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Q13794

- APR_HUMAN

UniProt

Q13794 - APR_HUMAN

Protein

Phorbol-12-myristate-13-acetate-induced protein 1

Gene

PMAIP1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    Promotes activation of caspases and apoptosis. Promotes mitochondrial membrane changes and efflux of apoptogenic proteins from the mitochondria. Contributes to p53/TP53-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.By similarity5 Publications

    GO - Molecular functioni

    1. protein binding Source: UniProtKB

    GO - Biological processi

    1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
    2. apoptotic process Source: MGI
    3. cellular response to glucose starvation Source: UniProtKB
    4. cellular response to hypoxia Source: UniProtKB
    5. defense response to virus Source: BHF-UCL
    6. intrinsic apoptotic signaling pathway Source: UniProtKB
    7. intrinsic apoptotic signaling pathway by p53 class mediator Source: UniProtKB
    8. intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: Ensembl
    9. negative regulation of fibroblast proliferation Source: Ensembl
    10. negative regulation of mitochondrial membrane potential Source: UniProtKB
    11. positive regulation of apoptotic process Source: UniProtKB
    12. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    13. positive regulation of DNA damage response, signal transduction by p53 class mediator Source: UniProtKB
    14. positive regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
    15. positive regulation of glucose metabolic process Source: UniProtKB
    16. positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
    17. positive regulation of neuron apoptotic process Source: Ensembl
    18. positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: Reactome
    19. positive regulation of protein oligomerization Source: UniProtKB
    20. positive regulation of release of cytochrome c from mitochondria Source: UniProtKB
    21. proteasomal protein catabolic process Source: UniProtKB
    22. reactive oxygen species metabolic process Source: UniProtKB
    23. regulation of mitochondrial membrane permeability Source: UniProtKB
    24. release of cytochrome c from mitochondria Source: Ensembl
    25. response to dsRNA Source: HGNC
    26. response to UV Source: Ensembl
    27. response to X-ray Source: Ensembl
    28. T cell homeostasis Source: UniProtKB

    Keywords - Biological processi

    Apoptosis

    Enzyme and pathway databases

    ReactomeiREACT_1194. Activation of NOXA and translocation to mitochondria.
    REACT_330. BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Phorbol-12-myristate-13-acetate-induced protein 1
    Short name:
    PMA-induced protein 1
    Alternative name(s):
    Immediate-early-response protein APR
    Protein Noxa
    Gene namesi
    Name:PMAIP1
    Synonyms:NOXA
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 18

    Organism-specific databases

    HGNCiHGNC:9108. PMAIP1.

    Subcellular locationi

    Mitochondrion 2 Publications

    GO - Cellular componenti

    1. cytosol Source: UniProtKB
    2. mitochondrial outer membrane Source: Reactome
    3. mitochondrion Source: UniProtKB
    4. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi29 – 291L → A: Reduced interaction with BAX. 2 Publications
    Mutagenesisi29 – 291L → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-32 and E-32. 2 Publications
    Mutagenesisi32 – 321F → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-29 and E-36. 2 Publications
    Mutagenesisi32 – 321F → I: Alters specificity of protein interaction and enhances pro-apoptotic activity; when associated with E-35. 2 Publications
    Mutagenesisi35 – 351K → E: Alters specificity of protein interaction and enhances pro-apoptotic activity; when associated with I-32. 1 Publication
    Mutagenesisi36 – 361L → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-29 and E-32. 1 Publication

    Organism-specific databases

    PharmGKBiPA33434.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 5454Phorbol-12-myristate-13-acetate-induced protein 1PRO_0000064644Add
    BLAST

    Proteomic databases

    MaxQBiQ13794.
    PRIDEiQ13794.

    PTM databases

    PhosphoSiteiQ13794.

    Expressioni

    Tissue specificityi

    Highly expressed in adult T-cell leukemia cell line.

    Inductioni

    Up-regulated by p53/TP53, phorbol esters, double-stranded RNA, IFNB1/IFN-beta and viruses.3 Publications

    Gene expression databases

    ArrayExpressiQ13794.
    BgeeiQ13794.
    CleanExiHS_PMAIP1.
    GenevestigatoriQ13794.

    Interactioni

    Subunit structurei

    Interacts with MCL1, BCL2A1 and BAX.5 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    BCL2P104153EBI-707392,EBI-77694
    BCL2P10415-13EBI-707392,EBI-4370304
    MCL1Q078205EBI-707392,EBI-1003422

    Protein-protein interaction databases

    BioGridi111379. 12 interactions.
    IntActiQ13794. 10 interactions.
    MINTiMINT-1391244.
    STRINGi9606.ENSP00000326119.

    Structurei

    Secondary structure

    1
    54
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi21 – 4020

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3MQPX-ray2.24B19-43[»]
    ProteinModelPortaliQ13794.
    SMRiQ13794. Positions 18-45.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ13794.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni41 – 5010Required for mitochondrial location

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi29 – 379BH3

    Domaini

    The BH3 motif is essential for pro-apoptotic activity.

    Sequence similaritiesi

    Belongs to the PMAIP1 family.Curated

    Phylogenomic databases

    eggNOGiNOG119326.
    HOGENOMiHOG000034020.
    HOVERGENiHBG004273.
    KOiK10131.
    OrthoDBiEOG7PP59Z.
    PhylomeDBiQ13794.

    Family and domain databases

    InterProiIPR024140. Noxa.
    [Graphical view]
    PANTHERiPTHR14299. PTHR14299. 1 hit.
    PfamiPF15150. PMAIP1. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q13794-1) [UniParc]FASTAAdd to Basket

    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

    MPGKKARKNA QPSPARAPAE LEVECATQLR RFGDKLNFRQ KLLNLISKLF   50
    CSGT 54
    Length:54
    Mass (Da):6,030
    Last modified:November 1, 1996 - v1
    Checksum:i291A142B27167E70
    GO
    Isoform 2 (identifier: Q13794-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         20-54: ELEVECATQLRRFGDKLNFRQKLLNLISKLFCSGT → GPAGTAGTAR...HQFEERLHCN

    Note: No experimental confirmation available.

    Show »
    Length:136
    Mass (Da):14,955
    Checksum:i055764B25628E4FC
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei20 – 5435ELEVE…FCSGT → GPAGTAGTARDQAGFAIGMQ LRFTRGKKLLSSSLSSSPLA LPRGHEEQVQVAGSRVCYST QEIWRQTELPAETSESDIQT LLLRNLTASKTCMRGLLQKS FLRRCTFHQFEERLHCN in isoform 2. 1 PublicationVSP_056247Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D90070 mRNA. Translation: BAA14111.1.
    AK311943 mRNA. Translation: BAG34884.1.
    AC107990 Genomic DNA. No translation available.
    BC013120 mRNA. Translation: AAH13120.1.
    BC032663 mRNA. Translation: AAH32663.1.
    CCDSiCCDS11975.1.
    PIRiI37018.
    RefSeqiNP_066950.1. NM_021127.2.
    UniGeneiHs.96.

    Genome annotation databases

    EnsembliENST00000269518; ENSP00000269518; ENSG00000141682.
    ENST00000316660; ENSP00000326119; ENSG00000141682.
    GeneIDi5366.
    KEGGihsa:5366.
    UCSCiuc002lic.2. human.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D90070 mRNA. Translation: BAA14111.1 .
    AK311943 mRNA. Translation: BAG34884.1 .
    AC107990 Genomic DNA. No translation available.
    BC013120 mRNA. Translation: AAH13120.1 .
    BC032663 mRNA. Translation: AAH32663.1 .
    CCDSi CCDS11975.1.
    PIRi I37018.
    RefSeqi NP_066950.1. NM_021127.2.
    UniGenei Hs.96.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3MQP X-ray 2.24 B 19-43 [» ]
    ProteinModelPortali Q13794.
    SMRi Q13794. Positions 18-45.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111379. 12 interactions.
    IntActi Q13794. 10 interactions.
    MINTi MINT-1391244.
    STRINGi 9606.ENSP00000326119.

    PTM databases

    PhosphoSitei Q13794.

    Proteomic databases

    MaxQBi Q13794.
    PRIDEi Q13794.

    Protocols and materials databases

    DNASUi 5366.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000269518 ; ENSP00000269518 ; ENSG00000141682 .
    ENST00000316660 ; ENSP00000326119 ; ENSG00000141682 .
    GeneIDi 5366.
    KEGGi hsa:5366.
    UCSCi uc002lic.2. human.

    Organism-specific databases

    CTDi 5366.
    GeneCardsi GC18P057540.
    HGNCi HGNC:9108. PMAIP1.
    MIMi 604959. gene.
    neXtProti NX_Q13794.
    PharmGKBi PA33434.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG119326.
    HOGENOMi HOG000034020.
    HOVERGENi HBG004273.
    KOi K10131.
    OrthoDBi EOG7PP59Z.
    PhylomeDBi Q13794.

    Enzyme and pathway databases

    Reactomei REACT_1194. Activation of NOXA and translocation to mitochondria.
    REACT_330. BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members.

    Miscellaneous databases

    EvolutionaryTracei Q13794.
    GeneWikii Phorbol-12-myristate-13-acetate-induced_protein_1.
    GenomeRNAii 5366.
    NextBioi 20800.
    PROi Q13794.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q13794.
    Bgeei Q13794.
    CleanExi HS_PMAIP1.
    Genevestigatori Q13794.

    Family and domain databases

    InterProi IPR024140. Noxa.
    [Graphical view ]
    PANTHERi PTHR14299. PTHR14299. 1 hit.
    Pfami PF15150. PMAIP1. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    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.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "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 1 AND 2).
      Tissue: Ovary and Uterus.
    5. "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] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INDUCTION.
    6. "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] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INDUCTION, SUBCELLULAR LOCATION, INTERACTION WITH BAX, MUTAGENESIS OF LEU-29.
    7. "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] [Europe PMC] [Abstract]
      Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF PHE-32 AND LYS-35, INTERACTION WITH MCL1.
    8. "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] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH MCL1, INDUCTION, SUBCELLULAR LOCATION.
    9. Cited for: FUNCTION, MUTAGENESIS OF LEU-29; PHE-32 AND LEU-36, INTERACTION WITH MCL1.
    10. "Crystal structure of human BFL-1 in complex with NOXA BH3 peptide."
      Northeast structural genomics consortium (NESG)
      Submitted (JUL-2010) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS) OF 19-43 IN COMPLEX WITH BCL2A1.

    Entry informationi

    Entry nameiAPR_HUMAN
    AccessioniPrimary (citable) accession number: Q13794
    Secondary accession number(s): B2R4T7, Q8N589
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 105 of the entry and version 1 of the sequence. [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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 18
      Human chromosome 18: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3