Prss12 serine protease 12 neurotrypsin (motopsin) [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Prss12provided by MGI
Official Full Name: serine protease 12 neurotrypsin (motopsin)provided by MGI
Primary source: MGI:MGI:1100881
See related: Ensembl:ENSMUSG00000027978 AllianceGenome:MGI:1100881
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Bssp-3; motopsin
Summary: Enables serine-type endopeptidase activity. Involved in exocytosis. Acts upstream of or within zymogen activation. Located in several cellular components, including dendrite; synaptic cleft; and terminal bouton. Is active in Schaffer collateral - CA1 synapse; glutamatergic synapse; and presynapse. Is expressed in several structures, including alimentary system; central nervous system; genitourinary system; immune system; and sensory organ. Human ortholog(s) of this gene implicated in autosomal recessive intellectual developmental disorder 1 and intellectual disability. Orthologous to human PRSS12 (serine protease 12). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Broad expression in limb E14.5 (RPKM 5.7), frontal lobe adult (RPKM 5.1) and 20 other tissues See more
Orthologs: human all
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Genomic context

Location:: 3 G1; 3 54.58 cM

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	3	NC_000069.7 (123240562..123300251)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	3	NC_000069.6 (123446913..123506602)

Chromosome 3 - NC_000069.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Overexpression of Motopsin, an Extracellular Serine Protease Related to Intellectual Disability, Promotes Adult Neurogenesis and Neuronal Responsiveness in the Dentate Gyrus.
Title: Overexpression of Motopsin, an Extracellular Serine Protease Related to Intellectual Disability, Promotes Adult Neurogenesis and Neuronal Responsiveness in the Dentate Gyrus.
This study determined the crystal structure of the third scavenger receptor cysteine-rich (SRCR) domain of murine neurotrypsin, immediately preceding the C-terminal serine-protease (SP) domain and performed a comparative structural analysis using homologous SRCR structures.
Title: Structural characterization of the third scavenger receptor cysteine-rich domain of murine neurotrypsin.
This study identifies Tequila and neurotrypsin as new genes repressed by presenilins and reveals a novel mechanism used by presenilins to modulate CREB signaling based on controlling CREB recruitment.
Title: Presenilins regulate neurotrypsin gene expression and neurotrypsin-dependent agrin cleavage via cyclic AMP response element-binding protein (CREB) modulation.
co-expression of sez-6 with motopsin restored the effect of motopsin at the basal level, while sez-6 expression alone showed no effects on cell morphology. Our results suggest that the interaction of motopsin and sez-6 modulates neuronal cell morphology
Title: A mental retardation gene, motopsin/prss12, modulates cell morphology by interaction with seizure-related gene 6.
Our results indicate that an extracellular protease, motopsin, preferentially affects social behaviors, and modulates the functions of hippocampal neurons.
Title: A mental retardation gene, motopsin/neurotrypsin/prss12, modulates hippocampal function and social interaction.
Detailed analyses indicated that presynaptic action potential firing is necessary for the release of neurotrypsin, whereas postsynaptic NMDA receptor activation is necessary for the neurotrypsin-dependent cleavage of agrin.
Title: Coincident pre- and postsynaptic activation induces dendritic filopodia via neurotrypsin-dependent agrin cleavage.
neurotrypsin exclusively cleaves glycanated variants of agrin; neurotrypsin-dependent cleavage of agrin was concentrated at synapses, where the most heavily glycanated variants of agrin predominate
Title: Neurotrypsin cleaves agrin locally at the synapse.
motopsin has multiple functions, such as axon outgrowth, arranging perineuronal environment, and maintaining neuronal plasticity, partly in coordination with other proteases including tissue plasminogen activator.
Title: Enzymatic properties and localization of motopsin (PRSS12), a protease whose absence causes mental retardation.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2)
Targeted (4) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Prss12 (e-PCR), detects polymorphism
- UniSTS:496012

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables peptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables serine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in exocytosis	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within proteolysis	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within zymogen activation	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in Schaffer collateral - CA1 synapse	IDA Inferred from Direct Assay more info	PubMed
located_in axon	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
is_active_in dendrite	IBA Inferred from Biological aspect of Ancestor more info
located_in dendrite	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in presynapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in presynapse	ISO Inferred from Sequence Orthology more info
located_in synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in synaptic cleft	IBA Inferred from Biological aspect of Ancestor more info
located_in synaptic cleft	IDA Inferred from Direct Assay more info	PubMed
is_active_in terminal bouton	IBA Inferred from Biological aspect of Ancestor more info
located_in terminal bouton	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: neurotrypsin

Names: brain-specific serine protease 3; protease, serine 12 neurotrypsin (motopsin); serine protease 12

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_008939.2 → NP_032965.1 neurotrypsin precursor

See identical proteins and their annotated locations for NP_032965.1

Status: VALIDATED

Source sequence(s)

AC110240, AC124005

Consensus CDS

CCDS17817.1

UniProtKB/Swiss-Prot

O08762

Related

ENSMUSP00000029603.9, ENSMUST00000029603.10

Conserved Domains (5) summary

smart00020
Location:516 → 755

Tryp_SPc; Trypsin-like serine protease

smart00130
Location:83 → 159

KR; Kringle domain

smart00202
Location:166 → 265

SR; Scavenger receptor Cys-rich

cd00190
Location:517 → 758

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

pfam00530
Location:171 → 265

SRCR; Scavenger receptor cysteine-rich domain