Details for: UBL4A

Gene ID: 8266

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: UBL4A

Ensembl ID: ENSG00000102178

Description: ubiquitin like 4A

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 4.59
    rCSI 4.15%
    PRS 92.49
  • bronchus fibroblast of lung CL2000093
    CSI 3.89
    rCSI 3.16%
    PRS 92.93
  • rod bipolar cell CL0000751
    CSI 3.72
    rCSI 6.68%
    PRS 89.37
  • megakaryocyte CL0000556
    CSI 3.42
    rCSI 14.83%
    PRS 93.66
  • skin fibroblast CL0002620
    CSI 3.3
    rCSI 2.84%
    PRS 92.88
  • epithelial cell of lung CL0000082
    CSI 3.15
    rCSI 2.61%
    PRS 94.32
  • platelet CL0000233
    CSI 2.83
    rCSI 11.74%
    PRS 89.81
  • neural crest cell CL0011012
    CSI 2.82
    rCSI 2.23%
    PRS 88.01
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.79
    rCSI 2.42%
    PRS 94.87
  • ionocyte CL0005006
    CSI 2.49
    rCSI 2.67%
    PRS 94.33
  • erythrocyte CL0000232
    CSI 2.46
    rCSI 5.59%
    PRS 91.35
  • mesodermal cell CL0000222
    CSI 2.44
    rCSI 2.93%
    PRS 92.51
  • common myeloid progenitor CL0000049
    CSI 2.44
    rCSI 1.97%
    PRS 94.34
  • colon epithelial cell CL0011108
    CSI 2.17
    rCSI 2.27%
    PRS 91.45
  • pulmonary ionocyte CL0017000
    CSI 2.09
    rCSI 2.54%
    PRS 95.8
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 1.98
    rCSI 5.85%
    PRS 92.95
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.92
    rCSI 2.3%
    PRS 83.47
  • CD4-positive, alpha-beta cytotoxic T cell CL0000934
    CSI 1.92
    rCSI 2.63%
    PRS 98.72
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.85
    rCSI 3.26%
    PRS 82.73
  • fallopian tube secretory epithelial cell CL4030006
    CSI 1.75
    rCSI 1.68%
    PRS 92.24
  • peripheral nervous system neuron CL2000032
    CSI 1.46
    rCSI 1.99%
    PRS 87.96
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.31
    rCSI 1.58%
    PRS 75.83
  • mesenchymal cell CL0008019
    CSI 1.25
    rCSI 3.17%
    PRS 89.47
  • microcirculation associated smooth muscle cell CL0008035
    CSI 1.13
    rCSI 3.27%
    PRS 92.8
  • primitive red blood cell CL0002355
    CSI 1.03
    rCSI 5.56%
    PRS 94.05
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.99
    rCSI 2.41%
    PRS 81.28
  • erythroid progenitor cell CL0000038
    CSI 0.86
    rCSI 4.92%
    PRS 94.53
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.61
    rCSI 1.92%
    PRS 84.44
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.59
    rCSI 2.13%
    PRS 81.63
  • cytotoxic T cell CL0000910
    CSI 0.36
    rCSI 2.07%
    PRS 91.52

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.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • 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 [UBL4A](/details-gene/8266) (Ubiquitin Like 4A) is a protein-coding gene located on the X chromosome that encodes a small ubiquitin-like protein [Link](https://doi.org/10.1093/hmg/5.5.659). Initially characterized as a widely expressed 'housekeeping' gene, its product is structurally similar to ubiquitin [Link](https://doi.org/10.1073/pnas.85.3.851). The primary function of [UBL4A](/details-gene/8266) is associated with protein homeostasis, specifically in the post-translational targeting and insertion of tail-anchored proteins into the endoplasmic reticulum membrane. This crucial role is supported by its involvement as a ribosome-associating factor that chaperones nascent membrane proteins [Link](https://doi.org/10.1038/nature09296). **Overall**, expression data indicates that [UBL4A](/details-gene/8266) has high significance in a diverse range of cell types, including hematopoietic progenitors such as [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) and stromal cells like [bronchus fibroblast of lung](/details-cell/CL2000093), suggesting its fundamental importance in cellular development and maintenance. The gene has a clinical association with an X-linked mental retardation syndrome ([312070](https://omim.org/entry/312070)). ## Cellular Roles and Expression Landscape The expression profile of [UBL4A](/details-gene/8266) reveals its widespread importance across various cellular lineages, consistent with its function in fundamental protein management processes. **Overall**, the gene shows the highest significance in hematopoietic precursors and their descendants. It is a top marker in [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 4.59), [megakaryocyte](/details-cell/CL0000556) (CSI: 3.42), and [granulocyte monocyte progenitor cell](/details-cell/CL0000557) (CSI: 2.79), as well as mature blood cells like [platelet](/details-cell/CL0000233) and [erythrocyte](/details-cell/CL0000232). This pattern suggests a critical role for [UBL4A](/details-gene/8266) in the development, differentiation, and maintenance of blood cell lineages, which are characterized by high rates of protein synthesis and turnover. Beyond the hematopoietic system, [UBL4A](/details-gene/8266) is also highly significant in stromal and specialized cell types. It is prominently expressed in fibroblasts, including [bronchus fibroblast of lung](/details-cell/CL2000093) (CSI: 3.89) and [skin fibroblast](/details-cell/CL0002620) (CSI: 3.30), cells responsible for synthesizing and secreting large quantities of extracellular matrix proteins. Furthermore, its high CSI in specialized cells such as the [rod bipolar cell](/details-cell/CL0000751) of the retina and various epithelial cells ([epithelial cell of lung](/details-cell/CL0000082), [colon epithelial cell](/details-cell/CL0011108)) underscores its broad utility in cells with demanding protein processing and trafficking requirements. The collective data portrays [UBL4A](/details-gene/8266) as a key facilitator of protein homeostasis essential for the function of multiple, distinct cell lineages. ## Pathways and Molecular Function The functional annotations for [UBL4A](/details-gene/8266) center on protein targeting, modification, and degradation, highlighting its role as a key regulator of proteostasis. Its most well-defined function is in protein localization, specifically the 'Post-translational protein targeting to endoplasmic reticulum membrane' ([GO:0006620](https://www.ebi.ac.uk/QuickGO/term/GO:0006620)) and the 'Insertion of tail-anchored proteins into the endoplasmic reticulum membrane' ([R-HSA-9609523](https://reactome.org/content/detail/R-HSA-9609523)). Research demonstrates that the [UBL4A](/details-gene/8266) protein, as part of the BAG6/BAT3 complex, acts as a chaperone that captures and delivers newly synthesized tail-anchored membrane proteins from the ribosome to the ER membrane for correct insertion [Link](https://doi.org/10.1038/nature09296), [Link](https://doi.org/10.1126/science.aah6130). In addition to protein targeting, [UBL4A](/details-gene/8266) is implicated in the 'Ubiquitin-dependent protein catabolic process' ([GO:0006511](https://www.ebi.ac.uk/QuickGO/term/GO:0006511)) and the 'Regulation of protein stability' ([GO:0031647](https://www.ebi.ac.uk/QuickGO/term/GO:0031647)). This suggests a dual role where it not only facilitates the proper localization of proteins but also participates in the quality control pathway that triages mislocalized or misfolded proteins for degradation by the proteasome [Link](https://doi.org/10.1016/j.molcel.2011.05.010), [Link](https://doi.org/10.1038/nature10181). This function is critical in all cells but particularly in those with high secretory or protein synthesis loads, such as the hematopoietic progenitors and fibroblasts where [UBL4A](/details-gene/8266) expression is most significant. Its molecular functions include 'Protein binding' ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)) and 'Protein-folding chaperone binding' ([GO:0051087](https://www.ebi.ac.uk/QuickGO/term/GO:0051087)), which are consistent with its role within larger protein complexes that manage nascent polypeptides. ## Research Directions The widespread significance of [UBL4A](/details-gene/8266) in fundamental cellular processes, combined with its prominent role in specific progenitor and stromal cell types, presents several avenues for future investigation. Based on the available data, several testable hypotheses can be proposed: 1. Given its high significance in [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) and [granulocyte monocyte progenitor cell](/details-cell/CL0000557), [UBL4A](/details-gene/8266) is indispensable for hematopoietic differentiation. Its loss may impair the correct membrane insertion of key lineage-specific receptors, leading to skewed lineage commitment or developmental arrest. 2. The high CSI of [UBL4A](/details-gene/8266) in fibroblasts ([bronchus fibroblast of lung](/details-cell/CL2000093), [skin fibroblast](/details-cell/CL0002620)) suggests it is a critical factor in extracellular matrix (ECM) homeostasis. Dysregulation of [UBL4A](/details-gene/8266) could disrupt the synthesis and secretion of ECM proteins like collagens, potentially contributing to the pathology of fibrotic diseases. A key experiment to test the first hypothesis would involve the use of a hematopoietic-specific conditional knockout mouse model. Deletion of [UBL4A](/details-gene/8266) in hematopoietic stem cells (e.g., using a Vav-Cre system) would allow for detailed analysis of its impact on blood cell development. Progenitor populations could be quantified via flow cytometry, and their differentiation potential could be assessed using in vitro colony-forming unit (CFU) assays. Furthermore, proteomic analysis of membrane fractions from knockout progenitor cells could identify specific tail-anchored proteins whose localization is dependent on [UBL4A](/details-gene/8266). From a therapeutic perspective, [UBL4A](/details-gene/8266) presents a challenging target. As a "housekeeping" gene essential for protein homeostasis, systemic inhibition would likely lead to broad cellular toxicity. However, in diseases characterized by excessive or aberrant protein production, such as certain cancers or fibrotic conditions, [UBL4A](/details-gene/8266) might be upregulated and could represent a context-dependent vulnerability. In such scenarios, targeted inhibition of [UBL4A](/details-gene/8266) function or its interaction with specific protein partners could be a viable strategy to selectively disrupt the proteostasis of pathological cells.

Genular Protein ID: 1297848998

Symbol: UBL4A_HUMAN

Name: Ubiquitin-like protein GDX

UniProtKB Accession Codes:

P11441 Q5HY80

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 EMDB 3 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 13 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 6 PDBsum 6 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2829204

Title: A 'housekeeping' gene on the X chromosome encodes a protein similar to ubiquitin.

PubMed ID: 2829204

DOI: 10.1073/pnas.85.3.851

PubMed ID: 8733135

Title: Long-range sequence analysis in Xq28: thirteen known and six candidate genes in 219.4 kb of high GC DNA between the RCP/GCP and G6PD loci.

PubMed ID: 8733135

DOI: 10.1093/hmg/5.5.659

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

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: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20676083

Title: A ribosome-associating factor chaperones tail-anchored membrane proteins.

PubMed ID: 20676083

DOI: 10.1038/nature09296

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21636303

Title: A ubiquitin ligase-associated chaperone holdase maintains polypeptides in soluble states for proteasome degradation.

PubMed ID: 21636303

DOI: 10.1016/j.molcel.2011.05.010

PubMed ID: 21743475

Title: Protein targeting and degradation are coupled for elimination of mislocalized proteins.

PubMed ID: 21743475

DOI: 10.1038/nature10181

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24424410

Title: USP13 antagonizes gp78 to maintain functionality of a chaperone in ER-associated degradation.

PubMed ID: 24424410

DOI: 10.7554/elife.01369

PubMed ID: 28104892

Title: Mechanistic basis for a molecular triage reaction.

PubMed ID: 28104892

DOI: 10.1126/science.aah6130

PubMed ID: 25713138

Title: Structure of a BAG6 (Bcl-2-associated athanogene 6)-Ubl4a (ubiquitin-like protein 4a) complex reveals a novel binding interface that functions in tail-anchored protein biogenesis.

PubMed ID: 25713138

DOI: 10.1074/jbc.m114.631804

PubMed ID: 25535373

Title: Bag6 complex contains a minimal tail-anchor-targeting module and a mock BAG domain.

PubMed ID: 25535373

DOI: 10.1073/pnas.1402745112

Sequence Information:

  • Length: 157
  • Mass: 17777
  • Checksum: 9D6EE2D20D2C4C60
  • Sequence:
    • MQLTVKALQG RECSLQVPED ELVSTLKQLV SEKLNVPVRQ QRLLFKGKAL ADGKRLSDYS 
IGPNSKLNLV VKPLEKVLLE EGEAQRLADS PPPQVWQLIS KVLARHFSAA DASRVLEQLQ 
RDYERSLSRL TLDDIERLAS RFLHPEVTET MEKGFSK