An official website of the United States government

Sharpin - SHANK-associated RH domain interactor (Norway rat)

Gene
Symbol
Dates
  • Create:
    2016-09-14
  • Modify:
    2025-01-15
Description
Enables identical protein binding activity. Predicted to be involved in several processes, including proteasome-mediated ubiquitin-dependent protein catabolic process; protein linear polyubiquitination; and regulation of signal transduction. Predicted to act upstream of or within apoptotic nuclear changes; keratinization; and mitochondrion organization. Located in dendrite. Is active in glutamatergic synapse and postsynaptic density. Orthologous to human SHARPIN (SHANK associated RH domain interactor).

1 Names and Identifiers

1.1 Synonyms

  • Conneck1
  • sharpin
  • SHANK-associated RH domain interacting protein
  • shank-associated RH domain-interacting protein
  • shank-interacting protein

1.2 Other Identifiers

1.2.1 Ensembl ID

1.2.2 Alliance Gene ID

1.2.3 Bgee Gene ID

1.2.4 RGD ID

1.2.5 Wikidata

3 Proteins

3.1 Protein Function

Component of the LUBAC complex which conjugates linear polyubiquitin chains in a head-to-tail manner to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation. LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways. Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation. LUBAC is recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex. The LUBAC complex is also involved in innate immunity by conjugating linear polyubiquitin chains at the surface of bacteria invading the cytosol to form the ubiquitin coat surrounding bacteria. LUBAC is not able to initiate formation of the bacterial ubiquitin coat, and can only promote formation of linear polyubiquitins on pre-existing ubiquitin. The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation. Together with OTULIN, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis.

3.2 Protein 3D Structures

3.2.1 AlphaFold Structures

Highly accurate protein structure prediction with AlphaFold. Nature. 2021 Aug;596(7873):583-589. DOI:10.1038/s41586-021-03819-2. PMID:34265844; PMCID:PMC8371605

3.3 Protein Targets

4 Interactions and Pathways

4.1 Interactions

5 Expression

6 Literature

6.1 Consolidated References

6.2 Gene-Chemical Co-Occurrences in Literature

6.3 Gene-Gene Co-Occurrences in Literature

6.4 Gene-Disease Co-Occurrences in Literature

7 Patents

7.1 Gene-Chemical Co-Occurrences in Patents

7.2 Gene-Gene Co-Occurrences in Patents

7.3 Gene-Disease Co-Occurrences in Patents

8 Information Sources

  1. NCBI Gene
    LICENSE
    NCBI Website and Data Usage Policies and Disclaimers
    https://www.ncbi.nlm.nih.gov/home/about/policies/
  2. PubChem
  3. Alliance of Genome Resources
    LICENSE
    All annotations and data produced by Alliance members that are accessible from alliancegenome.org are distributed under a CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
    https://www.alliancegenome.org/privacy-warranty-licensing
  4. BioGRID
    LICENSE
    The MIT License (MIT); Copyright Mike Tyers Lab
    https://wiki.thebiogrid.org/doku.php/terms_and_conditions
  5. STRING: functional protein association networks
  6. NCBI Gene Expression Omnibus (GEO)
  7. Rat Genome Database (RGD)
    LICENSE
    Creative Commons Attribution 4.0 International license (CC BY 4.0)
    https://creativecommons.org/licenses/by/4.0/
  8. Swiss Institute of Bioinformatics Bgee
    LICENSE
    Creative Commons Zero license (CC0)
    https://www.bgee.org/about/
  9. UniProt
    LICENSE
    We have chosen to apply the Creative Commons Attribution (CC BY 4.0, http://creativecommons.org/licenses/by/4.0/) License to all copyrightable parts of our databases.
    https://www.uniprot.org/help/license
  10. Wikidata
  11. AlphaFold DB
    LICENSE
    All of the data provided is freely available for both academic and commercial use under Creative Commons Attribution 4.0 (CC-BY 4.0) licence terms.
    https://alphafold.ebi.ac.uk/faq
CONTENTS