Details for: DUSP10

Gene ID: 11221

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: DUSP10

Ensembl ID: ENSG00000143507

Description: dual specificity phosphatase 10

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • memory T cell CL0000813
    CSI 10.4
    rCSI 20.03%
    PRS 89.79
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 8.64
    rCSI 8.8%
    PRS 78.55
  • nasal mucosa goblet cell CL0002480
    CSI 5.83
    rCSI 6.76%
    PRS 73.38
  • lung ciliated cell CL1000271
    CSI 5.52
    rCSI 6.39%
    PRS 57.18
  • pancreatic acinar cell CL0002064
    CSI 4.45
    rCSI 5.92%
    PRS 72.94
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 4.44
    rCSI 13.9%
    PRS 52.1
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 4.06
    rCSI 3.99%
    PRS 82.18
  • mature T cell CL0002419
    CSI 4.05
    rCSI 3.15%
    PRS 83.55
  • myeloid leukocyte CL0000766
    CSI 3.26
    rCSI 3%
    PRS 68.39
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 3.12
    rCSI 3.77%
    PRS 75.42
  • inhibitory interneuron CL0000498
    CSI 3.07
    rCSI 7.09%
    PRS 55.02
  • interneuron CL0000099
    CSI 2.88
    rCSI 5.78%
    PRS 55.73
  • immature B cell CL0000816
    CSI 2.83
    rCSI 2.1%
    PRS 79.91
  • lung secretory cell CL1000272
    CSI 2.78
    rCSI 6.89%
    PRS 65.17
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 2.76
    rCSI 4.63%
    PRS 47.98
  • mesodermal cell CL0000222
    CSI 2.74
    rCSI 3.29%
    PRS 64.72
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.73
    rCSI 2.12%
    PRS 69.3
  • double negative thymocyte CL0002489
    CSI 2.71
    rCSI 1.89%
    PRS 78.06
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.57
    rCSI 2.22%
    PRS 71.56
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.54
    rCSI 1.71%
    PRS 80.15
  • elicited macrophage CL0000861
    CSI 2.44
    rCSI 2.24%
    PRS 75.57
  • T follicular helper cell CL0002038
    CSI 2.43
    rCSI 1.82%
    PRS 81.38
  • choroid plexus epithelial cell CL0000706
    CSI 2.34
    rCSI 3.84%
    PRS 55.66
  • hepatocyte CL0000182
    CSI 2.33
    rCSI 4.18%
    PRS 65.99
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.33
    rCSI 2.79%
    PRS 47.75
  • granulocyte CL0000094
    CSI 2.28
    rCSI 3.48%
    PRS 75.76
  • pro-B cell CL0000826
    CSI 2.23
    rCSI 1.84%
    PRS 69.1
  • precursor B cell CL0000817
    CSI 2.22
    rCSI 1.95%
    PRS 75.53
  • squamous epithelial cell CL0000076
    CSI 2.2
    rCSI 5.23%
    PRS 69.49
  • bronchus fibroblast of lung CL2000093
    CSI 2.18
    rCSI 1.77%
    PRS 67
  • keratinocyte CL0000312
    CSI 2.13
    rCSI 1.79%
    PRS 70.39
  • alpha-beta T cell CL0000789
    CSI 2.06
    rCSI 2.41%
    PRS 82.35
  • CD4-positive helper T cell CL0000492
    CSI 2.03
    rCSI 1.54%
    PRS 80.15
  • conjunctival epithelial cell CL1000432
    CSI 2.03
    rCSI 3.11%
    PRS 67.34
  • hematopoietic stem cell CL0000037
    CSI 2.03
    rCSI 1.35%
    PRS 69.6
  • intrahepatic cholangiocyte CL0002538
    CSI 1.96
    rCSI 4.71%
    PRS 75.06
  • early lymphoid progenitor CL0000936
    CSI 1.91
    rCSI 1.68%
    PRS 72.13
  • Kupffer cell CL0000091
    CSI 1.87
    rCSI 4.27%
    PRS 66.79
  • T-helper 1 cell CL0000545
    CSI 1.81
    rCSI 3.26%
    PRS 86.47
  • CD8-positive, alpha-beta cytotoxic T cell CL0000794
    CSI 1.8
    rCSI 2.15%
    PRS 85
  • ionocyte CL0005006
    CSI 1.78
    rCSI 1.9%
    PRS 66.64
  • stem cell CL0000034
    CSI 1.74
    rCSI 1.68%
    PRS 57.73
  • Mueller cell CL0000636
    CSI 1.72
    rCSI 3.93%
    PRS 58.21
  • T-helper 17 cell CL0000899
    CSI 1.69
    rCSI 1.34%
    PRS 86.71
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.67
    rCSI 1.29%
    PRS 67.75
  • group 3 innate lymphoid cell CL0001071
    CSI 1.67
    rCSI 1.25%
    PRS 72.43
  • Langerhans cell CL0000453
    CSI 1.64
    rCSI 2.5%
    PRS 81.27
  • dendritic cell, human CL0001056
    CSI 1.6
    rCSI 2.45%
    PRS 75.89
  • pulmonary ionocyte CL0017000
    CSI 1.53
    rCSI 1.87%
    PRS 73.98
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 1.51
    rCSI 7.56%
    PRS 79.31
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.5
    rCSI 1.35%
    PRS 63.75
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.47
    rCSI 1.83%
    PRS 46.06
  • lung neuroendocrine cell CL1000223
    CSI 1.45
    rCSI 2.15%
    PRS 71.81
  • mononuclear phagocyte CL0000113
    CSI 1.42
    rCSI 3.14%
    PRS 70.57
  • enteric smooth muscle cell CL0002504
    CSI 1.42
    rCSI 2.02%
    PRS 68.5
  • luminal epithelial cell of mammary gland CL0002326
    CSI 1.4
    rCSI 2.55%
    PRS 80.5
  • retinal rod cell CL0000604
    CSI 1.4
    rCSI 2.47%
    PRS 63.21
  • enteroendocrine cell CL0000164
    CSI 1.39
    rCSI 1.9%
    PRS 67.58
  • periportal region hepatocyte CL0019026
    CSI 1.39
    rCSI 5.41%
    PRS 69.83
  • innate lymphoid cell CL0001065
    CSI 1.37
    rCSI 2.83%
    PRS 67.07
  • fallopian tube secretory epithelial cell CL4030006
    CSI 1.37
    rCSI 1.31%
    PRS 66.26
  • retinal cone cell CL0000573
    CSI 1.34
    rCSI 2.16%
    PRS 56.18
  • ciliated epithelial cell CL0000067
    CSI 1.34
    rCSI 1.17%
    PRS 54.47
  • regulatory T cell CL0000815
    CSI 1.29
    rCSI 1.5%
    PRS 74.54
  • pancreatic ductal cell CL0002079
    CSI 1.29
    rCSI 2.51%
    PRS 69.61
  • plasmablast CL0000980
    CSI 1.24
    rCSI 0.97%
    PRS 73.26
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 1.22
    rCSI 3.48%
    PRS 85.74
  • forebrain radial glial cell CL0013000
    CSI 1.16
    rCSI 3.72%
    PRS 71.21
  • common myeloid progenitor CL0000049
    CSI 1.13
    rCSI 0.92%
    PRS 68.5
  • corneal epithelial cell CL0000575
    CSI 1.06
    rCSI 3.04%
    PRS 77.13
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 1.05
    rCSI 2.09%
    PRS 82.84
  • basket cell CL0000118
    CSI 1.02
    rCSI 6.41%
    PRS 48.44
  • sst GABAergic cortical interneuron CL4023017
    CSI 0.96
    rCSI 1.23%
    PRS 49.23
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 0.95
    rCSI 1.62%
    PRS 83.35
  • deuterosomal cell CL4033044
    CSI 0.94
    rCSI 3.18%
    PRS 68.74
  • enteroendocrine cell of small intestine CL0009006
    CSI 0.93
    rCSI 2.04%
    PRS 78.04
  • basophil CL0000767
    CSI 0.81
    rCSI 1.7%
    PRS 82.69
  • lung resident memory CD8-positive, alpha-beta T cell CL4033039
    CSI 0.73
    rCSI 1.88%
    PRS 89.06
  • mesenchymal cell CL0008019
    CSI 0.7
    rCSI 1.79%
    PRS 60.45
  • mammary gland epithelial cell CL0002327
    CSI 0.69
    rCSI 2.44%
    PRS 78
  • retinal ganglion cell CL0000740
    CSI 0.65
    rCSI 1.43%
    PRS 52.55
  • lung resident memory CD4-positive, alpha-beta T cell CL4033038
    CSI 0.59
    rCSI 5.79%
    PRS 89.49
  • eosinophil CL0000771
    CSI 0.4
    rCSI 2.63%
    PRS 90.27
  • central nervous system neuron CL2000029
    CSI 0.31
    rCSI 2.26%
    PRS 53.14
  • cytotoxic T cell CL0000910
    CSI 0.23
    rCSI 1.33%
    PRS 74.82

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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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 [DUSP10](/details-gene/11221), or Dual Specificity Phosphatase 10, is a protein-coding gene located on chromosome 1q41. It encodes a member of the MAP kinase phosphatase (MKP) family, which are critical negative regulators of mitogen-activated protein kinase (MAPK) signaling cascades. Functionally, [DUSP10](/details-gene/11221) dephosphorylates key kinases such as JNK and p38, thereby modulating cellular responses to stress, inflammation, and differentiation cues [Link](https://doi.org/10.1038/sj.onc.1203185). Expression data highlights its significant role in the immune system, with particularly high significance in various T lymphocyte populations, including [memory T cell](/details-cell/CL0000813)s and [double-positive, alpha-beta thymocyte](/details-cell/CL0000809)s. Its broad expression pattern, which also includes secretory and neuronal cell types, suggests a pleiotropic role in regulating cellular homeostasis across different tissues. ## Cellular Roles and Expression Landscape The expression profile of [DUSP10](/details-gene/11221) indicates a prominent function within the immune system, particularly in T cell biology. **Overall**, it shows the highest significance in [memory T cell](/details-cell/CL0000813) (CSI: 10.40) and developing [double-positive, alpha-beta thymocyte](/details-cell/CL0000809)s (CSI: 8.64), suggesting a role throughout the T cell lifecycle, from thymic selection to the establishment of immunological memory. Its elevated expression in [CD4-positive, CD25-positive, alpha-beta regulatory T cell](/details-cell/CL0000792)s is consistent with its annotated function in the '[Positive regulation of regulatory t cell differentiation](/details-cell/GO:0045591)' ([GO:0045591](https://www.ebi.ac.uk/QuickGO/term/GO:0045591)), pointing to a role in maintaining immune tolerance. Beyond the T cell lineage, [DUSP10](/details-gene/11221) is also significantly expressed in other immune populations, including [myeloid leukocyte](/details-cell/CL0000766)s and [CD1c-positive myeloid dendritic cell](/details-cell/CL0002399)s, which aligns with its documented involvement in the response to lipopolysaccharide ([GO:0032496](https://www.ebi.ac.uk/QuickGO/term/GO:0032496)). Furthermore, [DUSP10](/details-gene/11221) shows notable expression in non-immune cells, particularly secretory and barrier cells like [nasal mucosa goblet cell](/details-cell/CL0002480)s, [lung ciliated cell](/details-cell/CL1000271)s, and [pancreatic acinar cell](/details-cell/CL0002064)s. This suggests a broader homeostatic function, possibly related to its role in the negative regulation of epithelial cell migration and proliferation ([GO:0010633](https://www.ebi.ac.uk/QuickGO/term/GO:0010633), [GO:0050680](https://www.ebi.ac.uk/QuickGO/term/GO:0050680)). A distinct expression signature is also observed in specific neuronal subtypes, such as the [chandelier pvalb GABAergic cortical interneuron](/details-cell/CL4023036), indicating a potential modulatory role in neural signaling circuits. ## Pathways and Molecular Function [DUSP10](/details-gene/11221) functions primarily as a MAP kinase phosphatase ([GO:0033549](https://www.ebi.ac.uk/QuickGO/term/GO:0033549)), exerting control over cellular signaling by dephosphorylating threonine and tyrosine residues on its target kinases. Its major role is the '[Negative regulation of mapk pathway](/details-pathway/R-HSA-5675221)' ([R-HSA-5675221](https://reactome.org/content/detail/R-HSA-5675221)), which is central to the '[Mapk family signaling cascades](/details-pathway/R-HSA-5683057)' ([R-HSA-5683057](https://reactome.org/content/detail/R-HSA-5683057)). It specifically targets stress-activated kinases, contributing to the '[Negative regulation of jnk cascade](/details-cell/GO:0046329)' ([GO:0046329](https://www.ebi.ac.uk/QuickGO/term/GO:0046329)) and the '[Negative regulation of p38mapk cascade](/details-cell/GO:1903753)' ([GO:1903753](https://www.ebi.ac.uk/QuickGO/term/GO:1903753)), as established in early characterization studies [Link](https://doi.org/10.1074/jbc.274.28.19949). This is accomplished through direct physical interaction, as indicated by its annotated molecular functions of '[Jun kinase binding](/details-cell/GO:0008432)' ([GO:0008432](https://www.ebi.ac.uk/QuickGO/term/GO:0008432)) and '[Mitogen-activated protein kinase p38 binding](/details-cell/GO:0048273)' ([GO:0048273](https://www.ebi.ac.uk/QuickGO/term/GO:0048273)). Structurally, it operates within both the '[Cytoplasm](/details-cell/GO:0005737)' ([GO:0005737](https://www.ebi.ac.uk/QuickGO/term/GO:0005737)) and the '[Nucleus](/details-cell/GO:0005634)' ([GO:0005634](https://www.ebi.ac.uk/QuickGO/term/GO:0005634)), allowing it to regulate distinct signaling events in different subcellular compartments. These regulatory activities are crucial for controlling a wide array of biological processes, from the '[Regulation of adaptive immune response](/details-cell/GO:0002819)' ([GO:0002819](https://www.ebi.ac.uk/QuickGO/term/GO:0002819)) to '[Oligodendrocyte differentiation](/details-cell/GO:0048709)' ([GO:0048709](https://www.ebi.ac.uk/QuickGO/term/GO:0048709)). ## Research Directions The function of [DUSP10](/details-gene/11221) as a negative regulator of MAPK signaling, combined with its high expression in T cells, positions it as a key modulator of immune responses. Dysregulation of [DUSP10](/details-gene/11221) could contribute to autoimmune diseases (through insufficient signaling dampening) or cancer immune evasion (through excessive suppression of anti-tumor T cells by regulatory T cells). Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis 1:** Given its high expression in [CD4-positive, CD25-positive, alpha-beta regulatory T cell](/details-cell/CL0000792)s and its role in their differentiation, [DUSP10](/details-gene/11221) is essential for maintaining the stability and suppressive function of the regulatory T cell lineage. Its loss would lead to Treg instability and a breakdown of peripheral tolerance. 2. **Hypothesis 2:** In mucosal tissues, the expression of [DUSP10](/details-gene/11221) in cells like [nasal mucosa goblet cell](/details-cell/CL0002480)s and [lung ciliated cell](/details-cell/CL1000271)s serves as a homeostatic brake to prevent excessive inflammatory responses and epithelial proliferation following environmental insults or infection. A key experiment to test the first hypothesis would involve generating a T-cell-specific conditional knockout of [DUSP10](/details-gene/11221) in mice (e.g., using a *Cd4*-Cre driver). These mice could then be challenged in models of autoimmunity, such as experimental autoimmune encephalomyelitis (EAE). The prediction would be that knockout mice exhibit an exacerbated disease phenotype, characterized by reduced numbers of stable, functional regulatory T cells and hyper-activated effector T cells in the central nervous system. This could be quantified by flow cytometry for Treg markers (Foxp3, CD25), functional *in vitro* suppression assays, and phospho-proteomic analysis of sorted T cells to confirm hyperactivation of JNK and p38 pathways. As a therapeutic target, [DUSP10](/details-gene/11221) presents a dual opportunity. For autoimmune diseases, a small-molecule activator of [DUSP10](/details-gene/11221) phosphatase activity could potentially restore immune homeostasis by dampening pro-inflammatory MAPK signaling. Conversely, in oncology, targeted **inhibition** of [DUSP10](/details-gene/11221) within the tumor microenvironment could represent a novel immunotherapeutic strategy to destabilize immunosuppressive regulatory T cells and enhance the efficacy of anti-tumor immune responses.

Genular Protein ID: 3194919034

Symbol: DUS10_HUMAN

Name: Dual specificity protein phosphatase 10

UniProtKB Accession Codes:

Q9Y6W6 D3DTB4 Q6GSI4 Q9H9Z5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 2 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChEBI 12 ChEMBL 1 DEPOD 1 DMDM 1 DNASU 1 DisGeNET 1 EC 3 ELM 1 EMBL 11 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 32 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 15 PDBsum 15 PRINTS 2 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 3 RefSeq 1 Rhea 9 SABIO-RK 1 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 10391943

Title: Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5.

PubMed ID: 10391943

DOI: 10.1074/jbc.274.28.19949

PubMed ID: 10597297

Title: MKP5, a new member of the MAP kinase phosphatase family, which selectively dephosphorylates stress-activated kinases.

PubMed ID: 10597297

DOI: 10.1038/sj.onc.1203185

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 29043977

Title: A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis.

PubMed ID: 29043977

DOI: 10.7554/elife.27356

PubMed ID: 16806267

Title: Crystal structure of the catalytic domain of human MAP kinase phosphatase 5: structural insight into constitutively active phosphatase.

PubMed ID: 16806267

DOI: 10.1016/j.jmb.2006.05.059

PubMed ID: 17400920

Title: Crystal structure of the MAP kinase binding domain and the catalytic domain of human MKP5.

PubMed ID: 17400920

DOI: 10.1110/ps.062712807

PubMed ID: 22375048

Title: A distinct interaction mode revealed by the crystal structure of the kinase p38alpha with the MAPK binding domain of the phosphatase MKP5.

PubMed ID: 22375048

DOI: 10.1126/scisignal.2002241

Sequence Information:

  • Length: 482
  • Mass: 52642
  • Checksum: A8CB74ABF9498CD4
  • Sequence:
    • MPPSPLDDRV VVALSRPVRP QDLNLCLDSS YLGSANPGSN SHPPVIATTV VSLKAANLTY 
MPSSSGSARS LNCGCSSASC CTVATYDKDN QAQTQAIAAG TTTTAIGTST TCPANQMVNN 
NENTGSLSPS SGVGSPVSGT PKQLASIKII YPNDLAKKMT KCSKSHLPSQ GPVIIDCRPF 
MEYNKSHIQG AVHINCADKI SRRRLQQGKI TVLDLISCRE GKDSFKRIFS KEIIVYDENT 
NEPSRVMPSQ PLHIVLESLK REGKEPLVLK GGLSSFKQNH ENLCDNSLQL QECREVGGGA 
SAASSLLPQP IPTTPDIENA ELTPILPFLF LGNEQDAQDL DTMQRLNIGY VINVTTHLPL 
YHYEKGLFNY KRLPATDSNK QNLRQYFEEA FEFIEEAHQC GKGLLIHCQA GVSRSATIVI 
AYLMKHTRMT MTDAYKFVKG KRPIISPNLN FMGQLLEFEE DLNNGVTPRI LTPKLMGVET 
VV