39294.1; -; mRNA.
EMBL; AK088770; BAC40561.1; -; mRNA.
EMBL; AK167934; BAE39938.1; -; mRNA.
EMBL; BC027411; AAH27411.1; ALT_INIT; mRNA.
CCDS; CCDS28115.1; -. [Q8BMT4-1]
CCDS; CCDS84220.1; -. [Q8BMT4-1]
CCDS; CCDS84221.1; -. [Q8BMT4-2]
RefSeq; NP_001334110.1; NM_001347181.1. [Q8BMT4-1]
RefSeq; NP_001334111.1; NM_001347182.1. [Q8BMT4-2]
RefSeq; NP_666181.2; NM_146069.4. [Q8BMT4-1]
RefSeq; XP_006522137.1; XM_006522074.3. [Q8BMT4-1]
RefSeq; XP_006522138.1; XM_006522075.1. [Q8BMT4-1]
RefSeq; XP_006522139.1; XM_006522076.2. [Q8BMT4-1]
RefSeq; XP_006522140.1; XM_006522077.3. [Q8BMT4-1]
RefSeq; XP_017172451.1; XM_017316962.1. [Q8BMT4-1]
UniGene; Mm.33498; -.
ProteinModelPortal; Q8BMT4; -.
DIP; DIP-60840N; -.
IntAct; Q8BMT4; 1.
STRING; 10090.ENSMUSP00000110817; -.
iPTMnet; Q8BMT4; -.
PhosphoSitePlus; Q8BMT4; -.
PaxDb; Q8BMT4; -.
PeptideAtlas; Q8BMT4; -.
PRIDE; Q8BMT4; -.
Ensembl; ENSMUST00000099991; ENSMUSP00000097571; ENSMUSG00000052384. [Q8BMT4-1]
Ensembl; ENSMUST00000115163; ENSMUSP00000110817; ENSMUSG00000052384. [Q8BMT4-3]
Ensembl; ENSMUST00000115165; ENSMUSP00000110819; ENSMUSG00000052384. [Q8BMT4-2]
Ensembl; ENSMUST00000126869; ENSMUSP00000116388; ENSMUSG00000052384. [Q8BMT4-1]
Ensembl; ENSMUST00000143682; ENSMUSP00000119349; ENSMUSG00000052384. [Q8BMT4-1]
GeneID; 224109; -.
KEGG; mmu:224109; -.
UCSC; uc007yyg.1; mouse. [Q8BMT4-1]
UCSC; uc007yyh.1; mouse. [Q8BMT4-3]
UCSC; uc007yyi.1; mouse. [Q8BMT4-2]
CTD; 375387; -.
MGI; MGI:2445095; Nrros.
eggNOG; KOG0619; Eukaryota.
eggNOG; COG4886; LUCA.
GeneTree; ENSGT00710000106753; -.
HOGENOM; HOG000113368; -.
HOVERGEN; HBG081928; -.
InParanoid; Q8BMT4; -.
OMA; QNPYDCC; -.
OrthoDB; EOG091G03PI; -.
PhylomeDB; Q8BMT4; -.
TreeFam; TF317167; -.
ChiTaRS; Nrros; mouse.
PRO; PR:Q8BMT4; -.
Proteomes; UP000000589; Chromosome 16.
Bgee; ENSMUSG00000052384; Expressed in 121 organ(s), highest expression level in thymus.
CleanEx; MM_LRRC33; -.
ExpressionAtlas; Q8BMT4; baseline and differential.
Genevisible; Q8BMT4; MM.
GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
GO; GO:0006955; P:immune response; IMP:UniProtKB.
GO; GO:0006954; P:inflammatory response; IMP:UniProtKB.
GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
GO; GO:0006801; P:superoxide metabolic process; IMP:UniProtKB.
GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; TAS:UniProtKB.
Gene3D; 3.80.10.10; -; 3.
InterPro; IPR001611; Leu-rich_rpt.
InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
InterPro; IPR032675; LRR_dom_sf.
Pfam; PF00560; LRR_1; 1.
Pfam; PF13855; LRR_8; 2.
SMART; SM00369; LRR_TYP; 11.
PROSITE; PS51450; LRR; 17.
1: Evidence at protein level;
Alternative splicing; Cell membrane; Complete proteome;
Endoplasmic reticulum; Glycoprotein; Immunity; Inflammatory response;
Innate immunity; Leucine-rich repeat; Membrane; Reference proteome;
Repeat; Signal; Transmembrane; Transmembrane helix.
SIGNAL 1 28 {ECO:0000255}.
CHAIN 29 693 Negative regulator of reactive oxygen
species.
/FTId=PRO_0000042661.
TOPO_DOM 29 651 Extracellular. {ECO:0000255}.
TRANSMEM 652 672 Helical. {ECO:0000255}.
TOPO_DOM 673 693 Cytoplasmic. {ECO:0000255}.
DOMAIN 29 57 LRRNT.
REPEAT 58 79 LRR 1.
REPEAT 82 103 LRR 2.
REPEAT 106 127 LRR 3.
REPEAT 133 155 LRR 4.
REPEAT 158 179 LRR 5.
REPEAT 182 203 LRR 6.
REPEAT 206 227 LRR 7.
REPEAT 228 239 LRR 8.
REPEAT 251 272 LRR 9.
REPEAT 273 294 LRR 10.
REPEAT 329 350 LRR 11.
REPEAT 353 374 LRR 12.
REPEAT 377 398 LRR 13.
REPEAT 403 424 LRR 14.
REPEAT 427 448 LRR 15.
REPEAT 463 484 LRR 16.
REPEAT 486 507 LRR 17.
REPEAT 512 533 LRR 18.
REPEAT 537 558 LRR 19.
REPEAT 559 580 LRR 20.
REPEAT 585 605 LRR 21.
CARBOHYD 74 74 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 85 85 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 155 155 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 232 232 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 292 292 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 309 309 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 312 312 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 408 408 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 424 424 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 500 500 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 623 623 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
VAR_SEQ 1 36 MEFPPLWLCLGFHFLIVEWRSGPGTATAASQGGCKV -> M
RPAEPPGPAGA (in isoform 2).
{ECO:0000303|PubMed:16141072}.
/FTId=VSP_016019.
VAR_SEQ 1 1 M -> MQEPLETGSIESSGTGNVVVSHQRAVPEM (in
isoform 3).
{ECO:0000303|PubMed:16141072}.
/FTId=VSP_016020.
CONFLICT 520 520 D -> E (in Ref. 2; BAC25907).
{ECO:0000305}.
CONFLICT 566 566 R -> H (in Ref. 2; BAC25907).
{ECO:0000305}.
SEQUENCE 693 AA; 77140 MW; 6B4520019DF98BD2 CRC64;
MEFPPLWLCL GFHFLIVEWR SGPGTATAAS QGGCKVVDGV ADCRGLNLAS VPSSLPPHSR
MLILDANPLK DLWNHSLQAY PRLENLSLHS CHLDRISHYA FREQGHLRNL VLADNRLSEN
YKESAAALHT LLGLRRLDLS GNSLTEDMAA LMLQNLSSLE VVSLARNTLM RLDDSIFEGL
EHLVELDLQR NYIFEIEGGA FDGLTELRRL NLAYNNLPCI VDFSLTQLRF LNVSYNILEW
FLAAREEVAF ELEILDLSHN QLLFFPLLPQ CGKLHTLLLQ DNNMGFYREL YNTSSPQEMV
AQFLLVDGNV TNITTVNLWE EFSSSDLSAL RFLDMSQNQF RHLPDGFLKK TPSLSHLNLN
QNCLKMLHIR EHEPPGALTE LDLSHNQLAE LHLAPGLTGS LRNLRVFNLS SNQLLGVPTG
LFDNASSITT IDMSHNQISL CPQMVPVDWE GPPSCVDFRN MGSLRSLSLD GCGLKALQDC
PFQGTSLTHL DLSSNWGVLN GSISPLWAVA PTLQVLSLRD VGLGSGAAEM DFSAFGNLRA
LDLSGNSLTS FPKFKGSLAL RTLDLRRNSL TALPQRVVSE QPLRGLQTIY LSQNPYDCCG
VEGWGALQQH FKTVADLSMV TCNLSSKIVR VVELPEGLPQ GCKWEQVDTG LFYLVLILPS
CLTLLVACTV VFLTFKKPLL QVIKSRCHWS SIY


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