AP4S1

Protein identityUniProt · HPA

UniProt accession

Q9Y587

Gene

AP4S1

Ensembl

ENSG00000100478

Chromosome

14

Canonical length

144 aa

Protein class

Disease related genes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Transporters

Subcellular location

Vesicles

OverviewNCBI Gene

This gene encodes a member of the adaptor complexes small subunit protein family. These proteins are components of the heterotetrameric adaptor protein complexes, which play important roles in the secretory and endocytic pathways by mediating vesicle formation and sorting of integral membrane proteins. The encoded protein is the small subunit of adaptor protein complex-4, which is associated with both clathrin- and nonclathrin-coated vesicles. Mutations in this gene are associated with spastic quadriplegic cerebral palsy-6. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6. [provided by RefSeq, Dec 2011]

Canonical amino-acid sequenceUniProt

144 residues, UniProt reviewed canonical sequence.

>Q9Y587|AP4S1
     1  MIKFFLMVNK QGQTRLSKYY EHVDINKRTL LETEVIKSCL SRSNEQCSFI EYKDFKLIYR
    61  QYAALFIVVG VNDTENEMAI YEFIHNFVEV LDEYFSRVSE LDIMFNLDKV HIILDEMVLN
   121  GCIVETNRAR ILAPLLILDK MSES

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AP4S1 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

0

Mean surface accessibility (rSASA)

0.29

Highest tissue expression

14 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about AP4S1.

Disease | AllUniProt

Conditions AP4S1 is implicated in, by any mechanism.

• Spastic paraplegia 52, autosomal recessive (SPG52) MIM:614067

Disease | GeneticClinVar

25 pathogenic / likely-pathogenic of 170 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Spastic paraplegia
• Hereditary spastic paraplegia 52
• Inborn genetic diseases
• AP4S1-related disorder
• Neurodevelopmental disorder

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)

1.63

gnomAD pLI

0

gnomAD missense Z

-0.01

DepMap mean gene effect

0

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

• intracellular protein localization
• protein targeting
• protein transport
• vesicle-mediated transport

Cellular components

• AP-4 adaptor complex
• endosome lumen
• trans-Golgi network
• trans-Golgi network membrane

Protein domainsUniProt · Pfam · InterPro

• Longin-like domain superfamily
• Adaptor protein complex, sigma subunit
• AP complex, mu/sigma subunit
• Clathrin adaptor complex small chain

KeywordsUniProt

• Golgi apparatus
• Hereditary spastic paraplegia
• Membrane
• Neurodegeneration
• Protein transport
• Transport

InteractionsUniProt · HPA

Protein binding partners of AP4S1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AP4B1