PTTG1_MOUSE
ID PTTG1_MOUSE Reviewed; 199 AA.
AC Q9CQJ7; O88887; Q9Z2E6;
DT 25-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Securin;
DE AltName: Full=Pituitary tumor-transforming gene 1 protein;
GN Name=Pttg1; Synonyms=Pttg;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND MUTAGENESIS OF PRO-142.
RX PubMed=10713046; DOI=10.1074/jbc.275.11.7459;
RA Wang Z., Melmed S.;
RT "Pituitary tumor transforming gene (PTTG) transforming and transactivation
RT activity.";
RL J. Biol. Chem. 275:7459-7461(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Kidney, Stomach, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N;
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 [4]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10727870; DOI=10.1016/s0925-4773(00)00243-4;
RA Tarabykin V., Britanova O., Fradkov A., Voss A., Katz L.S., Lukyanov S.,
RA Gruss P.;
RT "Expression of PTTG and prc1 genes during telencephalic neurogenesis.";
RL Mech. Dev. 92:301-304(2000).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-162, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-162, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Regulatory protein, which plays a central role in chromosome
CC stability, in the p53/TP53 pathway, and DNA repair. Probably acts by
CC blocking the action of key proteins. During the mitosis, it blocks
CC Separase/ESPL1 function, preventing the proteolysis of the cohesin
CC complex and the subsequent segregation of the chromosomes. At the onset
CC of anaphase, it is ubiquitinated, conducting to its destruction and to
CC the liberation of ESPL1. Its function is however not limited to a
CC blocking activity, since it is required to activate ESPL1. Negatively
CC regulates the transcriptional activity and related apoptosis activity
CC of p53/TP53. The negative regulation of p53/TP53 may explain the strong
CC transforming capability of the protein when it is overexpressed. May
CC also play a role in DNA repair via its interaction with Ku, possibly by
CC connecting DNA damage-response pathways with sister chromatid
CC separation (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with RPS10 and DNAJA1. Interacts with the caspase-
CC like ESPL1, and prevents its protease activity probably by covering its
CC active site. Interacts with p53/TP53 and blocks its activity probably
CC by blocking its binding to DNA. Interacts with the Ku 70 kDa subunit of
CC ds-DNA kinase. Interacts with PTTG1IP (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9CQJ7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9CQJ7-2; Sequence=VSP_006998, VSP_006999;
CC -!- DEVELOPMENTAL STAGE: During the stages 11.5-13.5 dpc it is expressed in
CC most tissues of the embryo. Within the telencephalon, it is exclusively
CC expressed inside of the ventricular zone (VZ). The expression reaches
CC its peak by 15.5 dpc and starts to decrease by 18.5 dpc, and is not
CC detectable in the adult brains. Most of the cells expressing it were
CC found in the lower part of the ventricular zone.
CC {ECO:0000269|PubMed:10727870}.
CC -!- DOMAIN: The N-terminal destruction box (D-box) acts as a recognition
CC signal for degradation via the ubiquitin-proteasome pathway.
CC {ECO:0000250}.
CC -!- DOMAIN: The TEK-boxes are required for 'Lys-11'-linked ubiquitination
CC and facilitate the transfer of the first ubiquitin and ubiquitin chain
CC nucleation. TEK-boxes may direct a catalytically competent orientation
CC of the UBE2C/UBCH10-ubiquitin thioester with the acceptor lysine
CC residue (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated at Ser-162 by CDC2 during mitosis. {ECO:0000250}.
CC -!- PTM: Phosphorylated in vitro by ds-DNA kinase. {ECO:0000250}.
CC -!- PTM: Ubiquitinated through 'Lys-11' linkage of ubiquitin moieties by
CC the anaphase promoting complex (APC) at the onset of anaphase,
CC conducting to its degradation. 'Lys-11'-linked ubiquitination is
CC mediated by the E2 ligase UBE2C/UBCH10 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the securin family. {ECO:0000305}.
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DR EMBL; AF069051; AAC62954.1; -; mRNA.
DR EMBL; AF071209; AAC83236.1; -; mRNA.
DR EMBL; AK002473; BAB22127.1; -; mRNA.
DR EMBL; AK008704; BAB25844.1; -; mRNA.
DR EMBL; AK088387; BAC40321.1; -; mRNA.
DR EMBL; BC023324; AAH23324.1; -; mRNA.
DR CCDS; CCDS24556.1; -. [Q9CQJ7-2]
DR CCDS; CCDS48771.1; -. [Q9CQJ7-1]
DR RefSeq; NP_001124526.1; NM_001131054.1. [Q9CQJ7-1]
DR RefSeq; NP_038945.2; NM_013917.2. [Q9CQJ7-2]
DR RefSeq; XP_006533578.1; XM_006533515.3.
DR RefSeq; XP_006533579.1; XM_006533516.3. [Q9CQJ7-1]
DR AlphaFoldDB; Q9CQJ7; -.
DR SMR; Q9CQJ7; -.
DR BioGRID; 206016; 1.
DR IntAct; Q9CQJ7; 1.
DR STRING; 10090.ENSMUSP00000020687; -.
DR iPTMnet; Q9CQJ7; -.
DR PhosphoSitePlus; Q9CQJ7; -.
DR EPD; Q9CQJ7; -.
DR jPOST; Q9CQJ7; -.
DR MaxQB; Q9CQJ7; -.
DR PaxDb; Q9CQJ7; -.
DR PRIDE; Q9CQJ7; -.
DR ProteomicsDB; 301886; -. [Q9CQJ7-1]
DR ProteomicsDB; 301887; -. [Q9CQJ7-2]
DR DNASU; 30939; -.
DR Ensembl; ENSMUST00000020685; ENSMUSP00000020685; ENSMUSG00000020415. [Q9CQJ7-2]
DR Ensembl; ENSMUST00000020687; ENSMUSP00000020687; ENSMUSG00000020415. [Q9CQJ7-1]
DR Ensembl; ENSMUST00000101340; ENSMUSP00000098894; ENSMUSG00000020415. [Q9CQJ7-1]
DR Ensembl; ENSMUST00000117446; ENSMUSP00000112841; ENSMUSG00000020415. [Q9CQJ7-2]
DR Ensembl; ENSMUST00000118368; ENSMUSP00000112834; ENSMUSG00000020415. [Q9CQJ7-1]
DR Ensembl; ENSMUST00000121638; ENSMUSP00000112815; ENSMUSG00000020415. [Q9CQJ7-1]
DR GeneID; 30939; -.
DR KEGG; mmu:30939; -.
DR UCSC; uc007imn.2; mouse. [Q9CQJ7-2]
DR UCSC; uc011xth.1; mouse. [Q9CQJ7-1]
DR CTD; 9232; -.
DR MGI; MGI:1353578; Pttg1.
DR VEuPathDB; HostDB:ENSMUSG00000020415; -.
DR eggNOG; ENOG502S2GG; Eukaryota.
DR GeneTree; ENSGT00390000009693; -.
DR HOGENOM; CLU_1363209_0_0_1; -.
DR InParanoid; Q9CQJ7; -.
DR OMA; SWESNLL; -.
DR OrthoDB; 1296347at2759; -.
DR PhylomeDB; Q9CQJ7; -.
DR TreeFam; TF330797; -.
DR Reactome; R-MMU-174154; APC/C:Cdc20 mediated degradation of Securin.
DR Reactome; R-MMU-174178; APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
DR Reactome; R-MMU-2467813; Separation of Sister Chromatids.
DR BioGRID-ORCS; 30939; 3 hits in 110 CRISPR screens.
DR ChiTaRS; Pttg1; mouse.
DR PRO; PR:Q9CQJ7; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9CQJ7; protein.
DR Bgee; ENSMUSG00000020415; Expressed in ciliary body and 253 other tissues.
DR ExpressionAtlas; Q9CQJ7; baseline and differential.
DR Genevisible; Q9CQJ7; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IDA:MGI.
DR GO; GO:0031072; F:heat shock protein binding; ISO:MGI.
DR GO; GO:0043022; F:ribosome binding; ISO:MGI.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007059; P:chromosome segregation; IGI:MGI.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0045143; P:homologous chromosome segregation; IDA:MGI.
DR GO; GO:0007064; P:mitotic sister chromatid cohesion; IGI:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:2000816; P:negative regulation of mitotic sister chromatid separation; IBA:GO_Central.
DR GO; GO:0001558; P:regulation of cell growth; ISO:MGI.
DR InterPro; IPR006940; Securin_separation_inhibitor.
DR PANTHER; PTHR10418; PTHR10418; 1.
DR Pfam; PF04856; Securin; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell cycle; Cell division;
KW Chromosome partition; Cytoplasm; DNA damage; DNA repair; Mitosis; Nucleus;
KW Phosphoprotein; Proto-oncogene; Reference proteome; Repeat; SH3-binding;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O95997"
FT CHAIN 2..199
FT /note="Securin"
FT /id="PRO_0000206362"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 68..105
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 58..61
FT /note="D-box"
FT MOTIF 68..70
FT /note="TEK-box 1"
FT MOTIF 91..93
FT /note="TEK-box 2"
FT MOTIF 179..192
FT /note="SH3-binding"
FT COMPBIAS 79..102
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O95997"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT VAR_SEQ 174..188
FT /note="DPLYSPPSALSTLDV -> GKGVRSNSGCKQLVT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10713046"
FT /id="VSP_006998"
FT VAR_SEQ 189..199
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10713046"
FT /id="VSP_006999"
FT MUTAGEN 142
FT /note="P->A,L: Strongly reduces transactivation and
FT transforming capability."
FT /evidence="ECO:0000269|PubMed:10713046"
FT CONFLICT 16
FT /note="R -> S (in Ref. 3; AAH23324)"
FT /evidence="ECO:0000305"
FT CONFLICT 28
FT /note="T -> S (in Ref. 3; AAH23324)"
FT /evidence="ECO:0000305"
FT CONFLICT 29
FT /note="G -> S (in Ref. 1; AAC83236)"
FT /evidence="ECO:0000305"
FT CONFLICT 53
FT /note="V -> L (in Ref. 3; AAH23324)"
FT /evidence="ECO:0000305"
FT CONFLICT 122..124
FT /note="Missing (in Ref. 1; AAC62954)"
FT /evidence="ECO:0000305"
FT CONFLICT 129
FT /note="E -> G (in Ref. 1; AAC83236)"
FT /evidence="ECO:0000305"
FT CONFLICT 144
FT /note="M -> I (in Ref. 1; AAC62954)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 199 AA; 21725 MW; 82E6A39B8B96F853 CRC64;
MATLIFVDKD NEEPGRRLAS KDGLKLGTGV KALDGKLQVS TPRVGKVFNA PAVPKASRKA
LGTVNRVAEK PMKTGKPLQP KQPTLTGKKI TEKSTKTQSS VPAPDDAYPE IEKFFPFNPL
DFESFDLPEE HQISLLPLNG VPLMTLNEER GLEKLLHLGP PSPLKTPFLS WESDPLYSPP
SALSTLDVEL PPVCYDADI
