SPPL3
Signal peptide peptidase-like 3
Also known as: DKFZP586C1324, IMP2, MGC126674, MGC126676, MGC90402, PSL4, SPPL3_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q8TCT6
- Gene
- SPPL3
- Ensembl
- ENSG00000157837
- Chromosome
- 12
- Canonical length
- 384 aa
- Protein class
- Enzymes, Predicted membrane proteins
- Subcellular location
- Vesicles,Plasma membrane
- Quaternary structure
- Homodimer
OverviewNCBI Gene
Enables aspartic endopeptidase activity, intramembrane cleaving and protein homodimerization activity. Involved in T cell receptor signaling pathway; membrane protein proteolysis; and positive regulation of calcineurin-NFAT signaling cascade. Located in Golgi-associated vesicle membrane; endoplasmic reticulum; and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]
Canonical amino-acid sequenceUniProt
384 residues, UniProt reviewed canonical sequence.
>Q8TCT6|SPPL3
1 MAEQTYSWAY SLVDSSQVST FLISILLIVY GSFRSLNMDF ENQDKEKDSN SSSGSFNGNS
61 TNNSIQTIDS TQALFLPIGA SVSLLVMFFF FDSVQVVFTI CTAVLATIAF AFLLLPMCQY
121 LTRPCSPQNK ISFGCCGRFT AAELLSFSLS VMLVLIWVLT GHWLLMDALA MGLCVAMIAF
181 VRLPSLKVSC LLLSGLLIYD VFWVFFSAYI FNSNVMVKVA TQPADNPLDV LSRKLHLGPN
241 VGRDVPRLSL PGKLVFPSST GSHFSMLGIG DIVMPGLLLC FVLRYDNYKK QASGDSCGAP
301 GPANISGRMQ KVSYFHCTLI GYFVGLLTAT VASRIHRAAQ PALLYLVPFT LLPLLTMAYL
361 KGDLRRMWSE PFHSKSSSSR FLEVLocalizationUniProt · AlphaFold · HPA
Whether an antibody against SPPL3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Other membrane
- Secreted
- No
- Transmembrane segments
- 9
- Mean surface accessibility (rSASA)
- 0.33
- Highest tissue expression
- 53 nTPM
Expression across tissuesHPA
Tissue
- skin: 53 nTPM
- parathyroid gland: 47 nTPM
- esophagus: 42 nTPM
- testis: 36 nTPM
- vagina: 32 nTPM
- ovary: 31 nTPM
Single-cell type
- suprabasal keratinocytes: 499 nCPM
- basal keratinocytes: 374 nCPM
- neutrophils: 351 nCPM
- esophageal suprabasal cells: 351 nCPM
- platelets: 347 nCPM
- neutrophil progenitors: 304 nCPM
Immune cell
- basophil: 4.8 nTPM
- plasmacytoid DC: 2.7 nTPM
- neutrophil: 2.2 nTPM
- myeloid DC: 2.1 nTPM
- MAIT T-cell: 1.8 nTPM
- memory CD8 T-cell: 1.7 nTPM
Brain region
- white matter: 72 nTPM
- hypothalamus: 71 nTPM
- cerebellum: 68 nTPM
- basal ganglia: 65 nTPM
- midbrain: 64 nTPM
- pons: 64 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.18
- gnomAD pLI
- 1
- gnomAD missense Z
- 3.44
- DepMap mean gene effect
- -0.01
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- membrane protein proteolysis
- positive regulation of calcineurin-NFAT signaling cascade
- positive regulation of cytosolic calcium ion concentration
- signal peptide processing
- T cell receptor signaling pathway
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of SPPL3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads SPPL3 as an antibody target. Whether an autoantibody or antibody against SPPL3 could matter depends on whether native SPPL3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
SPPL3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label SPPL3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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