ID   PTTG1_RAT               Reviewed;         199 AA.
AC   P97613;
DT   25-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   24-JAN-2024, entry version 143.
DE   RecName: Full=Securin;
DE   AltName: Full=Pituitary tumor-transforming gene 1 protein;
GN   Name=Pttg1; Synonyms=Pttg;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DISEASE.
RC   TISSUE=Pituitary tumor;
RX   PubMed=9092795; DOI=10.1210/mend.11.4.9911;
RA   Pei L., Melmed S.;
RT   "Isolation and characterization of a pituitary tumor-transforming gene
RT   (PTTG).";
RL   Mol. Endocrinol. 11:433-441(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9.
RC   STRAIN=Sprague-Dawley;
RX   PubMed=9478977; DOI=10.1074/jbc.273.9.5219;
RA   Pei L.;
RT   "Genomic organization and identification of an enhancer element containing
RT   binding sites for multiple proteins in rat pituitary tumor-transforming
RT   gene.";
RL   J. Biol. Chem. 273:5219-5225(1998).
RN   [3]
RP   TISSUE SPECIFICITY, AND INTERACTION WITH RPS10 AND DNAJA1.
RX   PubMed=9915854; DOI=10.1074/jbc.274.5.3151;
RA   Pei L.;
RT   "Pituitary tumor-transforming gene protein associates with ribosomal
RT   protein S10 and a novel human homologue of DnaJ in testicular cells.";
RL   J. Biol. Chem. 274:3151-3158(1999).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-162, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
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 the caspase-like ESPL1, and prevents its
CC       protease activity by covering its active site. Interacts with p53/TP53
CC       and blocks its activity probably by blocking its binding to DNA.
CC       Interacts with the Ku 70 kDa subunit of ds-DNA kinase. Interacts with
CC       PTTG1IP (By similarity). Interacts with RPS10 and DNAJA1. {ECO:0000250,
CC       ECO:0000269|PubMed:9915854}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed at low level in most tissues, except in
CC       adult testis, where it is highly expressed. Expressed in both
CC       spermatocytes and spermatids. {ECO:0000269|PubMed:9092795,
CC       ECO:0000269|PubMed:9915854}.
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 CDK1 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   -!- DISEASE: Note=Has strong transforming capabilities on a variety of cell
CC       lines including NIH 3T3 fibroblasts and on athymic nude mice.
CC       Overexpressed in animals suffering from pituitary adenomas. The
CC       transforming capability may be due to its interaction and regulation of
CC       p53/TP53 pathway. {ECO:0000269|PubMed:9092795}.
CC   -!- SIMILARITY: Belongs to the securin family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; U73030; AAB47974.1; -; mRNA.
DR   EMBL; AF021802; AAC40036.1; -; Genomic_DNA.
DR   RefSeq; NP_071786.1; NM_022391.3.
DR   RefSeq; XP_006246204.1; XM_006246142.1.
DR   RefSeq; XP_006246205.1; XM_006246143.3.
DR   RefSeq; XP_006246206.1; XM_006246144.1.
DR   RefSeq; XP_006246207.1; XM_006246145.3.
DR   AlphaFoldDB; P97613; -.
DR   BioGRID; 249000; 3.
DR   STRING; 10116.ENSRNOP00000005070; -.
DR   iPTMnet; P97613; -.
DR   PhosphoSitePlus; P97613; -.
DR   PaxDb; 10116-ENSRNOP00000005070; -.
DR   Ensembl; ENSRNOT00000005070.6; ENSRNOP00000005070.2; ENSRNOG00000003802.6.
DR   Ensembl; ENSRNOT00055032030; ENSRNOP00055025901; ENSRNOG00055018788.
DR   Ensembl; ENSRNOT00060036162; ENSRNOP00060029736; ENSRNOG00060020891.
DR   GeneID; 64193; -.
DR   KEGG; rno:64193; -.
DR   UCSC; RGD:68359; rat.
DR   AGR; RGD:68359; -.
DR   CTD; 9232; -.
DR   RGD; 68359; Pttg1.
DR   eggNOG; ENOG502S2GG; Eukaryota.
DR   GeneTree; ENSGT00390000009693; -.
DR   HOGENOM; CLU_1363209_0_0_1; -.
DR   InParanoid; P97613; -.
DR   OMA; PPVCYDF; -.
DR   OrthoDB; 4105310at2759; -.
DR   PhylomeDB; P97613; -.
DR   TreeFam; TF330797; -.
DR   Reactome; R-RNO-174154; APC/C:Cdc20 mediated degradation of Securin.
DR   Reactome; R-RNO-174178; APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
DR   Reactome; R-RNO-2467813; Separation of Sister Chromatids.
DR   PRO; PR:P97613; -.
DR   Proteomes; UP000002494; Chromosome 10.
DR   Bgee; ENSRNOG00000003802; Expressed in testis and 20 other cell types or tissues.
DR   ExpressionAtlas; P97613; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0005829; C:cytosol; ISO:RGD.
DR   GO; GO:0005634; C:nucleus; ISO:RGD.
DR   GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; ISO:RGD.
DR   GO; GO:0031072; F:heat shock protein binding; IPI:RGD.
DR   GO; GO:0140677; F:molecular function activator activity; ISO:RGD.
DR   GO; GO:0043022; F:ribosome binding; IPI:RGD.
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; ISO:RGD.
DR   GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR   GO; GO:0045143; P:homologous chromosome segregation; ISO:RGD.
DR   GO; GO:0007064; P:mitotic sister chromatid cohesion; ISO:RGD.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:RGD.
DR   GO; GO:0001558; P:regulation of cell growth; IMP:RGD.
DR   InterPro; IPR006940; Securin_separation_inhibitor.
DR   PANTHER; PTHR10418:SF2; SECURIN; 1.
DR   PANTHER; PTHR10418; SECURIN-3; 1.
DR   Pfam; PF04856; Securin; 1.
DR   Genevisible; P97613; RN.
PE   1: Evidence at protein level;
KW   Acetylation; Cell cycle; Cell division; Chromosome partition; Cytoplasm;
KW   DNA damage; DNA repair; Mitosis; Nucleus; Phosphoprotein; Proto-oncogene;
KW   Reference proteome; Repeat; SH3-binding; 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_0000206364"
FT   REGION          1..23
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          58..108
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        68..101
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:22673903"
SQ   SEQUENCE   199 AA;  21571 MW;  07D89438000FE378 CRC64;
     MATLIFVDKD NEEPGSRLAS KDGLKLGSGV KALDGKLQVS TPRVGKVFGA PGLPKASRKA
     LGTVNRVTEK PVKSSKPLQS KQPTLSVKKI TEKSTKTQGS APAPDDAYPE IEKFFPFDPL
     DFESFDLPEE HQISLLPLNG VPLMILNEER GLEKLLHLDP PSPLQKPFLP WESDPLPSPP
     SALSALDVEL PPVCYDADI
//