T53I1_HUMAN
ID T53I1_HUMAN Reviewed; 240 AA.
AC Q96A56; B2RCE5; Q969R9;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Tumor protein p53-inducible nuclear protein 1;
DE AltName: Full=Stress-induced protein;
DE AltName: Full=p53-dependent damage-inducible nuclear protein 1;
DE Short=p53DINP1;
GN Name=TP53INP1; Synonyms=P53DINP1, SIP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, INDUCTION, AND FUNCTION.
RC TISSUE=Thymus;
RX PubMed=11511362; DOI=10.1016/s1097-2765(01)00284-2;
RA Okamura S., Arakawa H., Tanaka T., Nakanishi H., Ng C.C., Taya Y.,
RA Monden M., Nakamura Y.;
RT "p53DINP1, a p53-inducible gene, regulate p53-dependent apoptosis.";
RL Mol. Cell 8:85-94(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INDUCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=12067065; DOI=10.1078/0171-9335-00248;
RA Tomasini R., Azizi Samir A.L., Pebusque M.-J., Calvo E.L., Totaro S.,
RA Dagorn J.-C., Dusetti N.J., Iovanna J.L.;
RT "p53-dependent expression of the stress-induced protein (SIP).";
RL Eur. J. Cell Biol. 81:294-301(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH TP53 AND HIPK2, AND SUBCELLULAR LOCATION.
RX PubMed=12851404; DOI=10.1074/jbc.m301979200;
RA Tomasini R., Samir A.A., Carrier A., Isnardon D., Cecchinelli B., Soddu S.,
RA Malissen B., Dagorn J.-C., Iovanna J.L., Dusetti N.J.;
RT "TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are
RT partners in regulating p53 activity.";
RL J. Biol. Chem. 278:37722-37729(2003).
RN [7]
RP INTERACTION WITH PRKCG.
RX PubMed=16377624; DOI=10.1074/jbc.m512074200;
RA Yoshida K., Liu H., Miki Y.;
RT "Protein kinase C delta regulates Ser46 phosphorylation of p53 tumor
RT suppressor in the apoptotic response to DNA damage.";
RL J. Biol. Chem. 281:5734-5740(2006).
RN [8]
RP FUNCTION, AND INTERACTION WITH GABARAP; GABARAPL2 AND MAP1LC3A.
RX PubMed=22421968; DOI=10.1038/cdd.2012.30;
RA Seillier M., Peuget S., Gayet O., Gauthier C., N'guessan P., Monte M.,
RA Carrier A., Iovanna J.L., Dusetti N.J.;
RT "TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins
RT through the LC3-interacting region (LIR) and promotes autophagy-dependent
RT cell death.";
RL Cell Death Differ. 19:1525-1535(2012).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH GABARAP; GABARAPL1;
RP GABARAPL2; MAP1LC3A; MAP1LC3B AND MAP1LC3C.
RX PubMed=22470510; DOI=10.1371/journal.pone.0034034;
RA Sancho A., Duran J., Garcia-Espana A., Mauvezin C., Alemu E.A., Lamark T.,
RA Macias M.J., Desalle R., Royo M., Sala D., Chicote J.U., Palacin M.,
RA Johansen T., Zorzano A.;
RT "DOR/Tp53inp2 and Tp53inp1 constitute a metazoan gene family encoding dual
RT regulators of autophagy and transcription.";
RL PLoS ONE 7:E34034-E34034(2012).
CC -!- FUNCTION: Antiproliferative and proapoptotic protein involved in cell
CC stress response which acts as a dual regulator of transcription and
CC autophagy. Acts as a positive regulator of autophagy. In response to
CC cellular stress or activation of autophagy, relocates to autophagosomes
CC where it interacts with autophagosome-associated proteins GABARAP,
CC GABARAPL1/L2, MAP1LC3A/B/C and regulates autophagy. Acts as an
CC antioxidant and plays a major role in p53/TP53-driven oxidative stress
CC response. Possesses both a p53/TP53-independent intracellular reactive
CC oxygen species (ROS) regulatory function and a p53/TP53-dependent
CC transcription regulatory function. Positively regulates p53/TP53 and
CC p73/TP73 and stimulates their capacity to induce apoptosis and regulate
CC cell cycle. In response to double-strand DNA breaks, promotes p53/TP53
CC phosphorylation on 'Ser-46' and subsequent apoptosis. Acts as a tumor
CC suppressor by inducing cell death by an autophagy and caspase-dependent
CC mechanism. Can reduce cell migration by regulating the expression of
CC SPARC. {ECO:0000269|PubMed:11511362, ECO:0000269|PubMed:22421968,
CC ECO:0000269|PubMed:22470510}.
CC -!- SUBUNIT: Interacts with p53/TP53 and HIPK2. Interacts with PRKCG,
CC GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3B AND MAP1LC3C.
CC {ECO:0000269|PubMed:12851404, ECO:0000269|PubMed:16377624,
CC ECO:0000269|PubMed:22421968, ECO:0000269|PubMed:22470510}.
CC -!- INTERACTION:
CC Q96A56; O95166: GABARAP; NbExp=3; IntAct=EBI-9986117, EBI-712001;
CC Q96A56; Q9H0R8: GABARAPL1; NbExp=9; IntAct=EBI-9986117, EBI-746969;
CC Q96A56; P60520: GABARAPL2; NbExp=6; IntAct=EBI-9986117, EBI-720116;
CC Q96A56; Q9BXW4: MAP1LC3C; NbExp=3; IntAct=EBI-9986117, EBI-2603996;
CC Q96A56; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-9986117, EBI-8652744;
CC Q96A56; Q13432: UNC119; NbExp=3; IntAct=EBI-9986117, EBI-711260;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Nucleus. Nucleus, PML body.
CC Cytoplasmic vesicle, autophagosome. Note=Shuttles between the nucleus
CC and the cytoplasm, depending on cellular stress conditions, and re-
CC localizes to autophagosomes on autophagy activation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=p53DINP1a, alpha, SIP27, TEAP;
CC IsoId=Q96A56-1; Sequence=Displayed;
CC Name=2; Synonyms=p53DINP1b, beta, SIP18;
CC IsoId=Q96A56-2; Sequence=VSP_013176;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:11511362, ECO:0000269|PubMed:12067065}.
CC -!- INDUCTION: By adriamycin, gamma irradiation and H(2)O(2), in a
CC p53/TP53-dependent way. At lower levels by UV irradiation. By TP73.
CC {ECO:0000269|PubMed:11511362, ECO:0000269|PubMed:12067065}.
CC -!- DOMAIN: The LC3 interacting region (LIR) motif mediates interaction
CC with GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3B and MAP1LC3C.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/TP53INP1ID42672ch8q22.html";
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DR EMBL; AB017926; BAB62149.1; -; mRNA.
DR EMBL; AB017927; BAB62150.1; -; mRNA.
DR EMBL; AB062056; BAB62151.1; -; Genomic_DNA.
DR EMBL; AB062056; BAB62152.1; -; Genomic_DNA.
DR EMBL; AF409114; AAL04513.1; -; mRNA.
DR EMBL; AF409115; AAL04514.1; -; mRNA.
DR EMBL; AK315071; BAG37542.1; -; mRNA.
DR EMBL; CH471060; EAW91740.1; -; Genomic_DNA.
DR EMBL; BC074813; AAH74813.1; -; mRNA.
DR EMBL; BC074868; AAH74868.1; -; mRNA.
DR CCDS; CCDS47899.1; -. [Q96A56-2]
DR CCDS; CCDS6265.1; -. [Q96A56-1]
DR RefSeq; NP_001129205.1; NM_001135733.1. [Q96A56-2]
DR RefSeq; NP_150601.1; NM_033285.3. [Q96A56-1]
DR RefSeq; XP_011515688.1; XM_011517386.2. [Q96A56-1]
DR AlphaFoldDB; Q96A56; -.
DR BioGRID; 125152; 33.
DR IntAct; Q96A56; 13.
DR STRING; 9606.ENSP00000344215; -.
DR iPTMnet; Q96A56; -.
DR PhosphoSitePlus; Q96A56; -.
DR BioMuta; TP53INP1; -.
DR DMDM; 61216823; -.
DR jPOST; Q96A56; -.
DR MassIVE; Q96A56; -.
DR PaxDb; Q96A56; -.
DR PeptideAtlas; Q96A56; -.
DR PRIDE; Q96A56; -.
DR ProteomicsDB; 75914; -. [Q96A56-1]
DR ProteomicsDB; 75915; -. [Q96A56-2]
DR Antibodypedia; 12951; 357 antibodies from 38 providers.
DR DNASU; 94241; -.
DR Ensembl; ENST00000342697.5; ENSP00000344215.4; ENSG00000164938.14. [Q96A56-1]
DR Ensembl; ENST00000448464.6; ENSP00000390063.2; ENSG00000164938.14. [Q96A56-2]
DR GeneID; 94241; -.
DR KEGG; hsa:94241; -.
DR MANE-Select; ENST00000342697.5; ENSP00000344215.4; NM_033285.4; NP_150601.1.
DR UCSC; uc003yhg.4; human. [Q96A56-1]
DR CTD; 94241; -.
DR DisGeNET; 94241; -.
DR GeneCards; TP53INP1; -.
DR HGNC; HGNC:18022; TP53INP1.
DR HPA; ENSG00000164938; Tissue enhanced (liver).
DR MIM; 606185; gene.
DR neXtProt; NX_Q96A56; -.
DR OpenTargets; ENSG00000164938; -.
DR PharmGKB; PA38278; -.
DR VEuPathDB; HostDB:ENSG00000164938; -.
DR eggNOG; ENOG502QTG4; Eukaryota.
DR GeneTree; ENSGT00530000063829; -.
DR HOGENOM; CLU_091034_1_0_1; -.
DR InParanoid; Q96A56; -.
DR OMA; TCHSLNE; -.
DR PhylomeDB; Q96A56; -.
DR TreeFam; TF333017; -.
DR PathwayCommons; Q96A56; -.
DR Reactome; R-HSA-6803204; TP53 Regulates Transcription of Genes Involved in Cytochrome C Release.
DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
DR SignaLink; Q96A56; -.
DR SIGNOR; Q96A56; -.
DR BioGRID-ORCS; 94241; 4 hits in 1082 CRISPR screens.
DR ChiTaRS; TP53INP1; human.
DR GeneWiki; TP53INP1; -.
DR GenomeRNAi; 94241; -.
DR Pharos; Q96A56; Tbio.
DR PRO; PR:Q96A56; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q96A56; protein.
DR Bgee; ENSG00000164938; Expressed in oviduct epithelium and 189 other tissues.
DR ExpressionAtlas; Q96A56; baseline and differential.
DR Genevisible; Q96A56; HS.
DR GO; GO:0005776; C:autophagosome; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0016209; F:antioxidant activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0048102; P:autophagic cell death; IMP:UniProtKB.
DR GO; GO:0000045; P:autophagosome assembly; IBA:GO_Central.
DR GO; GO:0071361; P:cellular response to ethanol; IEA:Ensembl.
DR GO; GO:0071447; P:cellular response to hydroperoxide; IEA:Ensembl.
DR GO; GO:0072703; P:cellular response to methyl methanesulfonate; IEA:Ensembl.
DR GO; GO:0034644; P:cellular response to UV; IEA:Ensembl.
DR GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:1904761; P:negative regulation of myofibroblast differentiation; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; TAS:UniProtKB.
DR GO; GO:0009408; P:response to heat; IEA:Ensembl.
DR InterPro; IPR029431; TP53INP.
DR InterPro; IPR029556; TP53INP1.
DR PANTHER; PTHR31671; PTHR31671; 1.
DR PANTHER; PTHR31671:SF0; PTHR31671:SF0; 1.
DR Pfam; PF14839; DOR; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Antioxidant; Apoptosis; Autophagy;
KW Cytoplasm; Cytoplasmic vesicle; Nucleus; Reference proteome; Transcription;
KW Transcription regulation; Tumor suppressor.
FT CHAIN 1..240
FT /note="Tumor protein p53-inducible nuclear protein 1"
FT /id="PRO_0000072406"
FT MOTIF 25..37
FT /note="LIR"
FT VAR_SEQ 159..240
FT /note="VEAQNEMGQHIHCYVAALAAHTTFLEQPKSFRPSQWIKEHSERQPLNRNSLR
FT RQNLTRDCHPRQVKHNGWVVHQPCPRQYNY -> ARKSCL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11511362,
FT ECO:0000303|PubMed:12067065"
FT /id="VSP_013176"
FT VARIANT 75
FT /note="C -> R (in dbSNP:rs11991800)"
FT /id="VAR_051404"
SQ SEQUENCE 240 AA; 27366 MW; 1950D66EDDB4A186 CRC64;
MFQRLNKMFV GEVSSSSNQE PEFNEKEDDE WILVDFIDTC TGFSAEEEEE EEDISEESPT
EHPSVFSCLP ASLECLADTS DSCFLQFESC PMEESWFITP PPCFTAGGLT TIKVETSPME
NLLIEHPSMS VYAVHNSCPG LSEATRGTDE LHSPSSPRVE AQNEMGQHIH CYVAALAAHT
TFLEQPKSFR PSQWIKEHSE RQPLNRNSLR RQNLTRDCHP RQVKHNGWVV HQPCPRQYNY
