IL1RAPL1, encoded by the IL1RAPL1 gene, is a transmembrane protein which belongs to a new Toll/IL-1 receptor family, with the high homology to interleukin-1 receptor accessory protein. However, it has no effect on immune signals. The encoded protein has 696 amino acids and contains an N-terminal signal peptide, three extracellular immunoglobulin (Ig)-like domains, a membrane-spanning domain, an intracellular Toll/IL-1R homology domain (TIR domain), and a long C-terminal tail interacting with multiple signaling molecules.
Basic Information of IL1RAPL1 | |
Protein Name | Interleukin-1 receptor accessory protein-like 1 |
Gene Name | IL1RAPL1 |
Aliases | IL1R8, MRX10, MRX21, MRX34, OPHN4, IL1RAPL, TIGIRR-2 |
Organism | Homo sapiens (Human) |
UniProt ID | Q9NZN1 |
TransmIL1RAPL1rane Times | 1 |
Length (aa) | 696 |
Sequence | MKAPIPHLILLYATFTQSLKVVTKRGSADGCTDWSIDIKKYQVLVGEPVRIKCALFYGYIRTNYSLAQSAGLSLMWYKSSGPGDFEEPIAFDGSRMSKEEDSIWFRPTLLQDSGLYACVIRNSTYCMKVSISLTVGENDTGLCYNSKMKYFEKAELSKSKEISCRDIEDFLLPTREPEILWYKECRTKTWRPSIVFKRDTLLIREVREDDIGNYTCELKYGGFVVRRTTELTVTAPLTDKPPKLLYPMESKLTIQETQLGDSANLTCRAFFGYSGDVSPLIYWMKGEKFIEDLDENRVWESDIRILKEHLGEQEVSISLIVDSVEEGDLGNYSCYVENGNGRRHASVLLHKRELMYTVELAGGLGAILLLLVCLVTIYKCYKIEIMLFYRNHFGAEELDGDNKDYDAYLSYTKVDPDQWNQETGEEERFALEILPDMLEKHYGYKLFIPDRDLIPTGTYIEDVARCVDQSKRLIIVMTPNYVVRRGWSIFELETRLRNMLVTGEIKVILIECSELRGIMNYQEVEALKHTIKLLTVIKWHGPKCNKLNSKFWKRLQYEMPFKRIEPITHEQALDVSEQGPFGELQTVSAISMAAATSTALATAHPDLRSTFHNTYHSQMRQKHYYRSYEYDVPPTGTLPLTSIGNQHTYCNIPMTLINGQRPQTKSSREQNPDEAHTNSAILPLLPRETSISSVIW |
IL1RAPL1 has been shown to play a role in the presynaptic differentiation, synapse formation as well as dendritic spine formation and stabilization. IL1RAPL1 can interact with particular splice variants of PTPδ localized at the presynaptic terminal to promote the excitatory synapse formation. IL1RAPL1 also regulates the vesicle cycling in the presynaptic membrane through suppressing calcium-dependent exocytosis and neurotransmitter release. The deficiency of IL1RAPL1 can decrease the number of dendritic protrusions in neuron culture, while IL1RAPL1 overexpression can increase staining signals of excitatory postsynaptic protein VGLUT1 and dendritic spine number. Many physiological studies have been revealed IL1RAPL1 is involved in the regulation of learning and memory abilities. IL1RAPL1 has been revealed to be mainly expressed in memory/concentration-associated encephalic regions, such as dentate fascia, osmosis epithelium, hippocampus, and piriform cortex, involved in the regulation of cognitive ability. Null mutations in IL1RAPL1 are associated with impaired memory and learning abilities. It has been revealed that IL1RAPL1 is linked to X-linked form of cognitive impairment and autism spectrum disorder.
Fig.1 Structure of the IL1RAPL1 protein.
The study reports a boy who carries a complex IL1RAPL1 intragenic rearrangement displays intellectual disability, unusual facial and digital anomalies.
The study indicates that the minor allele rs12007907-A in IL1RAPL gene is negatively linked to asthma susceptibility and IL-13 production and the association between them may depend on sex.
The authors suggest a specific function of IL1RAPL1 in regulating dendrite morphology which helps to explain the mechanism of the development of cognitive disorders mediated by IL1RAPL1.
The study shows that trans-synaptic PTPδ/IL1RAPL1 interaction plays an important role in synaptogenesis and intellectual disability.
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