Q96A56 (T53I1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tumor protein p53-inducible nuclear protein 1

Alternative name(s):
Stress-induced protein
p53-dependent damage-inducible nuclear protein 1
Short name=p53DINP1

Gene names

Name:	TP53INP1
Synonyms:	P53DINP1, SIP

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	240 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Antiproliferative and proapoptotic protein involved in cell stress response which acts as a dual regulator of transcription and autophagy. Acts as a positive regulator of autophagy. In response to cellular stress or activation of autophagy, relocates to autophagosomes where it interacts with autophagosome-associated proteins GABARAP, GABARAPL1/L2, MAP1LC3A/B/C and regulates autophagy. Acts as an antioxidant and plays a major role in p53/TP53-driven oxidative stress response. Possesses both a p53/TP53-independent intracellular reactive oxygen species (ROS) regulatory function and a p53/TP53-dependent transcription regulatory function. Positively regulates p53/TP53 and p73/TP73 and stimulates their capacity to induce apoptosis and regulate cell cycle. In response to double-strand DNA breaks, promotes p53/TP53 phosphorylation on 'Ser-46' and subsequent apoptosis. Acts as a tumor suppressor by inducing cell death by an autophagy and caspase-dependent mechanism. Can reduce cell migration by regulating the expression of SPARC. Ref.1 Ref.8 Ref.9
Subunit structure	Interacts with p53/TP53 and HIPK2. Interacts with PRKCG, GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3B AND MAP1LC3C. Ref.6 Ref.7 Ref.8 Ref.9
Subcellular location	Cytoplasm › cytosol. Nucleus. Nucleus › PML body. Cytoplasmic vesicle › autophagosome. Note: Shuttles between the nucleus and the cytoplasm, depending on cellular stress conditions, and re-localizes to autophagosomes on autophagy activation. Ref.1 Ref.6 Ref.9
Tissue specificity	Ubiquitously expressed. Ref.1 Ref.2
Induction	By adriamycin, gamma irradiation and H2O2, in a p53/TP53-dependent way. At lower levels by UV irradiation. By TP73. Ref.1 Ref.2
Domain	The LC3 interacting region (LIR) motif mediates interaction with GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3B and MAP1LC3C.

Ontologies

Keywords
Biological process	Apoptosis Autophagy Transcription Transcription regulation
Cellular component	Cytoplasm Cytoplasmic vesicle Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Tumor suppressor
Molecular function	Activator Antioxidant
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW autophagic cell death Inferred from mutant phenotype Ref.8. Source: UniProtKB autophagy Inferred from electronic annotation. Source: UniProtKB-KW cell cycle arrest Traceable author statement Ref.8. Source: UniProtKB induction of apoptosis Inferred from electronic annotation. Source: Compara negative regulation of cell migration Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of autophagy Inferred from mutant phenotype Ref.8Ref.9. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from direct assay Ref.9. Source: UniProtKB response to stress Traceable author statement Ref.8. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	PML body Inferred from electronic annotation. Source: UniProtKB-SubCell autophagic vacuole Inferred from direct assay Ref.8Ref.9. Source: UniProtKB cytoplasmic vesicle Inferred from electronic annotation. Source: UniProtKB-KW cytosol Inferred from direct assay Ref.9. Source: UniProtKB nucleus Inferred from direct assay Ref.9. Source: UniProtKB
Molecular_function	antioxidant activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96A56-1)

Also known as: p53DINP1a; alpha; SIP27; TEAP;

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.

Isoform 2 (identifier: Q96A56-2)

Also known as: p53DINP1b; beta; SIP18;

The sequence of this isoform differs from the canonical sequence as follows:
     159-240: VEAQNEMGQH...HQPCPRQYNY → ARKSCL

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 240	240	Tumor protein p53-inducible nuclear protein 1		PRO_0000072406
Regions
	Motif	25 – 37	13	LIR
	Compositional bias	14 – 17	4	Poly-Ser
	Compositional bias	20 – 61	42	Glu-rich
Natural variations
	Alternative sequence	159 – 240	82	VEAQN…RQYNY → ARKSCL in isoform 2.		VSP_013176
	Natural variant	75	1	C → R. Corresponds to variant rs11991800 [ dbSNP | Ensembl ].		VAR_051404

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (p53DINP1a) (alpha) (SIP27) (TEAP) [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 1950D66EDDB4A186	FASTA	240	27,366
	10 20 30 40 50 60 MFQRLNKMFV GEVSSSSNQE PEFNEKEDDE WILVDFIDTC TGFSAEEEEE EEDISEESPT 70 80 90 100 110 120 EHPSVFSCLP ASLECLADTS DSCFLQFESC PMEESWFITP PPCFTAGGLT TIKVETSPME 130 140 150 160 170 180 NLLIEHPSMS VYAVHNSCPG LSEATRGTDE LHSPSSPRVE AQNEMGQHIH CYVAALAAHT 190 200 210 220 230 240 TFLEQPKSFR PSQWIKEHSE RQPLNRNSLR RQNLTRDCHP RQVKHNGWVV HQPCPRQYNY
	Isoform 2 (p53DINP1b) (beta) (SIP18) [UniParc]. Checksum: 8C5B27F2CFB47B8E	FASTA	164	18,244
	10 20 30 40 50 60 MFQRLNKMFV GEVSSSSNQE PEFNEKEDDE WILVDFIDTC TGFSAEEEEE EEDISEESPT 70 80 90 100 110 120 EHPSVFSCLP ASLECLADTS DSCFLQFESC PMEESWFITP PPCFTAGGLT TIKVETSPME 130 140 150 160 NLLIEHPSMS VYAVHNSCPG LSEATRGTDE LHSPSSPRAR KSCL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"p53DINP1, a p53-inducible gene, regulate p53-dependent apoptosis." Okamura S., Arakawa H., Tanaka T., Nakanishi H., Ng C.C., Taya Y., Monden M., Nakamura Y. Mol. Cell 8:85-94(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, FUNCTION. Tissue: Thymus.
[2]	"p53-dependent expression of the stress-induced protein (SIP)." Tomasini R., Azizi Samir A.L., Pebusque M.-J., Calvo E.L., Totaro S., Dagorn J.-C., Dusetti N.J., Iovanna J.L. Eur. J. Cell Biol. 81:294-301(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INDUCTION, TISSUE SPECIFICITY.
[3]	"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] (ISOFORM 1). Tissue: Trachea.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM 1). Tissue: Lung.
[6]	"TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activity." Tomasini R., Samir A.A., Carrier A., Isnardon D., Cecchinelli B., Soddu S., Malissen B., Dagorn J.-C., Iovanna J.L., Dusetti N.J. J. Biol. Chem. 278:37722-37729(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TP53 AND HIPK2, SUBCELLULAR LOCATION.
[7]	"Protein kinase C delta regulates Ser46 phosphorylation of p53 tumor suppressor in the apoptotic response to DNA damage." Yoshida K., Liu H., Miki Y. J. Biol. Chem. 281:5734-5740(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PRKCG.
[8]	"TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death." Seillier M., Peuget S., Gayet O., Gauthier C., N'guessan P., Monte M., Carrier A., Iovanna J.L., Dusetti N.J. Cell Death Differ. 19:1525-1535(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH GABARAP; GABARAPL2 AND MAP1LC3A.
[9]	"DOR/Tp53inp2 and Tp53inp1 constitute a metazoan gene family encoding dual regulators of autophagy and transcription." Sancho A., Duran J., Garcia-Espana A., Mauvezin C., Alemu E.A., Lamark T., Macias M.J., Desalle R., Royo M., Sala D., Chicote J.U., Palacin M., Johansen T., Zorzano A. PLoS ONE 7:E34034-E34034(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH GABARAP; GABARAPL1; GABARAPL2; MAP1LC3A; MAP1LC3B AND MAP1LC3C.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB017926 mRNA. Translation: BAB62149.1. AB017927 mRNA. Translation: BAB62150.1. AB062056 Genomic DNA. Translation: BAB62151.1. AB062056 Genomic DNA. Translation: BAB62152.1. AF409114 mRNA. Translation: AAL04513.1. AF409115 mRNA. Translation: AAL04514.1. AK315071 mRNA. Translation: BAG37542.1. CH471060 Genomic DNA. Translation: EAW91740.1. BC074813 mRNA. Translation: AAH74813.1. BC074868 mRNA. Translation: AAH74868.1.
IPI	IPI00059265. IPI00554684.
RefSeq	NP_001129205.1. NM_001135733.1. NP_150601.1. NM_033285.3.
UniGene	Hs.492261.
3D structure databases
ProteinModelPortal	Q96A56.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000344215.
Polymorphism databases
DMDM	61216823.
Proteomic databases
PRIDE	Q96A56.
Protocols and materials databases
DNASU	94241.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000342697; ENSP00000344215; ENSG00000164938. ENST00000448464; ENSP00000390063; ENSG00000164938.
GeneID	94241.
KEGG	hsa:94241.
UCSC	uc003yhg.3. human. uc003yhh.3. human.
Organism-specific databases
CTD	94241.
GeneCards	GC08M095938.
HGNC	HGNC:18022. TP53INP1.
HPA	HPA005856.
MIM	606185. gene.
neXtProt	NX_Q96A56.
PharmGKB	PA38278.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG39796.
HOGENOM	HOG000010288.
HOVERGEN	HBG055647.
InParanoid	Q96A56.
KO	K15310.
OMA	MFVGEVN.
OrthoDB	EOG451DRJ.
PhylomeDB	Q96A56.
Gene expression databases
ArrayExpress	Q96A56.
Bgee	Q96A56.
CleanEx	HS_TP53INP1.
Genevestigator	Q96A56.
GermOnline	ENSG00000164938. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other
ChiTaRS	TP53INP1. human.
GenomeRNAi	94241.
NextBio	78499.
SOURCE	Search...

Entry information

Entry name

T53I1_HUMAN

Accession

Primary (citable) accession number: Q96A56
Secondary accession number(s): B2RCE5, Q969R9

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	December 1, 2001
Last modified:	April 3, 2013
This is version 78 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.