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Protein

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

Gene

PMAIP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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: InterPro
  • apoptotic process Source: MGI
  • cellular response to DNA damage stimulus Source: InterPro
  • 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
  • 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 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
  • proteasomal protein catabolic process Source: UniProtKB
  • protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: Reactome
  • reactive oxygen species metabolic process Source: UniProtKB
  • regulation of apoptotic process Source: Reactome
  • regulation of mitochondrial membrane permeability Source: UniProtKB
  • release of cytochrome c from mitochondria Source: InterPro
  • response to dsRNA Source: HGNC
  • T cell homeostasis Source: UniProtKB

Keywordsi

Biological processApoptosis

Enzyme and pathway databases

ReactomeiR-HSA-111448 Activation of NOXA and translocation to mitochondria
R-HSA-111453 BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
R-HSA-6803204 TP53 Regulates Transcription of Genes Involved in Cytochrome C Release
SIGNORiQ13794

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
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

EuPathDBiHostDB:ENSG00000141682.11
HGNCiHGNC:9108 PMAIP1
MIMi604959 gene
neXtProtiNX_Q13794

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

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi29L → A: Reduced interaction with BAX. 2 Publications1
Mutagenesisi29L → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-32 and E-32. 2 Publications1
Mutagenesisi32F → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-29 and E-36. 2 Publications1
Mutagenesisi32F → I: Alters specificity of protein interaction and enhances pro-apoptotic activity; when associated with E-35. 2 Publications1
Mutagenesisi35K → E: Alters specificity of protein interaction and enhances pro-apoptotic activity; when associated with I-32. 1 Publication1
Mutagenesisi36L → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-29 and E-32. 1 Publication1

Organism-specific databases

DisGeNETi5366
OpenTargetsiENSG00000141682
PharmGKBiPA33434

Polymorphism and mutation databases

BioMutaiPMAIP1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000646441 – 54Phorbol-12-myristate-13-acetate-induced protein 1Add BLAST54

Proteomic databases

EPDiQ13794
MaxQBiQ13794
PaxDbiQ13794
PeptideAtlasiQ13794
PRIDEiQ13794

PTM databases

iPTMnetiQ13794
PhosphoSitePlusiQ13794

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

BgeeiENSG00000141682
CleanExiHS_PMAIP1
ExpressionAtlasiQ13794 baseline and differential
GenevisibleiQ13794 HS

Organism-specific databases

HPAiHPA051063

Interactioni

Subunit structurei

Interacts with MCL1, BCL2A1 and BAX.5 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi111379, 11 interactors
CORUMiQ13794
IntActiQ13794, 12 interactors
MINTiQ13794
STRINGi9606.ENSP00000326119

Structurei

Secondary structure

154
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi21 – 40Combined sources20

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiQ13794

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni41 – 50Required for mitochondrial location10

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi29 – 37BH39

Domaini

The BH3 motif is essential for pro-apoptotic activity.

Sequence similaritiesi

Belongs to the PMAIP1 family.Curated

Phylogenomic databases

eggNOGiENOG410J6XT Eukaryota
ENOG4111AWA LUCA
GeneTreeiENSGT00530000065105
HOGENOMiHOG000034020
HOVERGENiHBG004273
InParanoidiQ13794
KOiK10131
OMAiWRQTELP
OrthoDBiEOG091G0V5H
PhylomeDBiQ13794

Family and domain databases

InterProiView protein in InterPro
IPR024140 Noxa
PANTHERiPTHR14299 PTHR14299, 1 hit
PfamiView protein in Pfam
PF15150 PMAIP1, 1 hit

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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05624720 – 54ELEVE…FCSGT → GPAGTAGTARDQAGFAIGMQ LRFTRGKKLLSSSLSSSPLA LPRGHEEQVQVAGSRVCYST QEIWRQTELPAETSESDIQT LLLRNLTASKTCMRGLLQKS FLRRCTFHQFEERLHCN in isoform 2. 1 PublicationAdd BLAST35

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.3 human [Q13794-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiAPR_HUMAN
AccessioniPrimary (citable) accession number: Q13794
Secondary accession number(s): B2R4T7, Q8N589
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1996
Last modified: March 28, 2018
This is version 134 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

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health