Q96PH1 (NOX5_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 96.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: NADPH oxidase 5 EC=1.6.3.- | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) [Reference proteome] | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 765 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | 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. Ref.1 Ref.10 Ref.14 |
| Cofactor | FAD. Ref.11 Magnesium. Ref.11 |
| Enzyme regulation | 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. Ref.11 |
| Subcellular location | Membrane; Multi-pass membrane protein Potential Ref.14. Isoform v2: Endoplasmic reticulum Ref.14. Isoform v5: Endoplasmic reticulum Ref.14. |
| Tissue specificity | 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). Ref.1 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 |
| Developmental stage | Expressed in fetal tissues. Ref.9 |
| Induction | |
| Domain | 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. |
| Sequence similarities | Contains 4 EF-hand domains. Contains 1 FAD-binding FR-type domain. Contains 1 ferric oxidoreductase domain. |
| Biophysicochemical properties | Kinetic parameters: KM=1.06 µM for calcium Ref.11 |
| Sequence caution | The sequence AAG33638.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAB15319.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAB84897.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. |
Ontologies
Alternative products
| This entry describes 6 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform v3 (identifier: Q96PH1-1) 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. | ||||||
| Isoform v1 (identifier: Q96PH1-3) Also known as: NOX5alpha; The sequence of this isoform differs from the canonical sequence as follows: 109-136: Missing. | ||||||
| Isoform v2 (identifier: Q96PH1-4) Also known as: NOX5beta; The sequence of this isoform differs from the canonical sequence as follows: 1-18: Missing. 109-136: Missing. | ||||||
| Isoform v4 (identifier: Q96PH1-2) Also known as: NOX5delta; The sequence of this isoform differs from the canonical sequence as follows: 1-18: Missing. | ||||||
| Isoform v5 (identifier: Q96PH1-5) Also known as: NOX5epsilon; NOX5S; The sequence of this isoform differs from the canonical sequence as follows: 1-200: Missing. | ||||||
| Isoform v6 (identifier: Q96PH1-6) 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. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 765 | 765 | NADPH oxidase 5 | PRO_0000224995 | |||||
Regions | |||||||||
| Topological domain | 1 – 238 | 238 | Cytoplasmic Potential | ||||||
| Transmembrane | 239 – 259 | 21 | Helical; Potential | ||||||
| Topological domain | 260 – 266 | 7 | Extracellular Potential | ||||||
| Transmembrane | 267 – 289 | 23 | Helical; Potential | ||||||
| Topological domain | 290 – 317 | 28 | Cytoplasmic Potential | ||||||
| Transmembrane | 318 – 338 | 21 | Helical; Potential | ||||||
| Topological domain | 339 – 362 | 24 | Extracellular Potential | ||||||
| Transmembrane | 363 – 383 | 21 | Helical; Potential | ||||||
| Topological domain | 384 – 394 | 11 | Cytoplasmic Potential | ||||||
| Transmembrane | 395 – 417 | 23 | Helical; Potential | ||||||
| Topological domain | 418 – 434 | 17 | Extracellular Potential | ||||||
| Transmembrane | 435 – 455 | 21 | Helical; Potential | ||||||
| Topological domain | 456 – 583 | 128 | Cytoplasmic Potential | ||||||
| Transmembrane | 584 – 604 | 21 | Helical; Potential | ||||||
| Topological domain | 605 – 765 | 161 | Extracellular Potential | ||||||
| Domain | 26 – 56 | 31 | EF-hand 1 | ||||||
| Domain | 57 – 92 | 36 | EF-hand 2 | ||||||
| Domain | 93 – 156 | 64 | EF-hand 3; atypical; contains an insert of 28 residues | ||||||
| Domain | 165 – 200 | 36 | EF-hand 4 | ||||||
| Domain | 293 – 440 | 148 | Ferric oxidoreductase | ||||||
| Domain | 441 – 577 | 137 | FAD-binding FR-type | ||||||
| Calcium binding | 39 – 49 | 11 | 1 Potential | ||||||
| Calcium binding | 70 – 81 | 12 | 2 Potential | ||||||
| Calcium binding | 106 – 108 | 3 | 3; first part Potential | ||||||
| Calcium binding | 137 – 146 | 10 | 3; second part Potential | ||||||
| Calcium binding | 178 – 189 | 12 | 4 Potential | ||||||
| Region | 1 – 169 | 169 | N-terminal regulatory region; interacts with the C-terminal catalytic region in a calcium-dependent manner | ||||||
| Region | 449 – 565 | 117 | C-terminal catalytic region | ||||||
| Compositional bias | 374 – 380 | 7 | Poly-Leu | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 200 | 200 | Missing in isoform v5. | VSP_017326 | |||||
| Alternative sequence | 1 – 18 | 18 | Missing in isoform v2 and isoform v4. | VSP_017327 | |||||
| Alternative sequence | 1 – 17 | 17 | MNTSG…EGCRG → MAFVCAGLSD in isoform v6. | VSP_041619 | |||||
| Alternative sequence | 109 – 136 | 28 | Missing in isoform v1, isoform v2 and isoform v6. | VSP_017328 | |||||
| Natural variant | 576 | 1 | R → H. Corresponds to variant rs2277552 [ dbSNP | Ensembl ]. | VAR_055820 | |||||
| Natural variant | 759 | 1 | R → G. Corresponds to variant rs7168025 [ dbSNP | Ensembl ]. | VAR_055821 | |||||
Experimental info | |||||||||
| Mutagenesis | 49 | 1 | E → Q: Loss of binding of 1 calcium molecule. No effect on catalytic activity. Ref.11 | ||||||
| Sequence conflict | 208 | 1 | A → T in AAG33638. Ref.8 | ||||||
| Sequence conflict | 272 | 1 | G → S in AAI25099. Ref.7 | ||||||
| Sequence conflict | 375 | 1 | L → P in BAG37241. Ref.3 | ||||||
| Sequence conflict | 380 | 1 | L → F in BAB84884. Ref.2 | ||||||
| Sequence conflict | 380 | 1 | L → F in BAB84897. Ref.2 | ||||||
| Sequence conflict | 380 | 1 | L → F in BAB15319. Ref.3 | ||||||
| Sequence conflict | 380 | 1 | L → F in BAG37241. Ref.3 | ||||||
| Sequence conflict | 380 | 1 | L → F in EAW77830. Ref.6 | ||||||
| Sequence conflict | 380 | 1 | L → F in AAI25098. Ref.7 | ||||||
| Sequence conflict | 380 | 1 | L → F in AAI25099. Ref.7 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "A Ca(2+)-activated NADPH oxidase in testis, spleen, and lymph nodes." Banfi B., Molnar G., Maturana A., Steger K., Hegedus B., Demaurex N., Krause K.-H. J. Biol. Chem. 276:37594-37601(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS V1; V2; V3 AND V4), FUNCTION, TISSUE SPECIFICITY. Tissue: Spleen and Testis. |
| [2] | "The nucleotide sequence of a long cDNA clone isolated from human spleen." Jikuya H., Takano J., Nomura N., Kikuno R., Nagase T., Ohara O. Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM V5), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 98-765 (ISOFORMS V3/V4). Tissue: Spleen. |
| [3] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM V4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 159-765 (ISOFORMS V1/V2/V3/V4/V6). Tissue: Kidney epithelium and Spleen. |
| [4] | NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM V5). |
| [5] | "Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. Nusbaum C.Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS V2 AND V6). |
| [8] | "Point mutations in the proline-rich region of p22phox are dominant inhibitors of Nox1- and Nox2-dependent reactive oxygen generation." Kawahara T., Ritsick D., Cheng G., Lambeth J.D. J. Biol. Chem. 280:31859-31869(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 177-765 (ISOFORMS V1/V2/V3/V4/V6). Tissue: Spleen. |
| [9] | "Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5." Cheng G., Cao Z., Xu X., van Meir E.G., Lambeth J.D. Gene 269:131-140(2001) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. |
| [10] | "NOX5 NAD(P)H oxidase regulates growth and apoptosis in DU 145 prostate cancer cells." Brar S.S., Corbin Z., Kennedy T.P., Hemendinger R., Thornton L., Bommarius B., Arnold R.S., Whorton A.R., Sturrock A.B., Huecksteadt T.P., Quinn M.T., Krenitsky K., Ardie K.G., Lambeth J.D., Hoidal J.R. Am. J. Physiol. 285:C353-C369(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY. |
| [11] | "Mechanism of Ca2+ activation of the NADPH oxidase 5 (NOX5)." Banfi B., Tirone F., Durussel I., Knisz J., Moskwa P., Molnar G.Z., Krause K.-H., Cox J.A. J. Biol. Chem. 279:18583-18591(2004) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, COFACTOR, MUTAGENESIS OF GLU-49, BIOPHYSICOCHEMICAL PROPERTIES. |
| [12] | "NAD(P)H oxidase 4 mediates transforming growth factor-beta1-induced differentiation of cardiac fibroblasts into myofibroblasts." Cucoranu I., Clempus R., Dikalova A., Phelan P.J., Ariyan S., Dikalov S., Sorescu D. Circ. Res. 97:900-907(2005) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION. |
| [13] | "Expression and activity of NOX5 in the circulating malignant B cells of hairy cell leukemia." Kamiguti A.S., Serrander L., Lin K., Harris R.J., Cawley J.C., Allsup D.J., Slupsky J.R., Krause K.-H., Zuzel M. J. Immunol. 175:8424-8430(2005) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY. |
| [14] | "NOX5 variants are functionally active in endothelial cells." BelAiba R.S., Djordjevic T., Petry A., Diemer K., Bonello S., Banfi B., Hess J., Pogrebniak A., Bickel C., Gorlach A. Free Radic. Biol. Med. 42:446-459(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | 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. |
| IPI | IPI00044456. IPI00739004. IPI00739568. IPI00740953. IPI00742061. IPI01020736. |
| RefSeq | NP_001171708.1. NM_001184779.1. NP_001171709.1. NM_001184780.1. NP_078781.3. NM_024505.3. |
| UniGene | Hs.657932. |
3D structure databases | |
| ProteinModelPortal | Q96PH1. |
| ModBase | Search... |
Protein-protein interaction databases | |
| MINT | MINT-4651944. |
| STRING | 9606.ENSP00000260364. |
Protein family/group databases | |
| PeroxiBase | 6024. HsNOx05. |
| TCDB | 5.B.1.1.5. phagocyte (gp91phox) NADPH oxidase family. |
Polymorphism databases | |
| DMDM | 74717091. |
Proteomic databases | |
| PaxDb | Q96PH1. |
| PRIDE | Q96PH1. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000260364; ENSP00000454143; ENSG00000255346. ENST00000388866; ENSP00000373518; ENSG00000255346. ENST00000448182; ENSP00000410887; ENSG00000255346. ENST00000455873; ENSP00000416828; ENSG00000255346. ENST00000530406; ENSP00000432440; ENSG00000255346. |
| GeneID | 79400. |
| KEGG | hsa:79400. |
| UCSC | uc002arp.2. human. uc002arq.2. human. uc002arr.2. human. uc010bid.2. human. |
Organism-specific databases | |
| CTD | 79400. |
| GeneCards | GC15P069222. |
| H-InvDB | HIX0012384. |
| HGNC | HGNC:14874. NOX5. |
| HPA | HPA019362. |
| MIM | 606572. gene. |
| neXtProt | NX_Q96PH1. |
| PharmGKB | PA31693. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | NOG287712. |
| HOVERGEN | HBG082052. |
| InParanoid | Q96PH1. |
| OMA | LTRAYWH. |
Gene expression databases | |
| Bgee | Q96PH1. |
| CleanEx | HS_NOX5. |
| Genevestigator | Q96PH1. |
| GermOnline | ENSG00000137808. Homo sapiens. |
Family and domain databases | |
| Gene3D | 1.10.238.10. 1 hit. |
| InterPro | IPR011992. EF-hand-like_dom. 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. IPR017938. Riboflavin_synthase-like_b-brl. [Graphical view] |
| Pfam | PF13202. EF_hand_3. 1 hit. PF13405. EF_hand_4. 1 hit. PF08022. FAD_binding_8. 1 hit. PF01794. Ferric_reduct. 1 hit. PF08030. NAD_binding_6. 1 hit. [Graphical view] |
| SMART | SM00054. EFh. 2 hits. [Graphical view] |
| SUPFAM | SSF63380. Riboflavin_synthase_like_b-brl. 1 hit. |
| PROSITE | PS00018. EF_HAND_1. 2 hits. PS50222. EF_HAND_2. 3 hits. PS51384. FAD_FR. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| BindingDB | Q96PH1. |
| ChEMBL | CHEMBL1926497. |
| GenomeRNAi | 79400. |
| NextBio | 68361. |
| SOURCE | Search... |
Entry information
| Entry name | NOX5_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q96PH1 Secondary accession number(s): B2RBJ4 Q9HAM8 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any 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. | ||||||||
Relevant documents
| Human chromosome 15 Human chromosome 15: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
