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Protein

NADPH oxidase 5

Gene

NOX5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Calcium-dependent NADPH oxidase that generates superoxide. Also functions as a calcium-dependent proton channel and may regulate redox-dependent processes in lymphocytes and spermatozoa. May play a role in cell growth and apoptosis. Isoform v2 and isoform v5 are involved in endothelial generation of reactive oxygen species (ROS), proliferation and angiogenesis and contribute to endothelial response to thrombin.3 Publications

Cofactori

Protein has several cofactor binding sites:

Enzyme regulationi

Activated by calcium which induces conformational changes and interaction between the N-terminal regulatory region and the C-terminal catalytic region. Inhibited by diphenylene iodonium.1 Publication

Kineticsi

  1. KM=1.06 µM for calcium1 Publication

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Calcium bindingi39 – 491PROSITE-ProRule annotationAdd BLAST11
    Calcium bindingi70 – 812PROSITE-ProRule annotationAdd BLAST12
    Calcium bindingi106 – 1083; first partPROSITE-ProRule annotation3
    Calcium bindingi137 – 1463; second partPROSITE-ProRule annotation10
    Calcium bindingi178 – 1894PROSITE-ProRule annotationAdd BLAST12

    GO - Molecular functioni

    • calcium ion binding Source: InterPro
    • flavin adenine dinucleotide binding Source: UniProtKB
    • heme binding Source: UniProtKB
    • NADP binding Source: UniProtKB
    • proton channel activity Source: UniProtKB
    • superoxide-generating NADPH oxidase activity Source: UniProtKB

    GO - Biological processi

    • angiogenesis Source: UniProtKB
    • apoptotic process Source: UniProtKB
    • cell proliferation Source: UniProtKB
    • cellular response to oxidative stress Source: Reactome
    • cytokine secretion Source: UniProtKB
    • cytoskeleton-dependent cytokinesis Source: UniProtKB
    • endothelial cell proliferation Source: UniProtKB
    • oxidation-reduction process Source: UniProtKB
    • positive regulation of reactive oxygen species metabolic process Source: UniProtKB
    • regulation of fusion of sperm to egg plasma membrane Source: UniProtKB
    • regulation of proton transport Source: UniProtKB
    • superoxide anion generation Source: UniProtKB

    Keywordsi

    Molecular functionIon channel, Oxidoreductase
    Biological processAngiogenesis, Electron transport, Ion transport, Transport
    LigandCalcium, FAD, Flavoprotein, Metal-binding, NADP

    Enzyme and pathway databases

    ReactomeiR-HSA-3299685 Detoxification of Reactive Oxygen Species
    SIGNORiQ96PH1

    Protein family/group databases

    PeroxiBasei6024 HsNOx05
    TCDBi5.B.1.1.5 the phagocyte (gp91(phox)) nadph oxidase family

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    NADPH oxidase 5 (EC:1.6.3.-)
    Gene namesi
    Name:NOX5
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 15

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000255346.9
    HGNCiHGNC:14874 NOX5
    MIMi606572 gene
    neXtProtiNX_Q96PH1

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 238CytoplasmicSequence analysisAdd BLAST238
    Transmembranei239 – 259HelicalSequence analysisAdd BLAST21
    Topological domaini260 – 266ExtracellularSequence analysis7
    Transmembranei267 – 289HelicalSequence analysisAdd BLAST23
    Topological domaini290 – 317CytoplasmicSequence analysisAdd BLAST28
    Transmembranei318 – 338HelicalSequence analysisAdd BLAST21
    Topological domaini339 – 362ExtracellularSequence analysisAdd BLAST24
    Transmembranei363 – 383HelicalSequence analysisAdd BLAST21
    Topological domaini384 – 394CytoplasmicSequence analysisAdd BLAST11
    Transmembranei395 – 417HelicalSequence analysisAdd BLAST23
    Topological domaini418 – 434ExtracellularSequence analysisAdd BLAST17
    Transmembranei435 – 455HelicalSequence analysisAdd BLAST21
    Topological domaini456 – 583CytoplasmicSequence analysisAdd BLAST128
    Transmembranei584 – 604HelicalSequence analysisAdd BLAST21
    Topological domaini605 – 765ExtracellularSequence analysisAdd BLAST161

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi49E → Q: Loss of binding of 1 calcium molecule. No effect on catalytic activity. 1 Publication1

    Organism-specific databases

    DisGeNETi79400
    OpenTargetsiENSG00000255346
    PharmGKBiPA31693

    Chemistry databases

    ChEMBLiCHEMBL1926497

    Polymorphism and mutation databases

    BioMutaiNOX5
    DMDMi74717091

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002249951 – 765NADPH oxidase 5Add BLAST765

    Proteomic databases

    PaxDbiQ96PH1
    PeptideAtlasiQ96PH1
    PRIDEiQ96PH1

    PTM databases

    iPTMnetiQ96PH1
    PhosphoSitePlusiQ96PH1

    Expressioni

    Tissue specificityi

    Mainly expressed in pachytene spermatocytes of testis and in lymphocyte-rich areas of spleen and lymph nodes. Isoform v1 is expressed in spleen. Isoform v2 is expressed in testis. Also detected in ovary, placenta, pancreas, cardiac fibroblasts. Expressed in B-cells and prostate malignant cells. Isoform v1 and isoform v3 are expressed in epithelial colorectal adenocarcinoma cells. Isoform v2 and isoform v4 are expressed in endothelial cells. Isoform v1, isoform v2, isoform v3 and isoform v4 are expressed in pulmonary artery smooth muscle cells. Isoform v2 and isoform v5 are expressed in microvascular endothelial cells (at protein level).6 Publications

    Developmental stagei

    Expressed in fetal tissues.1 Publication

    Inductioni

    Down-regulated by TGFB1.1 Publication

    Gene expression databases

    BgeeiENSG00000255346
    CleanExiHS_NOX5
    ExpressionAtlasiQ96PH1 baseline and differential
    GenevisibleiQ96PH1 HS

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CALMP621573EBI-7305642,EBI-397403From Bos taurus.

    Protein-protein interaction databases

    BioGridi122660, 12 interactors
    IntActiQ96PH1, 1 interactor
    STRINGi9606.ENSP00000373518

    Chemistry databases

    BindingDBiQ96PH1

    Structurei

    3D structure databases

    ProteinModelPortaliQ96PH1
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini26 – 56EF-hand 1PROSITE-ProRule annotationAdd BLAST31
    Domaini57 – 92EF-hand 2PROSITE-ProRule annotationAdd BLAST36
    Domaini93 – 156EF-hand 3; atypical; contains an insert of 28 residuesPROSITE-ProRule annotationAdd BLAST64
    Domaini165 – 200EF-hand 4PROSITE-ProRule annotationAdd BLAST36
    Domaini293 – 440Ferric oxidoreductaseAdd BLAST148
    Domaini441 – 577FAD-binding FR-typePROSITE-ProRule annotationAdd BLAST137

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni1 – 169N-terminal regulatory region; interacts with the C-terminal catalytic region in a calcium-dependent mannerAdd BLAST169
    Regioni449 – 565C-terminal catalytic regionAdd BLAST117

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Compositional biasi374 – 380Poly-Leu7

    Domaini

    Isoform v1 and isoform v2 of this protein have four functional EF-hand calcium-binding domains. Isoform v3 and isoform v4 have the third EF-hand domain interrupted by an insert.

    Keywords - Domaini

    Repeat, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG0039 Eukaryota
    ENOG410XNZY LUCA
    GeneTreeiENSGT00550000074350
    HOVERGENiHBG082052
    InParanoidiQ96PH1
    KOiK21424
    OMAiFDCSFIA
    OrthoDBiEOG091G019B
    PhylomeDBiQ96PH1
    TreeFamiTF324099

    Family and domain databases

    CDDicd00051 EFh, 2 hits
    InterProiView protein in InterPro
    IPR011992 EF-hand-dom_pair
    IPR018247 EF_Hand_1_Ca_BS
    IPR002048 EF_hand_dom
    IPR013112 FAD-bd_8
    IPR017927 Fd_Rdtase_FAD-bd
    IPR013130 Fe3_Rdtase_TM_dom
    IPR013121 Fe_red_NAD-bd_6
    IPR029648 NOX5
    IPR017938 Riboflavin_synthase-like_b-brl
    PANTHERiPTHR11972:SF58 PTHR11972:SF58, 1 hit
    PfamiView protein in Pfam
    PF13202 EF-hand_5, 1 hit
    PF13405 EF-hand_6, 1 hit
    PF08022 FAD_binding_8, 1 hit
    PF01794 Ferric_reduct, 1 hit
    PF08030 NAD_binding_6, 1 hit
    SMARTiView protein in SMART
    SM00054 EFh, 2 hits
    SUPFAMiSSF47473 SSF47473, 2 hits
    SSF63380 SSF63380, 2 hits
    PROSITEiView protein in PROSITE
    PS00018 EF_HAND_1, 2 hits
    PS50222 EF_HAND_2, 3 hits
    PS51384 FAD_FR, 1 hit

    Sequences (6)i

    Sequence statusi: Complete.

    This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform v3 (identifier: Q96PH1-1) [UniParc]FASTAAdd to basket
    Also known as: NOX5gamma

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MNTSGDPAQT GPEGCRGTMS AEEDARWLRW VTQQFKTIAG EDGEISLQEF
    60 70 80 90 100
    KAALHVKESF FAERFFALFD SDRSGTITLQ ELQEALTLLI HGSPMDKLKF
    110 120 130 140 150
    LFQVYDIDVC ARQGASAGTE WGAGAGPHWA SSPLGTGSGS IDPDELRTVL
    160 170 180 190 200
    QSCLRESAIS LPDEKLDQLT LALFESADAD GNGAITFEEL RDELQRFPGV
    210 220 230 240 250
    MENLTISAAH WLTAPAPRPR PRRPRQLTRA YWHNHRSQLF CLATYAGLHV
    260 270 280 290 300
    LLFGLAASAH RDLGASVMVA KGCGQCLNFD CSFIAVLMLR RCLTWLRATW
    310 320 330 340 350
    LAQVLPLDQN IQFHQLMGYV VVGLSLVHTV AHTVNFVLQA QAEASPFQFW
    360 370 380 390 400
    ELLLTTRPGI GWVHGSASPT GVALLLLLLL MFICSSSCIR RSGHFEVFYW
    410 420 430 440 450
    THLSYLLVWL LLIFHGPNFW KWLLVPGILF FLEKAIGLAV SRMAAVCIME
    460 470 480 490 500
    VNLLPSKVTH LLIKRPPFFH YRPGDYLYLN IPTIARYEWH PFTISSAPEQ
    510 520 530 540 550
    KDTIWLHIRS QGQWTNRLYE SFKASDPLGR GSKRLSRSVT MRKSQRSSKG
    560 570 580 590 600
    SEILLEKHKF CNIKCYIDGP YGTPTRRIFA SEHAVLIGAG IGITPFASIL
    610 620 630 640 650
    QSIMYRHQKR KHTCPSCQHS WIEGVQDNMK LHKVDFIWIN RDQRSFEWFV
    660 670 680 690 700
    SLLTKLEMDQ AEEAQYGRFL ELHMYMTSAL GKNDMKAIGL QMALDLLANK
    710 720 730 740 750
    EKKDSITGLQ TRTQPGRPDW SKVFQKVAAE KKGKVQVFFC GSPALAKVLK
    760
    GHCEKFGFRF FQENF
    Length:765
    Mass (Da):86,439
    Last modified:December 1, 2001 - v1
    Checksum:i96B57225BF919682
    GO
    Isoform v1 (identifier: Q96PH1-3) [UniParc]FASTAAdd to basket
    Also known as: NOX5alpha

    The sequence of this isoform differs from the canonical sequence as follows:
         109-136: Missing.

    Show »
    Length:737
    Mass (Da):83,774
    Checksum:i33B3AC250C36F6E9
    GO
    Isoform v2 (identifier: Q96PH1-4) [UniParc]FASTAAdd to basket
    Also known as: NOX5beta

    The sequence of this isoform differs from the canonical sequence as follows:
         1-18: Missing.
         109-136: Missing.

    Show »
    Length:719
    Mass (Da):82,013
    Checksum:i04F7BA7C78B1AEDB
    GO
    Isoform v4 (identifier: Q96PH1-2) [UniParc]FASTAAdd to basket
    Also known as: NOX5delta

    The sequence of this isoform differs from the canonical sequence as follows:
         1-18: Missing.

    Show »
    Length:747
    Mass (Da):84,678
    Checksum:i86B46366672B6E4A
    GO
    Isoform v5 (identifier: Q96PH1-5) [UniParc]FASTAAdd to basket
    Also known as: NOX5epsilon, NOX5S

    The sequence of this isoform differs from the canonical sequence as follows:
         1-200: Missing.

    Show »
    Length:565
    Mass (Da):64,652
    Checksum:i94785B98A61214F6
    GO
    Isoform v6 (identifier: Q96PH1-6) [UniParc]FASTAAdd to basket
    Also known as: NOX5zeta

    The sequence of this isoform differs from the canonical sequence as follows:
         1-17: MNTSGDPAQTGPEGCRG → MAFVCAGLSD
         109-136: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:730
    Mass (Da):83,109
    Checksum:i93B21AF3A0A1CE79
    GO

    Sequence cautioni

    The sequence AAG33638 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence BAB15319 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence BAB84897 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti208A → T in AAG33638 (PubMed:15994299).Curated1
    Sequence conflicti272G → S in AAI25099 (PubMed:15489334).Curated1
    Sequence conflicti375L → P in BAG37241 (PubMed:14702039).Curated1
    Sequence conflicti380L → F in BAB84884 (Ref. 2) Curated1
    Sequence conflicti380L → F in BAB84897 (Ref. 2) Curated1
    Sequence conflicti380L → F in BAB15319 (PubMed:14702039).Curated1
    Sequence conflicti380L → F in BAG37241 (PubMed:14702039).Curated1
    Sequence conflicti380L → F in EAW77830 (Ref. 6) Curated1
    Sequence conflicti380L → F in AAI25098 (PubMed:15489334).Curated1
    Sequence conflicti380L → F in AAI25099 (PubMed:15489334).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_055820576R → H. Corresponds to variant dbSNP:rs2277552Ensembl.1
    Natural variantiVAR_055821759R → G. Corresponds to variant dbSNP:rs7168025Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0173261 – 200Missing in isoform v5. 1 PublicationAdd BLAST200
    Alternative sequenceiVSP_0173271 – 18Missing in isoform v2 and isoform v4. 3 PublicationsAdd BLAST18
    Alternative sequenceiVSP_0416191 – 17MNTSG…EGCRG → MAFVCAGLSD in isoform v6. 1 PublicationAdd BLAST17
    Alternative sequenceiVSP_017328109 – 136Missing in isoform v1, isoform v2 and isoform v6. 2 PublicationsAdd BLAST28

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF325189 mRNA Translation: AAK57193.1
    AF325190 mRNA Translation: AAK57194.1
    AF353088 mRNA Translation: AAK57338.1
    AF353089 mRNA Translation: AAK57339.1
    AK074058 mRNA Translation: BAB84884.1
    AK074071 mRNA Translation: BAB84897.1 Different initiation.
    AK026011 mRNA Translation: BAB15319.1 Different initiation.
    AK314689 mRNA Translation: BAG37241.1
    DQ314884 Genomic DNA Translation: ABC40743.1
    AC027088 Genomic DNA No translation available.
    AC087639 Genomic DNA No translation available.
    CH471082 Genomic DNA Translation: EAW77830.1
    BC125097 mRNA Translation: AAI25098.1
    BC125098 mRNA Translation: AAI25099.1
    AF317889 mRNA Translation: AAG33638.1 Different initiation.
    CCDSiCCDS32276.2 [Q96PH1-1]
    CCDS53953.1 [Q96PH1-6]
    CCDS53954.1 [Q96PH1-3]
    RefSeqiNP_001171708.1, NM_001184779.1 [Q96PH1-3]
    NP_001171709.1, NM_001184780.1 [Q96PH1-6]
    NP_078781.3, NM_024505.3 [Q96PH1-1]
    UniGeneiHs.657932

    Genome annotation databases

    EnsembliENST00000260364; ENSP00000454143; ENSG00000255346 [Q96PH1-2]
    ENST00000388866; ENSP00000373518; ENSG00000255346 [Q96PH1-1]
    ENST00000448182; ENSP00000410887; ENSG00000255346 [Q96PH1-4]
    ENST00000455873; ENSP00000416828; ENSG00000255346 [Q96PH1-6]
    ENST00000530406; ENSP00000432440; ENSG00000255346 [Q96PH1-3]
    GeneIDi79400
    KEGGihsa:79400
    UCSCiuc002arp.3 human [Q96PH1-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiNOX5_HUMAN
    AccessioniPrimary (citable) accession number: Q96PH1
    Secondary accession number(s): B2RBJ4
    , Q08AN2, Q08AN3, Q8TEQ1, Q8TER4, Q96PH2, Q96PJ8, Q96PJ9, Q9H6E0, Q9HAM8
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 7, 2006
    Last sequence update: December 1, 2001
    Last modified: March 28, 2018
    This is version 138 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 15
      Human chromosome 15: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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