NOX4_PONAB
ID NOX4_PONAB Reviewed; 578 AA.
AC Q5R5C5; Q5RCG3; Q5RE61;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=NADPH oxidase 4;
DE EC=1.6.3.-;
GN Name=NOX4;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). {ECO:0000250}.
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, relocalizes and stabilizes CYBA/p22phox.
CC Interacts with TLR4. Interacts with protein disulfide isomerase (By
CC similarity). Interacts with PPP1R15A (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Multi-pass membrane protein {ECO:0000250}. Cell junction, focal
CC adhesion {ECO:0000250}. Cell membrane {ECO:0000250}. Note=May localize
CC to plasma membrane and focal adhesions. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5R5C5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5R5C5-2; Sequence=VSP_019065;
CC -!- PTM: N-glycosylation is required for the function. {ECO:0000250}.
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DR EMBL; CR857676; CAH89946.1; -; mRNA.
DR EMBL; CR858307; CAH90544.1; -; mRNA.
DR EMBL; CR860937; CAH93041.1; -; mRNA.
DR RefSeq; NP_001124912.1; NM_001131440.1.
DR RefSeq; NP_001128890.1; NM_001135418.1.
DR RefSeq; XP_009245205.1; XM_009246930.1. [Q5R5C5-1]
DR AlphaFoldDB; Q5R5C5; -.
DR SMR; Q5R5C5; -.
DR STRING; 9601.ENSPPYP00000004298; -.
DR Ensembl; ENSPPYT00000004472; ENSPPYP00000004298; ENSPPYG00000003756. [Q5R5C5-1]
DR Ensembl; ENSPPYT00000046242; ENSPPYP00000034182; ENSPPYG00000003756. [Q5R5C5-2]
DR GeneID; 100171782; -.
DR GeneID; 100189825; -.
DR KEGG; pon:100171782; -.
DR CTD; 50507; -.
DR eggNOG; KOG0039; Eukaryota.
DR GeneTree; ENSGT00940000159621; -.
DR HOGENOM; CLU_005646_3_1_1; -.
DR InParanoid; Q5R5C5; -.
DR OMA; FIRGTHV; -.
DR OrthoDB; 936110at2759; -.
DR TreeFam; TF105354; -.
DR Proteomes; UP000001595; Chromosome 11.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
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:0050664; F:oxidoreductase activity, acting on NAD(P)H, oxygen as acceptor; IEA:UniProt.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IEA:UniProt.
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 2: Evidence at transcript level;
KW Alternative splicing; Cell junction; Cell membrane; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Membrane; NADP; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..578
FT /note="NADPH oxidase 4"
FT /id="PRO_0000238982"
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..103
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 104..124
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 125..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 CARBOHYD 230
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..19
FT /note="MAVSWRSWLANEGVKHLCL -> MGEEVWRKREEVIFSEHSFSFYPLNIFAP
FT FVLFPDYFCLLE (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_019065"
FT CONFLICT 246
FT /note="H -> R (in Ref. 1; CAH90544/CAH89946)"
FT /evidence="ECO:0000305"
FT CONFLICT 306
FT /note="N -> D (in Ref. 1; CAH93041)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 578 AA; 66921 MW; C4D5C2839D617571 CRC64;
MAVSWRSWLA NEGVKHLCLF IWLSMNVLLF WKTFLLYNQG PEYHYLHQML GLGLCLSRAS
ASVLNLNCSL ILLPMCRTLL AYLRGSQKVP SRRTRRLLDK SRTFHITCGV TICIFSGVHV
AAHLVNALNF SVNYSEDFVE LNAARYRDED PRKLLFTTVP GLTGVCMVVV LFLMITASTY
AIRVSNYDIF WYTHNLFFVF YMLLTLHVSG GLLKYQTNLD THPPGCISLN RTSSQNISLP
EYFSEHFHEP FPEGFSKPEE FTQNTFVKIC MEEPRFQANF PQTWLWISGP LCLYCAERLY
RYIRSNKPVT IISVISHPSD VMEIRMVKEN FKARPGQYIT LHCPSVSALE NHPFTLTMCP
TETKATFGVH LKIVGDWTER FRDLLLPPSS QDSEILPFIQ SRNYPKLYID GPFGSPFEES
LNYEVSLCVA GGIGVTPFAS ILNTLLDDWK PYKLRRLYFI WVCRDIQSFR WFADLLCMLH
NKFWQENRPD YVNIQLYLSQ TDGIQKIIGE KYHALNSRLF IGRPRWKLLF DEIAKYNRGK
TVGVFCCGPN SLSKTLHKLS NQINSYGTRF EYNKESFS
