Details for: STAMBPL1

Gene ID: 57559

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: STAMBPL1

Ensembl ID: ENSG00000138134

Description: STAM binding protein like 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • stem cell CL0000034
    CSI 16.7
    rCSI 16.1%
    PRS 82.81
  • L6b glutamatergic cortical neuron CL4023038
    CSI 10.97
    rCSI 34.27%
    PRS 74.27
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 10.55
    rCSI 39.87%
    PRS 73.14
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 9.93
    rCSI 23.75%
    PRS 76.25
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 9.49
    rCSI 5.6%
    PRS 97.59
  • tracheobronchial smooth muscle cell CL0019019
    CSI 9.17
    rCSI 16.17%
    PRS 90.82
  • plasmacytoid dendritic cell, human CL0001058
    CSI 8.11
    rCSI 5.66%
    PRS 90.95
  • mesothelial cell CL0000077
    CSI 6.63
    rCSI 25.92%
    PRS 68.89
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 5.54
    rCSI 19.93%
    PRS 70.85
  • amacrine cell CL0000561
    CSI 4.57
    rCSI 13.24%
    PRS 78.45
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 4.56
    rCSI 3.27%
    PRS 96.44
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 4.54
    rCSI 26.75%
    PRS 73.33
  • mature T cell CL0002419
    CSI 4.05
    rCSI 3.15%
    PRS 96.09
  • alveolar adventitial fibroblast CL4028006
    CSI 3.95
    rCSI 6.24%
    PRS 88.57
  • double negative thymocyte CL0002489
    CSI 3.9
    rCSI 2.71%
    PRS 95.83
  • interneuron CL0000099
    CSI 3.85
    rCSI 7.73%
    PRS 80.5
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 3.79
    rCSI 9.21%
    PRS 70.63
  • fibroblast of lung CL0002553
    CSI 3.66
    rCSI 3.41%
    PRS 88.72
  • neuron CL0000540
    CSI 3.61
    rCSI 9.61%
    PRS 75.42
  • Mueller cell CL0000636
    CSI 3.42
    rCSI 7.8%
    PRS 80.46
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.98
    rCSI 2.01%
    PRS 96.5
  • hepatic stellate cell CL0000632
    CSI 2.9
    rCSI 10.85%
    PRS 82.02
  • activated CD4-positive, alpha-beta T cell CL0000896
    CSI 2.76
    rCSI 2.55%
    PRS 96.81
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 2.74
    rCSI 7.14%
    PRS 88.95
  • fibroblast of cardiac tissue CL0002548
    CSI 2.65
    rCSI 12.7%
    PRS 88.13
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.64
    rCSI 3.16%
    PRS 73.02
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 2.62
    rCSI 2.58%
    PRS 96.4
  • alveolar type 1 fibroblast cell CL4028004
    CSI 2.44
    rCSI 2.67%
    PRS 89.16
  • common dendritic progenitor CL0001029
    CSI 2.39
    rCSI 3%
    PRS 93.43
  • group 3 innate lymphoid cell CL0001071
    CSI 2.39
    rCSI 1.8%
    PRS 91.55
  • basal cell CL0000646
    CSI 2.33
    rCSI 3.12%
    PRS 85.18
  • dopaminergic neuron CL0000700
    CSI 2.31
    rCSI 13.05%
    PRS 76.03
  • colon epithelial cell CL0011108
    CSI 2.28
    rCSI 2.38%
    PRS 85.16
  • intestinal tuft cell CL0019032
    CSI 2.25
    rCSI 3.45%
    PRS 90.01
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.18
    rCSI 2.71%
    PRS 70.68
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 2
    rCSI 3.43%
    PRS 95.15
  • intestinal epithelial cell CL0002563
    CSI 1.85
    rCSI 1.93%
    PRS 85.29
  • cardiac muscle cell CL0000746
    CSI 1.84
    rCSI 2.64%
    PRS 79.06
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.8
    rCSI 3.01%
    PRS 72.88
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 1.76
    rCSI 1.61%
    PRS 95.75
  • retinal ganglion cell CL0000740
    CSI 1.72
    rCSI 3.79%
    PRS 75.77
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.67
    rCSI 2.15%
    PRS 73.98
  • blood vessel smooth muscle cell CL0019018
    CSI 1.59
    rCSI 12.89%
    PRS 83.71
  • regular atrial cardiac myocyte CL0002129
    CSI 1.56
    rCSI 5.03%
    PRS 84.35
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.51
    rCSI 36.32%
    PRS 70.92
  • glutamatergic neuron CL0000679
    CSI 1.48
    rCSI 3.03%
    PRS 75.43
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 1.46
    rCSI 4.2%
    PRS 97.7
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 1.3
    rCSI 4.27%
    PRS 75.2
  • direct pathway medium spiny neuron CL4023026
    CSI 1.27
    rCSI 30.49%
    PRS 70.46
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.01
    rCSI 1.79%
    PRS 72.35
  • GABAergic neuron CL0000617
    CSI 0.95
    rCSI 3.17%
    PRS 73.21
  • central nervous system neuron CL2000029
    CSI 0.89
    rCSI 6.57%
    PRS 77.68
  • glial cell CL0000125
    CSI 0.84
    rCSI 3.21%
    PRS 80.36
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.74
    rCSI 2.33%
    PRS 76.32
  • medium spiny neuron CL1001474
    CSI 0.28
    rCSI 2.38%
    PRS 78.33

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 [STAMBPL1](/details-gene/57559) (STAM binding protein like 1) encodes a deubiquitinating enzyme (DUB) belonging to the JAMM/MPN domain-containing metalloprotease family. Functionally, it is recognized for its specific [K63-linked deubiquitinase activity](/details-go/GO0061578) and its role in critical cellular processes such as the positive regulation of [TORC1 signaling](/details-go/GO1904263) and general [protein deubiquitination](/details-go/GO0016579). The **Overall** expression data indicates that [STAMBPL1](/details-gene/57559) is a gene of broad significance, showing high expression in diverse and functionally distinct cell types. It is most prominent in [stem cell](/details-cell/CL0000034)s, various subtypes of glutamatergic neurons such as [L6b glutamatergic cortical neuron](/details-cell/CL4023038)s, and key immune populations including [central memory CD4-positive, alpha-beta T cell](/details-cell/CL0000904)s, suggesting a fundamental role in cellular homeostasis, development, and immunity. ## Cellular Roles and Expression Landscape The expression profile of [STAMBPL1](/details-gene/57559) highlights its importance across a wide spectrum of cell lineages, pointing to a role in fundamental cellular maintenance rather than as a marker for a single, specific cell type. **Overall**, the gene exhibits its highest significance (CSI: 16.70) in [stem cell](/details-cell/CL0000034)s, which suggests a potential role in the regulation of pluripotency or self-renewal, possibly through the modulation of protein turnover. A second major site of high significance is the central nervous system, particularly within various subtypes of glutamatergic neurons, including [L6b glutamatergic cortical neuron](/details-cell/CL4023038) (CSI: 10.97), [near-projecting glutamatergic cortical neuron](/details-cell/CL4023012) (CSI: 10.55), and [L4 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4030063) (CSI: 9.93). This pattern suggests a crucial function in neuronal activity, synaptic maintenance, or proteostasis within these excitatory neurons. [STAMBPL1](/details-gene/57559) also plays a notable role within the immune system. It is significantly expressed in both the innate and adaptive compartments, including [plasmacytoid dendritic cell, human](/details-cell/CL0001058) (CSI: 8.11) and multiple T cell populations like [central memory CD4-positive, alpha-beta T cell](/details-cell/CL0000904) (CSI: 9.49) and [mature T cell](/details-cell/CL0002419) (CSI: 4.05). Its expression in these cells is consistent with a role for deubiquitination in regulating immune cell signaling and survival. Furthermore, its significance in structural cells like [tracheobronchial smooth muscle cell](/details-cell/CL0019019) (CSI: 9.17) and [mesothelial cell](/details-cell/CL0000077) (CSI: 6.63) underscores its widespread functional importance. ## Pathways and Molecular Function [STAMBPL1](/details-gene/57559) is a metalloprotease that functions as a deubiquitinase, a role supported by extensive functional annotations. It is a key component of the [Deubiquitination](/details-pathway/R-HSA-5688426) and [Metabolism of proteins](/details-pathway/R-HSA-392499) pathways. Its molecular function is defined as a [metal-dependent deubiquitinase activity](/details-go/GO0140492) ([Link](https://pubmed.ncbi.nlm.nih.gov/12810066/)), with a specific preference for cleaving K63-linked polyubiquitin chains ([GO:0061578](/details-go/GO0061578)) ([Link](https://doi.org/10.1038/nature07254)). This type of deubiquitination is often associated with non-degradative signaling pathways, unlike the K48-linked chains that typically target proteins for proteasomal degradation. A critical function of [STAMBPL1](/details-gene/57559) is its involvement in the [positive regulation of TORC1 signaling](/details-go/GO1904263). Recent research has shown that it acts in concert with the E3 ligase RNF167 to modulate mTOR activity, a central regulator of cell growth, proliferation, and metabolism, with significant implications for cancer progression ([Link](https://doi.org/10.1016/j.molcel.2022.01.002)). This role is consistent with its annotation for [cellular response to l-leucine](/details-go/GO0071233), as amino acids are key activators of the mTORC1 pathway. The protein is localized to several cellular compartments, including the [cytosol](/details-go/GO0005829), [endosome](/details-go/GO0005768), and [membrane](/details-go/GO0016020), aligning with its function in modulating membrane-associated signaling complexes like mTORC1. ## Research Directions The widespread yet significant expression of [STAMBPL1](/details-gene/57559) in diverse, key cell types, coupled with its role in the fundamentally important mTOR pathway, opens up several avenues for future investigation. **Proposed Hypotheses:** 1. **Neuronal Function:** Given its high significance in multiple glutamatergic neuron subtypes and its regulation of mTOR, [STAMBPL1](/details-gene/57559) may be a critical regulator of synaptic plasticity and neuronal proteostasis. Dysregulation of [STAMBPL1](/details-gene/57559) could contribute to neurodevelopmental or neurodegenerative disorders by altering local protein synthesis and degradation at the synapse. 2. **Stem Cell Maintenance:** The top-ranked significance of [STAMBPL1](/details-gene/57559) in [stem cell](/details-cell/CL0000034)s suggests it is essential for maintaining the undifferentiated state. It could function by deubiquitinating and stabilizing key pluripotency factors or by preventing the accumulation of differentiation-promoting proteins through its influence on protein turnover pathways. 3. **Immune Cell Memory:** Its high expression in [central memory CD4-positive, alpha-beta T cell](/details-cell/CL0000904)s suggests a role in the long-term survival and function of memory T cells. [STAMBPL1](/details-gene/57559) might regulate the stability of signaling proteins crucial for T cell survival and recall responses. **Suggested Experimental Approach:** To test the hypothesis regarding its role in neuronal function, a compelling experiment would be to generate a conditional knockout mouse model using a Camk2a-Cre driver to specifically delete [STAMBPL1](/details-gene/57559) in forebrain excitatory neurons. The functional consequences could be assessed using electrophysiological recordings in hippocampal slices to measure long-term potentiation (LTP), a cellular correlate of learning and memory. Concurrently, phosphoproteomics and total proteomics of synaptosome preparations from these mice could be performed to identify dysregulated mTORC1 pathway targets and other synaptic proteins, directly linking the molecular function of [STAMBPL1](/details-gene/57559) to synaptic physiology. **Therapeutic Potential:** [STAMBPL1](/details-gene/57559) represents a promising therapeutic target, particularly in oncology. Its role as a positive regulator of mTOR signaling suggests that its **inhibition** could be an effective strategy to suppress tumor growth in cancers dependent on this pathway ([Link](https://doi.org/10.1016/j.molcel.2022.01.002)). The development of specific small molecule inhibitors against its deubiquitinase activity is an active area of research ([Link](https://doi.org/10.1016/j.jbc.2021.101107)). However, the broad expression of [STAMBPL1](/details-gene/57559) across many healthy tissues, including neurons and immune cells, raises potential concerns for on-target toxicity. Therefore, therapeutic strategies may require tumor-specific drug delivery systems or the development of highly selective inhibitors that can distinguish it from other related deubiquitinases to achieve a favorable therapeutic window.

Genular Protein ID: 2787219344

Symbol: STALP_HUMAN

Name: STAM-binding protein-like 1

UniProtKB Accession Codes:

Q96FJ0 B3KPA7 Q5T9N4 Q5T9N9 Q7Z420 Q9P2H4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 8 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 3 EvolutionaryTrace 1 GO 11 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 9 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12810066

Title: Identification of AMSH-LP containing a Jab1/MPN domain metalloenzyme motif.

PubMed ID: 12810066

DOI: 10.1016/s0006-291x(03)01009-x

PubMed ID: 10718198

Title: Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro.

PubMed ID: 10718198

DOI: 10.1093/dnares/7.1.65

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

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: 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: 35114100

Title: E3 ligase RNF167 and deubiquitinase STAMBPL1 modulate mTOR and cancer progression.

PubMed ID: 35114100

DOI: 10.1016/j.molcel.2022.01.002

PubMed ID: 18758443

Title: Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains.

PubMed ID: 18758443

DOI: 10.1038/nature07254

PubMed ID: 34425109

Title: Structural and functional characterization of ubiquitin variant inhibitors for the JAMM-family deubiquitinases STAMBP and STAMBPL1.

PubMed ID: 34425109

DOI: 10.1016/j.jbc.2021.101107

Sequence Information:

  • Length: 436
  • Mass: 49783
  • Checksum: 722662C76A734102
  • Sequence:
    • MDQPFTVNSL KKLAAMPDHT DVSLSPEERV RALSKLGCNI TISEDITPRR YFRSGVEMER 
MASVYLEEGN LENAFVLYNK FITLFVEKLP NHRDYQQCAV PEKQDIMKKL KEIAFPRTDE 
LKNDLLKKYN VEYQEYLQSK NKYKAEILKK LEHQRLIEAE RKRIAQMRQQ QLESEQFLFF 
EDQLKKQELA RGQMRSQQTS GLSEQIDGSA LSCFSTHQNN SLLNVFADQP NKSDATNYAS 
HSPPVNRALT PAATLSAVQN LVVEGLRCVV LPEDLCHKFL QLAESNTVRG IETCGILCGK 
LTHNEFTITH VIVPKQSAGP DYCDMENVEE LFNVQDQHDL LTLGWIHTHP TQTAFLSSVD 
LHTHCSYQLM LPEAIAIVCS PKHKDTGIFR LTNAGMLEVS ACKKKGFHPH TKEPRLFSIC 
KHVLVKDIKI IVLDLR