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 27-MAR-2024, entry version 173. 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 (ISOFORM RP V2), TISSUE SPECIFICITY, AND CATALYTIC ACTIVITY (ISOFORM V2). 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, TISSUE SPECIFICITY, AND CATALYTIC ACTIVITY. 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 (ISOFORM V2), COFACTOR (ISOFORM V2), MUTAGENESIS OF RP GLU-31 (ISOFORM V2), BIOPHYSICOCHEMICAL PROPERTIES (ISOFORM V2), FUNCTION RP (ISOFORM V2), CATALYTIC ACTIVITY (ISOFORM V2), AND N-TERMINAL REGULATORY EF RP DOMAIN (ISOFORM V2). 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 (ISOFORM V2), CATALYTIC ACTIVITY (ISOFORM V2), SUBCELLULAR RP LOCATION (ISOFORM V2), AND ACTIVITY REGULATION (ISOFORM V2). RX PubMed=17587483; DOI=10.1016/j.biochi.2007.05.004; RA Serrander L., Jaquet V., Bedard K., Plastre O., Hartley O., Arnaudeau S., RA Demaurex N., Schlegel W., Krause K.H.; RT "NOX5 is expressed at the plasma membrane and generates superoxide in RT response to protein kinase C activation."; RL Biochimie 89:1159-1167(2007). RN [15] RP FUNCTION (ISOFORMS V2 AND V5), TISSUE SPECIFICITY (ISOFORMS V1; V2; V3; V4 RP AND V5), SUBCELLULAR LOCATION (ISOFORMS V2 AND V5), AND CATALYTIC ACTIVITY RP (ISOFORMS V2 AND V5). 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). RN [16] RP FUNCTION (ISOFORM V1), CATALYTIC ACTIVITY (ISOFORM V1), SUBUNIT (ISOFORM RP V1), AND MUTAGENESIS OF LEU-277; PRO-567 AND ASP-656 (ISOFORM V1). RX PubMed=21319793; DOI=10.1021/bi1020088; RA Kawahara T., Jackson H.M., Smith S.M., Simpson P.D., Lambeth J.D.; RT "Nox5 forms a functional oligomer mediated by self-association of its RT dehydrogenase domain."; RL Biochemistry 50:2013-2025(2011). RN [17] RP FUNCTION (ISOFORM V2), CATALYTIC ACTIVITY (ISOFORM V2), PHOSPHORYLATION AT RP SER-475; THR-494; SER-498; SER-502 AND SER-659 (ISOFORM V2), AND RP MUTAGENESIS OF SER-475; THR-494; SER-498; SER-502 AND SER-659 (ISOFORM V2). RX PubMed=21642394; DOI=10.1124/mol.110.070193; RA Pandey D., Gratton J.P., Rafikov R., Black S.M., Fulton D.J.; RT "Calcium/calmodulin-dependent kinase II mediates the phosphorylation and RT activation of NADPH oxidase 5."; RL Mol. Pharmacol. 80:407-415(2011). RN [18] RP FUNCTION (ISOFORMS V1 AND V2), CATALYTIC ACTIVITY (ISOFORMS V1 AND V2), RP ABSENCE OF CATALYTIC ACTIVITY (ISOFORMS V3; V4 AND V5), TISSUE SPECIFICITY RP (ISOFORMS V1 AND V2), AND DOMAIN. RX PubMed=22427510; DOI=10.1152/ajpheart.00910.2011; RA Pandey D., Patel A., Patel V., Chen F., Qian J., Wang Y., Barman S.A., RA Venema R.C., Stepp D.W., Rudic R.D., Fulton D.J.; RT "Expression and functional significance of NADPH oxidase 5 (Nox5) and its RT splice variants in human blood vessels."; RL Am. J. Physiol. 302:H1919-H1928(2012). RN [19] RP FUNCTION (ISOFORM V2), CATALYTIC ACTIVITY (ISOFORM V2), S-NITROSYLATION AT RP CYS-107; CYS-246; CYS-519 AND CYS-694 (ISOFORM V2), PHOSPHORYLATION AT RP SER-490; THR-494 AND SER-498 (ISOFORM V2), AND MUTAGENESIS OF CYS-107; RP CYS-519 AND CYS-694 (ISOFORM V2). RX PubMed=22387196; DOI=10.1016/j.freeradbiomed.2012.02.029; RA Qian J., Chen F., Kovalenkov Y., Pandey D., Moseley M.A., Foster M.W., RA Black S.M., Venema R.C., Stepp D.W., Fulton D.J.; RT "Nitric oxide reduces NADPH oxidase 5 (Nox5) activity by reversible S- RT nitrosylation."; RL Free Radic. Biol. Med. 52:1806-1819(2012). RN [20] RP FUNCTION (ISOFORM V2), CATALYTIC ACTIVITY (ISOFORM V2), PHOSPHORYLATION AT RP SER-490; THR-494 AND SER-498 (ISOFORM V2), AND MUTAGENESIS OF SER-490; RP THR-494 AND SER-498 (ISOFORM V2). RX PubMed=24505490; DOI=10.1371/journal.pone.0088405; RA Chen F., Yu Y., Haigh S., Johnson J., Lucas R., Stepp D.W., Fulton D.J.; RT "Regulation of NADPH oxidase 5 by protein kinase C isoforms."; RL PLoS ONE 9:e88405-e88405(2014). RN [21] RP FUNCTION (ISOFORMS V2 AND V5), CATALYTIC ACTIVITY (ISOFORMS V2 AND V5), RP ACTIVITY REGULATION (ISOFORM V2), SUBCELLULAR LOCATION (ISOFORM V2), AND RP MUTAGENESIS OF GLU-110; SER-111; ALA-112; ILE-113; SER-114; LEU-115 AND RP PRO-116 (ISOFORM V2). RX PubMed=36653838; DOI=10.1002/1873-3468.14577; RA Miyano K., Kajikawa M.; RT "Ca2+ -binding-region-dependent cell surface localization of NADPH oxidase RT Nox5."; RL FEBS Lett. 597:702-713(2023). RN [22] {ECO:0007744|PDB:6SZ5} RP X-RAY CRYSTALLOGRAPHY (2.23 ANGSTROMS) OF 674-684 (ISOFORM V2) IN COMPLEX RP WITH CALMODULIN, AND N-TERMINAL REGULATORY EF DOMAIN (ISOFORM V2) AND RP C-TERMINAL CATALYTIC DEHYDROGENASE DOMAIN (ISOFORM V2). RX PubMed=31785178; DOI=10.1111/febs.15160; RA Millana Fananas E., Todesca S., Sicorello A., Masino L., Pompach P., RA Magnani F., Pastore A., Mattevi A.; RT "On the mechanism of calcium-dependent activation of NADPH oxidase 5 RT (NOX5)."; RL FEBS J. 287:2486-2503(2020). CC -!- FUNCTION: Calcium-dependent NADPH oxidase that catalyzes the generation CC of superoxide from molecular oxygen utilizing NADPH as an electron CC donor (PubMed:12686516). May play a role in cell growth and apoptosis CC (PubMed:12686516). {ECO:0000269|PubMed:12686516}. CC -!- FUNCTION: [Isoform v2]: Calcium-dependent NADPH oxidase that catalyzes CC the generation of superoxide from molecular oxygen utilizing NADPH as CC an electron donor (PubMed:11483596, PubMed:14982937, PubMed:17275676, CC PubMed:21642394, PubMed:24505490, PubMed:36653838, PubMed:17587483, CC PubMed:22427510, PubMed:22387196). Also functions as a calcium- CC dependent proton channel and may regulate redox-dependent processes in CC lymphocytes and spermatozoa (PubMed:11483596). Involved in endothelial CC generation of reactive oxygen species (ROS), proliferation and CC angiogenesis and contribute to endothelial response to thrombin CC (PubMed:17275676). {ECO:0000269|PubMed:11483596, CC ECO:0000269|PubMed:14982937, ECO:0000269|PubMed:17275676, CC ECO:0000269|PubMed:17587483, ECO:0000269|PubMed:21642394, CC ECO:0000269|PubMed:22387196, ECO:0000269|PubMed:22427510, CC ECO:0000269|PubMed:24505490, ECO:0000269|PubMed:36653838}. CC -!- FUNCTION: [Isoform v1]: Calcium-dependent NADPH oxidase that catalyzes CC the generation of superoxide from molecular oxygen utilizing NADPH as CC an electron donor. {ECO:0000269|PubMed:21319793, CC ECO:0000269|PubMed:22427510}. CC -!- FUNCTION: [Isoform v5]: Calcium-dependent NADPH oxidase that catalyzes CC the generation of superoxide from molecular oxygen utilizing NADPH as CC an electron donor (PubMed:17275676, PubMed:36653838). According to CC PubMed:22427510, lacks enzyme activity (PubMed:22427510). Involved in CC endothelial generation of reactive oxygen species (ROS), proliferation CC and angiogenesis and contribute to endothelial response to thrombin CC (PubMed:17275676). {ECO:0000269|PubMed:17275676, CC ECO:0000269|PubMed:22427510, ECO:0000269|PubMed:36653838}. CC -!- FUNCTION: [Isoform v4]: Lacks calcium-dependent NADPH oxidase activity. CC {ECO:0000269|PubMed:22427510}. CC -!- FUNCTION: [Isoform v3]: Lacks calcium-dependent NADPH oxidase activity. CC {ECO:0000269|PubMed:22427510}. CC -!- CATALYTIC ACTIVITY: CC Reaction=NADPH + 2 O2 = H(+) + NADP(+) + 2 superoxide; CC Xref=Rhea:RHEA:63180, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:18421, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC Evidence={ECO:0000269|PubMed:12686516}; CC -!- CATALYTIC ACTIVITY: [Isoform v2]: CC Reaction=NADPH + 2 O2 = H(+) + NADP(+) + 2 superoxide; CC Xref=Rhea:RHEA:63180, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:18421, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC Evidence={ECO:0000269|PubMed:11483596, ECO:0000269|PubMed:14982937, CC ECO:0000269|PubMed:17275676, ECO:0000269|PubMed:17587483, CC ECO:0000269|PubMed:21642394, ECO:0000269|PubMed:22387196, CC ECO:0000269|PubMed:22427510, ECO:0000269|PubMed:24505490, CC ECO:0000269|PubMed:36653838}; CC -!- CATALYTIC ACTIVITY: [Isoform v1]: CC Reaction=NADPH + 2 O2 = H(+) + NADP(+) + 2 superoxide; CC Xref=Rhea:RHEA:63180, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:18421, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC Evidence={ECO:0000269|PubMed:21319793, ECO:0000269|PubMed:22427510}; CC -!- CATALYTIC ACTIVITY: [Isoform v5]: CC Reaction=NADPH + 2 O2 = H(+) + NADP(+) + 2 superoxide; CC Xref=Rhea:RHEA:63180, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:18421, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC Evidence={ECO:0000269|PubMed:17275676, ECO:0000269|PubMed:36653838}; CC -!- COFACTOR: [Isoform v2]: 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: [Isoform v2]: Activated by calcium which induces CC conformational changes and interaction between the N-terminal CC regulatory region and the C-terminal catalytic region. Inhibited by CC diphenylene iodonium. {ECO:0000269|PubMed:14982937, CC ECO:0000269|PubMed:17587483, ECO:0000269|PubMed:36653838}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform v2]: CC Kinetic parameters: CC KM=1.06 uM for calcium {ECO:0000269|PubMed:14982937}; CC -!- SUBUNIT: [Isoform v1]: Homooligomer. {ECO:0000269|PubMed:21319793}. CC -!- INTERACTION: CC Q96PH1-4; P62157: CALM; Xeno; NbExp=3; IntAct=EBI-7305642, EBI-397403; CC -!- SUBCELLULAR LOCATION: [Isoform v2]: Endoplasmic reticulum CC {ECO:0000269|PubMed:17275676, ECO:0000269|PubMed:17587483}. Cell CC membrane {ECO:0000269|PubMed:17587483, ECO:0000269|PubMed:36653838}; CC Multi-pass membrane protein {ECO:0000255}. Note=Calcium-sensitive CC association and dissociation between the N- and C-terminal domains CC appears to facilitate its localization to the cell membrane. CC {ECO:0000269|PubMed:36653838}. CC -!- SUBCELLULAR LOCATION: [Isoform v5]: Endoplasmic reticulum CC {ECO:0000269|PubMed:17275676}. 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. Also CC detected in ovary, placenta, pancreas, cardiac fibroblasts. Expressed CC in B-cells and prostate malignant cells. {ECO:0000269|PubMed:11376945, CC ECO:0000269|PubMed:11483596, ECO:0000269|PubMed:12686516, CC ECO:0000269|PubMed:16179589, ECO:0000269|PubMed:16339585}. CC -!- TISSUE SPECIFICITY: [Isoform v1]: Expressed in spleen CC (PubMed:11483596). Expressed in endothelial cells, pulmonary artery CC smooth muscle cells and epithelial colorectal adenocarcinoma cells CC (PubMed:17275676, PubMed:22427510). {ECO:0000269|PubMed:11483596, CC ECO:0000269|PubMed:17275676, ECO:0000269|PubMed:22427510}. CC -!- TISSUE SPECIFICITY: [Isoform v2]: Expressed in microvascular CC endothelial cells (at protein level) (PubMed:17275676). Expressed in CC testis (PubMed:11483596). Expressed in endothelial cells and pulmonary CC artery smooth muscle cells (PubMed:17275676, PubMed:22427510). CC {ECO:0000269|PubMed:11483596, ECO:0000269|PubMed:17275676, CC ECO:0000269|PubMed:22427510}. CC -!- TISSUE SPECIFICITY: [Isoform v3]: Expressed in pulmonary artery smooth CC muscle cells and epithelial colorectal adenocarcinoma cells. CC {ECO:0000269|PubMed:17275676}. CC -!- TISSUE SPECIFICITY: [Isoform v4]: Expressed in endothelial cells and CC pulmonary artery smooth muscle cells. {ECO:0000269|PubMed:17275676}. CC -!- TISSUE SPECIFICITY: [Isoform v5]: Expressed in microvascular CC endothelial cells (at protein level). {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 v2]: The C-lobe of the N-terminal calmodulin-like CC regulatory EF-domain acquires a folded and ordered structure upon CC calcium binding, and as a consequence, it is able to bind the C- CC terminal catalytic dehydrogenase domain, triggering enzyme activation. CC {ECO:0000269|PubMed:31785178}. CC -!- DOMAIN: [Isoform v1]: The C-terminal catalytic dehydrogenase domain CC mediates its homooligomerization. {ECO:0000269|PubMed:21319793}. CC -!- DOMAIN: [Isoform v3]: Absence of enzyme activity may be because the CC third EF-hand domain is interrupted by an insert. CC {ECO:0000305|PubMed:22427510}. CC -!- DOMAIN: [Isoform v4]: Absence of enzyme activity may be because the CC third EF-hand domain is interrupted by an insert. CC {ECO:0000305|PubMed:22427510}. CC -!- DOMAIN: [Isoform v5]: Absence of enzyme activity may be due to absence CC of EF-hand domains. {ECO:0000305|PubMed:22427510}. CC -!- PTM: [Isoform v2]: Phosphorylation at Ser-475 by CaMK2 and at Ser-490, CC Thr-494 and Ser-498 by PKC/PRKCA positively regulates its catalytic CC activity. {ECO:0000269|PubMed:21642394, ECO:0000269|PubMed:24505490}. CC -!- PTM: [Isoform v2]: S-nitrosylation in response to nitric oxide inhibits CC its catalytic activity. {ECO:0000269|PubMed:22387196}. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 9606-ENSP00000373518; -. DR PeptideAtlas; 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; 295 antibodies from 30 providers. DR DNASU; 79400; -. DR Ensembl; ENST00000388866.8; ENSP00000373518.3; ENSG00000255346.11. [Q96PH1-1] DR Ensembl; ENST00000530406.7; ENSP00000432440.2; ENSG00000255346.11. [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 AGR; HGNC:14874; -. DR CTD; 79400; -. DR DisGeNET; 79400; -. DR GeneCards; NOX5; -. DR HGNC; HGNC:14874; NOX5. DR HPA; ENSG00000255346; Tissue enriched (lymphoid). DR HPA; ENSG00000290203; Not detected. 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; QWTTRLY; -. DR OrthoDB; 367877at2759; -. 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; 14 hits in 1148 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 141 other cell types or tissues. DR ExpressionAtlas; Q96PH1; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0043020; C:NADPH oxidase complex; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. 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:0106292; F:superoxide-generating NADPH oxidase activity; IEA:RHEA. 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:0006952; P:defense response; IBA:GO_Central. 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 CDD; cd06186; NOX_Duox_like_FAD_NADP; 1. DR Gene3D; 1.10.238.10; EF-hand; 1. DR Gene3D; 3.40.50.80; Nucleotide-binding domain of ferredoxin-NADP reductase (FNR) module; 1. DR Gene3D; 2.40.30.10; Translation factors; 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 PANTHER; PTHR11972; NADPH OXIDASE; 1. DR PANTHER; PTHR11972:SF58; NADPH OXIDASE 5; 1. 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 SFLD; SFLDS00052; Ferric_Reductase_Domain; 1. DR SFLD; SFLDG01168; Ferric_reductase_subgroup_(FRE; 1. DR SFLD; SFLDG01169; NADPH_oxidase_subgroup_(NOX); 1. DR SMART; SM00054; EFh; 2. DR SUPFAM; SSF47473; EF-hand; 1. DR SUPFAM; SSF52343; Ferredoxin reductase-like, C-terminal NADP-linked domain; 1. DR SUPFAM; SSF63380; Riboflavin synthase domain-like; 1. DR PROSITE; PS00018; EF_HAND_1; 2. DR PROSITE; PS50222; EF_HAND_2; 3. DR PROSITE; PS51384; FAD_FR; 1. DR Genevisible; Q96PH1; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Angiogenesis; Calcium; Cell membrane; 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 122..141 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" 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 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; FT BAB15319/BAG37241, 6; EAW77830 and 7; AAI25098/AAI25099)" FT /evidence="ECO:0000305" FT HELIX 721..728 FT /evidence="ECO:0007829|PDB:6SZ5" FT REGION Q96PH1-3:416..737 FT /note="C-terminal catalytic dehydrogenase domain" FT /evidence="ECO:0000305|PubMed:21319793" FT MUTAGEN Q96PH1-3:277 FT /note="L->R: Loss of activity but no effect on protein FT levels." FT /evidence="ECO:0000269|PubMed:21319793" FT MUTAGEN Q96PH1-3:567 FT /note="P->H: Loss of activity but no effect on protein FT levels." FT /evidence="ECO:0000269|PubMed:21319793" FT MUTAGEN Q96PH1-3:656 FT /note="D->A: Loss of activity but no effect on protein FT levels." FT /evidence="ECO:0000269|PubMed:21319793" FT REGION Q96PH1-4:1..161 FT /note="N-terminal regulatory EF domain" FT /evidence="ECO:0000269|PubMed:14982937, FT ECO:0000305|PubMed:31785178" FT REGION Q96PH1-4:1..77 FT /note="N-terminal lobe of N-terminal regulatory EF domain" FT /evidence="ECO:0000305|PubMed:31785178" FT REGION Q96PH1-4:78..161 FT /note="C-terminal lobe of N-terminal regulatory EF domain" FT /evidence="ECO:0000305|PubMed:31785178" FT REGION Q96PH1-4:398..719 FT /note="C-terminal catalytic dehydrogenase domain" FT /evidence="ECO:0000305|PubMed:31785178" FT MOD_RES Q96PH1-4:107 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:22387196" FT MOD_RES Q96PH1-4:246 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:22387196" FT MOD_RES Q96PH1-4:475 FT /note="Phosphoserine; by CaMK2" FT /evidence="ECO:0000269|PubMed:21642394" FT MOD_RES Q96PH1-4:490 FT /note="Phosphothreonine; by PKC/PRKCA" FT /evidence="ECO:0000269|PubMed:22387196, FT ECO:0000269|PubMed:24505490" FT MOD_RES Q96PH1-4:494 FT /note="Phosphothreonine; by CaMK2 and PKC/PRKCA" FT /evidence="ECO:0000269|PubMed:21642394, FT ECO:0000269|PubMed:22387196, ECO:0000269|PubMed:24505490" FT MOD_RES Q96PH1-4:498 FT /note="Phosphoserine; by CaMK2 and PKC/PRKCA" FT /evidence="ECO:0000269|PubMed:21642394, FT ECO:0000269|PubMed:22387196, ECO:0000269|PubMed:24505490" FT MOD_RES Q96PH1-4:502 FT /note="Phosphoserine; by CaMK2" FT /evidence="ECO:0000269|PubMed:21642394" FT MOD_RES Q96PH1-4:519 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:22387196" FT MOD_RES Q96PH1-4:659 FT /note="Phosphoserine; by CaMK2" FT /evidence="ECO:0000269|PubMed:21642394" FT MOD_RES Q96PH1-4:694 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:22387196" FT MUTAGEN Q96PH1-4:31 FT /note="E->Q: Loss of binding of 1 calcium molecule. No FT effect on catalytic activity." FT /evidence="ECO:0000269|PubMed:14982937" FT MUTAGEN Q96PH1-4:107 FT /note="C->S: Substantial loss of catalytic activity." FT /evidence="ECO:0000269|PubMed:22387196" FT MUTAGEN Q96PH1-4:110 FT /note="E->A: No effect on cell membrane localization and FT catalytic activity." FT /evidence="ECO:0000269|PubMed:36653838" FT MUTAGEN Q96PH1-4:111 FT /note="S->A: No effect on cell membrane localization and FT catalytic activity." FT /evidence="ECO:0000269|PubMed:36653838" FT MUTAGEN Q96PH1-4:112 FT /note="A->N: No effect on cell membrane localization and FT catalytic activity." FT /evidence="ECO:0000269|PubMed:36653838" FT MUTAGEN Q96PH1-4:113 FT /note="I->N: Significant reduction in cell membrane FT localization and catalytic activity. Reduced FT calcium-dependent interaction between the N-terminal FT regulatory region and the C-terminal catalytic region." FT /evidence="ECO:0000269|PubMed:36653838" FT MUTAGEN Q96PH1-4:114 FT /note="S->A: No effect on cell membrane localization and FT catalytic activity." FT /evidence="ECO:0000269|PubMed:36653838" FT MUTAGEN Q96PH1-4:115 FT /note="L->A: Significant reduction in cell membrane FT localization and catalytic activity. No effect on FT calcium-dependent interaction between the N-terminal FT regulatory region and the C-terminal catalytic region." FT /evidence="ECO:0000269|PubMed:36653838" FT MUTAGEN Q96PH1-4:116 FT /note="P->A: No effect on cell membrane localization and FT catalytic activity." FT /evidence="ECO:0000269|PubMed:36653838" FT MUTAGEN Q96PH1-4:475 FT /note="S->A: Loss of CaMK2-mediated activation of its FT activity." FT /evidence="ECO:0000269|PubMed:21642394" FT MUTAGEN Q96PH1-4:490 FT /note="S->A: Loss of PKC/PRKCA-mediated activation of its FT activity; when associated with A-494 and A-498." FT /evidence="ECO:0000269|PubMed:24505490" FT MUTAGEN Q96PH1-4:494 FT /note="T->A: No effect on CaMK2-mediated activation of its FT activity. Loss of PKC/PRKCA-mediated activation of its FT activity; when associated with A-490 and A-498." FT /evidence="ECO:0000269|PubMed:21642394, FT ECO:0000269|PubMed:24505490" FT MUTAGEN Q96PH1-4:498 FT /note="S->A: No effect on CaMK2-mediated activation of its FT activity. Loss of PKC/PRKCA-mediated activation of its FT activity; when associated with A-490 and A-494." FT /evidence="ECO:0000269|PubMed:21642394, FT ECO:0000269|PubMed:24505490" FT MUTAGEN Q96PH1-4:502 FT /note="S->A: No effect on CaMK2-mediated activation of its FT activity." FT /evidence="ECO:0000269|PubMed:21642394" FT MUTAGEN Q96PH1-4:519 FT /note="C->S: Very significant loss of catalytic activity." FT /evidence="ECO:0000269|PubMed:22387196" FT MUTAGEN Q96PH1-4:549 FT /note="P->H: No effect on cell membrane localization but FT loss of catalytic activity." FT /evidence="ECO:0000269|PubMed:36653838" FT MUTAGEN Q96PH1-4:659 FT /note="S->A: No effect on CaMK2-mediated activation of its FT activity." FT /evidence="ECO:0000269|PubMed:21642394" FT MUTAGEN Q96PH1-4:694 FT /note="C->S: Reduced nitrosylation. Very significant loss FT of catalytic activity." FT /evidence="ECO:0000269|PubMed:22387196" 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 //