| HGNC Family | Signal-regulatory proteins (SIRP), Immunoglobulin superfamily domain containing |
| Name | signal-regulatory protein delta |
| Description | Predicted to be located in extracellular region. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Mar 2025] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNeurotrypsin, also known as motopsin, is a synaptic serine protease secreted by neuronal cells in an activity‐dependent manner that specifically cleaves the heparan sulfate proteoglycan agrin at defined sites. This cleavage, which occurs preferentially on heavily glycanated agrin variants localized at synapses, is critical for the formation and dynamic remodeling of excitatory synapses, thereby impacting cognitive processes such as learning and memory. The protease acts as a coincidence detector that integrates presynaptic action potential firing and postsynaptic NMDA receptor activation to regulate dendritic filopodia formation—a precursor to mature synapse establishment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its enzymatic processing of agrin, neurotrypsin/motopsin influences neuronal architecture and behavior. Deficiencies in this protease result in severe intellectual disability in humans, altered social behaviors in mice, and notable changes in dendritic spine density and morphology—findings supported by studies reporting decreased apical spine density and aberrant dendritic maturation in hippocampal neurons. In addition, its multi-domain structure, which includes several scavenger receptor cysteine-rich domains, is implicated in interactions with partners such as seizure-related gene 6 (sez-6), potentially modulating neurite outgrowth and synaptic environment organization."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRegulation of neurotrypsin expression and activity involves complex transcriptional and post-translational mechanisms. Presenilins, acting through γ-secretase–independent pathways, modulate neurotrypsin gene expression by influencing CREB signaling and epigenetic marks at its promoter, thereby indirectly controlling agrin cleavage. Structural studies of its conserved SRCR domains reveal potential calcium-binding sites that might further regulate its proteolytic activity. Moreover, studies of motopsin overexpression demonstrate that not only does altered protease activity impact dendritic spine composition, but it may also play a role in promoting adult neurogenesis, highlighting its multifaceted contribution to neuronal plasticity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alexander Stephan, José María Mateos, Serguei V Kozlov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neurotrypsin cleaves agrin locally at the synapse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.07-100008"}], "href": "https://doi.org/10.1096/fj.07-100008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18230682"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18230682"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kazumasa Matsumoto-Miyai, Ewa Sokolowska, Andreas Zurlinden, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Coincident pre- and postsynaptic activation induces dendritic filopodia via neurotrypsin-dependent agrin cleavage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2009.02.034"}], "href": "https://doi.org/10.1016/j.cell.2009.02.034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19303856"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19303856"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shinichi Mitsui, Yoji Osako, Fumiaki Yokoi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A mental retardation gene, motopsin/neurotrypsin/prss12, modulates hippocampal function and social interaction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Neurosci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1460-9568.2009.07029.x"}], "href": "https://doi.org/10.1111/j.1460-9568.2009.07029.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20092579"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20092579"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shinichi Mitsui, Nozomi Yamaguchi, Yoji Osako, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Enzymatic properties and localization of motopsin (PRSS12), a protease whose absence causes mental retardation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.brainres.2006.11.094"}], "href": "https://doi.org/10.1016/j.brainres.2006.11.094"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17223089"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17223089"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shinichi Mitsui, Chiharu Hidaka, Mutsuo Furihata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A mental retardation gene, motopsin/prss12, modulates cell morphology by interaction with seizure-related gene 6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2013.04.112"}], "href": "https://doi.org/10.1016/j.bbrc.2013.04.112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23770366"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23770366"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Angels Almenar-Queralt, Sonia N Kim, Christopher Benner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Presenilins regulate neurotrypsin gene expression and neurotrypsin-dependent agrin cleavage via cyclic AMP response element-binding protein (CREB) modulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.513705"}], "href": "https://doi.org/10.1074/jbc.M113.513705"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24145027"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24145027"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Anselmo Canciani, Gianluca Catucci, Federico Forneris "}, {"type": "b", "children": [{"type": "t", "text": "Structural characterization of the third scavenger receptor cysteine-rich domain of murine neurotrypsin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Protein Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pro.3587"}], "href": "https://doi.org/10.1002/pro.3587"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30748049"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30748049"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Shiori Miyata, Masayuki Tsuda, Shinichi Mitsui "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of Motopsin, an Extracellular Serine Protease Related to Intellectual Disability, Promotes Adult Neurogenesis and Neuronal Responsiveness in the Dentate Gyrus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Neurobiol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12035-023-03890-y"}], "href": "https://doi.org/10.1007/s12035-023-03890-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38153682"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38153682"}]}]}]}
|
| Synonyms | PTPNS1L2, DJ576H24.4 |
| Proteins | SIRPD_HUMAN |
| NCBI Gene ID | 128646 |
| API | |
| Download Associations | |
| Predicted Functions |
 |
| Co-expressed Genes |
|
| Expression in Tissues and Cell Lines |
|
SIRPD has 1,372 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 60 datasets.
Click the + buttons to view associations for SIRPD from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of SIRPD gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset. | |
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of SIRPD gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray | tissue samples with high or low expression of SIRPD gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of SIRPD gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset. | |
| BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of SIRPD gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of SIRPD gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| CCLE Cell Line Gene Expression Profiles | cell lines with high or low expression of SIRPD gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
| ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of SIRPD gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of SIRPD gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset. | |
| ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of SIRPD gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| CM4AI KOLF21J CRISPRi Gene Perturbation Atlas | gene perturbations changing expression of SIRPD gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing SIRPD protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with SIRPD protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| COSMIC Cell Line Gene CNV Profiles | cell lines with high or low copy number of SIRPD gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with SIRPD gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by SIRPD gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores 2025 | diseases associated with SIRPD gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with SIRPD gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with SIRPD gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at SIRPD gene from the ENCODE Histone Modification Site Profiles dataset. | |
| ENCODE Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of SIRPD gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of SIRPD gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing SIRPD from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of SIRPD gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of SIRPD gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of SIRPD gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of SIRPD gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing SIRPD protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GTEx eQTL 2025 | SNPs regulating expression of SIRPD gene from the GTEx eQTL 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of SIRPD gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of SIRPD gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with SIRPD gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| GWASdb SNP-Disease Associations | diseases associated with SIRPD gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset. | |
| GWASdb SNP-Phenotype Associations | phenotypes associated with SIRPD gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset. | |
| Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of SIRPD gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
| HPA Tissue Gene Expression Profiles | tissues with high or low expression of SIRPD gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
| HPA Tissue Protein Expression Profiles | tissues with high or low expression of SIRPD protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset. | |
| HPA Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of SIRPD gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with SIRPD gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| IMPC Knockout Mouse Phenotypes | phenotypes of mice caused by SIRPD gene knockout from the IMPC Knockout Mouse Phenotypes dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for SIRPD protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of SIRPD gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of SIRPD gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of SIRPD gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of SIRPD gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain SIRPD protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by SIRPD gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of SIRPD gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| Pathway Commons Protein-Protein Interactions | interacting proteins for SIRPD from the Pathway Commons Protein-Protein Interactions dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at SIRPD gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of SIRPD gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of SIRPD gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of SIRPD gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of SIRPD gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of SIRPD gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores | tissues with high expression of SIRPD protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of SIRPD protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores | tissues with high expression of SIRPD protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of SIRPD protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with SIRPD protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
