Reviewed,
UniProtKB/Swiss-Prot Q13794 (APR_HUMAN)
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March 24, 2009.
Version 58.
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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents
Names and origin
| Protein names | Recommended name: Phorbol-12-myristate-13-acetate-induced protein 1 Short name=PMA-induced protein 1 Alternative name(s): Immediate-early-response protein APR NOXA | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 54 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Promotes activation of caspases and apoptosis. Promotes mitochondrial membrane changes and efflux of apoptogenic proteins from the mitochondria. Contributes to p53-dependent apoptosis after radiation exposure. Promotes proteasomal degradation of MCL1. Competes with BAK1 for binding to MCL1 and can displace BAK1 from its binding site on MCL1 By similarity. Competes with BIM/BCL2L11 for binding to MCL1 and can displace BIM/BCL2L11 from its binding site on MCL1. |
| Subunit structure | |
| Subcellular location | |
| Tissue specificity | Highly expressed in adult T-cell leukemia cell line. |
| Induction | Up-regulated by p53, phorbol esters, double-stranded RNA, interferon-beta, and virus. Ref.5 Ref.7 Ref.4 |
| Domain | The BH3 motif is essential for pro-apoptotic activity. |
| Sequence similarities | Belongs to the PMAIP1 family. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Apoptosis |
| Cellular component | Mitochondrion |
| Gene Ontology (GO) | |
| Biological process | activation of caspase activity Ref.5 Inferred from direct assay. Source: HGNC cell structure disassembly during apoptosis Ref.5Inferred from direct assay. Source: HGNC induction of apoptosis Ref.5Inferred from direct assay. Source: HGNC release of cytochrome c from mitochondria Ref.5Inferred from direct assay. Source: HGNC response to dsRNA Ref.5Inferred from direct assay. Source: HGNC virus-infected cell apoptosis Ref.5Inferred from direct assay. Source: HGNC |
| Cellular component | mitochondrion Ref.5 Inferred from direct assay. Source: HGNC |
| Molecular function | protein binding Ref.5 Ref.6 Inferred from physical interaction. Source: IntAct |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| Bcl2a1 | Q07440 | 1 | EBI-707392,EBI-707754 | From a different organism. |
| MCL1 | Q07820 | 1 | EBI-707392,EBI-1003422 | |
| Mcl1 | P97287 | 1 | EBI-707392,EBI-707292 | From a different organism. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 54 | 54 | Phorbol-12-myristate-13-acetate-induced protein 1 | PRO_0000064644 | |||||
Regions | |||||||||
| Region | 41 – 50 | 10 | Required for mitochondrial location | ||||||
| Motif | 29 – 37 | 9 | BH3 | ||||||
Experimental info | |||||||||
| Mutagenesis | 29 | 1 | L → A: Reduced interaction with BAX. Ref.5 Ref.8 | ||||||
| Mutagenesis | 29 | 1 | L → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-32 and E-32. Ref.5 Ref.8 | ||||||
| Mutagenesis | 32 | 1 | F → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-29 and E-36. Ref.6 Ref.8 | ||||||
| Mutagenesis | 32 | 1 | F → I: Alters specificity of protein interaction and enhances pro-apoptotic activity; when associated with E-35. Ref.6 Ref.8 | ||||||
| Mutagenesis | 35 | 1 | K → E: Alters specificity of protein interaction and enhances pro-apoptotic activity; when associated with I-32. Ref.6 | ||||||
| Mutagenesis | 36 | 1 | L → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-29 and E-32. Ref.8 | ||||||
Sequences
References
| « Hide 'large scale' references | |
| [1] | "Molecular cloning and characterization of a cDNA for a novel phorbol-12-myristate-13-acetate-responsive gene that is highly expressed in an adult T-cell leukemia cell line." Hijikata M., Kato N., Sato T., Kagami Y., Shimotohno K. J. Virol. 64:4632-4639(1990) [PubMed: 2398525] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [2] | "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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [3] | "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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Ovary. |
| [4] | "Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis." Oda E., Ohki R., Murasawa H., Nemoto J., Shibue T., Yamashita T., Tokino T., Taniguchi T., Tanaka N. Science 288:1053-1058(2000) [PubMed: 10807576] [Abstract] Cited for: FUNCTION, INDUCTION. |
| [5] | "Involvement of Noxa in cellular apoptotic responses to interferon, double-stranded RNA, and virus infection." Sun Y., Leaman D.W. J. Biol. Chem. 280:15561-15568(2005) [PubMed: 15705586] [Abstract] Cited for: FUNCTION, INDUCTION, SUBCELLULAR LOCATION, INTERACTION WITH BAX, MUTAGENESIS OF LEU-29. |
| [6] | "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function." Chen L., Willis S.N., Wei A., Smith B.J., Fletcher J.I., Hinds M.G., Colman P.M., Day C.L., Adams J.M., Huang D.C.S. Mol. Cell 17:393-403(2005) [PubMed: 15694340] [Abstract] Cited for: FUNCTION, MASS SPECTROMETRY, MUTAGENESIS OF PHE-32 AND LYS-35, INTERACTION WITH MCL1. |
| [7] | "Functional linkage between NOXA and Bim in mitochondrial apoptotic events." Han J., Goldstein L.A., Hou W., Rabinowich H. J. Biol. Chem. 282:16223-16231(2007) [PubMed: 17374615] [Abstract] Cited for: FUNCTION, INTERACTION WITH MCL1, INDUCTION, SUBCELLULAR LOCATION. |
| [8] | "Structural insights into the degradation of Mcl-1 induced by BH3 domains." Czabotar P.E., Lee E.F., van Delft M.F., Day C.L., Smith B.J., Huang D.C.S., Fairlie W.D., Hinds M.G., Colman P.M. Proc. Natl. Acad. Sci. U.S.A. 104:6217-6222(2007) [PubMed: 17389404] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LEU-29; PHE-32 AND LEU-36, INTERACTION WITH MCL1. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| D90070 mRNA. Translation: BAA14111.1. AK311943 mRNA. Translation: BAG34884.1. BC013120 mRNA. Translation: AAH13120.1. | |
| IPI | IPI00015177. |
| PIR | I37018. |
| RefSeq | NP_066950.1. |
| UniGene | Hs.96 |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q13794. 7 interactions. |
Genome annotation databases | |
| Ensembl | ENSG00000141682. Homo sapiens. [Contig view] |
| GeneID | 5366. |
| KEGG | hsa:5366. |
Organism-specific databases | |
| GeneCards | GC18P055718. |
| H-InvDB | HIX0014485. |
| HGNC | HGNC:9108. PMAIP1. |
| MIM | 604959. gene. |
| PharmGKB | PA33434. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOVERGEN | Q13794. |
Enzyme and pathway databases | |
| Reactome | REACT_578. Apoptosis. |
Gene expression databases | |
| ArrayExpress | Q13794. |
| Bgee | Q13794. |
| CleanEx | HS_PMAIP1. |
| GermOnline | ENSG00000141682. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR000712. Bcl2_BH. [Graphical view] |
| PROSITE | PS01259. BH3. False negative. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 20800. |
| SOURCE | Search... |
Entry information
| Entry name | APR_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q13794 Secondary accession number(s): B2R4T7 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 18 Human chromosome 18: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |
