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O95997

- PTTG1_HUMAN

UniProt

O95997 - PTTG1_HUMAN

Protein

Securin

Gene

PTTG1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 116 (01 Oct 2014)
      Sequence version 1 (01 May 1999)
      Previous versions | rss
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    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

    1. cysteine-type endopeptidase inhibitor activity Source: UniProtKB
    2. protein binding Source: UniProtKB
    3. sequence-specific DNA binding transcription factor activity Source: ProtInc

    GO - Biological processi

    1. anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Source: Reactome
    2. chromosome organization Source: InterPro
    3. chromosome segregation Source: UniProtKB-KW
    4. DNA repair Source: UniProtKB-KW
    5. mitotic cell cycle Source: Reactome
    6. mitotic nuclear division Source: UniProtKB-KW
    7. negative regulation of endopeptidase activity Source: GOC
    8. regulation of transcription, DNA-templated Source: GOC
    9. spermatogenesis Source: ProtInc
    10. transcription from RNA polymerase II promoter Source: ProtInc

    Keywords - Biological processi

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

    Enzyme and pathway databases

    ReactomeiREACT_150471. Separation of Sister Chromatids.
    REACT_6761. APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
    REACT_6871. APC/C:Cdc20 mediated degradation of Securin.

    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
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:9690. PTTG1.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: ProtInc
    2. cytosol Source: Reactome
    3. nucleus Source: ProtInc

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi61 – 611R → A: Abolishes ubiquitination and subsequent degradation; when associated with A-64. 1 Publication
    Mutagenesisi64 – 641L → A: Abolishes ubiquitination and subsequent degradation; when associated with A-61. 1 Publication
    Mutagenesisi163 – 1631P → A: Strongly reduces transforming capability; when associated with L-170; A-172 and L-173. 1 Publication
    Mutagenesisi165 – 1651S → A: Abolishes phosphorylation. 1 Publication
    Mutagenesisi170 – 1734PSPP → LSAL: Strongly reduces transforming capability; when associated with A-163.

    Keywords - Diseasei

    Proto-oncogene

    Organism-specific databases

    PharmGKBiPA34033.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 202201SecurinPRO_0000206361Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine1 Publication
    Modified residuei165 – 1651Phosphoserine; by CDK11 Publication

    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

    MaxQBiO95997.
    PaxDbiO95997.
    PRIDEiO95997.

    PTM databases

    PhosphoSiteiO95997.

    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

    ArrayExpressiO95997.
    BgeeiO95997.
    CleanExiHS_PTTG1.
    GenevestigatoriO95997.

    Organism-specific databases

    HPAiCAB008373.
    HPA008890.

    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. 34 interactions.
    DIPiDIP-56460N.
    IntActiO95997. 3 interactions.
    STRINGi9606.ENSP00000344936.

    Structurei

    3D structure databases

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

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi61 – 644D-box
    Motifi71 – 733TEK-box 1
    Motifi94 – 963TEK-box 2
    Motifi163 – 17311SH3-bindingAdd
    BLAST

    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

    eggNOGiNOG42896.
    HOGENOMiHOG000035097.
    HOVERGENiHBG053264.
    InParanoidiO95997.
    KOiK06635.
    OMAiGTRVAPK.
    OrthoDBiEOG7MPRH0.
    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

    MATLIYVDKE NGEPGTRVVA KDGLKLGSGP SIKALDGRSQ VSTPRFGKTF    50
    DAPPALPKAT RKALGTVNRA TEKSVKTKGP LKQKQPSFSA KKMTEKTVKA 100
    KSSVPASDDA YPEIEKFFPF NPLDFESFDL PEEHQIAHLP LSGVPLMILD 150
    EERELEKLFQ LGPPSPVKMP SPPWESNLLQ SPSSILSTLD VELPPVCCDI 200
    DI 202
    Length:202
    Mass (Da):22,024
    Last modified:May 1, 1999 - v1
    Checksum:i5F4740619AB8856F
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    UCSCiuc003lyj.3. human.

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS4353.1.
    RefSeqi NP_001269311.1. NM_001282382.1.
    NP_001269312.1. NM_001282383.1.
    NP_004210.1. NM_004219.3.
    UniGenei Hs.350966.

    3D structure databases

    DisProti DP00521.
    ProteinModelPortali O95997.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114663. 34 interactions.
    DIPi DIP-56460N.
    IntActi O95997. 3 interactions.
    STRINGi 9606.ENSP00000344936.

    PTM databases

    PhosphoSitei O95997.

    Proteomic databases

    MaxQBi O95997.
    PaxDbi O95997.
    PRIDEi O95997.

    Protocols and materials databases

    DNASUi 9232.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000352433 ; ENSP00000344936 ; ENSG00000164611 .
    ENST00000393964 ; ENSP00000377536 ; ENSG00000164611 .
    ENST00000520452 ; ENSP00000430642 ; ENSG00000164611 .
    GeneIDi 9232.
    KEGGi hsa:9232.
    UCSCi uc003lyj.3. human.

    Organism-specific databases

    CTDi 9232.
    GeneCardsi GC05P159781.
    H-InvDB HIX0034255.
    HGNCi HGNC:9690. PTTG1.
    HPAi CAB008373.
    HPA008890.
    MIMi 604147. gene.
    neXtProti NX_O95997.
    PharmGKBi PA34033.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG42896.
    HOGENOMi HOG000035097.
    HOVERGENi HBG053264.
    InParanoidi O95997.
    KOi K06635.
    OMAi GTRVAPK.
    OrthoDBi EOG7MPRH0.
    PhylomeDBi O95997.
    TreeFami TF330797.

    Enzyme and pathway databases

    Reactomei REACT_150471. Separation of Sister Chromatids.
    REACT_6761. APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
    REACT_6871. APC/C:Cdc20 mediated degradation of Securin.

    Miscellaneous databases

    GeneWikii PTTG1.
    GenomeRNAii 9232.
    NextBioi 34605.
    PROi O95997.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O95997.
    Bgeei O95997.
    CleanExi HS_PTTG1.
    Genevestigatori O95997.

    Family and domain databases

    InterProi IPR018008. Securin_separation-inh_met.
    IPR006940. Securin_separation_inhibitor.
    [Graphical view ]
    PANTHERi PTHR10418. PTHR10418. 1 hit.
    Pfami PF04856. Securin. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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. 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. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].

    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: October 1, 2014
    This is version 116 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

    External Data

    Dasty 3