Q13794 (APR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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
Protein Noxa

Gene names

Name:	PMAIP1
Synonyms:	NOXA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	54 AA.
Sequence status	Complete.
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/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 process	Apoptosis
Cellular component	Mitochondrion
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell homeostasis Inferred from sequence or structural similarity. Source: UniProtKB activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay Ref.5. Source: HGNC cellular component disassembly involved in execution phase of apoptosis Inferred from direct assay Ref.5. Source: HGNC 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 induction of apoptosis Inferred from direct assay PubMed 14500711. Source: UniProtKB intrinsic apoptotic signaling pathway by p53 class mediator Inferred from mutant phenotype PubMed 15102863. Source: UniProtKB negative regulation of fibroblast proliferation Inferred from electronic annotation. Source: Compara 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 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: Compara 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: Compara response to DNA damage stimulus Inferred from electronic annotation. Source: Compara response to UV Inferred from electronic annotation. Source: Compara response to X-ray Inferred from electronic annotation. Source: Compara response to dsRNA Inferred from direct assay Ref.5. Source: HGNC virus-infected cell apoptotic process Inferred from direct assay Ref.5. Source: HGNC
Cellular_component	cytosol Inferred from direct assay PubMed 21145489. Source: UniProtKB mitochondrial outer membrane Traceable author statement. Source: Reactome nucleus Inferred from direct assay PubMed 12879012. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCL2	P10415	3	EBI-707392,EBI-77694
BCL2	P10415-1	3	EBI-707392,EBI-4370304
MCL1	Q07820	4	EBI-707392,EBI-1003422

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. Ref.5 Ref.8

Mutagenesis

29

1

L → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-32 and E-32. Ref.5 Ref.8

Mutagenesis

32

1

F → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-29 and E-36. Ref.6 Ref.8

Mutagenesis

32

1

F → I: Alters specificity of protein interaction and enhances pro-apoptotic activity; when associated with E-35. Ref.6 Ref.8

Mutagenesis

35

1

K → E: Alters specificity of protein interaction and enhances pro-apoptotic activity; when associated with I-32. Ref.6

Mutagenesis

36

1

L → E: Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-29 and E-32. Ref.8

Secondary structure

1

.

.

.

54

Helix Strand Turn

Details...

Helix

21 – 40

20

Sequences

	Sequence		Length	Mass (Da)
	Q13794 [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] [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. , 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, 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.

IPI

IPI00015177.

PIR

I37018.

RefSeq

NP_066950.1. NM_021127.2.

UniGene

Hs.96.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3MQP	X-ray	2.24	B	19-43	[»]

ProteinModelPortal

Q13794.

SMR

Q13794. Positions 18-45.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13794. 7 interactions.

MINT

MINT-1391244.

STRING

9606.ENSP00000326119.

PTM databases

PhosphoSite

Q13794.

Proteomic databases

PRIDE

Q13794.

Protocols and materials databases

DNASU

5366.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000316660; ENSP00000326119; ENSG00000141682.

GeneID

5366.

KEGG

hsa:5366.

UCSC

uc002lic.2. human.

Organism-specific databases

CTD

5366.

GeneCards

GC18P057540.

HGNC

HGNC:9108. PMAIP1.

MIM

604959. gene.

neXtProt

NX_Q13794.

PharmGKB

PA33434.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG119326.

HOGENOM

HOG000034020.

HOVERGEN

HBG004273.

KO

K10131.

OrthoDB

EOG4QC16X.

Enzyme and pathway databases

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

Q13794.

Bgee

Q13794.

CleanEx

HS_PMAIP1.

Genevestigator

Q13794.

GermOnline

ENSG00000141682. Homo sapiens.

Family and domain databases

InterPro

IPR024140. PMA-induced_Noxa.
[Graphical view]

PANTHER

PTHR14299. PTHR14299. 1 hit.

PROSITE

PS01259. BH3. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q13794.

GenomeRNAi

5366.

NextBio

20800.

SOURCE

Search...

Entry information

Entry name

APR_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 93 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.