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PTTG1IP (pituitary tumor-transforming 1 interacting protein)

Written2008-01Vicki Smith, Chris McCabe
Division of Medical Sciences, 2nd Floor IBR, University of Birmingham, Edgbaston, Birmingham B12 5TT, UK

(Note : for Links provided by Atlas : click)


Alias (NCBI)C21orf1
HGNC Alias symbPBF
HGNC Previous nameC21orf3
HGNC Previous namepituitary tumor-transforming 1 interacting protein
LocusID (NCBI) 754
Atlas_Id 41944
Location 21q22.3  [Link to chromosome band 21q22]
Location_base_pair Starts at 44849598 and ends at 44873690 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping PTTG1IP.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
AVL9 (7p14.3)::PTTG1IP (21q22.3)PTTG1IP (21q22.3)::CES2 (16q22.1)PTTG1IP (21q22.3)::CLDN4 (7q11.23)
PTTG1IP (21q22.3)::CNIH4 (1q42.11)PTTG1IP (21q22.3)::DIP2C (10p15.3)PTTG1IP (21q22.3)::GEMIN2 (14q21.1)
PTTG1IP (21q22.3)::MRPL33 (2p23.2)PTTG1IP (21q22.3)::NCOA6 (20q11.22)PTTG1IP (21q22.3)::PLP1 (Xq22.2)
PTTG1IP (21q22.3)::PTTG1IP (21q22.3)PTTG1IP (21q22.3)::SIM2 (21q22.13)


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.


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.


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 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 Pituitary tumours
Disease PTTG1IP is overexpressed in pituitary tumours compared with normal pituitary tissue.


PTTG and PBF repress the human sodium iodide symporter.
Boelaert K, Smith VE, Stratford AL, Kogai T, Tannahill LA, Watkinson JC, Eggo MC, Franklyn JA, McCabe CJ
Oncogene. 2007 ; 26 (30) : 4344-4356.
PMID 17297475
A novel binding factor facilitates nuclear translocation and transcriptional activation function of the pituitary tumor-transforming gene product.
Chien W, Pei L
The Journal of biological chemistry. 2000 ; 275 (25) : 19422-19427.
PMID 10781616
Expression of pituitary tumour transforming gene (PTTG) and fibroblast growth factor-2 (FGF-2) in human pituitary adenomas: relationships to clinical tumour behaviour.
McCabe CJ, Khaira JS, Boelaert K, Heaney AP, Tannahill LA, Hussain S, Mitchell R, Olliff J, Sheppard MC, Franklyn JA, Gittoes NJ
Clinical endocrinology. 2003 ; 58 (2) : 141-150.
PMID 12580928
Identification of novel genes of the bone-specific transcription factor Runx2.
Stock M, Schäfer H, Fliegauf M, Otto F
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2004 ; 19 (6) : 959-972.
PMID 15190888
Pituitary tumor transforming gene binding factor: a novel transforming gene in thyroid tumorigenesis.
Stratford AL, Boelaert K, Tannahill LA, Kim DS, Warfield A, Eggo MC, Gittoes NJ, Young LS, Franklyn JA, McCabe CJ
The Journal of clinical endocrinology and metabolism. 2005 ; 90 (7) : 4341-4349.
PMID 15886233
Cloning of a novel human putative type Ia integral membrane protein mapping to 21q22.3.
Yaspo ML, Aaltonen J, Horelli-Kuitunen N, Peltonen L, Lehrach H
Genomics. 1998 ; 49 (1) : 133-136.
PMID 9570958


This paper should be referenced as such :
Smith, V ; McCabe, C
PTTG1IP (pituitary tumor-transforming 1 interacting protein)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(5):385-386.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)PTTG1IP   13524
Entrez_Gene (NCBI)PTTG1IP    PTTG1 interacting protein
AliasesC21orf1; C21orf3; PBF
GeneCards (Weizmann)PTTG1IP
Ensembl hg19 (Hinxton)ENSG00000183255 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000183255 [Gene_View]  ENSG00000183255 [Sequence]  chr21:44849598-44873690 [Contig_View]  PTTG1IP [Vega]
ICGC DataPortalENSG00000183255
Genatlas (Paris)PTTG1IP
Genetics Home Reference (NIH)PTTG1IP
Genomic and cartography
GoldenPath hg38 (UCSC)PTTG1IP  -     chr21:44849598-44873690 -  21q22.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PTTG1IP  -     21q22.3   [Description]    (hg19-Feb_2009)
GoldenPathPTTG1IP - 21q22.3 [CytoView hg19]  PTTG1IP - 21q22.3 [CytoView hg38]
Genome Data Viewer NCBIPTTG1IP [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AF149785 AK094882 AK095586 AK290139 AK293318
RefSeq transcript (Entrez)NM_001286822 NM_004339
Consensus coding sequences : CCDS (NCBI)PTTG1IP
Gene Expression Viewer (FireBrowse)PTTG1IP [ Firebrowse - Broad ]
GenevisibleExpression of PTTG1IP in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)754
GTEX Portal (Tissue expression)PTTG1IP
Human Protein AtlasENSG00000183255-PTTG1IP [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP53801   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP53801  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP53801
Domains : Interpro (EBI)PSI    PTTG1IP   
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Domain families : Smart (EMBL)PSI (SM00423)  
Conserved Domain (NCBI)PTTG1IP
AlphaFold pdb e-kbP53801   
Human Protein Atlas [tissue]ENSG00000183255-PTTG1IP [tissue]
Protein Interaction databases
IntAct (EBI)P53801
Ontologies - Pathways
Ontology : AmiGOp53 binding  molecular_function  protein binding  nucleus  nucleus  nucleoplasm  cytoplasm  cytoplasm  protein import into nucleus  protein import into nucleus  membrane  integral component of membrane  positive regulation of protein ubiquitination  negative regulation of DNA damage response, signal transduction by p53 class mediator  extracellular exosome  negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator  positive regulation of cellular protein catabolic process  
Ontology : EGO-EBIp53 binding  molecular_function  protein binding  nucleus  nucleus  nucleoplasm  cytoplasm  cytoplasm  protein import into nucleus  protein import into nucleus  membrane  integral component of membrane  positive regulation of protein ubiquitination  negative regulation of DNA damage response, signal transduction by p53 class mediator  extracellular exosome  negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator  positive regulation of cellular protein catabolic process  
Atlas of Cancer Signalling NetworkPTTG1IP
Wikipedia pathwaysPTTG1IP
Orthology - Evolution
GeneTree (enSembl)ENSG00000183255
Phylogenetic Trees/Animal Genes : TreeFamPTTG1IP
Homologs : HomoloGenePTTG1IP
Homology/Alignments : Family Browser (UCSC)PTTG1IP
Gene fusions - Rearrangements
Fusion : MitelmanPTTG1IP::CLDN4 [21q22.3/7q11.23]  
Fusion : MitelmanPTTG1IP::SIM2 [21q22.3/21q22.13]  
Fusion : QuiverPTTG1IP
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPTTG1IP [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PTTG1IP
Exome Variant ServerPTTG1IP
GNOMAD BrowserENSG00000183255
Varsome BrowserPTTG1IP
ACMGPTTG1IP variants
Genomic Variants (DGV)PTTG1IP [DGVbeta]
DECIPHERPTTG1IP [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPTTG1IP 
ICGC Data PortalPTTG1IP 
TCGA Data PortalPTTG1IP 
Broad Tumor PortalPTTG1IP
OASIS PortalPTTG1IP [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPTTG1IP  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DPTTG1IP
Mutations and Diseases : HGMDPTTG1IP
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)PTTG1IP
DoCM (Curated mutations)PTTG1IP
CIViC (Clinical Interpretations of Variants in Cancer)PTTG1IP
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry PTTG1IP
NextProtP53801 [Medical]
Target ValidationPTTG1IP
Huge Navigator PTTG1IP [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDPTTG1IP
Pharm GKB GenePA34034
Clinical trialPTTG1IP
DataMed IndexPTTG1IP
PubMed46 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:26:18 CEST 2021

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