SNW1 (SNW domain containing 1)

2017-08-01   Cagla Ece Olgun , Mesut Muyan 

Middle East Technical University, Department of Biological Sciences, Cankaya 06800, Ankara, Turkey; colgun@metu.edu.tr; mmuyan@metu.edu.tr

Identity

HGNC
LOCATION
14q24.3. Genomic coordinates: 14: 77717599-77761220
IMAGE
Atlas Image
LEGEND
Human SNW1 located on chromosome 14q24.3 is on the reverse strand. (https://www.ncbi.nlm.nih.gov/gene/22938, 2017)
LOCUSID
ALIAS
Bx42,FUN20,NCOA-62,PRPF45,Prp45,SKIIP,SKIP,SKIP1

Abstract

SNW1 is a spliceosomal component and transcriptional co-regulator that provides a modulatory coupling of transcription initiation and splicing. SNW1 appears to be an essential cancer cell survival factor by co-transcriptionally regulating mRNA splicing of proteins involved in cell cycle checkpoints. As a co-regulator, SNW1 is shown to attune the activity of a number of transcription factors, including nuclear hormone receptors as well as CBF1, Smad2\/3, and MyoD by modulating a transition step between the repressing and activating transcription complex assembly. SNW1 is also involved in the cell cycle progression through the involvement in cell cycle checkpoint-dependent changes in gene expressions during cellular proliferation and viral infections.

DNA/RNA

Atlas Image
Exons are shown in boxes; introns are indicated by lines. The encoding exons are in blue. The start codon ATG and stop codon TAG are shown.

Description

The human SNW1 gene contains 14 exons.

Transcription

As a result of alternative splicing, SNW1 has two transcript variants (https://www.ncbi.nlm.nih.gov/gene/22938, 2017). The transcript 1, the long isoform, has 2207 nt mRNA which encodes a 571 amino acid (aa)-long protein (protein ID: NP_001305773.1). The transcript 2, which has 2146 nucleotides, differs in the 3 UTR and displays multiple coding region differences compared to transcript 1. One of the coding region differences results in a frame shift, giving rise to the isoform 2, which has 536 amino-acids with a distinct carboxyl-terminus (protein ID: NP_036377.1).

Pseudogene

There is one reported pseudogene located on chromosome 1 (https://www.ncbi.nlm.nih.gov/gene/22938, 2017).

Proteins

Note

SNW domain containing protein 1 is also known as nuclear protein SkiP, nuclear receptor coactivator NcoA-62 or Ski interacting protein (SKIP).

Description

The genes encoding SNW proteins are present throughout eukaryotic phylla, including lower eukaryotes, plants, fungi and animals. There is only one gene per genome, which encodes for a 60-80 kDa protein that predominantly localizes to the nucleus (Folk at al., 2004). SNW1 is suggested to contain protein interaction domains as well as a carboxyl-terminally located dimerization domain (Folk at al., 2004).

Expression

SNW1 is expressed in the brain, endocrine tissues, bone marrow and immune system, muscle, lung, liver, gall bladder, pancreas, gastrointestinal tract, kidney, urinary bladder, male and female specific tissues, adipose and soft tissues and skin, in which the expression levels are high except kidney (http://www.proteinatlas.org/ENSG00000100603-SNW1/tissue, 2017).

Localisation

SNW1 localizes in the nucleus (Dahl et al., 1998).

Function

SNW1 acts as a co-regulator for transcriptions regulated by vitamin D and RARA / RARB / RARG (retinoic acid receptors) as well as steroid hormone receptors including NR3C1 (glucocorticoid receptor), ESR1 / ESR2 (estrogen receptors), and AR (androgen receptor) (Folk at al., 2004). SNW1 also plays critical roles in the function of v-Ski avian retroviral oncogene, bone morphogenetic protein (BMP) during vertebrate embryogenesis (Wu et al, 2011), telomere function (Lackner et al, 2011) and Notch signaling-mediated transcription (Vasquez-Del Carpio, 2013). SNW1 is reported to counteract transcriptional repression induced by RB1 (retinoblastoma protein) as well (Prathapam et al. 2002). In addition to being a transcriptional co-regulator, SNW1 is an integral component of spliceosome by interacting with the U5 small nuclear ribonucleoprotein (snRNP) subcomplex of the activated spliceosome as a part of the PRPF19/nineteen complex (NTC) (Neubauer et al, 1998; Makarova et al, 2004). SNW1 inactivation is reported to cause a rapid loss of sister chromatid cohesion (Van Der Lelij et al, 2014) mitotic spindle and cytokinesis defects (Kittler et al, 2004; Kittler et al, 2005). It is also suggested that the involvement of SNW1 in the p21-gene specific splicing is critical for cancer cell survival under stress (Chen et al, 2011).

Homology

Homologs of SNW1 are found in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.pombe, M.oryzae, N.crassa, A.thaliana, rice, and frog (https://www.ncbi.nlm.nih.gov/gene/22938, 2017).

Mutations

Note

There are no gene mutations described for SNW1.

Implicated in

Entity name
Bladder cancer
Note
SNW1 displays a higher expression in bladder tumor tissue than surrounding normal adjacent tissues. Higher expression of SNW1 appears to be correlated with poor prognosis of bladder cancer. It is also reported that high-grade urothelial carcinoma samples express higher levels of SNW1 compared with low-grade urothelial carcinoma samples (Wang et al., 2014).
Entity name
Breast cancer
Note
Immunohistochemical and western blot analyses of breast carcinoma samples showed that the SNW1 expression is augmented in breast cancer tissues compared with adjacent noncancerous tissues. SNW1 overexpression appears to have a positive correlation with the histological grade of cancerous tissues. Moreover, it is suggested that there is an inverse relationship between the SNW1 expression and pathologic prognostic parameters including estrogen (ER) and progesterone receptors status. In ER positive cell models derived from breast carcinoma, there is a lower expression of SNW1 when it is compared with the expression levels of SNW1 in ER negative cell models (Liu et al., 2014).
Entity name
Hepatocellular carcinoma
Note
Expression analyses of SNW1 with samples of hepatocellular carcinoma patients and normal liver samples revealed that SNW1 is overexpressed in cancerous cells when compared with noncancerous liver samples. There is a positive correlation between high SNW1 expression and aggressiveness of hepatocellular carcinoma (Liu et al., 2013).
Entity name
Malignant pleural mesothelioma
Note
As in other cancer types, SNW1 is overexpressed in malignant pleural mesotheliomas (MPM) patients, which is correlated with poor prognosis. Overexpression of SNW1 also correlates with a reduced survival rate in MPM patient cohort (Turkcu et al., 2016).

Bibliography

Pubmed IDLast YearTitleAuthors
214600372011SKIP counteracts p53-mediated apoptosis via selective regulation of p21Cip1 mRNA splicing.Chen Y et al
95690251998The Ski oncoprotein interacts with Skip, the human homolog of Drosophila Bx42.Dahl R et al
150524072004Transcriptional coregulator SNW/SKIP: the concealed tie of dissimilar pathways.Folk P et al
156953302005RNA interference rescue by bacterial artificial chromosome transgenesis in mammalian tissue culture cells.Kittler R et al
217608792011A siRNA-based screen for genes involved in chromosome end protection.Lackner DH et al
236960202013High SKIP expression is correlated with poor prognosis and cell proliferation of hepatocellular carcinoma.Liu G et al
241507872014Expression and prognostic role of SKIP in human breast carcinoma.Liu X et al
151756532004A subset of human 35S U5 proteins, including Prp19, function prior to catalytic step 1 of splicing.Makarova OV et al
97315291998Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex.Neubauer G et al
124665512002Skip interacts with the retinoblastoma tumor suppressor and inhibits its transcriptional repression activity.Prathapam T et al
275438642016Comparison of SKIP expression in malignant pleural mesotheliomas with Ki-67 proliferation index and prognostic parameters.Türkcü G et al
212453872011Assembly of a Notch transcriptional activation complex requires multimerization.Vasquez-Del Carpio R et al
248179662014SKIP expression is correlated with clinical prognosis in patients with bladder cancer.Wang L et al
213588022011SNW1 is a critical regulator of spatial BMP activity, neural plate border formation, and neural crest specification in vertebrate embryos.Wu MY et al
252573092014SNW1 enables sister chromatid cohesion by mediating the splicing of sororin and APC2 pre-mRNAs.van der Lelij P et al

Other Information

Locus ID:

NCBI: 22938
MIM: 603055
HGNC: 16696
Ensembl: ENSG00000100603

Variants:

dbSNP: 22938
ClinVar: 22938
TCGA: ENSG00000100603
COSMIC: SNW1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000100603ENST00000261531Q13573
ENSG00000100603ENST00000554324G3V5R3
ENSG00000100603ENST00000554775G3V4X8
ENSG00000100603ENST00000555761G3V3A4
ENSG00000100603ENST00000556428G3V4E0

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
Notch signaling pathwayKEGGko04330
Notch signaling pathwayKEGGhsa04330
SpliceosomeKEGGko03040
SpliceosomeKEGGhsa03040
Spliceosome, 35S U5-snRNPKEGGhsa_M00355
Epstein-Barr virus infectionKEGGhsa05169
Epstein-Barr virus infectionKEGGko05169
Viral carcinogenesisKEGGhsa05203
Viral carcinogenesisKEGGko05203
Spliceosome, 35S U5-snRNPKEGGM00355
DiseaseREACTOMER-HSA-1643685
Diseases of signal transductionREACTOMER-HSA-5663202
Signaling by NOTCH1 in CancerREACTOMER-HSA-2644603
Signaling by NOTCH1 PEST Domain Mutants in CancerREACTOMER-HSA-2644602
Constitutive Signaling by NOTCH1 PEST Domain MutantsREACTOMER-HSA-2644606
Signaling by NOTCH1 HD+PEST Domain Mutants in CancerREACTOMER-HSA-2894858
Constitutive Signaling by NOTCH1 HD+PEST Domain MutantsREACTOMER-HSA-2894862
Signal TransductionREACTOMER-HSA-162582
Signaling by TGF-beta Receptor ComplexREACTOMER-HSA-170834
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimerREACTOMER-HSA-2173793
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcriptionREACTOMER-HSA-2173796
Signaling by NOTCHREACTOMER-HSA-157118
Pre-NOTCH Expression and ProcessingREACTOMER-HSA-1912422
Pre-NOTCH Transcription and TranslationREACTOMER-HSA-1912408
Signaling by NOTCH1REACTOMER-HSA-1980143
NOTCH1 Intracellular Domain Regulates TranscriptionREACTOMER-HSA-2122947
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Notch-HLH transcription pathwayREACTOMER-HSA-350054
Processing of Capped Intron-Containing Pre-mRNAREACTOMER-HSA-72203
mRNA SplicingREACTOMER-HSA-72172
mRNA Splicing - Major PathwayREACTOMER-HSA-72163

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
221726772011Arl8 and SKIP act together to link lysosomes to kinesin-1.81
189963442008Structure and function of Salmonella SifA indicate that its interactions with SKIP, SseJ, and RhoA family GTPases induce endosomal tubulation.63
159054092005A human splicing factor, SKIP, associates with P-TEFb and enhances transcription elongation by HIV-1 Tat.60
128400152003Nuclear coactivator-62 kDa/Ski-interacting protein is a nuclear matrix-associated coactivator that may couple vitamin D receptor-mediated transcription and RNA splicing.58
198528512009Asthma and genes encoding components of the vitamin D pathway.44
198187112009SKIP interacts with c-Myc and Menin to promote HIV-1 Tat transactivation.36
214600372011SKIP counteracts p53-mediated apoptosis via selective regulation of p21Cip1 mRNA splicing.30
252573092014SNW1 enables sister chromatid cohesion by mediating the splicing of sororin and APC2 pre-mRNAs.24
161029182005CHES1/FOXN3 interacts with Ski-interacting protein and acts as a transcriptional repressor.19
263937902015Dynamic Contacts of U2, RES, Cwc25, Prp8 and Prp45 Proteins with the Pre-mRNA Branch-Site and 3' Splice Site during Catalytic Activation and Step 1 Catalysis in Yeast Spliceosomes.18

Citation

Cagla Ece Olgun ; Mesut Muyan

SNW1 (SNW domain containing 1)

Atlas Genet Cytogenet Oncol Haematol. 2017-08-01

Online version: http://atlasgeneticsoncology.org/gene/42348/snw1