SPPL3 signal peptide peptidase like 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SPPL3provided by HGNC
Official Full Name: signal peptide peptidase like 3provided by HGNC
Primary source: HGNC:HGNC:30424
See related: Ensembl:ENSG00000157837 MIM:608240
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: IMP2; PSH1; PSL4; PRO4332; MDHV1887
Expression: Ubiquitous expression in skin (RPKM 21.6), testis (RPKM 17.3) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 12q24.31

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
109.20200815	current	GRCh38.p13 (GCF_000001405.39)	12	NC_000012.12 (120762510..120904358, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (121200313..121342155, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Data suggest that activation of the metalloproteinase ADAM10 by signal peptide peptidase-like 3 (SPPL3) triggered by mutant BRAF(V600E) was a critical transformation event.
Title: Multiepitope tissue analysis reveals SPPL3-mediated ADAM10 activation as a key step in the transformation of melanocytes.
Secretome analysis identifies novel signal Peptide peptidase-like 3 substrates and reveals a role of Sppl3 in multiple Golgi glycosylation pathways
Title: Secretome analysis identifies novel signal Peptide peptidase-like 3 (Sppl3) substrates and reveals a role of Sppl3 in multiple Golgi glycosylation pathways.
Authors demonstrate that SPPL3 alters the pattern of cellular N-glycosylation by triggering the proteolytic release of active site-containing ectodomains of glycosidases and glycosyltransferases.
Title: Shedding of glycan-modifying enzymes by signal peptide peptidase-like 3 (SPPL3) regulates cellular N-glycosylation.
SPPL3 substrates identified on a proteome-wide scale in human and murine cells include numerous glycan-modifying enzymes residing in the Golgi network and implicated in distinct glycosylation pathways, including N-glycosylation, mucin-type O-glycosylation, O-mannosylation and glycosaminoglycan biosynthesis.
Title: Secretome analysis identifies novel signal Peptide peptidase-like 3 (Sppl3) substrates and reveals a role of Sppl3 in multiple Golgi glycosylation pathways.
SPPL3 cleaves Golgi type II membrane proteins leading to their secretion. SPPL3 substrates include Golgi glycosyltransferases MGAT5, B4GALT1, and B3GNT1. By facilitating disengagement of these glycosyltransferases from their membrane anchors, SPPL3 causes their premature secretion and consequently orchestrates the extent of N-glycosylation on human and murine cells.
Title: Shedding of glycan-modifying enzymes by signal peptide peptidase-like 3 (SPPL3) regulates cellular N-glycosylation.
SPPL3 enhances the signal-induced association of stromal interaction molecule 1
Title: A protease-independent function for SPPL3 in NFAT activation.
human SPPL3 is the first GxGD-type aspartyl protease shown to be capable of acting like a sheddase, similar to members of the rhomboid family, which belong to the class of intramembrane-cleaving serine proteases.
Title: Foamy virus envelope protein is a substrate for signal peptide peptidase-like 3 (SPPL3).
SPPL2b is targeted through the secretory pathway to endosomes/lysosomes, whereas SPP and SPPL3 are restricted to the ER.
Title: Differential localization and identification of a critical aspartate suggest non-redundant proteolytic functions of the presenilin homologues SPPL2b and SPPL3.
SPPL3 cleaves a SPP substrate, but a more distantly related homologue SPPL2b does not, providing strong evidence that the malaria SPP and human SPPL3 have conserved active sites, while the active sites SPPL2b is distinct
Title: Intramembrane proteolytic cleavage by human signal peptide peptidase like 3 and malaria signal peptide peptidase.
SPP, SPPL2a, -2b, -2c, and -3 probably cleave type II-oriented substrate peptides as shown by consensus analysis
Title: Consensus analysis of signal peptide peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared with presenilins.

Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae. GeneReviews: Not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2560 (e-PCR)
- UniSTS:37928

A006Q41 (e-PCR)
- UniSTS:15920

D8S2279 (e-PCR)
- UniSTS:473907

RH66303 (e-PCR)
- UniSTS:56900

D12S2073 (e-PCR), detects polymorphism
- UniSTS:57157

NoName (e-PCR)
- UniSTS:483686

RH93199 (e-PCR)
- UniSTS:88684

D1S1423 (e-PCR)
- UniSTS:149619

SGC34924 (e-PCR)
- UniSTS:55193

RH103879 (e-PCR)
- UniSTS:98204

D4S2372 (e-PCR)
- UniSTS:24744

RH44592 (e-PCR)
- UniSTS:15846

RH75805 (e-PCR)
- UniSTS:92138

Homology

Homologs of the SPPL3 gene: The SPPL3 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, A.thaliana, rice, and frog.
Orthologs from Annotation Pipeline: 336 organisms have orthologs with human gene SPPL3
Orthologs

Clone Names

MGC90402, MGC126674, MGC126676, DKFZp586C1324

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
aspartic endopeptidase activity, intramembrane cleaving	IBA Inferred from Biological aspect of Ancestor more info	PubMed
aspartic endopeptidase activity, intramembrane cleaving	IDA Inferred from Direct Assay more info	PubMed
aspartic endopeptidase activity, intramembrane cleaving	IMP Inferred from Mutant Phenotype more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
T cell receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
T cell receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
NOT membrane protein ectodomain proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed
membrane protein proteolysis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
membrane protein proteolysis	IDA Inferred from Direct Assay more info	PubMed
positive regulation of calcineurin-NFAT signaling cascade	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of cytosolic calcium ion concentration	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of protein binding	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of protein dephosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
signal peptide processing	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
Golgi apparatus	IEA Inferred from Electronic Annotation more info
Golgi-associated vesicle membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Golgi-associated vesicle membrane	IDA Inferred from Direct Assay more info	PubMed
endoplasmic reticulum-Golgi intermediate compartment membrane	ISS Inferred from Sequence or Structural Similarity more info
integral component of cytoplasmic side of endoplasmic reticulum membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
integral component of cytoplasmic side of endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
integral component of lumenal side of endoplasmic reticulum membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
integral component of lumenal side of endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info
rough endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: signal peptide peptidase-like 3

Names: SPP-like 3; intramembrane protease 2; presenilin homologous protein 1; presenilin-like protein 4

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_139015.5 → NP_620584.2 signal peptide peptidase-like 3

See identical proteins and their annotated locations for NP_620584.2

Status: VALIDATED

Source sequence(s)

AC069214, AC069234

Consensus CDS

CCDS9208.1

UniProtKB/Swiss-Prot

Q8TCT6

UniProtKB/TrEMBL

Q9UG23

Related

ENSP00000288680.4, ENST00000353487.7

Conserved Domains (1) summary

pfam04258
Location:61 → 374

Peptidase_A22B; Signal peptide peptidase

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20200815

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p13 Primary Assembly

Range

120762510..120904358 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011537925.2 → XP_011536227.1 signal peptide peptidase-like 3 isoform X1

Conserved Domains (1) summary

pfam04258
Location:61 → 374

Peptidase_A22B; Signal peptide peptidase