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Protein

Securin

Gene

PTTG1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • peptidase inhibitor activity Source: GO_Central
  • transcription factor activity, sequence-specific DNA binding Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000164611-MONOMER.
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

HGNCiHGNC:9690. PTTG1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: ProtInc
  • cytosol Source: Reactome
  • nucleus Source: ProtInc
Complete GO annotation...

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

Protein-protein interaction databases

BioGridi114663. 71 interactors.
DIPiDIP-56460N.
IntActiO95997. 17 interactors.
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

InterProiIPR018008. Securin_separation-inh_met.
IPR006940. Securin_separation_inhibitor.
[Graphical view]
PANTHERiPTHR10418. PTHR10418. 1 hit.
PfamiPF04856. Securin. 1 hit.
[Graphical view]

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.

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

3D structure databases

DisProtiDP00521.
ProteinModelPortaliO95997.
SMRiO95997.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114663. 71 interactors.
DIPiDIP-56460N.
IntActiO95997. 17 interactors.
STRINGi9606.ENSP00000344936.

PTM databases

iPTMnetiO95997.
PhosphoSitePlusiO95997.

Proteomic databases

EPDiO95997.
PaxDbiO95997.
PeptideAtlasiO95997.
PRIDEiO95997.

Protocols and materials databases

DNASUi9232.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi9232.
DisGeNETi9232.
GeneCardsiPTTG1.
H-InvDBHIX0034255.
HGNCiHGNC:9690. PTTG1.
HPAiCAB008373.
HPA008890.
HPA045034.
MIMi604147. gene.
neXtProtiNX_O95997.
OpenTargetsiENSG00000164611.
PharmGKBiPA34033.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000164611-MONOMER.
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.

Miscellaneous databases

GeneWikiiPTTG1.
GenomeRNAii9232.
PROiO95997.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164611.
CleanExiHS_PTTG1.
ExpressionAtlasiO95997. baseline and differential.
GenevisibleiO95997. HS.

Family and domain databases

InterProiIPR018008. Securin_separation-inh_met.
IPR006940. Securin_separation_inhibitor.
[Graphical view]
PANTHERiPTHR10418. PTHR10418. 1 hit.
PfamiPF04856. Securin. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPTTG1_HUMAN
AccessioniPrimary (citable) accession number: O95997
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 25, 2003
Last sequence update: May 1, 1999
Last modified: November 2, 2016
This is version 137 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.