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Q13794 (APR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:PMAIP1
Synonyms:NOXA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length54 AA.
Sequence statusComplete.
Protein existenceEvidence 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/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. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8

Subunit structure

Interacts with MCL1, BCL2A1 and BAX. Ref.5 Ref.6 Ref.7 Ref.8

Subcellular location

Mitochondrion Ref.5 Ref.7.

Tissue specificity

Highly expressed in adult T-cell leukemia cell line.

Induction

Up-regulated by p53/TP53, phorbol esters, double-stranded RNA, IFNB1/IFN-beta and viruses. Ref.4 Ref.5 Ref.7

Domain

The BH3 motif is essential for pro-apoptotic activity.

Sequence similarities

Belongs to the PMAIP1 family.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentMitochondrion
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

activation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from electronic annotation. Source: Ensembl

apoptotic process

Inferred from mutant phenotype PubMed 17599062. Source: MGI

cellular response to glucose starvation

Inferred from mutant phenotype PubMed 21145489. Source: UniProtKB

cellular response to hypoxia

Inferred from expression pattern PubMed 14699081PubMed 20810912. Source: UniProtKB

defense response to virus

Inferred from direct assay Ref.5. Source: BHF-UCL

intrinsic apoptotic signaling pathway

Inferred from direct assay PubMed 14500711. Source: UniProtKB

intrinsic apoptotic signaling pathway by p53 class mediator

Inferred from mutant phenotype PubMed 15102863. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

Inferred from electronic annotation. Source: Ensembl

negative regulation of fibroblast proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of mitochondrial membrane potential

Inferred from sequence or structural similarity PubMed 14699081. Source: UniProtKB

positive regulation of DNA damage response, signal transduction by p53 class mediator

Inferred from mutant phenotype PubMed 15102863. Source: UniProtKB

positive regulation of apoptotic process

Inferred from direct assay PubMed 21145489. Source: UniProtKB

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 14699081. Source: UniProtKB

positive regulation of extrinsic apoptotic signaling pathway via death domain receptors

Inferred from direct assay Ref.5. Source: BHF-UCL

positive regulation of glucose metabolic process

Inferred from direct assay PubMed 21145489. Source: UniProtKB

positive regulation of intrinsic apoptotic signaling pathway

Inferred from direct assay PubMed 21454712. Source: UniProtKB

positive regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway

Traceable author statement. Source: Reactome

positive regulation of protein oligomerization

Inferred from direct assay PubMed 17024184. Source: UniProtKB

positive regulation of release of cytochrome c from mitochondria

Inferred from direct assay PubMed 14500711PubMed 14699081Ref.5. Source: UniProtKB

proteasomal protein catabolic process

Inferred from direct assay PubMed 15901672. Source: UniProtKB

reactive oxygen species metabolic process

Inferred from direct assay PubMed 14699081. Source: UniProtKB

regulation of mitochondrial membrane permeability

Inferred from direct assay PubMed 14500711. Source: UniProtKB

release of cytochrome c from mitochondria

Inferred from electronic annotation. Source: Ensembl

response to UV

Inferred from electronic annotation. Source: Ensembl

response to X-ray

Inferred from electronic annotation. Source: Ensembl

response to dsRNA

Inferred from direct assay Ref.5. Source: HGNC

   Cellular_componentcytosol

Inferred from direct assay PubMed 21145489. Source: UniProtKB

mitochondrial outer membrane

Traceable author statement. Source: Reactome

mitochondrion

Inferred from direct assay PubMed 14500711PubMed 15102863PubMed 21145489. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 12879012. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 5454Phorbol-12-myristate-13-acetate-induced protein 1
PRO_0000064644

Regions

Region41 – 5010Required for mitochondrial location
Motif29 – 379BH3

Experimental info

Mutagenesis291L → A: Reduced interaction with BAX. Ref.5 Ref.8
Mutagenesis291L → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-32 and E-32. Ref.5 Ref.8
Mutagenesis321F → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-29 and E-36. Ref.6 Ref.8
Mutagenesis321F → I: Alters specificity of protein interaction and enhances pro-apoptotic activity; when associated with E-35. Ref.6 Ref.8
Mutagenesis351K → E: Alters specificity of protein interaction and enhances pro-apoptotic activity; when associated with I-32. Ref.6
Mutagenesis361L → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-29 and E-32. Ref.8

Secondary structure

... 54
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q13794 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 291A142B27167E70

FASTA546,030
        10         20         30         40         50 
MPGKKARKNA QPSPARAPAE LEVECATQLR RFGDKLNFRQ KLLNLISKLF CSGT 

« Hide

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] [Europe PMC] [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. expand/collapse author list , 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].
[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION BY 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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF LEU-29; PHE-32 AND LEU-36, INTERACTION WITH MCL1.
[9]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D90070 mRNA. Translation: BAA14111.1.
AK311943 mRNA. Translation: BAG34884.1.
BC013120 mRNA. Translation: AAH13120.1.
PIRI37018.
RefSeqNP_066950.1. NM_021127.2.
UniGeneHs.96.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3MQPX-ray2.24B19-43[»]
ProteinModelPortalQ13794.
SMRQ13794. Positions 18-45.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111379. 12 interactions.
IntActQ13794. 10 interactions.
MINTMINT-1391244.
STRING9606.ENSP00000326119.

PTM databases

PhosphoSiteQ13794.

Proteomic databases

PRIDEQ13794.

Protocols and materials databases

DNASU5366.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000316660; ENSP00000326119; ENSG00000141682.
GeneID5366.
KEGGhsa:5366.
UCSCuc002lic.2. human.

Organism-specific databases

CTD5366.
GeneCardsGC18P057540.
HGNCHGNC:9108. PMAIP1.
MIM604959. gene.
neXtProtNX_Q13794.
PharmGKBPA33434.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG119326.
HOGENOMHOG000034020.
HOVERGENHBG004273.
KOK10131.
OrthoDBEOG7PP59Z.
PhylomeDBQ13794.

Enzyme and pathway databases

ReactomeREACT_578. Apoptosis.

Gene expression databases

ArrayExpressQ13794.
BgeeQ13794.
CleanExHS_PMAIP1.
GenevestigatorQ13794.

Family and domain databases

InterProIPR024140. Noxa.
[Graphical view]
PANTHERPTHR14299. PTHR14299. 1 hit.
PfamPF15150. PMAIP1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ13794.
GeneWikiPhorbol-12-myristate-13-acetate-induced_protein_1.
GenomeRNAi5366.
NextBio20800.
PROQ13794.
SOURCESearch...

Entry information

Entry nameAPR_HUMAN
AccessionPrimary (citable) accession number: Q13794
Secondary accession number(s): B2R4T7
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM