SHARPIN
SHANK-Associated RH Domain Interactor; Regulator of NF-κB and Ubiquitination
Gene Information Card
| Symbol | SHARPIN |
|---|---|
| Full Name | SHANK-Associated RH Domain Interactor |
| Gene Type | Protein coding |
| Chromosomal Location | 8q24.3 |
| NCBI Gene ID | 81858 ncbi.nlm.nih.gov/gene/81858 |
| Ensembl ID | ENSG00000144711 |
| UniProt ID | Q9H0F6 |
| OMIM ID | 611885 |
| HGNC ID | 25321 |
| Aliases | SHARPIN, SIPL1, hSharpin, PSEC0166 |
Description
SHARPIN encodes a protein that functions as a component of the linear ubiquitin chain assembly complex (LUBAC), which conjugates linear polyubiquitin chains to substrates, thereby regulating NF-κB activation and immune signaling. It is also involved in cell adhesion and cytoskeletal organization via interaction with SHANK proteins.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Chronic proliferative dermatitis (cpdm) | Loss of SHARPIN leads to impaired NF-κB activation and increased apoptosis, causing skin inflammation and immune dysregulation. | Mouse model (cpdm); OMIM 611885 |
| Primary immunodeficiency | SHARPIN mutations impair LUBAC function, reducing NF-κB signaling and leading to recurrent infections. | Human case reports; ClinVar |
| Cancer (various) | SHARPIN overexpression or mutation may alter NF-κB activity, promoting tumorigenesis. | COSMIC; literature review |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Lymph node | 8.3 | Medium |
| Spleen | 7.1 | Medium |
| Bone marrow | 6.4 | Low |
| Brain | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HeLa | 10.8 | Moderate expression |
| Jurkat | 7.5 | Moderate expression |
| K562 | 5.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.196C>T (p.Gln66*) | Nonsense | Rare | Loss of function; truncation of SHARPIN protein |
| c.340G>A (p.Glu114Lys) | Missense | Rare | Impaired LUBAC assembly; reduced NF-κB activation |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of translation initiation; complete loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate SHARPIN or abolish its expression, leading to defective LUBAC activity and impaired NF-κB signaling.
Gain of Function (GOF)
Not well documented; potential overexpression in some cancers may enhance NF-κB activity.
Dominant Negative (DN)
Missense mutations that disrupt LUBAC complex formation without complete loss of wild-type allele.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity (GO:0004842) | • protein binding (GO:0005515) |
| • I-kappaB kinase/NF-kappaB signaling (GO:0007249) | • cytoplasm (GO:0005737) |
| • cytosol (GO:0005829) |
Pathways
• NF-kappa B signaling pathway (KEGG hsa04064)
• Linear ubiquitination pathway (Reactome R-HSA-983168)
• TNF signaling pathway (KEGG hsa04668)
Protein Summary
SHARPIN is a 387-amino acid protein containing a ubiquitin-like (UBL) domain and a RH domain. It is a core component of LUBAC, which catalyzes linear (M1-linked) ubiquitination of target proteins such as NEMO and RIPK1, promoting NF-κB activation and cell survival. SHARPIN also interacts with SHANK proteins at synapses, suggesting roles in neuronal signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SHARPIN Knockout HEK293 Cell Line | EDJ-KQ51774 | Human | 81858 | Details Get a Quote |
| SHARPIN Knockout HeLa Cell Line | EDJ-KQ57423 | Human | 81858 | Details Get a Quote |
| SHARPIN Knockout A-549 Cell Line | EDJ-KQ65928 | Human | 81858 | Details Get a Quote |
| SHARPIN Knockout HCT 116 Cell Line | EDJ-KQ74354 | Human | 81858 | Details Get a Quote |
