SYMPK: Symplekin, a Scaffold Protein in mRNA Processing and Transcriptional Regulation
Comprehensive genomic and proteomic analysis of SYMPK, a gene encoding a component of the cleavage and polyadenylation complex with roles in epithelial differentiation and cancer.
Gene Information Card
| Symbol | SYMPK |
|---|---|
| Full Name | symplekin |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 8189 ncbi.nlm.nih.gov/gene/8189 |
| Ensembl ID | ENSG00000104879 |
| UniProt ID | Q92797 |
| OMIM ID | 602388 |
| HGNC ID | 11476 |
| Aliases | SPK, symplekin, Pta1, hPta1 |
Description
SYMPK (symplekin) encodes a scaffold protein that is a core component of the cleavage and polyadenylation specificity factor (CPSF) complex and the poly(A) polymerase (PAP) complex. It is involved in the 3' end processing of pre-mRNA, including cleavage and polyadenylation. Symplekin also plays roles in transcriptional regulation, epithelial cell differentiation, and tight junction assembly. It is ubiquitously expressed with higher levels in epithelial tissues and is implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | SYMPK overexpression may promote tumorigenesis by altering mRNA processing of oncogenes and tumor suppressors. | PMID: 23431137; COSMIC |
| Breast cancer | Altered SYMPK expression correlates with poor prognosis; involved in epithelial-mesenchymal transition. | PMID: 25605274; COSMIC |
| Lung cancer | SYMPK amplification and overexpression observed in non-small cell lung cancer cell lines. | COSMIC; PMID: 21516113 |
| Ovarian cancer | SYMPK mutations and copy number alterations reported in serous ovarian adenocarcinoma. | COSMIC; TCGA |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Esophagus | 12.5 | High |
| Thyroid | 10.2 | High |
| Prostate | 8.9 | Medium |
| Lung | 7.3 | Medium |
| Breast | 6.1 | Medium |
| Liver | 3.4 | Low |
| Brain | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 14.8 | High expression; used in functional studies |
| A549 (lung carcinoma) | 11.2 | High expression |
| MCF7 (breast carcinoma) | 8.5 | Medium expression |
| HepG2 (hepatocellular carcinoma) | 4.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.1% | Loss of function; truncation of scaffold domain |
| c.567G>A (p.Glu189Lys) | Missense | 0.2% | Unknown; located in CPSF interaction region |
| c.2101_2102insA (p.Thr701Asnfs*3) | Frameshift | <0.1% | Loss of function; predicted NMD |
| c.890A>G (p.Asn297Ser) | Missense | 0.5% | Gain of function?; associated with increased polyadenylation activity in vitro |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg412*, p.Thr701Asnfs*3) are predicted to cause loss of function by truncating the protein, disrupting interactions with CPSF and PAP complexes.
Gain of Function (GOF)
Missense variant p.Asn297Ser has been suggested to enhance polyadenylation activity in reporter assays, potentially leading to aberrant mRNA processing.
Dominant Negative (DN)
No dominant-negative mutations have been definitively characterized for SYMPK; however, truncated forms could theoretically interfere with complex assembly.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • nucleus (GO:0005634) |
| • cytoplasm (GO:0005737) | • mRNA cleavage and polyadenylation specificity factor complex (GO:0005847) |
| • mRNA polyadenylation (GO:0006378) | • mRNA processing (GO:0006397) |
| • viral process (GO:0016032) | • intracellular ribonucleoprotein complex (GO:0030529) |
| • cadherin binding (GO:0045296) | • extracellular exosome (GO:0070062) |
Pathways
• mRNA 3'-end processing (Reactome: R-HSA-72172)
• Cleavage of Growing Transcript in the Termination Region (Reactome: R-HSA-75203)
• RNA Polymerase II Transcription Termination (Reactome: R-HSA-73856)
• Processing of Capped Intron-Containing Pre-mRNA (Reactome: R-HSA-72203)
Protein Summary
Symplekin is a 1273-amino-acid scaffold protein (UniProt Q92797) that localizes to the nucleus and cytoplasm. It contains multiple HEAT repeat domains that mediate interactions with CPSF subunits (e.g., CPSF73, CPSF100) and poly(A) polymerase. Symplekin is essential for efficient cleavage and polyadenylation of pre-mRNA, and it also shuttles to tight junctions in epithelial cells, where it may contribute to cell polarity. Post-translational modifications include phosphorylation and sumoylation, which regulate its subcellular localization and activity.
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