PTTG1IP (pituitary tumor-transforming 1 interacting protein)

2008-01-01   Vicki Smith , Chris McCabe 

Division of Medical Sciences, 2nd Floor IBR, University of Birmingham, Edgbaston, Birmingham B12 5TT, UK

Identity

HGNC
LOCATION
21q22.3
IMAGE
Atlas Image
LOCUSID
ALIAS
C21orf1,C21orf3,PBF
FUSION GENES

DNA/RNA

Atlas Image

Description

The PTTG1IP gene consists of 6 exons and spans 24.23 kb of genomic sequence on chromosome 21 (from position 45,093,941 bp to 45,118,169 bp in the reverse strand orientation).

Transcription

The mRNA transcribed from this gene is 2,736 nucleotides long.

Pseudogene

No pseudogene has been described.

Proteins

Atlas Image

Description

Identified through its interaction with pituitary tumor transforming 1 (PTTG), the PTTG1IP protein is 180 amino acids long with a molecular mass of approximately 25 kDa.
A putative signal peptide exists at the N-terminus (1-32). A domain of unknown function common to plexins, semaphorins and integrins (PSI) is located between residues 39-92. Adjacent to this is a putative transmembrane domain (95-122). A bipartite nuclear localisation signal (NLS) is located between amino acids 149 and 166. The C-terminal 30 amino acids of PTTG1IP contain the PTTG binding domain and a putative tyrosine-based sorting signal.
Potential post-translational modifications include putative phosphorlyation sites for cAMP- and cGMP-dependent kinase, protein kinase C and casein kinase II and five glycosylation sites for N-linked and O-linked oligosaccharides.

Expression

PTTG1IP is widely expressed and has been identified in all tissues examined including spleen, thymus, prostate, testis, ovary, small intestine, colon, leukocytes, spinal cord, thyroid, pituitary, lymph node, trachea, adrenal gland and bone marrow.

Localisation

A tagged PTTG1IP protein was located predominantly in the nucleus with partial expression also in the cytoplasm. Mutation of the NLS shifted PTTG1IP expression to a perinuclear and cytoplasm location. Other reports suggest that PTTG1IP is located predominantly in the cytoplasm.

Function

PTTG expression is predominantly nuclear in the presence of PTTG1IP. However, in the absence of PTTG1IP or with the NLS mutant of PTTG1IP, PTTG is mainly cytoplasmic. Hence, PTTG1IP is thought to facilitate the translocation of PTTG into the nucleus.
Itself upregulated by PTTG, PTTG1IP is required for the ability of PTTG to transactivate basic fibroblast growth factor (FGF2).
PTTG1IP has a described role in repressing iodide uptake into thyroid cells via transcriptional regulation of the sodium iodide symporter.
In MC3T3-El cells, PTTG1IP is regulated by the transcription factor Runx2, implying a role in osteoblast differentiation.

Mutations

Note

PTTG1IP has been sequenced in a series of thyroid tumours, but no mutations were evident. No mutations have been reported to date in any other studies.

Implicated in

Entity name
Thyroid tumours
Disease
Overexpression is observed in thyroid tumours compared to normal thyroid tissue.
Prognosis
PTTG1IP overexpression was significantly associated with early thyroid tumour recurrence.
PTTG1IP can repress the expression of the sodium iodide transporter (NIS) and inhibit iodide uptake in in vitro models of the thyroid. NIS mRNA expression was inhibited by PTTG1IP via the NIS upstream enhancer (NUE). A poorer prognosis in thyroid tumours with increased PTTG1IP expression might be inferred, therefore, as a significant reduction of iodide uptake would reduce the efficacy of ablative radioiodine therapy.
Oncogenesis
PTTG1IP transforms cells in vitro and is tumourigenic in vivo.
Entity name
Pituitary tumours
Disease
PTTG1IP is overexpressed in pituitary tumours compared with normal pituitary tissue.

Bibliography

Pubmed IDLast YearTitleAuthors
172974752007PTTG and PBF repress the human sodium iodide symporter.Boelaert K et al
107816162000A novel binding factor facilitates nuclear translocation and transcriptional activation function of the pituitary tumor-transforming gene product.Chien W et al
125809282003Expression of pituitary tumour transforming gene (PTTG) and fibroblast growth factor-2 (FGF-2) in human pituitary adenomas: relationships to clinical tumour behaviour.McCabe CJ et al
151908882004Identification of novel genes of the bone-specific transcription factor Runx2.Stock M et al
158862332005Pituitary tumor transforming gene binding factor: a novel transforming gene in thyroid tumorigenesis.Stratford AL et al
95709581998Cloning of a novel human putative type Ia integral membrane protein mapping to 21q22.3.Yaspo ML et al

Other Information

Locus ID:

NCBI: 754
MIM: 603784
HGNC: 13524
Ensembl: ENSG00000183255

Variants:

dbSNP: 754
ClinVar: 754
TCGA: ENSG00000183255
COSMIC: PTTG1IP

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000183255ENST00000330938P53801
ENSG00000183255ENST00000397886A8MXQ1
ENSG00000183255ENST00000397887A8MZH8
ENSG00000183255ENST00000445724B4DPZ0

Expression (GTEx)

0
50
100
150
200
250
300
350
400

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
232215622013Hepatitis B virus mRNA-mediated miR-122 inhibition upregulates PTTG1-binding protein, which promotes hepatocellular carcinoma tumor growth and cell invasion.55
211292302010Pituitary tumor-transforming gene and its binding factor in endocrine cancer.18
256742212014MicroRNA-584 functions as a tumor suppressor and targets PTTG1IP in glioma.16
172974752007PTTG and PBF repress the human sodium iodide symporter.15
151786452004Expression of pituitary tumor transforming gene (PTTG) and its binding protein in human astrocytes and astrocytoma cells: function and regulation of PTTG in U87 astrocytoma cells.13
218441852011Proto-oncogene PBF/PTTG1IP regulates thyroid cell growth and represses radioiodide treatment.12
228889612013Prognostic significance of pituitary tumour-transforming gene-binding factor (PBF) expression in papillary thyroid carcinoma.11
236780372013Manipulation of PBF/PTTG1IP phosphorylation status; a potential new therapeutic strategy for improving radioiodine uptake in thyroid and other tumors.10
245060682014The PTTG1-binding factor (PBF/PTTG1IP) regulates p53 activity in thyroid cells.10
254084192016The proto-oncogene PBF binds p53 and is associated with prognostic features in colorectal cancer.9

Citation

Vicki Smith ; Chris McCabe

PTTG1IP (pituitary tumor-transforming 1 interacting protein)

Atlas Genet Cytogenet Oncol Haematol. 2008-01-01

Online version: http://atlasgeneticsoncology.org/gene/41944/pttg1ip