NOX5_HUMAN
ID NOX5_HUMAN Reviewed; 765 AA.
AC Q96PH1; B2RBJ4; Q08AN2; Q08AN3; Q8TEQ1; Q8TER4; Q96PH2; Q96PJ8; Q96PJ9;
AC Q9H6E0; Q9HAM8;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=NADPH oxidase 5;
DE EC=1.6.3.-;
GN Name=NOX5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS V1; V2; V3 AND V4), FUNCTION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Spleen, and Testis;
RX PubMed=11483596; DOI=10.1074/jbc.m103034200;
RA Banfi B., Molnar G., Maturana A., Steger K., Hegedus B., Demaurex N.,
RA Krause K.-H.;
RT "A Ca(2+)-activated NADPH oxidase in testis, spleen, and lymph nodes.";
RL J. Biol. Chem. 276:37594-37601(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM V5), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 98-765 (ISOFORMS V3/V4).
RC TISSUE=Spleen;
RA Jikuya H., Takano J., Nomura N., Kikuno R., Nagase T., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human spleen.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM V4), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 159-765 (ISOFORMS V1/V2/V3/V4/V6).
RC TISSUE=Kidney epithelium, and Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM V5).
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS V2 AND V6).
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).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 177-765 (ISOFORMS V1/V2/V3/V4/V6).
RC TISSUE=Spleen;
RX PubMed=15994299; DOI=10.1074/jbc.m501882200;
RA Kawahara T., Ritsick D., Cheng G., Lambeth J.D.;
RT "Point mutations in the proline-rich region of p22phox are dominant
RT inhibitors of Nox1- and Nox2-dependent reactive oxygen generation.";
RL J. Biol. Chem. 280:31859-31869(2005).
RN [9]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=11376945; DOI=10.1016/s0378-1119(01)00449-8;
RA Cheng G., Cao Z., Xu X., van Meir E.G., Lambeth J.D.;
RT "Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and
RT Nox5.";
RL Gene 269:131-140(2001).
RN [10]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12686516; DOI=10.1152/ajpcell.00525.2002;
RA Brar S.S., Corbin Z., Kennedy T.P., Hemendinger R., Thornton L.,
RA Bommarius B., Arnold R.S., Whorton A.R., Sturrock A.B., Huecksteadt T.P.,
RA Quinn M.T., Krenitsky K., Ardie K.G., Lambeth J.D., Hoidal J.R.;
RT "NOX5 NAD(P)H oxidase regulates growth and apoptosis in DU 145 prostate
RT cancer cells.";
RL Am. J. Physiol. 285:C353-C369(2003).
RN [11]
RP ACTIVITY REGULATION, COFACTOR, MUTAGENESIS OF GLU-49, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=14982937; DOI=10.1074/jbc.m310268200;
RA Banfi B., Tirone F., Durussel I., Knisz J., Moskwa P., Molnar G.Z.,
RA Krause K.-H., Cox J.A.;
RT "Mechanism of Ca2+ activation of the NADPH oxidase 5 (NOX5).";
RL J. Biol. Chem. 279:18583-18591(2004).
RN [12]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=16179589; DOI=10.1161/01.res.0000187457.24338.3d;
RA Cucoranu I., Clempus R., Dikalova A., Phelan P.J., Ariyan S., Dikalov S.,
RA Sorescu D.;
RT "NAD(P)H oxidase 4 mediates transforming growth factor-beta1-induced
RT differentiation of cardiac fibroblasts into myofibroblasts.";
RL Circ. Res. 97:900-907(2005).
RN [13]
RP TISSUE SPECIFICITY.
RX PubMed=16339585; DOI=10.4049/jimmunol.175.12.8424;
RA Kamiguti A.S., Serrander L., Lin K., Harris R.J., Cawley J.C., Allsup D.J.,
RA Slupsky J.R., Krause K.-H., Zuzel M.;
RT "Expression and activity of NOX5 in the circulating malignant B cells of
RT hairy cell leukemia.";
RL J. Immunol. 175:8424-8430(2005).
RN [14]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=17275676; DOI=10.1016/j.freeradbiomed.2006.10.054;
RA BelAiba R.S., Djordjevic T., Petry A., Diemer K., Bonello S., Banfi B.,
RA Hess J., Pogrebniak A., Bickel C., Gorlach A.;
RT "NOX5 variants are functionally active in endothelial cells.";
RL Free Radic. Biol. Med. 42:446-459(2007).
CC -!- FUNCTION: Calcium-dependent NADPH oxidase that generates superoxide.
CC Also functions as a calcium-dependent proton channel and may regulate
CC redox-dependent processes in lymphocytes and spermatozoa. May play a
CC role in cell growth and apoptosis. Isoform v2 and isoform v5 are
CC involved in endothelial generation of reactive oxygen species (ROS),
CC proliferation and angiogenesis and contribute to endothelial response
CC to thrombin. {ECO:0000269|PubMed:11483596, ECO:0000269|PubMed:12686516,
CC ECO:0000269|PubMed:17275676}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:14982937};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:14982937};
CC -!- ACTIVITY REGULATION: Activated by calcium which induces conformational
CC changes and interaction between the N-terminal regulatory region and
CC the C-terminal catalytic region. Inhibited by diphenylene iodonium.
CC {ECO:0000269|PubMed:14982937}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.06 uM for calcium {ECO:0000269|PubMed:14982937};
CC -!- INTERACTION:
CC Q96PH1-4; P62157: CALM; Xeno; NbExp=3; IntAct=EBI-7305642, EBI-397403;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform v2]: Endoplasmic reticulum.
CC -!- SUBCELLULAR LOCATION: [Isoform v5]: Endoplasmic reticulum.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=v3; Synonyms=NOX5gamma;
CC IsoId=Q96PH1-1; Sequence=Displayed;
CC Name=v1; Synonyms=NOX5alpha;
CC IsoId=Q96PH1-3; Sequence=VSP_017328;
CC Name=v2; Synonyms=NOX5beta;
CC IsoId=Q96PH1-4; Sequence=VSP_017327, VSP_017328;
CC Name=v4; Synonyms=NOX5delta;
CC IsoId=Q96PH1-2; Sequence=VSP_017327;
CC Name=v5; Synonyms=NOX5epsilon, NOX5S;
CC IsoId=Q96PH1-5; Sequence=VSP_017326;
CC Name=v6; Synonyms=NOX5zeta;
CC IsoId=Q96PH1-6; Sequence=VSP_041619, VSP_017328;
CC -!- TISSUE SPECIFICITY: Mainly expressed in pachytene spermatocytes of
CC testis and in lymphocyte-rich areas of spleen and lymph nodes. Isoform
CC v1 is expressed in spleen. Isoform v2 is expressed in testis. Also
CC detected in ovary, placenta, pancreas, cardiac fibroblasts. Expressed
CC in B-cells and prostate malignant cells. Isoform v1 and isoform v3 are
CC expressed in epithelial colorectal adenocarcinoma cells. Isoform v2 and
CC isoform v4 are expressed in endothelial cells. Isoform v1, isoform v2,
CC isoform v3 and isoform v4 are expressed in pulmonary artery smooth
CC muscle cells. Isoform v2 and isoform v5 are expressed in microvascular
CC endothelial cells (at protein level). {ECO:0000269|PubMed:11376945,
CC ECO:0000269|PubMed:11483596, ECO:0000269|PubMed:12686516,
CC ECO:0000269|PubMed:16179589, ECO:0000269|PubMed:16339585,
CC ECO:0000269|PubMed:17275676}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal tissues.
CC {ECO:0000269|PubMed:11376945}.
CC -!- INDUCTION: Down-regulated by TGFB1. {ECO:0000269|PubMed:16179589}.
CC -!- DOMAIN: Isoform v1 and isoform v2 of this protein have four functional
CC EF-hand calcium-binding domains. Isoform v3 and isoform v4 have the
CC third EF-hand domain interrupted by an insert.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG33638.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB15319.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB84897.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF325189; AAK57193.1; -; mRNA.
DR EMBL; AF325190; AAK57194.1; -; mRNA.
DR EMBL; AF353088; AAK57338.1; -; mRNA.
DR EMBL; AF353089; AAK57339.1; -; mRNA.
DR EMBL; AK074058; BAB84884.1; -; mRNA.
DR EMBL; AK074071; BAB84897.1; ALT_INIT; mRNA.
DR EMBL; AK026011; BAB15319.1; ALT_INIT; mRNA.
DR EMBL; AK314689; BAG37241.1; -; mRNA.
DR EMBL; DQ314884; ABC40743.1; -; Genomic_DNA.
DR EMBL; AC027088; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC087639; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471082; EAW77830.1; -; Genomic_DNA.
DR EMBL; BC125097; AAI25098.1; -; mRNA.
DR EMBL; BC125098; AAI25099.1; -; mRNA.
DR EMBL; AF317889; AAG33638.1; ALT_INIT; mRNA.
DR CCDS; CCDS32276.2; -. [Q96PH1-1]
DR CCDS; CCDS53953.1; -. [Q96PH1-6]
DR CCDS; CCDS53954.1; -. [Q96PH1-3]
DR RefSeq; NP_001171708.1; NM_001184779.1. [Q96PH1-3]
DR RefSeq; NP_001171709.1; NM_001184780.1. [Q96PH1-6]
DR RefSeq; NP_078781.3; NM_024505.3. [Q96PH1-1]
DR PDB; 6SZ5; X-ray; 2.23 A; B/C=19-765.
DR PDBsum; 6SZ5; -.
DR AlphaFoldDB; Q96PH1; -.
DR SMR; Q96PH1; -.
DR BioGRID; 122660; 47.
DR IntAct; Q96PH1; 9.
DR MINT; Q96PH1; -.
DR STRING; 9606.ENSP00000373518; -.
DR BindingDB; Q96PH1; -.
DR ChEMBL; CHEMBL1926497; -.
DR GuidetoPHARMACOLOGY; 3005; -.
DR PeroxiBase; 6024; HsNOx05.
DR TCDB; 5.B.1.1.5; the phagocyte (gp91(phox)) nadph oxidase family.
DR iPTMnet; Q96PH1; -.
DR PhosphoSitePlus; Q96PH1; -.
DR BioMuta; NOX5; -.
DR DMDM; 74717091; -.
DR jPOST; Q96PH1; -.
DR MassIVE; Q96PH1; -.
DR PaxDb; Q96PH1; -.
DR PeptideAtlas; Q96PH1; -.
DR PRIDE; Q96PH1; -.
DR ProteomicsDB; 77694; -. [Q96PH1-1]
DR ProteomicsDB; 77695; -. [Q96PH1-2]
DR ProteomicsDB; 77696; -. [Q96PH1-3]
DR ProteomicsDB; 77697; -. [Q96PH1-4]
DR ProteomicsDB; 77698; -. [Q96PH1-5]
DR ProteomicsDB; 77699; -. [Q96PH1-6]
DR Antibodypedia; 57978; 256 antibodies from 30 providers.
DR DNASU; 79400; -.
DR Ensembl; ENST00000260364.9; ENSP00000454143.1; ENSG00000255346.10. [Q96PH1-2]
DR Ensembl; ENST00000388866.8; ENSP00000373518.3; ENSG00000255346.10. [Q96PH1-1]
DR Ensembl; ENST00000448182.7; ENSP00000410887.3; ENSG00000255346.10. [Q96PH1-4]
DR Ensembl; ENST00000455873.7; ENSP00000416828.3; ENSG00000255346.10. [Q96PH1-6]
DR Ensembl; ENST00000530406.6; ENSP00000432440.2; ENSG00000255346.10. [Q96PH1-3]
DR GeneID; 79400; -.
DR KEGG; hsa:79400; -.
DR MANE-Select; ENST00000388866.8; ENSP00000373518.3; NM_024505.4; NP_078781.3.
DR UCSC; uc002arp.3; human. [Q96PH1-1]
DR CTD; 79400; -.
DR DisGeNET; 79400; -.
DR GeneCards; NOX5; -.
DR HGNC; HGNC:14874; NOX5.
DR HPA; ENSG00000255346; Group enriched (lymphoid tissue, testis).
DR MIM; 606572; gene.
DR neXtProt; NX_Q96PH1; -.
DR OpenTargets; ENSG00000255346; -.
DR PharmGKB; PA31693; -.
DR VEuPathDB; HostDB:ENSG00000255346; -.
DR eggNOG; KOG0039; Eukaryota.
DR GeneTree; ENSGT00940000162591; -.
DR HOGENOM; CLU_009773_0_0_1; -.
DR InParanoid; Q96PH1; -.
DR OMA; NFWKWFM; -.
DR PhylomeDB; Q96PH1; -.
DR TreeFam; TF324099; -.
DR PathwayCommons; Q96PH1; -.
DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species.
DR SABIO-RK; Q96PH1; -.
DR SignaLink; Q96PH1; -.
DR SIGNOR; Q96PH1; -.
DR BioGRID-ORCS; 79400; 12 hits in 1068 CRISPR screens.
DR ChiTaRS; NOX5; human.
DR GeneWiki; NOX5; -.
DR GenomeRNAi; 79400; -.
DR Pharos; Q96PH1; Tchem.
DR PRO; PR:Q96PH1; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q96PH1; protein.
DR Bgee; ENSG00000255346; Expressed in oocyte and 139 other tissues.
DR ExpressionAtlas; Q96PH1; baseline and differential.
DR Genevisible; Q96PH1; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; NAS:UniProtKB.
DR GO; GO:0020037; F:heme binding; NAS:UniProtKB.
DR GO; GO:0050661; F:NADP binding; NAS:UniProtKB.
DR GO; GO:0015252; F:proton channel activity; IDA:UniProtKB.
DR GO; GO:0016175; F:superoxide-generating NAD(P)H oxidase activity; IDA:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; NAS:UniProtKB.
DR GO; GO:0061640; P:cytoskeleton-dependent cytokinesis; NAS:UniProtKB.
DR GO; GO:0001935; P:endothelial cell proliferation; IDA:UniProtKB.
DR GO; GO:0001819; P:positive regulation of cytokine production; NAS:UniProtKB.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IDA:UniProtKB.
DR GO; GO:1902600; P:proton transmembrane transport; IDA:UniProtKB.
DR GO; GO:0043012; P:regulation of fusion of sperm to egg plasma membrane; NAS:UniProtKB.
DR GO; GO:0042554; P:superoxide anion generation; IDA:UniProtKB.
DR CDD; cd00051; EFh; 2.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
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; PF13202; EF-hand_5; 1.
DR Pfam; PF13405; EF-hand_6; 1.
DR Pfam; PF08022; FAD_binding_8; 1.
DR Pfam; PF01794; Ferric_reduct; 1.
DR Pfam; PF08030; NAD_binding_6; 1.
DR SMART; SM00054; EFh; 2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
DR PROSITE; PS51384; FAD_FR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Angiogenesis; Calcium;
KW Electron transport; Endoplasmic reticulum; FAD; Flavoprotein; Ion channel;
KW Ion transport; Membrane; Metal-binding; NADP; Oxidoreductase;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..765
FT /note="NADPH oxidase 5"
FT /id="PRO_0000224995"
FT TOPO_DOM 1..238
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 239..259
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 260..266
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 267..289
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 290..317
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 318..338
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 339..362
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 363..383
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 384..394
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 395..417
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 418..434
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 435..455
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 456..583
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 584..604
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 605..765
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 26..56
FT /note="EF-hand 1"
FT /evidence="ECO:0000305"
FT DOMAIN 57..92
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 93..156
FT /note="EF-hand 3; atypical; contains an insert of 28
FT residues"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 165..200
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 293..440
FT /note="Ferric oxidoreductase"
FT DOMAIN 441..577
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 1..169
FT /note="N-terminal regulatory region; interacts with the C-
FT terminal catalytic region in a calcium-dependent manner"
FT REGION 122..141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 449..565
FT /note="C-terminal catalytic region"
FT BINDING 42
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 44
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 49
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 70
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 72
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 74
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 76
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 81
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 106
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000305"
FT BINDING 108
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000305"
FT BINDING 138
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000305"
FT BINDING 140
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000305"
FT BINDING 145
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000305"
FT BINDING 178
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 180
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 182
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 189
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT VAR_SEQ 1..200
FT /note="Missing (in isoform v5)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_017326"
FT VAR_SEQ 1..18
FT /note="Missing (in isoform v2 and isoform v4)"
FT /evidence="ECO:0000303|PubMed:11483596,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
FT /id="VSP_017327"
FT VAR_SEQ 1..17
FT /note="MNTSGDPAQTGPEGCRG -> MAFVCAGLSD (in isoform v6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_041619"
FT VAR_SEQ 109..136
FT /note="Missing (in isoform v1, isoform v2 and isoform v6)"
FT /evidence="ECO:0000303|PubMed:11483596,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_017328"
FT VARIANT 576
FT /note="R -> H (in dbSNP:rs2277552)"
FT /id="VAR_055820"
FT VARIANT 759
FT /note="R -> G (in dbSNP:rs7168025)"
FT /id="VAR_055821"
FT MUTAGEN 49
FT /note="E->Q: Loss of binding of 1 calcium molecule. No
FT effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:14982937"
FT CONFLICT 208
FT /note="A -> T (in Ref. 8; AAG33638)"
FT /evidence="ECO:0000305"
FT CONFLICT 272
FT /note="G -> S (in Ref. 7; AAI25099)"
FT /evidence="ECO:0000305"
FT CONFLICT 375
FT /note="L -> P (in Ref. 3; BAG37241)"
FT /evidence="ECO:0000305"
FT CONFLICT 380
FT /note="L -> F (in Ref. 2; BAB84884/BAB84897, 3; BAB15319/
FT BAG37241, 6; EAW77830 and 7; AAI25098/AAI25099)"
FT /evidence="ECO:0000305"
FT HELIX 721..728
FT /evidence="ECO:0007829|PDB:6SZ5"
SQ SEQUENCE 765 AA; 86439 MW; 96B57225BF919682 CRC64;
MNTSGDPAQT GPEGCRGTMS AEEDARWLRW VTQQFKTIAG EDGEISLQEF KAALHVKESF
FAERFFALFD SDRSGTITLQ ELQEALTLLI HGSPMDKLKF LFQVYDIDVC ARQGASAGTE
WGAGAGPHWA SSPLGTGSGS IDPDELRTVL QSCLRESAIS LPDEKLDQLT LALFESADAD
GNGAITFEEL RDELQRFPGV MENLTISAAH WLTAPAPRPR PRRPRQLTRA YWHNHRSQLF
CLATYAGLHV LLFGLAASAH RDLGASVMVA KGCGQCLNFD CSFIAVLMLR RCLTWLRATW
LAQVLPLDQN IQFHQLMGYV VVGLSLVHTV AHTVNFVLQA QAEASPFQFW ELLLTTRPGI
GWVHGSASPT GVALLLLLLL MFICSSSCIR RSGHFEVFYW THLSYLLVWL LLIFHGPNFW
KWLLVPGILF FLEKAIGLAV SRMAAVCIME VNLLPSKVTH LLIKRPPFFH YRPGDYLYLN
IPTIARYEWH PFTISSAPEQ KDTIWLHIRS QGQWTNRLYE SFKASDPLGR GSKRLSRSVT
MRKSQRSSKG SEILLEKHKF CNIKCYIDGP YGTPTRRIFA SEHAVLIGAG IGITPFASIL
QSIMYRHQKR KHTCPSCQHS WIEGVQDNMK LHKVDFIWIN RDQRSFEWFV SLLTKLEMDQ
AEEAQYGRFL ELHMYMTSAL GKNDMKAIGL QMALDLLANK EKKDSITGLQ TRTQPGRPDW
SKVFQKVAAE KKGKVQVFFC GSPALAKVLK GHCEKFGFRF FQENF
