Q9JM54 (APR_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phorbol-12-myristate-13-acetate-induced protein 1

Alternative name(s):
Protein Noxa

Gene names

Name:	Pmaip1
Synonyms:	Noxa

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	103 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 BIM/BCL2L11 for binding to MCL1 and can displace BIM/BCL2L11 from its binding site on MCL1 By similarity. Competes with BAK1 for binding to MCL1 and can displace BAK1 from its binding site on MCL1. Ref.1 Ref.4 Ref.5 Ref.6 Ref.7
Subunit structure	Interacts with MCL1 and BAX By similarity. Ref.1 Ref.4 Ref.5 Ref.7
Subcellular location	Mitochondrion Ref.1.
Tissue specificity	Detected in thymocytes after irradiation with X-rays. Not detectable in untreated thymocytes (at protein level). Detected in embryonic neural precursor cells of the telencephalon Constitutively expressed at low levels in adult brain, testis, thymus, spleen, lung and kidney. Ref.6
Induction	Up-regulated after exposure to ionizing radiation and other genotoxic agents. Up-regulation is mediated by p53. Ref.6
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
Domain	Repeat
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	T cell homeostasis Inferred from mutant phenotype. Source: UniProtKB activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay. Source: UniProtKB negative regulation of fibroblast proliferation Inferred from mutant phenotype. Source: MGI negative regulation of mitochondrial membrane potential Inferred from direct assay. Source: UniProtKB positive regulation of DNA damage response, signal transduction by p53 class mediator Inferred from mutant phenotype. Source: UniProtKB positive regulation of neuron apoptosis Inferred from mutant phenotype. Source: MGI protein insertion into mitochondrial membrane involved in induction of apoptosis Inferred from mutant phenotype. Source: MGI release of cytochrome c from mitochondria Inferred from direct assay. Source: UniProtKB response to DNA damage stimulus Inferred from mutant phenotype. Source: MGI response to UV Inferred from mutant phenotype. Source: MGI response to X-ray Inferred from mutant phenotype. Source: MGI signal transduction by p53 class mediator resulting in induction of apoptosis Inferred from mutant phenotype. Source: UniProtKB
Cellular component	mitochondrion Inferred from direct assay Ref.1. Source: MGI
Molecular function	protein binding Inferred from physical interaction Ref.5. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MCL1	Q07820	2	EBI-709183,EBI-1003422	From a different organism.
Mcl1	P97287	2	EBI-709183,EBI-707292

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 103

103

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

PRO_0000333230

Regions

Region

90 – 99

10

Required for mitochondrial location By similarity

Motif

27 – 35

9

BH3 1

Motif

78 – 86

9

BH3 2

Experimental info

Mutagenesis

27

1

L → A: Loss of pro-apoptotic activity and of targeting to mitochondria; when associated with A-78. Ref.1

Mutagenesis

78

1

L → A: Loss of pro-apoptotic activity and of targeting to mitochondria; when associated with A-27. Ref.1

Secondary structure

1

.

.

.

103

Helix Strand Turn

Details...

Helix

71 – 93

23

Sequences

	Sequence		Length	Mass (Da)
	Q9JM54 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 9B9A5B04D5535E30	FASTA	103	11,566
	10 20 30 40 50 60 MPGRKARRNA PVNPTRAELP PEFAAQLRKI GDKVYCTWSA PDITVVLAQM PGKSQKSRMR 70 80 90 100 SPSPTRVPAD LKDECAQLRR IGDKVNLRQK LLNLISKLFN LVT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH MCL1, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF LEU-27 AND LEU-78.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Brain cortex, Dendritic cell, Kidney and Thymus.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Limb.
[4]	"Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins." Willis S.N., Chen L., Dewson G., Wei A., Naik E., Fletcher J.I., Adams J.M., Huang D.C.S. Genes Dev. 19:1294-1305(2005) [PubMed: 15901672] [Abstract] Cited for: FUNCTION, INTERACTION WITH MCL1.
[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, INTERACTION WITH MCL1.
[6]	"BH3-only proapoptotic Bcl-2 family members Noxa and Puma mediate neural precursor cell death." Akhtar R.S., Geng Y., Klocke B.J., Latham C.B., Villunger A., Michalak E.M., Strasser A., Carroll S.L., Roth K.A. J. Neurosci. 26:7257-7264(2006) [PubMed: 16822983] [Abstract] Cited for: FUNCTION, INDUCTION, TISSUE SPECIFICITY.
[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: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 68-93 IN COMPLEX WITH MCL1, STRUCTURE BY NMR OF 68-94 IN COMPLEX WITH MCL1, FUNCTION, MASS SPECTROMETRY, INTERACTION WITH MCL1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB041230 mRNA. Translation: BAA95781.1.
AK043856 mRNA. Translation: BAC31682.1.
AK088556 mRNA. Translation: BAC40421.1.
AK143990 mRNA. Translation: BAE25650.1.
AK169914 mRNA. Translation: BAE41454.1.
BC050821 mRNA. Translation: AAH50821.1.

IPI

IPI00124757.

RefSeq

NP_067426.1. NM_021451.2.

UniGene

Mm.271878.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JM6	NMR	-	A	68-93	[»]
2NLA	X-ray	2.80	B	68-93	[»]
2ROD	NMR	-	B	17-42	[»]

ProteinModelPortal

Q9JM54.

SMR

Q9JM54. Positions 17-43, 68-94.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9JM54. 2 interactions.

STRING

Q9JM54.

PTM databases

PhosphoSite

Q9JM54.

Proteomic databases

PRIDE

Q9JM54.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000025399; ENSMUSP00000025399; ENSMUSG00000024521.

GeneID

58801.

KEGG

mmu:58801.

UCSC

uc008fft.1. mouse.

Organism-specific databases

CTD

5366.

MGI

MGI:1930146. Pmaip1.

Phylogenomic databases

eggNOG

maNOG21706.

GeneTree

ENSGT00530000065105.

HOVERGEN

HBG095669.

InParanoid

Q9JM54.

OMA

RKARRNA.

OrthoDB

EOG4QC16X.

Gene expression databases

ArrayExpress

Q9JM54.

Bgee

Q9JM54.

Genevestigator

Q9JM54.

Family and domain databases

InterPro

IPR024140. PMA-induced_Noxa.
[Graphical view]

KO

K10131.

PANTHER

PTHR14299. PTHR14299. 1 hit.

PROSITE

PS01259. BH3. False negative.
[Graphical view]

ProtoNet

Search...

Other

NextBio

314374.

SOURCE

Search...

Entry information

Entry name

APR_MOUSE

Accession

Primary (citable) accession number: Q9JM54

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 20, 2008
Last sequence update:	October 1, 2000
Last modified:	November 16, 2011
This is version 83 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program