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Protein

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

Gene

PMAIP1

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

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 - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
  • apoptotic process Source: MGI
  • cellular response to glucose starvation Source: UniProtKB
  • cellular response to hypoxia Source: UniProtKB
  • defense response to virus Source: BHF-UCL
  • intrinsic apoptotic signaling pathway Source: UniProtKB
  • intrinsic apoptotic signaling pathway by p53 class mediator Source: UniProtKB
  • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: Ensembl
  • negative regulation of fibroblast proliferation Source: Ensembl
  • negative regulation of mitochondrial membrane potential Source: UniProtKB
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • positive regulation of DNA damage response, signal transduction by p53 class mediator Source: UniProtKB
  • positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
  • positive regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
  • positive regulation of glucose metabolic process Source: UniProtKB
  • positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  • positive regulation of neuron apoptotic process Source: Ensembl
  • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: Reactome
  • positive regulation of protein oligomerization Source: UniProtKB
  • positive regulation of release of cytochrome c from mitochondria Source: UniProtKB
  • programmed cell death Source: Reactome
  • proteasomal protein catabolic process Source: UniProtKB
  • reactive oxygen species metabolic process Source: UniProtKB
  • regulation of mitochondrial membrane permeability Source: UniProtKB
  • release of cytochrome c from mitochondria Source: Ensembl
  • response to dsRNA Source: HGNC
  • response to UV Source: Ensembl
  • response to X-ray Source: Ensembl
  • T cell homeostasis Source: UniProtKB
Complete GO annotation...

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 Componenti: Chromosome 18

Organism-specific databases

HGNCiHGNC:9108. PMAIP1.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • mitochondrial outer membrane Source: Reactome
  • mitochondrion Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

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.

Polymorphism and mutation databases

BioMutaiPMAIP1.

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

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 – 4020Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00530000065105.
HOGENOMiHOG000034020.
HOVERGENiHBG004273.
InParanoidiQ13794.
KOiK10131.
OMAiWRQTELP.
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. AlignAdd to basket

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

        10         20         30         40         50
MPGKKARKNA QPSPARAPAE LEVECATQLR RFGDKLNFRQ KLLNLISKLF

CSGT
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:
EMBLi
GenBanki
DDBJi
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. [Q13794-1]
PIRiI37018.
RefSeqiNP_066950.1. NM_021127.2. [Q13794-1]
UniGeneiHs.96.

Genome annotation databases

EnsembliENST00000269518; ENSP00000269518; ENSG00000141682. [Q13794-2]
ENST00000316660; ENSP00000326119; ENSG00000141682. [Q13794-1]
GeneIDi5366.
KEGGihsa:5366.
UCSCiuc002lic.2. human. [Q13794-1]
uc002lid.2. human.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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. [Q13794-1]
PIRiI37018.
RefSeqiNP_066950.1. NM_021127.2. [Q13794-1]
UniGeneiHs.96.

3D structure databases

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

Protein-protein interaction databases

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

PTM databases

PhosphoSiteiQ13794.

Polymorphism and mutation databases

BioMutaiPMAIP1.

Proteomic databases

MaxQBiQ13794.
PRIDEiQ13794.

Protocols and materials databases

DNASUi5366.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000269518; ENSP00000269518; ENSG00000141682. [Q13794-2]
ENST00000316660; ENSP00000326119; ENSG00000141682. [Q13794-1]
GeneIDi5366.
KEGGihsa:5366.
UCSCiuc002lic.2. human. [Q13794-1]
uc002lid.2. human.

Organism-specific databases

CTDi5366.
GeneCardsiGC18P057568.
HGNCiHGNC:9108. PMAIP1.
MIMi604959. gene.
neXtProtiNX_Q13794.
PharmGKBiPA33434.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG119326.
GeneTreeiENSGT00530000065105.
HOGENOMiHOG000034020.
HOVERGENiHBG004273.
InParanoidiQ13794.
KOiK10131.
OMAiWRQTELP.
OrthoDBiEOG7PP59Z.
PhylomeDBiQ13794.

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.

Miscellaneous databases

EvolutionaryTraceiQ13794.
GeneWikiiPhorbol-12-myristate-13-acetate-induced_protein_1.
GenomeRNAii5366.
NextBioi20800.
PROiQ13794.
SOURCEiSearch...

Gene expression databases

BgeeiQ13794.
CleanExiHS_PMAIP1.
GenevestigatoriQ13794.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  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: May 27, 2015
This is version 112 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.