Download Gene Section PTPRD (protein tyrosine phosphatase, receptor type, D)

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Gene Section
Review
PTPRD (protein tyrosine phosphatase, receptor
type, D)
Laavanya Parthasarathi, Raymond L Stallings
Royal College of Surgeons in Ireland and Children's Research Centre, Our Lady's Children's Hospital,
Crumlin, Dublin, Ireland (LP, RLS)
Published in Atlas Database: January 2009
Online updated version : http://AtlasGeneticsOncology.org/Genes/PTPRDID41927ch9p23.html
DOI: 10.4267/2042/44644
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2009 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Transcript Variant 5: This variant omits several
exons, and utilizes an alternate exon, in the coding
region. The resulting protein (isoform 5) retains the
same reading frame and has the same N- and Cterminus as isoform 1. This variant is 8848 bp in length
(Figure E).
Identity
Other names: EC 3.1.3.48; HPTP; HPTP-DELTA;
HPTPD; MGC119750; MGC119751; MGC119752;
MGC119753; PTPD; R-PTP-DELTA; R-PTP-delta
HGNC (Hugo): PTPRD
Location: 9p23
Pseudogene
No pseudogenes have been reported.
DNA/RNA
Protein
Description
Description
The PTPRD gene is composed of 36 coding sequence
exons and a 5' UTR spliced together from 11 noncoding exons.
Amino acids: 1912.
Molecular Weight: 214760 Da.
The PTPRD gene belongs to the receptor class 2A
subfamily of the protein-tyrosine phosphatases. It
contains an extracellular region composed of 8
fibronectin type-III domains and 3 Ig-like C2-type
(immunoglobulin-like)
domains,
a
single
transmembrane
segment
and
two
tandem
intracytoplasmic tyrosine-protein phosphatase domains.
Molecular Class: Receptor Tyrosine Phosphatase.
Molecular Function: Receptor Signalling Protein
Tyrosine Phosphatase Activity.
Biological Process: Cell Communication; Signal
Transduction.
Transcription
There are five known transcript variants for PTPRD.
Transcript Variant 1: This variant encodes the longest
isoform 1 and is 10078 bp in length (Figure A).
Transcript Variant 2: This variant lacks two separate
internal segments within the coding region. It thus
encodes a protein that lacks a 9 aa, and a 4 aa internal
fragments, as compared to isoform 1 and is 10039 bp in
length (Figure C).
Transcript Variant 3: This variant lacks an internal
segment within the coding region. It thus encodes a
protein that lacks a 9 aa internal fragment, as compared
to isoform 1 and is 10051 bp in length (Figure D).
Transcript Variant 4: This variant lacks an internal
segment within the coding region. It thus encodes a
protein that lacks a 411 aa internal fragment, and has
one amino acid change, as compared to isoform 1 and
is 8845 bp in length (Figure B).
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(12)
Expression
Brain, Kidney.
Multiple isoforms are generated by either alternate
splicing or by alternate transcriptional start sites in
968
PTPRD (protein tyrosine phosphatase, receptor type, D)
Parthasarathi L, Stallings RL
Figure A - E: Illustrates the differences between the known PTPRD isoforms, as described in the text.
process called 'ectodomain shedding' is thought to be
involved in receptor desensitization, signal transduction
and/or membrane localization. Plays key role in
promoting neurite growth and regulating axon
guidance.
a tissue specific manner. The predominant isoform in
brain has an extended 711 base pair 5' UTR (L
isoform), while the isoform (S) expressed in kidney
lacks the extended 5' UTR. In addition, the brain
isoform is characterized by the absence of exons 14 to
18 corresponding to amino acid residues 568 to 978 of
the 4th through 7th fibronectin III-like domain and by
the insertion of a 12 base pair mini-exon sequence
between exons 23 and 24 (Nair et al., 2008).
The full length PTPRD isoform has an extracellular
region containing three Ig-like and eight FN-III like
domains connected via a transmembrane peptide to an
intracellular region with two PTPase domains (A),
whereas another isoform lacks four of the eight FN-III
like domains (B). Furthermore, other PTPRD isoforms
exist that lack 9 AA within the second Ig-like domain
and 4 AA at the junction of the 2nd and 3rd Ig-like
domains (C) or 9 AAs within the 5th FN-III like domain
(D). The fifth isoform lacks four of the eight FN-III
like domains and has mutation in the second Ig-like
domain (E). RT-PCR analysis demonstrated that
PTPRD isoforms lacking these short peptides are
expressed in kidney, whereas isoforms containing these
peptides are expressed in the brain (Pulido et al., 1995).
Homology
PTPRD shares a PTP domain, involved in
dephosphorylating phosphorylated tyrosine residues,
with the other receptor-like protein tyrosine
phosphatases. The human and mouse PTPRD
sequences are 93% identical and 95% homologous.
Implicated in
Lung adenocarcinoma
Disease
Early evidence for the involvement of PTPRD in lung
adenocarcinoma came from the detection of
homozygous deletions in both primary tumours and cell
lines representing both small cell lung carcinoma and
non-small cell lung carcinoma (Cox et al., 2005; Zhao
et al., 2005; Sato et al., 2005; Nagayama et al., 2007).
In addition, somatically acquired PTPRD mutations
were found in 11 out of 188 lung adenocarcinoma
samples (Weir et al., 2007). Notably, three of the
mutations encode predicated inactivating changes in the
tyrosine phosphatase domain. Screening for somatic
mutations in 623 candidate genes using 188 primary
lung adenocarcinoma tissues also revealed sequence
changes in PTPRD (Ding et al., 2008).
Localisation
Membrane; Single-pass type I membrane protein.
Function
A cleavage occurs, separating the extracellular domain
from the transmembrane segment. This
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(12)
969
PTPRD (protein tyrosine phosphatase, receptor type, D)
Parthasarathi L, Stallings RL
Neuroblastoma
Pediatric asthma
Disease
High resolution a CGH analysis of neuroblastoma
(NBL) tumours and cell lines identified homozygous
and hemizygous intragenic deletions of the PTPRD
gene, implicating the gene as a candidate tumor
suppressor gene in this type of cancer (Stallings et al.,
2006). In addition, the 5' UTR of PTPRD, consisting of
11 noncoding exons, was found to be aberrantly spliced
in > 50% of NBL primary tumors and cell lines (Nair et
al., 2008). mRNA levels were determined to be
significantly reduced in unfavorable tumour subtypes
relative to more favorable tumor subtypes.
Disease
A whole-genome linkage disequilibrium mapping study
for asthma on 190 allergic and nonallergic asthma
children in Taiwan revealed that polymorphisms of
PTPRD are strongly associated with pediatric bronchial
asthma in the Taiwanese population (Shyur et al.,
2008).
References
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Disease
Both homozygous and hemizygous deletions affecting
the PTPRD gene have been reported in squamous cell
carcinoma (Purdie et al., 2007).
Colorectal carcinoma
Urushibara N, Karasaki H, Nakamura K, Mizuno Y, Ogawa K,
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Disease
PTPRD was found to be somatically mutated in
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Disease
A high frequency of deletions in the PTPRD gene were
detected in glioblastoma multiforme (GBM) tumours
using
Affymetrix
250K
single
nucleotide
polymorphism arrays (Solomon et al., 2008). Missense
and nonsense mutations of PTPRD were also identified
in a subset of the samples lacking deletions, including
an inherited mutation with somatic loss of the wild-type
allele. The same group also identified 10 somatically
acquired mutations in PTPRD among 7 of 57
melanoma tumors (12%). Ectopic reconstitution of
wild-type PTPRD expression in GBM and melanoma
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Disease
Genome-wide association study of RLS identified three
SNPs within the PTPRD gene in the chromosome 9
linkage region (RLS3) as nominally significant
(Winkelmann et al., 2007). PTPRD is identified as the
fourth genome-wide significant locus for RLS from the
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individuals and 4749 controls from Germany, Austria,
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Atlas Genet Cytogenet Oncol Haematol. 2009; 13(12)
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This article should be referenced as such:
Parthasarathi L, Stallings RL. PTPRD (protein tyrosine
phosphatase, receptor type, D). Atlas Genet Cytogenet Oncol
Haematol. 2009; 13(12):968-971.
Stark M, Hayward N. Genome-wide loss of heterozygosity and
copy number analysis in melanoma using high-density singlenucleotide polymorphism arrays. Cancer Res. 2007 Mar
15;67(6):2632-42
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