Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9BF7RC)

DOT Name SLP adapter and CSK-interacting membrane protein (SCIMP)
Synonyms SLP65/SLP76, Csk-interacting membrane protein
Gene Name SCIMP
Related Disease
Alzheimer disease ( )
UniProt ID
SCIMP_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF15050
Sequence
MDTFTVQDSTAMSWWRNNFWIILAVAIIVVSVGLGLILYCVCKWQLRRGKKWEIAKPLKH
KQVDEEKMYENVLNESPVQLPPLPPRNWPSLEDSSPQEAPSQPPATYSLVNKVKNKKTVS
IPSYIEPEDDYDDVEIPANTEKASF
Function
Lipid tetraspanin-associated transmembrane adapter/mediator that acts as a scaffold for Src-family kinases and other signaling proteins in immune cells. It is involved in major histocompatibility complex class II (MHC-II) signaling transduction in B cells, where it is required in generating the calcium response and enhancing ERK activity upon MHC-II stimulation. In dendritic cells, it is involved in sustaining CLEC7A/DECTIN1 signaling after CLEC7A activation by fungal beta-glucans. It also acts as an agonist-inducible signaling adapter for TLR1, TLR2, TLR3, TLR4, and TLR7 by selectively enabling the expression of pro-inflammatory cytokines IL6 and IL12B in macrophages and acting as a scaffold for phosphorylation of Toll-like receptors by Src-family kinases.
Tissue Specificity
Expressed in antigen-presenting cells, like peripheral blood leukocytes and monocyte-derived dendritic cells (MDDC) (at protein level) . Highly expressed in lymph nodes and spleen. Expressed in antigen-presenting cells . Faintly expressed in the majority of nonimmune system tissues .

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alzheimer disease DISF8S70 Strong Genetic Variation [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of SLP adapter and CSK-interacting membrane protein (SCIMP). [2]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of SLP adapter and CSK-interacting membrane protein (SCIMP). [3]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of SLP adapter and CSK-interacting membrane protein (SCIMP). [4]
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References

1 Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project.Alzheimers Dement. 2019 Oct;15(10):1333-1347. doi: 10.1016/j.jalz.2019.06.4950. Epub 2019 Aug 28.
2 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
3 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
4 BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.