PASD1 (PAS domain containing 1)

2013-04-01   Ghazala Khan , Barbara-Ann Guinn 

Identity

HGNC
LOCATION
Xq28
LOCUSID
ALIAS
CT63,OXTES1
FUSION GENES

DNA/RNA

Atlas Image
Structure of the PASD1 gene from which (A) PASD1_v1 and (B) PASD1_v2 and transcribed. Lines indicate introns, boxes exons, the filled box the retained intron in PASD1_v1, "atg" the predicted start site and "tga" the predicted stop site (Liggins et al., 2004a).

Description

113205 bases.

Transcription

The PASD1 gene is alternatively spliced into two transcripts named PASD1_v1 and PASD1_v2. PASD1_v2 lacks intron 14 and a retained stop signal (Liggins et al., 2004a). Differential splicing is predicted to create additional novel PASD1 isoforms as a protein smaller than PASD1_v1 and PASD1_v2 has been detected in OCi-Ly3 and FEPD cells (Cooper et al., 2006).
Transcripts found in 33% (4 of 12) acute myeloid leukaemia patients, 1 of 6 chronic myeloid leukaemia patients and 4 of 16 cell lines (Guinn et al., 2005).
Transcripts have been found in 5 of 11 multiple myeloma cell lines including THIEL and RPMI8226, and 14 of 16 primary multiple myeloma samples (Sahota et al., 2006), 22 of 25 B- and T-cell malignancy cell lines (Liggins et al., 2010).

Proteins

Atlas Image
Schematic illustration of the functional domains within the PASD1 protein. PASD1a protein translated from PASD1_v1 (A) and PASD1b translated from PASD1_v2 (B) are shown (Liggins et al., 2004a).

Description

Contains a Per Arnt Sim (PAS) domains in the N-terminal regions between aa 32-94 and aa 41-137 (Liggins et al., 2004a).

Expression

Expression highest in G361 (melanoma) and SW480 (colorectal adenocarcinoma) cell lines of a panel of nine tested. Expression in 25 of 68 solid tumours on matched tumour/normal arrays (Liggins et al., 2004a).
Expression restricted in normal tissues, placenta and testes, not detected in panel of normal tissue cDNAs. Expression also found in K562, Jurkats (T-cell leukaemia), Hn5 (head and neck cancer) and highest in H1299 (lung cancer) cell lines by real-time PCR (Guinn et al., 2005).
Of the normal tissues expression was restricted to testes and not found in a range of normal tissues including brain, liver, kidney, placenta, breast, uterus or ovary (Guinn et al., 2005; Cooper et al., 2006).
Expression of PASD1 was demonstrated in OCI-Ly3 (non-germinal centre diffuse large B-cell lymphoma-derived cells), FEDP (ALK-negative anaplastic large-cell lymphoma), Granta519 (mantle cell lymphoma) KM-H2 (Hodgkins lymphoma), K562 (chronic myeloid leukaemia) and Thiel (multiple myeloma) cell lines and 21/51 diffuse large B-cell lymphoma patients, 4/9 mantle cell lymphoma, 4/15 follicular lymphomas and a range of other tumour cells from patients with haematological malignancies (Cooper et al., 2006).
Expression has been detected in the multiple myeloma cell lines THIEL and RPMI8226, in the testis and in two of four primary multiple myeloma tumour samples (Sahota et al., 2006).
Not found in 78 basal cell carcinoma by real-time PCR (Ghafouri-Fard et al., 2010).

Localisation

In normal tissues expression was only found in the nuclei of a subpopulation of spermatogonia near the basal membrane in the testicular tubules (Cooper et al., 2006).
PASD1 protein has shown variable expression. In OCI-Ly3 cells, PASD1 expression was found on the membrane and in the cytoplasm. Nuclear staining of KM-H2, K562 and Thiel cells, nuclear and cytoplasmic staining of Granta519 (Cooper et al., 2006).

Function

The protein is thought to be a transcription factor (Entrez Gene). No role in human cell cycle (Denniss and Guinn, unpublished data). Detected by virtue of patient humoral responses (Liggins et al., 2004b; Guinn et al., 2005), it has shown to stimulate CD3+ (Guinn et al., 2005), CD4+ (Ait-Tahar et al., 2011) and CD8+ T cell responses (Ait-Tahar et al., 2009; Joseph-Pietras et al., 2010; Hardwick et al., submitted) in mixed lymphocyte reactions (MLR) and cytotoxic T lymphocyte (CTL) assays.

Homology

PASD1 has been identified in cow, chicken and mouse where it is known as GM1141 (Entrez Gene). Similarity to the CLOCK gene in mice which is essential for circadian behaviour.

Implicated in

Note
DLBCL is the most common type of non-Hodgkins lymphoma and is caused by malignant mature B lymphocytes. Around half the number of patients diagnosed die from the disease (Alizadeh et al., 2000). Using gene expression patterns two types of DLBCL have been identified, germinal centre B-like DLBCL and activated B-like DLBCL (Alizadeh et al., 2000). PASD1 antigen is recognized by DLBCL patient sera (Liggins et al., 2004b)
Prognosis
Germinal centre markers CD10, BCL6 and non-germinal centre marker MUM1 have been used to identify prognosis and survival of DLBCL patients. CD10 or BCL6 expression predicted better overall survival but MUM1 expression suggested worse overall survival (Hans et al., 2004). Germinal centre type associated with good prognosis. Patients with non-germinal centre type showed serum reactivity with PASD1, and PASD1_v2 expression was restricted to non-germinal cell lines (Liggins et al., 2004a).
Note
PASD1 was recognized by 35% of AML, 6% of CML and 10% of DLBCL sera but not the normal donor sera. Expression was found in 33% (4 of 12) AML and 17% (1 of 6) chronic myeloid leukaemia patient samples (Guinn et al., 2005) by RT-PCR and confirmed by RQ-PCR.
Entity name
Note
Cancer of the plasma cells in bone marrow. PASD1 expression has been seen in multiple myeloma cell lines by RT-PCR and in primary multiple myeloma samples by Q-PCR at presentation and previously treated cases (Sahota et al., 2006).

Bibliography

Pubmed IDLast YearTitleAuthors
208518622011CD4-positive T-helper cell responses to the PASD1 protein in patients with diffuse large B-cell lymphoma.Ait-Tahar K et al
106769512000Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.Alizadeh AA et al
170241122006PASD1, a DLBCL-associated cancer testis antigen and candidate for lymphoma immunotherapy.Cooper CD et al
198868872010Elevated expression levels of testis-specific genes TEX101 and SPATA19 in basal cell carcinoma and their correlation with clinical and pathological features.Ghafouri-Fard S et al
161126462005Humoral detection of leukaemia-associated antigens in presentation acute myeloid leukaemia.Guinn BA et al
145040782004Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray.Hans CP et al
208619112010DNA vaccines to target the cancer testis antigen PASD1 in human multiple myeloma.Joseph-Pietras D et al
207265022010A panel of cancer-testis genes exhibiting broad-spectrum expression in haematological malignancies.Liggins AP et al
171145742006PASD1 is a potential multiple myeloma-associated antigen.Sahota SS et al

Other Information

Locus ID:

NCBI: 139135
MIM: 300993
HGNC: 20686
Ensembl: ENSG00000166049

Variants:

dbSNP: 139135
ClinVar: 139135
TCGA: ENSG00000166049
COSMIC: PASD1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000166049ENST00000370357Q8IV76

Expression (GTEx)

0
5
10
15
20
25
30
35

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
259368012015Cancer/Testis Antigen PASD1 Silences the Circadian Clock.14
268920212016PASD1 promotes STAT3 activity and tumor growth by inhibiting TC45-mediated dephosphorylation of STAT3 in the nucleus.9
208619112010DNA vaccines to target the cancer testis antigen PASD1 in human multiple myeloma.4
314784312019Validation of immunogenic PASD1 peptides against HLA-A*24:02 colorectal cancer.0
315586912019PAS Domain Containing Repressor 1 (PASD1) Promotes Glioma Cell Proliferation Through Inhibiting Apoptosis In Vitro.0

Citation

Ghazala Khan ; Barbara-Ann Guinn

PASD1 (PAS domain containing 1)

Atlas Genet Cytogenet Oncol Haematol. 2013-04-01

Online version: http://atlasgeneticsoncology.org/gene/44567/pasd1