NOX4_RAT
ID NOX4_RAT Reviewed; 578 AA.
AC Q924V1; Q99M78;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=NADPH oxidase 4;
DE EC=1.6.3.-;
DE AltName: Full=Kidney oxidase-1;
DE Short=KOX-1;
DE AltName: Full=Kidney superoxide-producing NADPH oxidase;
GN Name=Nox4; Synonyms=Kox;
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 [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Vascular smooth muscle;
RX PubMed=11348997; DOI=10.1161/hh0901.090299;
RA Lassegue B., Sorescu D., Szoecs K., Yin Q., Akers M., Zhang Y., Grant S.L.,
RA Lambeth J.D., Griendling K.K.;
RT "Novel gp91(phox) homologues in vascular smooth muscle cells: nox1 mediates
RT angiotensin II-induced superoxide formation and redox-sensitive signaling
RT pathways.";
RL Circ. Res. 88:888-894(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11032835; DOI=10.1074/jbc.m007597200;
RA Shiose A., Kuroda J., Tsuruya K., Hirai M., Hirakata H., Naito S.,
RA Hattori M., Sakaki Y., Sumimoto H.;
RT "A novel superoxide-producing NAD(P)H oxidase in kidney.";
RL J. Biol. Chem. 276:1417-1423(2001).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=14670934; DOI=10.1161/01.atv.0000112024.13727.2c;
RA Hilenski L.L., Clempus R.E., Quinn M.T., Lambeth J.D., Griendling K.K.;
RT "Distinct subcellular localizations of Nox1 and Nox4 in vascular smooth
RT muscle cells.";
RL Arterioscler. Thromb. Vasc. Biol. 24:677-683(2004).
RN [4]
RP FUNCTION, INTERACTION WITH CYBA, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP HIS-119.
RX PubMed=15322091; DOI=10.1074/jbc.m406486200;
RA Ambasta R.K., Kumar P., Griendling K.K., Schmidt H.H.H.W., Busse R.,
RA Brandes R.P.;
RT "Direct interaction of the novel Nox proteins with p22phox is required for
RT the formation of a functionally active NADPH oxidase.";
RL J. Biol. Chem. 279:45935-45941(2004).
RN [5]
RP FUNCTION, AND INDUCTION.
RX PubMed=16135519; DOI=10.1074/jbc.m502412200;
RA Gorin Y., Block K., Hernandez J., Bhandari B., Wagner B., Barnes J.L.,
RA Abboud H.E.;
RT "Nox4 NAD(P)H oxidase mediates hypertrophy and fibronectin expression in
RT the diabetic kidney.";
RL J. Biol. Chem. 280:39616-39626(2005).
RN [6]
RP INTERACTION WITH PROTEIN DISULFIDE ISOMERASE, AND SUBCELLULAR LOCATION.
RX PubMed=16150729; DOI=10.1074/jbc.m509255200;
RA Janiszewski M., Lopes L.R., Carmo A.O., Pedro M.A., Brandes R.P.,
RA Santos C.X.C., Laurindo F.R.M.;
RT "Regulation of NAD(P)H oxidase by associated protein disulfide isomerase in
RT vascular smooth muscle cells.";
RL J. Biol. Chem. 280:40813-40819(2005).
CC -!- FUNCTION: Constitutive NADPH oxidase which generates superoxide
CC intracellularly upon formation of a complex with CYBA/p22phox.
CC Regulates signaling cascades probably through phosphatases inhibition.
CC May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium
CC channel and HIF1A activity. May regulate insulin signaling cascade. May
CC play a role in apoptosis, bone resorption and lipolysaccharide-mediated
CC activation of NFKB. {ECO:0000269|PubMed:15322091,
CC ECO:0000269|PubMed:16135519}.
CC -!- ACTIVITY REGULATION: Activated by insulin. Inhibited by diphenylene
CC iodonium. Inhibited by plumbagin. Activated by phorbol 12-myristate 13-
CC acetate (PMA) (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with TLR4 (By similarity). Interacts with,
CC relocalizes and stabilizes CYBA/p22phox. Interacts with protein
CC disulfide isomerase. Interacts with PPP1R15A (By similarity).
CC {ECO:0000250|UniProtKB:Q9NPH5, ECO:0000269|PubMed:15322091,
CC ECO:0000269|PubMed:16150729}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein. Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}. Cell junction, focal adhesion {ECO:0000305}.
CC Note=May localize to plasma membrane and focal adhesions.
CC -!- TISSUE SPECIFICITY: Expressed in vascular smooth muscle.
CC {ECO:0000269|PubMed:11348997}.
CC -!- INDUCTION: Up-regulated in diabetic kidney (at protein level).
CC {ECO:0000269|PubMed:16135519}.
CC -!- PTM: N-glycosylation is required for the function. {ECO:0000250}.
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DR EMBL; AY027527; AAK14799.1; -; mRNA.
DR EMBL; AB044086; BAB61724.1; -; mRNA.
DR RefSeq; NP_445976.1; NM_053524.1.
DR AlphaFoldDB; Q924V1; -.
DR SMR; Q924V1; -.
DR BioGRID; 250101; 3.
DR STRING; 10116.ENSRNOP00000018990; -.
DR PeroxiBase; 5409; RnoNOx04.
DR GlyGen; Q924V1; 1 site.
DR PhosphoSitePlus; Q924V1; -.
DR PaxDb; Q924V1; -.
DR Ensembl; ENSRNOT00000102096; ENSRNOP00000085650; ENSRNOG00000013925.
DR GeneID; 85431; -.
DR KEGG; rno:85431; -.
DR UCSC; RGD:620600; rat.
DR CTD; 50507; -.
DR RGD; 620600; Nox4.
DR eggNOG; KOG0039; Eukaryota.
DR GeneTree; ENSGT00940000159621; -.
DR HOGENOM; CLU_005646_3_1_1; -.
DR InParanoid; Q924V1; -.
DR OMA; FIRGTHV; -.
DR OrthoDB; 936110at2759; -.
DR BRENDA; 1.6.3.1; 5301.
DR Reactome; R-RNO-3299685; Detoxification of Reactive Oxygen Species.
DR PRO; PR:Q924V1; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000013925; Expressed in adult mammalian kidney and 12 other tissues.
DR Genevisible; Q924V1; RN.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0071944; C:cell periphery; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:ARUK-UCL.
DR GO; GO:0043020; C:NADPH oxidase complex; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:ARUK-UCL.
DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; IDA:ARUK-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0072341; F:modified amino acid binding; ISO:RGD.
DR GO; GO:0016174; F:NAD(P)H oxidase H2O2-forming activity; IDA:RGD.
DR GO; GO:0050664; F:oxidoreductase activity, acting on NAD(P)H, oxygen as acceptor; IDA:RGD.
DR GO; GO:1990782; F:protein tyrosine kinase binding; ISO:RGD.
DR GO; GO:0016175; F:superoxide-generating NAD(P)H oxidase activity; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0045453; P:bone resorption; ISO:RGD.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; ISO:RGD.
DR GO; GO:0000902; P:cell morphogenesis; ISS:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; IEP:RGD.
DR GO; GO:0071480; P:cellular response to gamma radiation; IEP:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; ISO:RGD.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEP:RGD.
DR GO; GO:0006952; P:defense response; IBA:GO_Central.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0003015; P:heart process; ISO:RGD.
DR GO; GO:0050667; P:homocysteine metabolic process; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0010729; P:positive regulation of hydrogen peroxide biosynthetic process; IMP:RGD.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:RGD.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISO:RGD.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IMP:RGD.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IMP:RGD.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; ISO:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0042554; P:superoxide anion generation; ISS:UniProtKB.
DR GO; GO:0006801; P:superoxide metabolic process; IDA:RGD.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR000778; Cyt_b245_heavy_chain.
DR InterPro; IPR013112; FAD-bd_8.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR013130; Fe3_Rdtase_TM_dom.
DR InterPro; IPR013121; Fe_red_NAD-bd_6.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR Pfam; PF08022; FAD_binding_8; 1.
DR Pfam; PF01794; Ferric_reduct; 1.
DR Pfam; PF08030; NAD_binding_6; 1.
DR PRINTS; PR00466; GP91PHOX.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS51384; FAD_FR; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Disulfide bond; Endoplasmic reticulum;
KW Glycoprotein; Membrane; NADP; Oxidoreductase; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..578
FT /note="NADPH oxidase 4"
FT /id="PRO_0000238983"
FT TOPO_DOM 1..16
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..62
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 63..83
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 84..104
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 105..125
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 126..154
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 155..175
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 176..188
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 189..209
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 210..424
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 425..445
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 446..578
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 58..303
FT /note="Ferric oxidoreductase"
FT DOMAIN 304..419
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 248..575
FT /note="Mediates interaction with TLR4"
FT /evidence="ECO:0000250"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 119
FT /note="H->L: Loss of interaction with CYBA/p22phox."
FT /evidence="ECO:0000269|PubMed:15322091"
FT CONFLICT 232
FT /note="T -> P (in Ref. 2; BAB61724)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 578 AA; 66469 MW; 474347299F994D92 CRC64;
MALSWRSWLA NEGVKHLCLL VWLSLNVLLF WKTFLLYNQG PEYYYIHQML GLGLCLSRAS
ASVLNLNCSL ILLPMCRTVL AYLRGSQKVP SRRTRRLLDK SKTLHITCGI TICIFSGVHV
AAHLVNALNF SVNYSEHFLA LNAARYQNED PRKLLFTTVP GLTGVCMVVV LFLMVTASTY
AIRVSNYDIF WYTHNLFFVF YMLLLLHVSG GLLKYQTNLD THPPGCISLN RTPSQNMSIA
DYVSEHFHGS LPGGFSKLED HYQKTLVKIC LEEPKFQAHF PQTWIWISGP LCLYCAERLY
RCIRSNKPVT IISVINHPSD VMELRMIKEN FKARPGQYII LHCPSVSALE NHPFTLTMCP
TETKATFGVH FKVVGDWTER FRDLLLPPSS QDSEILPFIQ SRNYPKLYID GPFGSPFEES
LNYEVSLCVA GGIGVTPFAS ILNTLLDDWK PYKLRRLYFI WVCRDIQSFQ WFADLLYVLH
NKFWQENRPD FVNIQLYLSQ TDGIQKIIGE KYHTLNSRLF IGRPRWKLLF DEIAKCNRGK
TVGVFCCGPS SISKTLHNLS NRNNSYGTKF EYNKESFS
