Seroatlas · Human Serome Atlas

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 FLEV

LocalizationUniProt · 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

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.

Canonical record: https://seroatlas.com/gene/SPPL3. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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