Reviewed, UniProtKB/Swiss-Prot Q13794 (APR_HUMAN)

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

Name:	PMAIP1
Synonyms:	NOXA

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	Interacts with MCL1 and BAX.
Subcellular location	Mitochondrion.
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.
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	caspase activation Ref.4 Inferred from direct assay. Source: HGNC cell structure disassembly during apoptosis Ref.4 Inferred from direct assay. Source: HGNC induction of apoptosis Ref.4 Inferred from direct assay. Source: HGNC release of cytochrome c from mitochondria Ref.4 Inferred from direct assay. Source: HGNC response to dsRNA Ref.4 Inferred from direct assay. Source: HGNC virus-infected cell apoptosis Ref.4 Inferred from direct assay. Source: HGNC
Cellular component	mitochondrion Ref.4 Inferred from direct assay. Source: HGNC
Molecular function	protein binding Ref.4 Ref.5 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
	Mutagenesis	29	1	L → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-32 and E-32
	Mutagenesis	32	1	F → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-29 and E-36
	Mutagenesis	32	1	F → I: Alters specificity of protein interaction and enhances pro-apoptotic activity; when associated with E-35
	Mutagenesis	35	1	K → E: Alters specificity of protein interaction and enhances pro-apoptotic activity; when associated with I-32
	Mutagenesis	36	1	L → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-29 and E-32

Sequences

	Sequence		Length	Mass (Da)
	Q13794-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 291A142B27167E70	FASTA	54	6,030
	10 20 30 40 50 MPGKKARKNA QPSPARAPAE LEVECATQLR RFGDKLNFRQ KLLNLISKLF CSGT

References

	« Hide 'large scale' referencesShow '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]	"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.
[3]	"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.
[4]	"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.
[5]	"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.
[6]	"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.
[7]	"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
EMBLGenBankDDBJ	D90070 mRNA. Translation: BAA14111.1. BC013120 mRNA. Translation: AAH13120.1.
PIR	I37018.
RefSeq	NP_066950.1.
UniGene	Hs.96
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13794.
Genome annotation databases
Ensembl	ENSG00000141682. Homo sapiens. [Contig view]
GeneID	5366.
KEGG	hsa:5366.
Organism-specific databases
H-InvDB	HIX0014485.
HGNC	HGNC:9108. PMAIP1.
MIM	604959. gene.
PharmGKB	PA33434.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	Q13794.
Enzyme and pathway databases
Reactome	REACT_578. Apoptosis.
Gene expression databases
ArrayExpress	Q13794.
CleanEx	HS_PMAIP1.
GermOnline	ENSG00000141682. Homo sapiens.
Family and domain databases
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

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	November 1, 1996
Last modified:	November 4, 2008
This is version 54 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)