CPLM-001698

Genbank Nucleotide ID

Protein Synonyms/Alias

Esp1-associated protein; Pituitary tumor-transforming gene 1 protein; Tumor-transforming protein 1; hPTTG

Homo sapiens (Human)

Position	Peptide	Type	References
9	ATLIYVDKENGEPGT	ubiquitination	[1]
21	PGTRVVAKDGLKLGS	ubiquitination	[2]
25	VVAKDGLKLGSGPSI	ubiquitination	[1, 2, 3]
33	LGSGPSIKALDGRSQ	ubiquitination	[1, 2, 3]
48	VSTPRFGKTFDAPPA	ubiquitination	[1, 3, 4]
101	TEKTVKAKSSVPASD	ubiquitination	[1, 3, 5]

[1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[2] Global identification of modular cullin-RING ligase substrates.
Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
[3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[4] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[5] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]

Functional Description

Regulatory protein, which plays a central role in chromosome stability, in the p53/TP53 pathway, and DNA repair. Probably acts by blocking the action of key proteins. During the mitosis, it blocks Separase/ESPL1 function, preventing the proteolysis of the cohesin complex and the subsequent segregation of the chromosomes. At the onset of anaphase, it is ubiquitinated, conducting to its destruction and to the liberation of ESPL1. Its function is however not limited to a blocking activity, since it is required to activate ESPL1. Negatively regulates the transcriptional activity and related apoptosis activity of TP53. The negative regulation of TP53 may explain the strong transforming capability of the protein when it is overexpressed. May also play a role in DNA repair via its interaction with Ku, possibly by connecting DNA damage-response pathways with sister chromatid separation.

MOTIF 61 64 D-box.
MOTIF 71 73 TEK-box 1.
MOTIF 94 96 TEK-box 2.
MOTIF 163 173 SH3-binding.
MOD_RES 102 102 Phosphoserine (By similarity).
MOD_RES 165 165 Phosphoserine; by CDK1.

Cell cycle; Cell division; Chromosome partition; Complete proteome; Cytoplasm; DNA damage; DNA repair; Mitosis; Nucleus; Phosphoprotein; Proto-oncogene; Reference proteome; Repeat; SH3-binding; Ubl conjugation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; TAS:Reactome.
GO:0005634; C:nucleus; IDA:HPA.
GO:0004869; F:cysteine-type endopeptidase inhibitor activity; NAS:UniProtKB.
GO:0003700; F:sequence-specific DNA binding transcription factor activity; TAS:ProtInc.
GO:0031145; P:anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; TAS:Reactome.
GO:0051301; P:cell division; IEA:UniProtKB-KW.
GO:0051276; P:chromosome organization; IEA:InterPro.
GO:0007059; P:chromosome segregation; IEA:UniProtKB-KW.
GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
GO:0007067; P:mitosis; IEA:UniProtKB-KW.
GO:0000278; P:mitotic cell cycle; TAS:Reactome.
GO:0007283; P:spermatogenesis; TAS:ProtInc.
GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc.

IPR018008; Securin_separation-inh_met.
IPR006940; Securin_separation_inhibitor.