AP4E1

Protein identityUniProt · HPA

UniProt accession

Q9UPM8

Gene

AP4E1

Ensembl

ENSG00000081014

Chromosome

15

Canonical length

1137 aa

Protein class

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

OverviewNCBI Gene

This gene encodes a member of the adaptor complexes large 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 a large subunit of adaptor protein complex-4, which is associated with both clathrin- and nonclathrin-coated vesicles. Disruption of this gene may be associated with cerebral palsy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

Canonical amino-acid sequenceUniProt

1137 residues, UniProt reviewed canonical sequence.

>Q9UPM8|AP4E1
     1  MSDIVEKTLT ALPGLFLQNQ PGGGPAAAKA SFSSRLGSLV RGITALTSKH EEEKLIQQEL
    61  SSLKATVSAP TTTLKMMKEC MVRLIYCEML GYDASFGYIH AIKLAQQGNL LEKRVGYLAV
   121  SLFLHESHEL LLLLVNTVVK DLQSTNLVEV CMALTVVSQI FPCEMIPAVL PLIEDKLQHS
   181  KEIVRRKAVL ALYKFHLIAP NQVQHIHIKF RKALCDRDVG VMAASLHIYL RMIKENSSGY
   241  KDLTGSFVTI LKQVVGGKLP VEFNYHSVPA PWLQIQLLRI LGLLGKDDQR TSELMYDVLD
   301  ESLRRAELNH NVTYAILFEC VHTVYSIYPK SELLEKAAKC IGKFVLSPKI NLKYLGLKAL
   361  TYVIQQDPTL ALQHQMTIIE CLDHPDPIIK RETLELLYRI TNAQNITVIV QKMLEYLHQS
   421  KEEYVIVNLV GKIAELAEKY APDNAWFIQT MNAVFSVGGD VMHPDIPNNF LRLLAEGFDD
   481  ETEDQQLRLY AVQSYLTLLD MENVFYPQRF LQVMSWVLGE YSYLLDKETP EEVIAKLYKL
   541  LMNDSVSSET KAWLIAAVTK LTSQAHSSNT VERLIHEFTI SLDTCMRQHA FELKHLHENV
   601  ELMKSLLPVD RSCEDLVVDA SLSFLDGFVA EGLSQGAAPY KPPHQRQEEK LSQEKVLNFE
   661  PYGLSFSSSG FTGRQSPAGI SLGSDVSGNS AETGLKETNS LKLEGIKKLW GKEGYLPKKE
   721  SKTGDESGAL PVPQESIMEN VDQAITKKDQ SQVLTQSKEE KEKQLLASSL FVGLGSESTI
   781  NLLGKADTVS HKFRRKSKVK EAKSGETTST HNMTCSSFSS LSNVAYEDDY YSNTLHDTGD
   841  KELKKFSLTS ELLDSESLTE LPLVEKFSYC SLSTPSLFAN NNMEIFHPPQ STAASVAKES
   901  SLASSFLEET TEYIHSNAME VCNNETISVS SYKIWKDDCL LMVWSVTNKS GLELKSADLE
   961  IFPAENFKVT EQPGCCLPVM EAESTKSFQY SVQIEKPFTE GNLTGFISYH MMDTHSAQLE
  1021  FSVNLSLLDF IRPLKISSDD FGKLWLSFAN DVKQNVKMSE SQAALPSALK TLQQKLRLHI
  1081  IEIIGNEGLL ACQLLPSIPC LLHCRVHADV LALWFRSSCS TLPDYLLYQC QKVMEGS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AP4E1 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)

0.37

Highest tissue expression

7.7 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about AP4E1.

Disease | AllUniProt

Conditions AP4E1 is implicated in, by any mechanism.

• Spastic paraplegia 51, autosomal recessive (SPG51) MIM:613744
• Stuttering, familial persistent 1 (STUT1) MIM:184450

Disease | GeneticClinVar

36 pathogenic / likely-pathogenic of 639 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Spastic paraplegia
• Hereditary spastic paraplegia 51
• Stuttering, familial persistent, 1
• ALG12-congenital disorder of glycosylation
• Abnormality of the nervous system

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)

0.43

gnomAD pLI

0

gnomAD missense Z

0.52

DepMap mean gene effect

-0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

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

Molecular functions

• cargo adaptor activity

Cellular components

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

Protein domainsUniProt · Pfam · InterPro

• Clathrin/coatomer adaptor, adaptin-like, N-terminal
• Armadillo-like helical
• Armadillo-type fold
• Adaptor Complexes Large Subunit
• Adaptin N terminal region
• Adaptor protein complex AP-4, epsilon subunit
• AP-4 complex subunit epsilon-1, C-terminal
• Adaptin AP4 complex epsilon appendage platform

KeywordsUniProt

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

InteractionsUniProt · HPA

Protein binding partners of AP4E1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GRIA2
• TEPSIN
• AP4B1