AP5Z1

Protein identityUniProt · HPA

UniProt accession

O43299

Gene

AP5Z1

Ensembl

ENSG00000242802

Chromosome

7

Canonical length

807 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Nuclear speckles

OverviewNCBI Gene

This gene was identified by genome-wide screen for genes involved in homologous recombination DNA double-strand break repair (HR-DSBR). The encoded protein was found in a complex with other proteins that have a role in HR-DSBR. Knockdown of this gene reduced homologous recombination, and mutations in this gene were found in patients with spastic paraplegia. It was concluded that this gene likely encodes a helicase (PMID:20613862). [provided by RefSeq, Jan 2011]

Canonical amino-acid sequenceUniProt

807 residues, UniProt reviewed canonical sequence.

>O43299|AP5Z1
     1  MFSAGAESLL HQAREIQDEE LKKFCSRICK LLQAEDLGPD TLDSLQRLFL IISATKYSRR
    61  LEKTCVDLLQ ATLGLPACPE QLQVLCAAIL REMSPSDSLS LAWDHTQNSR QLSLVASVLL
   121  AQGDRNEEVR AVGQGVLRAL ESRQPEGPSL RHLLPVMAKV VVLSPGTLQE DQATLLSKRL
   181  VDWLRYASLQ QGLPHSGGFF STPRARQPGP VTEVDGAVAT DFFTVLSSGH RFTDDQWLNV
   241  QAFSMLRAWL LHSGPEGPGT LDTDDRSEQE GSTLSVISAT SSAGRLLPPR ERLREVAFEY
   301  CQRLIEQSNR RALRKGDSDL QKACLVEAVL VLDVLCRQDP SFLYRSLSCL KALHGRVRGD
   361  PASVRVLLPL AHFFLSHGEA AAVDSEAVYQ HLFTRIPVEQ FHSPMLAFEF IQFCRDNLHL
   421  FSGHLSTLRL SFPNLFKFLA WNSPPLTSEF VALLPALVDA GTALEMLHAL LDLPCLTAVL
   481  DLQLRSAPAA SERPLWDTSL RAPSCLEAFR DPQFQGLFQY LLRPKASGAT ERLAPLHQLL
   541  QPMAGCARVA QCAQAVPTLL QAFFSAVTQV ADGSLINQLA LLLLGRSDSL YPAPGYAAGV
   601  HSVLSSQFLA LCTLKPSLVV ELARDLLEFL GSVNGLCSRA SLVTSVVWAI GEYLSVTYDR
   661  RCTVEQINKF FEALEALLFE VTQCRPSAAL PRCPPQVVTV LMTTLTKLAS RSQDLIPRAS
   721  LLLSKMRTLA HSPATSSTHS EEGAEAIRTR ATELLTLLKM PSVAQFVLTP STEVCSPRYH
   781  RDANTALPLA LRTVSRLVER EAGLMPG

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AP5Z1 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

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

14 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about AP5Z1.

Disease | AllUniProt

Conditions AP5Z1 is implicated in, by any mechanism.

• Spastic paraplegia 48, autosomal recessive (SPG48) MIM:613647

Disease | GeneticClinVar

72 pathogenic / likely-pathogenic of 1,266 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary spastic paraplegia 48
• Macular dystrophy with or without extraocular features
• Hereditary spastic paraplegia
• Retinal dystrophy
• Retinal 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)

1.47

gnomAD pLI

0

gnomAD missense Z

-2.97

DepMap mean gene effect

-0.01

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 12% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• autophagosome assembly
• axon development
• double-strand break repair via homologous recombination
• endosomal transport
• gene expression
• Golgi organization
• intracellular protein transport
• late endosome to Golgi transport
• lysosomal protein catabolic process
• lysosome organization
• vesicle-mediated transport

Cellular components

• AP-5 adaptor complex
• AP-type membrane coat adaptor complex
• cytoplasm
• late endosome
• lysosome
• nuclear speck
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Armadillo-like helical
• AP-5 complex subunit zeta-1
• AP-5 complex subunit zeta-1, ARM repeats domain
• AP-5 complex subunit zeta-1, C-terminal TPR domain
• AP-5 complex subunit zeta-1, N-terminal TPR domain
• AP-5 complex subunit, vesicle trafficking
• AP-5 complex subunit zeta-1, TPR repeats
• AP-5 complex subunit zeta-1, C-terminal TPR repeats

KeywordsUniProt

• Cytoplasm
• DNA damage
• DNA repair
• Hereditary spastic paraplegia
• Neurodegeneration
• Nucleus
• Protein transport
• Transport

InteractionsUniProt · HPA

Protein binding partners of AP5Z1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SPG11
• ZFYVE26