Details for: AP5B1

Gene ID: 91056

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: AP5B1

Ensembl ID: ENSG00000254470

Description: adaptor related protein complex 5 subunit beta 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • intermediate monocyte CL0002393
    CSI 5.38
    rCSI 8.12%
    PRS 99.38
  • melanocyte CL0000148
    CSI 4.57
    rCSI 3.38%
    PRS 97.17
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.81
    rCSI 2.17%
    PRS 99.24
  • CD14-positive monocyte CL0001054
    CSI 2.76
    rCSI 3.44%
    PRS 99.71
  • ependymal cell CL0000065
    CSI 2.66
    rCSI 5.39%
    PRS 90.85
  • extravillous trophoblast CL0008036
    CSI 2.62
    rCSI 3.24%
    PRS 97.57
  • promonocyte CL0000559
    CSI 1.91
    rCSI 3.28%
    PRS 99.01
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 0.81
    rCSI 4.87%
    PRS 99.45

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [AP5B1](/details-gene/91056) (adaptor related protein complex 5 subunit beta 1) is a protein-coding gene located on chromosome 11q13.1. It encodes a subunit of the Adaptor Protein 5 (AP-5) complex, a key component of the intracellular vesicle-mediated transport machinery. Functional annotations strongly link [AP5B1](/details-gene/91056) to the regulation of endosomal and lysosomal trafficking pathways. Expression data highlights its significant role primarily within the myeloid lineage, particularly in various monocyte subsets, as well as in specialized cell types such as [melanocyte](/details-cell/CL0000148)s and [ependymal cell](/details-cell/CL0000065)s, suggesting a fundamental role in protein sorting and transport in these distinct cellular contexts. ## Cellular Roles and Expression Landscape The expression profile of [AP5B1](/details-gene/91056) indicates a primary function in cells with high endocytic and secretory activity. **Overall**, the gene shows the highest significance in the monocyte lineage. It is a particularly strong marker for [intermediate monocyte](/details-cell/CL0002393)s (CSI: 5.38), and also shows high significance in [CD14-low, CD16-positive monocyte](/details-cell/CL0002396)s (CSI: 2.81), [CD14-positive monocyte](/details-cell/CL0001054)s (CSI: 2.76), [promonocyte](/details-cell/CL0000559)s (CSI: 1.91), and [CD14-positive, CD16-negative classical monocyte](/details-cell/CL0002057)s (CSI: 0.81). This consistent high expression across the monocyte differentiation spectrum suggests that [AP5B1](/details-gene/91056) is integral to core monocytic functions such as phagocytosis, antigen processing, and inflammatory responses, which are heavily reliant on endo-lysosomal trafficking. Beyond the immune system, [AP5B1](/details-gene/91056) is also highly significant in several specialized cell types. Its high CSI in [melanocyte](/details-cell/CL0000148)s (CSI: 4.57) suggests a role in the biogenesis and transport of melanosomes, the organelles responsible for pigment production. Furthermore, significant expression is noted in [ependymal cell](/details-cell/CL0000065)s (CSI: 2.66), which line the ventricles of the brain, and [extravillous trophoblast](/details-cell/CL0008036)s (CSI: 2.62), involved in placental development. This pattern implies that the trafficking pathways mediated by the AP-5 complex are critical for diverse biological processes including pigmentation, cerebrospinal fluid homeostasis, and maternal-fetal interactions. ## Pathways and Molecular Function The function of [AP5B1](/details-gene/91056) is centered on its role as a core component of the AP-5 adaptor complex ([GO:0044599](https://www.ebi.ac.uk/QuickGO/term/GO:0044599)). This complex is a crucial player in vesicle-mediated transport ([GO:0016192](https://www.ebi.ac.uk/QuickGO/term/GO:0016192)), specifically in the context of endosomal transport ([GO:0016197](https://www.ebi.ac.uk/QuickGO/term/GO:0016197)) and general protein transport ([GO:0015031](https://www.ebi.ac.uk/QuickGO/term/GO:0015031)). Research has established that the AP-5 complex is localized to the [late endosome](/details-go/GO:0005770) and [lysosomal membrane](/details-go/GO:0005765), where it is thought to mediate the retrieval of specific cargo proteins from these compartments, preventing their degradation and ensuring their correct localization within the cell ([Link](https://doi.org/10.1371/journal.pbio.1001170)). This function is consistent with its high expression in monocytes, which require precise control over the fate of phagocytosed material for effective antigen presentation and pathogen clearance. Similarly, in [melanocyte](/details-cell/CL0000148)s, such trafficking machinery is essential for sorting pigment-producing enzymes and structural proteins to developing melanosomes. ## Research Directions The specific roles of [AP5B1](/details-gene/91056)-mediated transport in different cell types present several avenues for future investigation. **Proposed Hypotheses:** 1. **Impaired Monocyte Function:** Given its high expression in monocytes and its role in the endo-lysosomal system, depletion of [AP5B1](/details-gene/91056) may impair phagosome maturation, leading to reduced efficiency in pathogen clearance and altered antigen presentation, thereby modulating the adaptive immune response. 2. **Pigmentation Defects:** In [melanocyte](/details-cell/CL0000148)s, [AP5B1](/details-gene/91056) could be essential for the proper trafficking of key melanogenic enzymes like tyrosinase to melanosomes. Its disruption could therefore lead to defects in melanin synthesis and result in hypopigmentation disorders. 3. **Neurological Involvement:** The AP-5 complex has been linked to hereditary spastic paraplegia ([Link](https://doi.org/10.1371/journal.pbio.1000408)). The notable expression of [AP5B1](/details-gene/91056) in [ependymal cell](/details-cell/CL0000065)s suggests that disruption of AP-5-mediated trafficking in these and other neural-associated cells could compromise cellular homeostasis and contribute to the pathology of certain neurodegenerative diseases. **Key Experimental Approach:** To test the hypothesis regarding monocyte function, a targeted knockout of [AP5B1](/details-gene/91056) could be generated in a human monocyte-like cell line (e.g., THP-1) using CRISPR-Cas9. The functional consequences would be assessed by comparing wild-type and knockout cells in several assays. A phagocytosis assay using fluorescently labeled bacteria or beads would quantify uptake efficiency. Phagosome maturation could be tracked via immunofluorescence by monitoring the acquisition of late endosomal and lysosomal markers (e.g., RAB7, LAMP1) over time. Finally, an antigen presentation assay, where monocytes are pulsed with a specific antigen and co-cultured with cognate T cells, would reveal any impact on T cell activation as measured by cytokine production or proliferation. **Therapeutic Potential:** As an intracellular component of a fundamental cellular trafficking pathway, [AP5B1](/details-gene/91056) presents a challenging therapeutic target. Global inhibition would likely cause significant toxicity due to the essential nature of endo-lysosomal transport. However, in the context of monogenic diseases caused by loss-of-function mutations in [AP5B1](/details-gene/91056) or other AP-5 subunits, therapeutic strategies would focus on restoration of function. Gene therapy approaches aimed at reintroducing a functional copy of the gene in affected cell types could be a viable long-term strategy, particularly for inherited disorders like certain forms of hereditary spastic paraplegia.

Genular Protein ID: 109876936

Symbol: AP5B1_HUMAN

Name: AP-5 complex subunit beta-1

UniProtKB Accession Codes:

Q2VPB7 A1L0S6 H6WUK2 Q0D2Q2 Q8N3J7 Q8WYH6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 10 Ensembl 1 GO 7 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 4 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 22022230

Title: The fifth adaptor protein complex.

PubMed ID: 22022230

DOI: 10.1371/journal.pbio.1001170

PubMed ID: 16554811

Title: Human chromosome 11 DNA sequence and analysis including novel gene identification.

PubMed ID: 16554811

DOI: 10.1038/nature04632

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 15498874

Title: Large-scale cDNA transfection screening for genes related to cancer development and progression.

PubMed ID: 15498874

DOI: 10.1073/pnas.0404089101

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 20613862

Title: A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia.

PubMed ID: 20613862

DOI: 10.1371/journal.pbio.1000408

Sequence Information:

  • Length: 878
  • Mass: 93949
  • Checksum: B1E8A2BBFE45872B
  • Sequence:
    • MGPLSRDAWA QRLGAFRASP SAFMAGPEGE DLGRDLLSDL RSEKLSEQTK VSLLALSMEY 
PAQLWPDASA AEVAATSLLD TLVLLPPRPS ALRRPLLLAA TTALAAGGAL GPTSGASCRL 
LPLLLGLAAG SDLGRGFVPA SEQRPLQATA CECLRELESC KPGLLGGSLG LLRGLLGQEG 
PVQPLSLLLA LALRNTLVLQ SRVGAGLGGL LTDKVSPTGG GPWDWTLVEE GDGRLQPQAP 
SWPAAEEGEG ERSLTAREHS PEEARELRAA VIQLLDTSYL LTPVAQAQLL WLLGWALRGL 
QGQPPALFKP QLVRLLGTAQ LTLLHAMLAL KAAFGEALFT AQDEALLLRR LTLAAQHPAL 
PPPTHLFYLH CVLSFPENWP LGPEGEEAAP LLLGPQLCRG LLPSLLHDPM ALLARLHLLC 
LLCAEEEEEE KGQLPSPRHY LEELLAGLRQ RAALDGGPRA LATLCFQASY LVACCLAGQP 
TVLTPLIHGL AQLYQARPML APHFVDLLDQ VDSELREPLK VVLRQVVVSR PGRDEALCWH 
LQMLAKVADG DAQSATLNFL QAAAAHCTNW DLQQGLLRVC RALLRAGVRG GLVDLLQVLA 
RQLEDPDGRD HARLYYILLA HLAAPKLGVA LGPSLAAPAL ASSLVAENQG FVAALMVQEA 
PALVRLSLGS HRVKGPLPVL KLQPEALEPI YSLELRFRVE GQLYAPLEAV HVPCLCPGRP 
ARPLLLPLQP RCPAPARLDV HALYTTSTGL TCHAHLPPLF VNFADLFLPF PQPPEGAGLG 
FFEELWDSCL PEGAESRVWC PLGPQGLEGL VSRHLEPFVV VAQPPTSYCV AIHLPPDSKL 
LLRLEAALAD GVPVALRTDD WAVLPLAGDY LRGLAAAV