Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O95997 (PTTG1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Securin
Alternative name(s):
Esp1-associated protein
Pituitary tumor-transforming gene 1 protein
Short name=Tumor-transforming protein 1
Short name=hPTTG
Gene names
Name:PTTG1
Synonyms:EAP1, PTTG, TUTR1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length202 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.9 Ref.10 Ref.12

Subunit structure

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. Ref.7 Ref.8 Ref.9 Ref.12

Subcellular location

Cytoplasm. Nucleus.

Tissue specificity

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. Ref.1

Developmental stage

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

Domain

The N-terminal destruction box (D-box) acts as a recognition signal for degradation via the ubiquitin-proteasome pathway By similarity. Ref.14

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. Ref.14

Post-translational modification

Phosphorylated at Ser-165 by CDK1 during mitosis. Ref.13

Phosphorylated in vitro by ds-DNA kinase. Ref.13

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. Ref.7 Ref.14

Sequence similarities

Belongs to the securin family.

Ontologies

Keywords
   Biological processCell cycle
Cell division
Chromosome partition
DNA damage
DNA repair
Mitosis
   Cellular componentCytoplasm
Nucleus
   DiseaseProto-oncogene
   DomainRepeat
SH3-binding
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA repair

Inferred from electronic annotation. Source: UniProtKB-KW

anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process

Traceable author statement. Source: Reactome

chromosome organization

Inferred from electronic annotation. Source: InterPro

chromosome segregation

Inferred from electronic annotation. Source: UniProtKB-KW

mitosis

Inferred from electronic annotation. Source: UniProtKB-KW

mitotic cell cycle

Traceable author statement. Source: Reactome

negative regulation of endopeptidase activity

Non-traceable author statement PubMed 12194817. Source: GOC

regulation of transcription, DNA-templated

Traceable author statement Ref.1. Source: GOC

spermatogenesis

Traceable author statement PubMed 9915854. Source: ProtInc

transcription from RNA polymerase II promoter

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentcytoplasm

Traceable author statement Ref.1. Source: ProtInc

cytosol

Traceable author statement. Source: Reactome

nucleus

Traceable author statement Ref.1. Source: ProtInc

   Molecular_functioncysteine-type endopeptidase inhibitor activity

Non-traceable author statement PubMed 12194817. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.15
Chain2 – 202201Securin
PRO_0000206361

Regions

Motif61 – 644D-box
Motif71 – 733TEK-box 1
Motif94 – 963TEK-box 2
Motif163 – 17311SH3-binding

Amino acid modifications

Modified residue21N-acetylalanine Ref.15
Modified residue1651Phosphoserine; by CDK1 Ref.13

Experimental info

Mutagenesis611R → A: Abolishes ubiquitination and subsequent degradation; when associated with A-64. Ref.7
Mutagenesis641L → A: Abolishes ubiquitination and subsequent degradation; when associated with A-61. Ref.7
Mutagenesis1631P → A: Strongly reduces transforming capability; when associated with L-170; A-172 and L-173. Ref.5
Mutagenesis1651S → A: Abolishes phosphorylation. Ref.13
Mutagenesis170 – 1734PSPP → LSAL: Strongly reduces transforming capability; when associated with A-163. Ref.5

Sequences

Sequence LengthMass (Da)Tools
O95997 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: 5F4740619AB8856F

FASTA20222,024
        10         20         30         40         50         60 
MATLIYVDKE NGEPGTRVVA KDGLKLGSGP SIKALDGRSQ VSTPRFGKTF DAPPALPKAT 

        70         80         90        100        110        120 
RKALGTVNRA TEKSVKTKGP LKQKQPSFSA KKMTEKTVKA KSSVPASDDA YPEIEKFFPF 

       130        140        150        160        170        180 
NPLDFESFDL PEEHQIAHLP LSGVPLMILD EERELEKLFQ LGPPSPVKMP SPPWESNLLQ 

       190        200 
SPSSILSTLD VELPPVCCDI DI 

« Hide

References

« Hide 'large scale' references
[1]"hPTTG, a human homologue of rat PTTG, is overexpressed in hematopoietic neoplasms. Evidence for a transcriptional activation function of hPTTG."
Dominguez A., Ramos-Morales F., Romero F., Rios R.M., Dreyfus F., Tortolero M., Pintor-Toro J.A.
Oncogene 17:2187-2193(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Thymus.
[2]Mu Y.
Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Pituitary adenoma.
[3]"Molecular cloning and characterization of the tumor transforming gene (TUTR1): a novel gene in human tumorigenesis."
Kakar S.S., Jennes L.
Cytogenet. Cell Genet. 84:211-216(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], DISEASE.
Tissue: Testis.
[4]"Molecular cloning, genomic organization, and identification of the promoter for the human pituitary tumor transforming gene (PTTG)."
Kakar S.S.
Gene 240:317-324(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Structure, expression, and function of human pituitary tumor-transforming gene (PTTG)."
Zhang X., Horwitz G.A., Prezant T.R., Valentini A., Nakashima M., Bronstein M.D., Melmed S.
Mol. Endocrinol. 13:156-166(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], DISEASE, MUTAGENESIS OF PRO-163 AND 170-PRO--PRO-173.
Tissue: Fetal liver.
[6]"Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas."
Zhang X., Horwitz G.A., Heaney A.P., Nakashima M., Prezant T.R., Bronstein M.D., Melmed S.
J. Clin. Endocrinol. Metab. 84:761-767(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: DISEASE.
[7]"Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis."
Zou H., McGarry T.J., Bernal T., Kirschner M.W.
Science 285:418-422(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ESPL1, UBIQUITINATION, MUTAGENESIS OF ARG-61 AND LEU-64.
[8]"A novel binding factor facilitates nuclear translocation and transcriptional activation function of the pituitary tumor-transforming gene product."
Chien W., Pei L.
J. Biol. Chem. 275:19422-19427(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTTG1IP.
[9]"Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase."
Romero F., Multon M.C., Ramos-Morales F., Dominguez A., Bernal J.A., Pintor-Toro J.A., Tortolero M.
Nucleic Acids Res. 29:1300-1307(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH KU.
[10]"Securin is required for chromosomal stability in human cells."
Jallepalli P.V., Waizenegger I.C., Bunz F., Langer S., Speicher M.R., Peters J.-M., Kinzler K.W., Vogelstein B., Lengauer C.
Cell 105:445-457(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Human pituitary tumor-transforming gene induces angiogenesis."
Ishikawa H., Heaney A.P., Yu R., Horwitz G.A., Melmed S.
J. Clin. Endocrinol. Metab. 86:867-874(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: DISEASE.
[12]"Human securin interacts with p53 and modulates p53-mediated transcriptional activity and apoptosis."
Bernal J.A., Luna R., Espina A., Lazaro I., Ramos-Morales F., Romero F., Arias C., Silva A., Tortolero M., Pintor-Toro J.A.
Nat. Genet. 32:306-311(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TP53, FUNCTION IN TP53 PATHWAY.
[13]"Cell cycle regulated expression and phosphorylation of hpttg proto-oncogene product."
Ramos-Morales F., Dominguez A., Romero F., Luna R., Multon M.-C., Pintor-Toro J.A., Tortolero M.
Oncogene 19:403-409(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-165, MUTAGENESIS OF SER-165.
[14]"Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex."
Jin L., Williamson A., Banerjee S., Philipp I., Rape M.
Cell 133:653-665(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, DOMAIN TEK-BOX.
[15]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ223953 mRNA. Translation: CAA11683.1.
AF095287 mRNA. Translation: AAC64409.1.
AF075242 mRNA. Translation: AAD19335.1.
AF167564 expand/collapse EMBL AC list , AF167560, AF167561, AF167562, AF167563 Genomic DNA. Translation: AAF06995.1.
RefSeqNP_001269311.1. NM_001282382.1.
NP_001269312.1. NM_001282383.1.
NP_004210.1. NM_004219.3.
UniGeneHs.350966.

3D structure databases

DisProtDP00521.
ProteinModelPortalO95997.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114663. 33 interactions.
DIPDIP-56460N.
IntActO95997. 3 interactions.
STRING9606.ENSP00000344936.

PTM databases

PhosphoSiteO95997.

Proteomic databases

PaxDbO95997.
PRIDEO95997.

Protocols and materials databases

DNASU9232.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000352433; ENSP00000344936; ENSG00000164611.
ENST00000393964; ENSP00000377536; ENSG00000164611.
ENST00000520452; ENSP00000430642; ENSG00000164611.
GeneID9232.
KEGGhsa:9232.
UCSCuc003lyj.3. human.

Organism-specific databases

CTD9232.
GeneCardsGC05P159781.
H-InvDBHIX0034255.
HGNCHGNC:9690. PTTG1.
HPACAB008373.
HPA008890.
MIM604147. gene.
neXtProtNX_O95997.
PharmGKBPA34033.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG42896.
HOGENOMHOG000035097.
HOVERGENHBG053264.
InParanoidO95997.
KOK06635.
OMAGTRVAPK.
OrthoDBEOG7MPRH0.
PhylomeDBO95997.
TreeFamTF330797.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.

Gene expression databases

ArrayExpressO95997.
BgeeO95997.
CleanExHS_PTTG1.
GenevestigatorO95997.

Family and domain databases

InterProIPR018008. Securin_separation-inh_met.
IPR006940. Securin_separation_inhibitor.
[Graphical view]
PANTHERPTHR10418. PTHR10418. 1 hit.
PfamPF04856. Securin. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPTTG1.
GenomeRNAi9232.
NextBio34605.
PROO95997.
SOURCESearch...

Entry information

Entry namePTTG1_HUMAN
AccessionPrimary (citable) accession number: O95997
Entry history
Integrated into UniProtKB/Swiss-Prot: March 25, 2003
Last sequence update: May 1, 1999
Last modified: April 16, 2014
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM