This manual synthesis was prepared from the reviewed UniProt record, the 30
current GOA rows, the cached GOA-linked publications, and three additional
primary studies. It was created because the first OpenScientist request timed
out without producing a report; a second request was attempted independently.
PTTG1 is the human securin protein and forms a stoichiometric regulatory complex
with ESPL1/separase. Before anaphase, PTTG1 acts as a pseudosubstrate inhibitor:
its motifs occupy the separase catalytic site and adjacent substrate-docking
surfaces. This directly supports cysteine-type endopeptidase inhibitor activity
and separase-securin complex membership.
PTTG1 is not only an inhibitor. Human knockout cells have defective separase
activation, and domain-dissection experiments distinguish separase-inhibitory
and separase-activating regions of PTTG1. The most specific supported activator
term is GO:0140608, cysteine-type endopeptidase activator activity.
PTTG1 prevents premature cohesin cleavage and thereby maintains sister-chromatid
cohesion until the metaphase-to-anaphase transition. APC/C recognizes PTTG1's
destruction motifs, polyubiquitinates it, and targets it for proteasomal
destruction. Separase is then released to cleave cohesin and permit chromatid
separation.
Human PTTG1 occupies both cytosolic and nuclear pools. It is highly expressed in
adult testis, and rat spermatocyte/spermatid expression plus interaction studies
suggest a role in spermatogenesis, but those data do not define a second core
molecular activity.
The cached versions of PMID:12194817, PMID:20360068, PMID:26496610,
PMID:9811450, PMID:9915854, and PMID:15929994 are abstract-only. No experimental
annotation was removed on the basis of missing full text. The three
proteome-scale interaction papers establish the design of their interaction
surveys in accessible text, while the exact PTTG1-ESPL1 pairs are represented
in GOA/IntAct; those rows are conservatively refined only from generic protein
binding to protease binding.