Reviewed, UniProtKB/Swiss-Prot O95997 (PTTG1_HUMAN)

Names and origin

Protein names

Recommended name:
    Securin
Alternative name(s):
    Pituitary tumor-transforming gene 1 protein
      Short name=hPTTG
      Short name=Tumor-transforming protein 1
    Esp1-associated protein

Gene names

Name:	PTTG1
Synonyms:	EAP1, PTTG, TUTR1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	202 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.9 Ref.12 Ref.8
Subcellular location	Cytoplasm. Nucleus.
Tissue specificity	Expressed at low level in most tissues, except in adult testis, where it is highly expressed. 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.16 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 thiolester with the acceptor lysine residue. Ref.16
Post-translational modification	Phosphorylated at Ser-165 by CDC2 during mitosis. Ref.13 Ref.14 Ref.15 Ref.17 Phosphorylated in vitro by ds-DNA kinase. Ref.13 Ref.14 Ref.15 Ref.17 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.16
Involvement in disease	Has strong transforming capabilities on a variety of cell lines including NIH 3T3 fibroblasts and on athymic nude mice. Overexpressed in many patients suffering from pituitary adenomas, primary epithelial neoplasias, and esophageal cancer. No mutation in the coding sequence has been observed. The transforming capability may be due to its interaction and regulation of TP53 pathway. Ref.1 Ref.3 Ref.5 Ref.6 Ref.11
Sequence similarities	Belongs to the securin family.

Ontologies

Keywords
Biological process	Cell cycle Cell division Chromosome partition DNA damage DNA repair Mitosis
Cellular component	Cytoplasm Nucleus
Disease	Proto-oncogene
Domain	Repeat SH3-binding
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW 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 spermatogenesis Traceable author statement. Source: ProtInc transcription from RNA polymerase II promoter Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytosol Inferred from Experiment. Source: Reactome nucleus Ref.1 Inferred from direct assay. Source: HPA
Molecular function	SH3 domain binding Inferred from electronic annotation. Source: UniProtKB-KW cysteine-type endopeptidase inhibitor activity Non-traceable author statement. Source: UniProtKB transcription factor activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 202	201	Securin		PRO_0000206361
Regions
	Motif	61 – 64	4	D-box
	Motif	71 – 73	3	TEK-box 1
	Motif	94 – 96	3	TEK-box 2
	Motif	163 – 173	11	SH3-binding
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.18
	Modified residue	102	1	Phosphoserine By similarity
	Modified residue	165	1	Phosphoserine; by CDC2 Ref.13 Ref.14 Ref.15 Ref.17
Experimental info
	Mutagenesis	61	1	R → A: Abolishes ubiquitination and subsequent degradation; when associated with A-64. Ref.7
	Mutagenesis	64	1	L → A: Abolishes ubiquitination and subsequent degradation; when associated with A-61. Ref.7
	Mutagenesis	163	1	P → A: Strongly reduces transforming capability; when associated with L-170; A-172 and L-173. Ref.5
	Mutagenesis	165	1	S → A: Abolishes phosphorylation. Ref.13
	Mutagenesis	170 – 173	4	PSPP → LSAL: Strongly reduces transforming capability; when associated with A-163. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	O95997-1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 5F4740619AB8856F	FASTA	202	22,024
	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

References

	« Hide 'large scale' referencesShow '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: 9811450] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DISEASE. 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: 10393434] [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: 10580151] [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: 9892021] [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: 10022450] [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: 10411507] [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: 10781616] [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: 11238996] [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: 11371342] [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: 11158059] [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: 12355087] [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: 10656688] [Abstract] Cited for: PHOSPHORYLATION AT SER-165, MUTAGENESIS OF SER-165.
[14]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, MASS SPECTROMETRY. Tissue: Epithelium.
[15]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, MASS SPECTROMETRY. Tissue: Epithelium.
[16]	"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: 18485873] [Abstract] Cited for: UBIQUITINATION, DOMAIN TEK-BOX.
[17]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, MASS SPECTROMETRY.
[18]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY.
+	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 , AF167560, AF167561, AF167562, AF167563 Genomic DNA. Translation: AAF06995.1.
IPI	IPI00003494.
RefSeq	NP_004210.1.
UniGene	Hs.350966
3D structure databases
DisProt	DP00521.
ModBase	Search...
Protein-protein interaction databases
STRING	O95997.
PTM databases
PhosphoSite	O95997.
Proteomic databases
PRIDE	O95997.
Genome annotation databases
Ensembl	ENST00000352433; ENSP00000344936; ENSG00000164611; Homo sapiens. [Genome view] ENST00000393964; ENSP00000377536; ENSG00000164611; Homo sapiens. [Genome view]
GeneID	9232.
KEGG	hsa:9232.
UCSC	uc003lyj.1. human.
Organism-specific databases
CTD	9232.
GeneCards	GC05P159781.
H-InvDB	HIX0031960.
HGNC	HGNC:9690. PTTG1.
HPA	CAB008373. HPA008890.
MIM	604147. gene.
PharmGKB	PA34033.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG125076.
HOVERGEN	O95997.
InParanoid	O95997.
OMA	ELPPVCY.
OrthoDB	EOG9RBT48.
PhylomeDB	O95997.
Enzyme and pathway databases
Reactome	REACT_152. Cell Cycle, Mitotic.
Gene expression databases
ArrayExpress	O95997.
Bgee	O95997.
CleanEx	HS_PTTG1.
Genevestigator	O95997.
GermOnline	ENSG00000164611. Homo sapiens.
Family and domain databases
InterPro	IPR018008. Securin_separation-inh_met. IPR006940. Securin_separation_inhibitor. [Graphical view]
PANTHER	PTHR10418. Securin. 1 hit.
Pfam	PF04856. Securin. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	34605.
SOURCE	Search...

Entry information

Entry name

PTTG1_HUMAN

Accession

Primary (citable) accession number: O95997

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 25, 2003
Last sequence update:	May 1, 1999
Last modified:	January 19, 2010
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.