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PTTG1IP (pituitary tumor-transforming 1 interacting protein)

Identity

Other namesC21orf1
C21orf3
PBF
HGNC (Hugo) PTTG1IP
LocusID (NCBI) 754
Location 21q22.3
Location_base_pair Starts at 46269500 and ends at 46293818 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 

DNA/RNA

 
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.

Protein

 
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 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.
  

External links

Nomenclature
HGNC (Hugo)PTTG1IP   13524
Entrez_Gene (NCBI)PTTG1IP  754  pituitary tumor-transforming 1 interacting protein
Cards
AtlasPTTG1IPID41944ch21q22
GeneCards (Weizmann)PTTG1IP
Ensembl (Hinxton)ENSG00000183255 [Gene_View]  chr21:46269500-46293818 [Contig_View]  PTTG1IP [Vega]
AceView (NCBI)PTTG1IP
Genatlas (Paris)PTTG1IP
euGene (Indiana)754
SOURCE (Stanford)NM_004339
Genomic and cartography
GoldenPath (UCSC)PTTG1IP  -  21q22.3   chr21:46269500-46293818 -  21q22.3   [Description]    (hg19-Feb_2009)
EnsemblPTTG1IP - 21q22.3 [CytoView]
Mapping of homologs : NCBIPTTG1IP [Mapview]
OMIM603784   
Gene and transcription
Genbank (Entrez)AF149785 AK094882 AK095586 AK290139 AK298557
RefSeq transcript (SRS)NM_004339
RefSeq transcript (Entrez)NM_004339
RefSeq genomic (SRS)AC_000153 NC_000021 NT_011515 NW_001838716
RefSeq genomic (Entrez)AC_000153 NC_000021 NT_011515 NW_001838716
Consensus coding sequences : CCDS (NCBI)PTTG1IP
Cluster EST : UnigeneHs.474010 [ SRS ] Hs.474010 [ NCBI ]
Alternative Splicing : Fast-db (Paris)4169
Alternative Splicing GalleryENSG00000183255
Gene ExpressionPTTG1IP [ NCBI-GEO ]   PTTG1IP [ EBI - ARRAY_EXPRESS ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP53801 (SRS) P53801 (Uniprot)
With graphics : InterProP53801
Splice isoforms : SwissVarP53801(Swissvar)
Domains : Interpro (SRS)Plexin-like   
Domains : Interpro (EBI)Plexin-like   
Related proteins : CluSTrP53801
Domain families : Pfam (SRS)
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Domain families : Smart (EMBL)PSI (SM00423)  
Blocks (Seattle)P53801
Human Protein AtlasENSG00000183255
HPRD04807
IPIIPI00023974   IPI00908407   IPI00911013   IPI00795434   IPI00794805   
Protein Interaction databases
DIP (DOE-UCLA)P53801
IntAct (EBI)P53801
FunCoupENSG00000183255
REACTOMEPTTG1IP
BioGRIDPTTG1IP
InParanoidP53801
Interologous Interaction database P53801
Polymorphism : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)PTTG1IP
SNP (GeneSNP Utah)PTTG1IP
SNP : HGBasePTTG1IP
Genetic variants : HAPMAPPTTG1IP
Somatic Mutations in Cancer : COSMICPTTG1IP 
CONAN: Copy Number AnalysisPTTG1IP 
Mutations and Diseases : HGMDPTTG1IP
OMIM603784   
GENETests603784   
Disease Genetic AssociationPTTG1IP
Huge Navigator PTTG1IP [HugePedia]  PTTG1IP [HugeCancerGEM]
Genomic VariantsPTTG1IP
snp3D : Map Gene to Disease754
General knowledge
Homologs : HomoloGenePTTG1IP
Homology/Alignments : Family Browser (UCSC)PTTG1IP
Phylogenetic Trees/Animal Genes : TreeFamPTTG1IP
Chemical/Protein Interactions : CTD754
Chemical/Pharm GKB GenePA34034
Clinical trialPTTG1IP
Cancer Resource (Charite)ENSG00000183255
Ontology : AmiGOmolecular_function  nucleus  cytoplasm  protein import into nucleus  membrane  integral to membrane  
Ontology : EGO-EBImolecular_function  nucleus  cytoplasm  protein import into nucleus  membrane  integral to membrane  
Other databases
Probes
Probes : ImagenesPTTG1IP Related clones (RZPD - Berlin)
Litterature
PubMed18 Pubmed reference(s) in Entrez
PubGenePTTG1IP
iHOPPTTG1IP

Bibliography

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
 
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, Schˆ§fer 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
 
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
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written01-2008Vicki Smith, Chris McCabe
Division of Medical Sciences, 2nd Floor IBR, University of Birmingham, Edgbaston, Birmingham B12 5TT, UK

Citation

This paper should be referenced as such :
Smith V, McCabe C . PTTG1IP (pituitary tumor-transforming 1 interacting protein). Atlas Genet Cytogenet Oncol Haematol. January 2008 .
URL : http://AtlasGeneticsOncology.org/Genes/PTTG1IPID41944ch21q22.html

This paper is referenced by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/38577/1/01-2008-PTTG1IPID41944ch21q22.pdf   [ Bibliographic record ]

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indexed on : Sat Apr 28 15:02:04 CEST 2012

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