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SPPL2A signal peptide peptidase like 2A [ Homo sapiens (human) ]

Gene ID: 84888, updated on 3-May-2025
Official Symbol
SPPL2Aprovided by HGNC
Official Full Name
signal peptide peptidase like 2Aprovided by HGNC
Primary source
HGNC:HGNC:30227
See related
Ensembl:ENSG00000138600 MIM:608238; AllianceGenome:HGNC:30227
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
IMP3; PSL2; IMD86
Summary
This gene encodes a member of the GXGD family of aspartic proteases, which are transmembrane proteins with two conserved catalytic motifs localized within the membrane-spanning regions, as well as a member of the signal peptide peptidase-like protease (SPPL) family. This protein is expressed in all major adult human tissues and localizes to late endosomal compartments and lysosomal membranes. A pseudogene of this gene also lies on chromosome 15. [provided by RefSeq, Feb 2012]
Expression
Ubiquitous expression in colon (RPKM 15.8), duodenum (RPKM 10.9) and 25 other tissues See more
Orthologs
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See SPPL2A in Genome Data Viewer
Location:
15q21.2
Exon count:
16
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (50702266..50765706, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (48509322..48573674, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (50994463..51057903, complement)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene transient receptor potential cation channel subfamily M member 7 Neighboring gene uncharacterized LOC128092252 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:50969254-50969754 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:50969755-50970255 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:50978082-50978946 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6429 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9397 Neighboring gene RNA, 7SL, cytoplasmic 354, pseudogene Neighboring gene MPRA-validated peak2334 silencer Neighboring gene HNF4 motif-containing MPRA enhancer 243 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6430 Neighboring gene Sharpr-MPRA regulatory region 3374 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:51104171-51104690 Neighboring gene ribosomal protein L32 pseudogene 30 Neighboring gene uncharacterized LOC124903490 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9398

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Associated conditions

Description Tests
Immunodeficiency 86
MedGen: C5561995 OMIM: 619549 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.
EBI GWAS Catalog
Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.
EBI GWAS Catalog
Products Interactant Other Gene Complex Source Pubs Description

Markers

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables aspartic endopeptidase activity, intramembrane cleaving IBA
Inferred from Biological aspect of Ancestor
more info
 
enables aspartic endopeptidase activity, intramembrane cleaving IDA
Inferred from Direct Assay
more info
PubMed 
enables aspartic endopeptidase activity, intramembrane cleaving IEA
Inferred from Electronic Annotation
more info
 
enables aspartic endopeptidase activity, intramembrane cleaving TAS
Traceable Author Statement
more info
 
enables hydrolase activity IEA
Inferred from Electronic Annotation
more info
 
enables peptidase activity IEA
Inferred from Electronic Annotation
more info
 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
enables protein homodimerization activity IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
is_active_in Golgi-associated vesicle membrane IBA
Inferred from Biological aspect of Ancestor
more info
 
located_in Golgi-associated vesicle membrane IDA
Inferred from Direct Assay
more info
PubMed 
is_active_in cytoplasmic side of endoplasmic reticulum membrane IBA
Inferred from Biological aspect of Ancestor
more info
 
located_in cytoplasmic side of endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
PubMed 
located_in cytoplasmic side of endoplasmic reticulum membrane IEA
Inferred from Electronic Annotation
more info
 
located_in endosome IEA
Inferred from Electronic Annotation
more info
 
located_in extracellular exosome HDA PubMed 
located_in intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
 
located_in late endosome IDA
Inferred from Direct Assay
more info
PubMed 
located_in late endosome membrane IEA
Inferred from Electronic Annotation
more info
 
is_active_in lumenal side of endoplasmic reticulum membrane IBA
Inferred from Biological aspect of Ancestor
more info
 
located_in lumenal side of endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
PubMed 
located_in lumenal side of endoplasmic reticulum membrane IEA
Inferred from Electronic Annotation
more info
 
located_in lysosomal membrane HDA PubMed 
is_active_in lysosomal membrane IBA
Inferred from Biological aspect of Ancestor
more info
 
located_in lysosomal membrane IEA
Inferred from Electronic Annotation
more info
 
located_in lysosome IEA
Inferred from Electronic Annotation
more info
 
located_in membrane IDA
Inferred from Direct Assay
more info
PubMed 
located_in membrane IEA
Inferred from Electronic Annotation
more info
 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 
located_in plasma membrane TAS
Traceable Author Statement
more info
 
Preferred Names
signal peptide peptidase-like 2A
Names
IMP-3
SPP-like 2A
intramembrane cleaving protease
intramembrane protease 3
presenilin-like protein 2
NP_116191.2
XP_005254779.1
XP_016878169.1
XP_016878170.1
XP_054234976.1
XP_054234977.1
XP_054234978.1
XP_054234979.1

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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)

  1. NM_001438111.1NP_001425040.1  signal peptide peptidase-like 2A isoform 2 precursor

    Status: REVIEWED

    Source sequence(s)
    AC012100
    UniProtKB/TrEMBL
    A0A8V8TN76
  2. NM_001438112.1NP_001425041.1  signal peptide peptidase-like 2A isoform 3 precursor

    Status: REVIEWED

    Source sequence(s)
    AC012100
    UniProtKB/TrEMBL
    A0A8V8TLY7, A0A8V8TLZ2
  3. NM_032802.4NP_116191.2  signal peptide peptidase-like 2A isoform 1 precursor

    See identical proteins and their annotated locations for NP_116191.2

    Status: REVIEWED

    Source sequence(s)
    AA988423, AC012100, AK027446, AY169314
    Consensus CDS
    CCDS10138.1
    UniProtKB/Swiss-Prot
    B2RDS0, Q8TAW1, Q8TCT8, Q96SZ8
    UniProtKB/TrEMBL
    A0A8V8TN76
    Related
    ENSP00000261854.5, ENST00000261854.10
    Conserved Domains (2) summary
    cd02129
    Location:41160
    PA_hSPPL_like; PA_hSPPL_like: Protease-associated domain containing human signal peptide peptidase-like (hSPPL)-like. This group contains various PA domain-containing proteins similar to hSPPL2a and 2b. These SPPLs are GxGD aspartic proteases. SPPL2a is sorted to the ...
    pfam04258
    Location:210496
    Peptidase_A22B; Signal peptide peptidase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

    Range
    50702266..50765706 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017022681.2XP_016878170.1  signal peptide peptidase-like 2A isoform X3

    Related
    ENSP00000513581.1, ENST00000698135.1
  2. XM_017022680.2XP_016878169.1  signal peptide peptidase-like 2A isoform X2

    UniProtKB/TrEMBL
    A0A8V8TLY7
  3. XM_005254722.4XP_005254779.1  signal peptide peptidase-like 2A isoform X1

    Conserved Domains (2) summary
    cd02129
    Location:41160
    PA_hSPPL_like; PA_hSPPL_like: Protease-associated domain containing human signal peptide peptidase-like (hSPPL)-like. This group contains various PA domain-containing proteins similar to hSPPL2a and 2b. These SPPLs are GxGD aspartic proteases. SPPL2a is sorted to the ...
    pfam04258
    Location:210514
    Peptidase_A22B; Signal peptide peptidase

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060939.1 Alternate T2T-CHM13v2.0

    Range
    48509322..48573674 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054379002.1XP_054234977.1  signal peptide peptidase-like 2A isoform X4

    UniProtKB/Swiss-Prot
    B2RDS0, Q8TAW1, Q8TCT8, Q96SZ8
    UniProtKB/TrEMBL
    A0A8V8TN76
  2. XM_054379001.1XP_054234976.1  signal peptide peptidase-like 2A isoform X1

    UniProtKB/TrEMBL
    A0A8V8TN76
  3. XM_054379004.1XP_054234979.1  signal peptide peptidase-like 2A isoform X3

  4. XM_054379003.1XP_054234978.1  signal peptide peptidase-like 2A isoform X2

    UniProtKB/TrEMBL
    A0A8V8TLY7