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Protein

Securin

Gene

PTTG1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.4 Publications

GO - Molecular functioni

  • cysteine-type endopeptidase inhibitor activity Source: UniProtKB
  • DNA binding transcription factor activity Source: ProtInc
  • peptidase inhibitor activity Source: GO_Central
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: CAFA
  • SH3 domain binding Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Biological processCell cycle, Cell division, Chromosome partition, DNA damage, DNA repair, Mitosis

Enzyme and pathway databases

ReactomeiR-HSA-174154 APC/C:Cdc20 mediated degradation of Securin
R-HSA-174178 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-HSA-2467813 Separation of Sister Chromatids
SIGNORiO95997

Names & Taxonomyi

Protein namesi
Recommended name:
Securin
Alternative name(s):
Esp1-associated protein
Pituitary tumor-transforming gene 1 protein
Short name:
Tumor-transforming protein 1
Short name:
hPTTG
Gene namesi
Name:PTTG1
Synonyms:EAP1, PTTG, TUTR1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000164611.12
HGNCiHGNC:9690 PTTG1
MIMi604147 gene
neXtProtiNX_O95997

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi61R → A: Abolishes ubiquitination and subsequent degradation; when associated with A-64. 1 Publication1
Mutagenesisi64L → A: Abolishes ubiquitination and subsequent degradation; when associated with A-61. 1 Publication1
Mutagenesisi163P → A: Strongly reduces transforming capability; when associated with L-170; A-172 and L-173. 1 Publication1
Mutagenesisi165S → A: Abolishes phosphorylation. 1 Publication1
Mutagenesisi170 – 173PSPP → LSAL: Strongly reduces transforming capability; when associated with A-163. 1 Publication4

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi9232
OpenTargetsiENSG00000164611
PharmGKBiPA34033

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002063612 – 202SecurinAdd BLAST201

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei165Phosphoserine; by CDK11 Publication1

Post-translational modificationi

Phosphorylated at Ser-165 by CDK1 during mitosis.1 Publication
Phosphorylated in vitro by ds-DNA kinase.1 Publication
Ubiquitinated through 'Lys-11' linkage of ubiquitin moieties by the anaphase promoting complex (APC) at the onset of anaphase, conducting to its degradation. 'Lys-11'-linked ubiquitination is mediated by the E2 ligase UBE2C/UBCH10.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO95997
PaxDbiO95997
PeptideAtlasiO95997
PRIDEiO95997

PTM databases

iPTMnetiO95997
PhosphoSitePlusiO95997

Expressioni

Tissue specificityi

Expressed at low level in most tissues, except in adult testis, where it is highly expressed. Overexpressed in many patients suffering from pituitary adenomas, primary epithelial neoplasias, and esophageal cancer.1 Publication

Developmental stagei

Low level during G1 and S phases. Peaks at M phase. During anaphase, it is degraded.

Gene expression databases

BgeeiENSG00000164611
CleanExiHS_PTTG1
ExpressionAtlasiO95997 baseline and differential
GenevisibleiO95997 HS

Organism-specific databases

HPAiCAB008373
HPA008890
HPA045034

Interactioni

Subunit structurei

Interacts with RPS10 and DNAJA1 (By similarity). Interacts with the caspase-like ESPL1, and prevents its protease activity probably by covering its active site. Interacts with TP53 and blocks its activity probably by blocking its binding to DNA. Interacts with the Ku 70 kDa subunit of ds-DNA kinase. Interacts with PTTG1IP.By similarity4 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114663, 78 interactors
CORUMiO95997
DIPiDIP-56460N
ELMiO95997
IntActiO95997, 18 interactors
MINTiO95997
STRINGi9606.ENSP00000344936

Structurei

3D structure databases

DisProtiDP00521
ProteinModelPortaliO95997
SMRiO95997
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi61 – 64D-box4
Motifi71 – 73TEK-box 13
Motifi94 – 96TEK-box 23
Motifi163 – 173SH3-bindingAdd BLAST11

Domaini

The N-terminal destruction box (D-box) acts as a recognition signal for degradation via the ubiquitin-proteasome pathway.By similarity
The TEK-boxes are required for 'Lys-11'-linked ubiquitination and facilitate the transfer of the first ubiquitin and ubiquitin chain nucleation. TEK-boxes may direct a catalytically competent orientation of the UBE2C/UBCH10-ubiquitin thioester with the acceptor lysine residue.1 Publication

Sequence similaritiesi

Belongs to the securin family.Curated

Keywords - Domaini

Repeat, SH3-binding

Phylogenomic databases

eggNOGiENOG410IVQH Eukaryota
ENOG410Z8MR LUCA
GeneTreeiENSGT00390000009693
HOGENOMiHOG000035097
HOVERGENiHBG053264
InParanoidiO95997
KOiK06635
OMAiFSAKKVT
OrthoDBiEOG091G0PAH
PhylomeDBiO95997
TreeFamiTF330797

Family and domain databases

InterProiView protein in InterPro
IPR006940 Securin_separation_inhibitor
PANTHERiPTHR10418 PTHR10418, 1 hit
PfamiView protein in Pfam
PF04856 Securin, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O95997-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATLIYVDKE NGEPGTRVVA KDGLKLGSGP SIKALDGRSQ VSTPRFGKTF
60 70 80 90 100
DAPPALPKAT RKALGTVNRA TEKSVKTKGP LKQKQPSFSA KKMTEKTVKA
110 120 130 140 150
KSSVPASDDA YPEIEKFFPF NPLDFESFDL PEEHQIAHLP LSGVPLMILD
160 170 180 190 200
EERELEKLFQ LGPPSPVKMP SPPWESNLLQ SPSSILSTLD VELPPVCCDI

DI
Length:202
Mass (Da):22,024
Last modified:May 1, 1999 - v1
Checksum:i5F4740619AB8856F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ223953 mRNA Translation: CAA11683.1
AF095287 mRNA Translation: AAC64409.1
AF075242 mRNA Translation: AAD19335.1
AF167564
, AF167560, AF167561, AF167562, AF167563 Genomic DNA Translation: AAF06995.1
CCDSiCCDS4353.1
RefSeqiNP_001269311.1, NM_001282382.1
NP_001269312.1, NM_001282383.1
NP_004210.1, NM_004219.3
UniGeneiHs.350966

Genome annotation databases

EnsembliENST00000352433; ENSP00000344936; ENSG00000164611
ENST00000393964; ENSP00000377536; ENSG00000164611
ENST00000520452; ENSP00000430642; ENSG00000164611
GeneIDi9232
KEGGihsa:9232

Similar proteinsi

Entry informationi

Entry nameiPTTG1_HUMAN
AccessioniPrimary (citable) accession number: O95997
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 25, 2003
Last sequence update: May 1, 1999
Last modified: May 23, 2018
This is version 150 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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