Details for: GTPBP1

Gene ID: 9567

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: GTPBP1

Ensembl ID: ENSG00000100226

Description: GTP binding protein 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • mucosal invariant T cell CL0000940
    CSI 25.27
    rCSI 20.42%
    PRS 85.48
  • plasmablast CL0000980
    CSI 16.04
    rCSI 12.62%
    PRS 82.16
  • granulocyte CL0000094
    CSI 6.25
    rCSI 9.55%
    PRS 84.2
  • memory T cell CL0000813
    CSI 5.46
    rCSI 10.52%
    PRS 93.91
  • small intestine goblet cell CL1000495
    CSI 5.38
    rCSI 11.78%
    PRS 82.28
  • myeloid dendritic cell CL0000782
    CSI 5.09
    rCSI 7.37%
    PRS 89.18
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 5.05
    rCSI 4.56%
    PRS 74.06
  • double negative thymocyte CL0002489
    CSI 3.81
    rCSI 2.65%
    PRS 87.42
  • rod bipolar cell CL0000751
    CSI 3.5
    rCSI 6.29%
    PRS 69.45
  • lung ciliated cell CL1000271
    CSI 3.48
    rCSI 4.02%
    PRS 67.93
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 3.44
    rCSI 6.07%
    PRS 56.9
  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.26
    rCSI 2.28%
    PRS 79.59
  • naive B cell CL0000788
    CSI 3.17
    rCSI 2.72%
    PRS 83.35
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 3.02
    rCSI 2.04%
    PRS 88.86
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 2.96
    rCSI 2.13%
    PRS 88.85
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.86
    rCSI 6.41%
    PRS 58.39
  • melanocyte CL0000148
    CSI 2.82
    rCSI 2.09%
    PRS 69.24
  • multi-ciliated epithelial cell CL0005012
    CSI 2.74
    rCSI 2.73%
    PRS 69.95
  • T-helper 17 cell CL0000899
    CSI 2.73
    rCSI 2.17%
    PRS 92.99
  • ciliated epithelial cell CL0000067
    CSI 2.66
    rCSI 2.34%
    PRS 64.92
  • neural crest cell CL0011012
    CSI 2.6
    rCSI 2.06%
    PRS 64.18
  • intestine goblet cell CL0019031
    CSI 2.6
    rCSI 2.31%
    PRS 74.15
  • erythrocyte CL0000232
    CSI 2.53
    rCSI 5.74%
    PRS 77.5
  • interneuron CL0000099
    CSI 2.5
    rCSI 5.02%
    PRS 65.92
  • hematopoietic stem cell CL0000037
    CSI 2.49
    rCSI 1.66%
    PRS 79.02
  • precursor B cell CL0000817
    CSI 2.46
    rCSI 2.15%
    PRS 83.97
  • colon epithelial cell CL0011108
    CSI 2.43
    rCSI 2.55%
    PRS 73.44
  • perivascular cell CL4033054
    CSI 2.43
    rCSI 3.32%
    PRS 80.84
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.36
    rCSI 2.93%
    PRS 55.63
  • BEST4+ enteroycte CL4030026
    CSI 2.34
    rCSI 2.91%
    PRS 77.46
  • pro-B cell CL0000826
    CSI 2.31
    rCSI 1.92%
    PRS 78.69
  • choroid plexus epithelial cell CL0000706
    CSI 2.31
    rCSI 3.78%
    PRS 65.46
  • alpha-beta T cell CL0000789
    CSI 2.3
    rCSI 2.69%
    PRS 90.01
  • placental villous trophoblast CL2000060
    CSI 2.27
    rCSI 3.51%
    PRS 75.36
  • erythroblast CL0000765
    CSI 2.25
    rCSI 5.96%
    PRS 83.08
  • Mueller cell CL0000636
    CSI 2.24
    rCSI 5.1%
    PRS 67.45
  • keratinocyte CL0000312
    CSI 2.23
    rCSI 1.87%
    PRS 79.44
  • ciliated cell CL0000064
    CSI 2.22
    rCSI 3.6%
    PRS 71.56
  • CD8-positive, alpha-beta memory T cell CL0000909
    CSI 2.22
    rCSI 2.32%
    PRS 90.37
  • conjunctival epithelial cell CL1000432
    CSI 2.14
    rCSI 3.26%
    PRS 76.59
  • CD4-positive helper T cell CL0000492
    CSI 2.12
    rCSI 1.61%
    PRS 88.42
  • goblet cell CL0000160
    CSI 2.11
    rCSI 1.99%
    PRS 75.28
  • cerebral cortex endothelial cell CL1001602
    CSI 2.02
    rCSI 3.49%
    PRS 67.16
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.99
    rCSI 1.53%
    PRS 78.52
  • granulocyte monocyte progenitor cell CL0000557
    CSI 1.93
    rCSI 1.67%
    PRS 80.51
  • promyelocyte CL0000836
    CSI 1.92
    rCSI 2.78%
    PRS 83.03
  • lung secretory cell CL1000272
    CSI 1.92
    rCSI 4.75%
    PRS 75.64
  • CD14-positive monocyte CL0001054
    CSI 1.87
    rCSI 2.33%
    PRS 85.77
  • vascular leptomeningeal cell CL4023051
    CSI 1.85
    rCSI 3.24%
    PRS 69.33
  • retina horizontal cell CL0000745
    CSI 1.85
    rCSI 2.82%
    PRS 72.88
  • mononuclear phagocyte CL0000113
    CSI 1.84
    rCSI 4.06%
    PRS 80.22
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.83
    rCSI 2.18%
    PRS 57.67
  • dendritic cell, human CL0001056
    CSI 1.83
    rCSI 2.81%
    PRS 85.16
  • mucus secreting cell CL0000319
    CSI 1.81
    rCSI 2.87%
    PRS 85.53
  • myeloid leukocyte CL0000766
    CSI 1.79
    rCSI 1.65%
    PRS 77.81
  • Langerhans cell CL0000453
    CSI 1.67
    rCSI 2.56%
    PRS 87.95
  • natural T-regulatory cell CL0000903
    CSI 1.66
    rCSI 3.14%
    PRS 95.33
  • colonocyte CL1000347
    CSI 1.63
    rCSI 2.34%
    PRS 77.56
  • luminal cell of prostate epithelium CL0002340
    CSI 1.61
    rCSI 8.66%
    PRS 84.55
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.61
    rCSI 2.07%
    PRS 58.96
  • retinal bipolar neuron CL0000748
    CSI 1.6
    rCSI 3.01%
    PRS 64.17
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.6
    rCSI 2.69%
    PRS 57.71
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 1.6
    rCSI 1.85%
    PRS 68.33
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.53
    rCSI 1.97%
    PRS 72.53
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 1.49
    rCSI 2.96%
    PRS 89.04
  • lung neuroendocrine cell CL1000223
    CSI 1.48
    rCSI 2.19%
    PRS 80.88
  • mature B cell CL0000785
    CSI 1.46
    rCSI 1.27%
    PRS 85.99
  • inhibitory interneuron CL0000498
    CSI 1.28
    rCSI 2.96%
    PRS 64.2
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 1.23
    rCSI 1.12%
    PRS 88.47
  • helper T cell CL0000912
    CSI 1.21
    rCSI 1.71%
    PRS 76.6
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 1.19
    rCSI 1.43%
    PRS 84.28
  • intestinal tuft cell CL0019032
    CSI 1.17
    rCSI 1.78%
    PRS 80.33
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.04
    rCSI 2.81%
    PRS 81.62
  • mature alpha-beta T cell CL0000791
    CSI 0.99
    rCSI 3.6%
    PRS 91.68
  • colon goblet cell CL0009039
    CSI 0.91
    rCSI 2.16%
    PRS 82.68
  • paneth cell of epithelium of small intestine CL1000343
    CSI 0.86
    rCSI 2.42%
    PRS 84.22
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.85
    rCSI 2.06%
    PRS 55.75
  • podocyte CL0000653
    CSI 0.77
    rCSI 3.43%
    PRS 76.6

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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  • 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 [GTPBP1](/details-gene/9567) (GTP Binding Protein 1) is a protein-coding gene located on chromosome 22q13.1. It encodes a GTP-binding protein with established [GTPase activity](/details-gene/GO:0003924) that plays a fundamental role in [cytoplasmic translation](/details-gene/GO:0002181), particularly in [translational elongation](/details-gene/GO:0006414). Expression data indicates that [GTPBP1](/details-gene/9567) is a highly significant gene in several immune cell populations, most notably in [mucosal invariant T cell](/details-cell/CL0000940) and antibody-secreting [plasmablast](/details-cell/CL0000980). This expression profile, combined with its function in protein synthesis, suggests it is a crucial regulator of effector functions in highly active immune cells. The gene is associated with a clinical phenotype cataloged in OMIM ([602245](https://omim.org/entry/602245)). ## Cellular Roles and Expression Landscape The expression profile of [GTPBP1](/details-gene/9567) highlights its central role in the immune system, particularly in cells requiring high rates of protein synthesis for their effector functions. **Overall**, the gene shows the highest significance in specialized lymphocyte populations. It is the top marker for [mucosal invariant T cell](/details-cell/CL0000940) (CSI: 25.27), an innate-like T cell subset critical for mucosal immunity. Its second-highest significance is in [plasmablast](/details-cell/CL0000980) (CSI: 16.04), which are terminally differentiated B cells responsible for massive antibody production. This pattern suggests that [GTPBP1](/details-gene/9567) is essential for the robust protein synthesis required for both cytokine release and antibody secretion. The gene's importance extends across both the innate and adaptive immune systems. Significant expression is observed in [granulocyte](/details-cell/CL0000094) (CSI: 6.25), multiple subsets of memory T cells including [memory T cell](/details-cell/CL0000813) (CSI: 5.46) and [CD4-positive, alpha-beta memory T cell](/details-cell/CL0000897) (CSI: 2.96), as well as antigen-presenting cells like [myeloid dendritic cell](/details-cell/CL0000782) (CSI: 5.09). Its expression in hematopoietic progenitors, such as [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 5.05), may indicate a role during immune cell development. Beyond the immune system, notable expression in [small intestine goblet cell](/details-cell/CL1000495) (CSI: 5.38) and [lung ciliated cell](/details-cell/CL1000271) (CSI: 3.48) is consistent with a role in metabolically active mucosal barrier cells. ## Pathways and Molecular Function Functionally, [GTPBP1](/details-gene/9567) is characterized by its core molecular activities of [GTP binding](/details-gene/GO:0005525) and [GTPase activity](/details-gene/GO:0003924), positioning it as a molecular switch that regulates cellular processes. The primary biological process it governs is [Cytoplasmic translation](/details-gene/GO:0002181), with a specific role as a [translation elongation factor](/details-gene/GO:0003746). This function is critical for protein synthesis and is consistent with its high expression in cells like [plasmablast](/details-cell/CL0000980) that are dedicated to secreting large quantities of protein. In addition to its role in translation, [GTPBP1](/details-gene/9567) is implicated in the broader [immune response](/details-gene/GO:0006955) and general [signal transduction](/details-gene/GO:0007165). Its association with the [cytoplasmic exosome (RNase complex)](/details-gene/GO:0000177) and its ability to bind RNA ([RNA binding](/details-gene/GO:0003723)) suggest an additional layer of regulation in mRNA stability and quality control, which would be vital in preventing the accumulation of aberrant proteins during high-volume translation. This dual role in promoting translation while potentially participating in RNA surveillance underscores its importance in maintaining cellular homeostasis during intense metabolic activity. ## Research Directions The specific and high expression of [GTPBP1](/details-gene/9567) in key effector immune cells, coupled with its fundamental role in protein synthesis, provides a strong basis for further investigation into its role in immunity and disease. **Proposed Hypotheses:** 1. Given its high significance in [plasmablast](/details-cell/CL0000980) and its function in translation, [GTPBP1](/details-gene/9567) may act as a rate-limiting factor for immunoglobulin synthesis. Its GTPase cycle could be directly regulated by signals from the B cell receptor or co-stimulatory molecules, thereby coupling antigen recognition to the massive upscale in antibody production required for a humoral response. 2. The exceptional expression of [GTPBP1](/details-gene/9567) in [mucosal invariant T cell](/details-cell/CL0000940) suggests it is essential for their rapid, pre-programmed effector functions. We hypothesize that [GTPBP1](/details-gene/9567) facilitates the preferential and rapid translation of pre-existing mRNA transcripts for key cytokines (e.g., IFN-γ, IL-17) upon T cell receptor activation, allowing these cells to mount an immediate defense at mucosal surfaces. **Experimental Approach:** To test the first hypothesis regarding the role of [GTPBP1](/details-gene/9567) in antibody production, a targeted experiment could be designed. One could use CRISPR-Cas9 to knock out [GTPBP1](/details-gene/9567) in primary human naive B cells. These knockout and control cells would then be differentiated *in vitro* into [plasmablast](/details-cell/CL0000980) using a cocktail of stimuli such as IL-21, CpG, and anti-CD40. The functional consequences would be assessed by quantifying immunoglobulin secretion via ELISA and measuring the rate of total protein synthesis using puromycin-incorporation assays. Furthermore, polysome profiling combined with RNA-sequencing could reveal if the loss of [GTPBP1](/details-gene/9567) leads to a global reduction in translation or a specific impairment in the translation of immunoglobulin heavy and light chain transcripts. **Therapeutic Potential:** The high and specific expression of [GTPBP1](/details-gene/9567) in terminally differentiated, antibody-producing cells makes it a potential therapeutic target for pathologies driven by excessive or pathogenic antibody production, such as multiple myeloma or certain autoimmune diseases (e.g., lupus, rheumatoid arthritis). As an enzyme with a distinct GTP-binding pocket, [GTPBP1](/details-gene/9567) is amenable to targeting with small molecule inhibitors. A therapeutic strategy would focus on **inhibition** to selectively dampen the protein synthesis capacity of malignant or autoreactive [plasmablast](/details-cell/CL0000980), thereby reducing the production of harmful antibodies while potentially sparing other cell types where it is expressed at lower levels.

Genular Protein ID: 1878978858

Symbol: GTPB1_HUMAN

Name: GTP-binding protein 1

UniProtKB Accession Codes:

O00178 Q6IC67

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 3 CPTAC 1 CTD 1 ChEBI 3 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 15 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10591208

Title: The DNA sequence of human chromosome 22.

PubMed ID: 10591208

DOI: 10.1038/990031

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: 15461802

Title: A genome annotation-driven approach to cloning the human ORFeome.

PubMed ID: 15461802

DOI: 10.1186/gb-2004-5-10-r84

PubMed ID: 9070279

Title: Identification of human and mouse GP-1, a putative member of a novel G-protein family.

PubMed ID: 9070279

DOI: 10.1006/bbrc.1997.6103

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

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: 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: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23186163

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

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

Sequence Information:

  • Length: 669
  • Mass: 72454
  • Checksum: 0814F4DC03740ABE
  • Sequence:
    • MATERSRSAM DSPVPASMFA PEPSSPGAAR AAAAAARLHG GFDSDCSEDG EALNGEPELD 
LTSKLVLVSP TSEQYDSLLR QMWERMDEGC GETIYVIGQG SDGTEYGLSE ADMEASYATV 
KSMAEQIEAD VILLRERQEA GGRVRDYLVR KRVGDNDFLE VRVAVVGNVD AGKSTLLGVL 
THGELDNGRG FARQKLFRHK HEIESGRTSS VGNDILGFDS EGNVVNKPDS HGGSLEWTKI 
CEKSTKVITF IDLAGHEKYL KTTVFGMTGH LPDFCMLMVG SNAGIVGMTK EHLGLALALN 
VPVFVVVTKI DMCPANILQE TLKLLQRLLK SPGCRKIPVL VQSKDDVIVT ASNFSSERMC 
PIFQISNVTG ENLDLLKMFL NLLSPRTSYR EEEPAEFQID DTYSVPGVGT VVSGTTLRGL 
IKLNDTLLLG PDPLGNFLSI AVKSIHRKRM PVKEVRGGQT ASFALKKIKR SSIRKGMVMV 
SPRLNPQASW EFEAEILVLH HPTTISPRYQ AMVHCGSIRQ TATILSMDKD CLRTGDKATV 
HFRFIKTPEY LHIDQRLVFR EGRTKAVGTI TKLLQTTNNS PMNSKPQQIK MQSTKKGPLT 
KRDEGGPSGG PAVGAPPPGD EASSVGAGQP AASSNLQPQP KPSSGGRRRG GQRHKVKSQG 
ACVTPASGC