Details for: PROX1

Gene ID: 5629

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: PROX1

Ensembl ID: ENSG00000117707

Description: prospero homeobox 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • VIP GABAergic cortical interneuron CL4023016
    CSI 39.66
    rCSI 47.37%
    PRS 55.33
  • sncg GABAergic cortical interneuron CL4023015
    CSI 37.71
    rCSI 60.64%
    PRS 57.14
  • retina horizontal cell CL0000745
    CSI 33.65
    rCSI 51.3%
    PRS 70.68
  • rod bipolar cell CL0000751
    CSI 31.9
    rCSI 57.33%
    PRS 67.07
  • ON-bipolar cell CL0000749
    CSI 28.1
    rCSI 41.76%
    PRS 74.56
  • hepatocyte CL0000182
    CSI 22.23
    rCSI 39.79%
    PRS 73.31
  • midzonal region hepatocyte CL0019028
    CSI 15.7
    rCSI 36.85%
    PRS 75.16
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 15.03
    rCSI 25.23%
    PRS 55.39
  • intestine goblet cell CL0019031
    CSI 14.39
    rCSI 12.77%
    PRS 71.85
  • H2 horizontal cell CL0004218
    CSI 13.76
    rCSI 68.41%
    PRS 69.37
  • Mueller cell CL0000636
    CSI 13.04
    rCSI 29.76%
    PRS 65.22
  • pancreatic A cell CL0000171
    CSI 13
    rCSI 13.62%
    PRS 77.3
  • centrilobular region hepatocyte CL0019029
    CSI 12.51
    rCSI 32.64%
    PRS 73.94
  • glycinergic amacrine cell CL4030028
    CSI 12.3
    rCSI 32.05%
    PRS 69.54
  • BEST4+ enteroycte CL4030026
    CSI 12.27
    rCSI 15.26%
    PRS 75.35
  • endothelial cell of lymphatic vessel CL0002138
    CSI 11.57
    rCSI 22.93%
    PRS 81.68
  • invaginating midget bipolar cell CL4033034
    CSI 11.53
    rCSI 68.09%
    PRS 66.83
  • goblet cell CL0000160
    CSI 11.3
    rCSI 10.68%
    PRS 73.17
  • retinal ganglion cell CL0000740
    CSI 11.05
    rCSI 24.4%
    PRS 59.71
  • M cell of gut CL0000682
    CSI 10.84
    rCSI 11.52%
    PRS 80.71
  • retinal bipolar neuron CL0000748
    CSI 10.81
    rCSI 20.24%
    PRS 61.86
  • lung neuroendocrine cell CL1000223
    CSI 10.66
    rCSI 15.77%
    PRS 78.58
  • cholangiocyte CL1000488
    CSI 10.26
    rCSI 61.46%
    PRS 77.09
  • periportal region hepatocyte CL0019026
    CSI 10.02
    rCSI 38.98%
    PRS 75.09
  • neural cell CL0002319
    CSI 10.01
    rCSI 37.79%
    PRS 56.97
  • hepatic stellate cell CL0000632
    CSI 9.84
    rCSI 36.87%
    PRS 66.07
  • ionocyte CL0005006
    CSI 8.96
    rCSI 9.61%
    PRS 74.62
  • Kupffer cell CL0000091
    CSI 8.96
    rCSI 20.48%
    PRS 74.71
  • pancreatic epsilon cell CL0005019
    CSI 8.94
    rCSI 41.67%
    PRS 85.33
  • intestinal tuft cell CL0019032
    CSI 8.73
    rCSI 13.34%
    PRS 78.19
  • enteroendocrine cell CL0000164
    CSI 8.68
    rCSI 11.86%
    PRS 74.52
  • endothelial cell of periportal hepatic sinusoid CL0019021
    CSI 8.53
    rCSI 39.12%
    PRS 80.12
  • P/D1 enteroendocrine cell CL0002268
    CSI 7.99
    rCSI 43.52%
    PRS 84.18
  • inhibitory interneuron CL0000498
    CSI 7.32
    rCSI 16.9%
    PRS 61.98
  • interneuron CL0000099
    CSI 7.16
    rCSI 14.38%
    PRS 63.55
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 6.77
    rCSI 19.98%
    PRS 75.63
  • enteroendocrine cell of small intestine CL0009006
    CSI 6.72
    rCSI 14.78%
    PRS 83.56
  • cardiac muscle cell CL0000746
    CSI 6.33
    rCSI 9.08%
    PRS 63.5
  • diffuse bipolar 6 cell CL4033032
    CSI 6.06
    rCSI 31.87%
    PRS 66.53
  • H1 horizontal cell CL0004217
    CSI 5.76
    rCSI 22.81%
    PRS 70.92
  • tuft cell of colon CL0009041
    CSI 5.68
    rCSI 13.22%
    PRS 81.98
  • neuroendocrine cell CL0000165
    CSI 5.53
    rCSI 21.37%
    PRS 84.65
  • pulmonary ionocyte CL0017000
    CSI 5.45
    rCSI 6.64%
    PRS 80.84
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 5.07
    rCSI 8.95%
    PRS 54.52
  • amacrine cell CL0000561
    CSI 4.61
    rCSI 13.36%
    PRS 63.17
  • paneth cell of epithelium of small intestine CL1000343
    CSI 4.56
    rCSI 12.78%
    PRS 82.54
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 4.53
    rCSI 11.71%
    PRS 69.04
  • GABAergic amacrine cell CL4030027
    CSI 4.47
    rCSI 15.3%
    PRS 60.98
  • blood vessel endothelial cell CL0000071
    CSI 4.22
    rCSI 8.76%
    PRS 71.07
  • regular ventricular cardiac myocyte CL0002131
    CSI 4.14
    rCSI 25.85%
    PRS 65.49
  • GABAergic neuron CL0000617
    CSI 4.13
    rCSI 13.82%
    PRS 58.12
  • diffuse bipolar 4 cell CL4033031
    CSI 3.99
    rCSI 45.67%
    PRS 63.64
  • brush cell CL0002204
    CSI 3.68
    rCSI 7.29%
    PRS 85.08
  • intrahepatic cholangiocyte CL0002538
    CSI 3.53
    rCSI 8.47%
    PRS 79.76
  • glial cell CL0000125
    CSI 3.49
    rCSI 13.28%
    PRS 64.39
  • diffuse bipolar 3a cell CL4033029
    CSI 3.46
    rCSI 23.56%
    PRS 67.94
  • neural progenitor cell CL0011020
    CSI 3.27
    rCSI 14.39%
    PRS 62.66
  • paneth cell CL0000510
    CSI 3.12
    rCSI 4.61%
    PRS 86.07
  • pancreatic D cell CL0000173
    CSI 3.09
    rCSI 3.04%
    PRS 76.64
  • cone retinal bipolar cell CL0000752
    CSI 2.84
    rCSI 37.12%
    PRS 78.39
  • small intestine goblet cell CL1000495
    CSI 2.79
    rCSI 6.12%
    PRS 80.31
  • type B pancreatic cell CL0000169
    CSI 2.65
    rCSI 5.88%
    PRS 72.88
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.64
    rCSI 4.21%
    PRS 77.73
  • Bergmann glial cell CL0000644
    CSI 2.61
    rCSI 3.57%
    PRS 66.03
  • pancreatic ductal cell CL0002079
    CSI 2.58
    rCSI 5.02%
    PRS 77.12
  • OFFx cell CL4033036
    CSI 2.58
    rCSI 12.15%
    PRS 67.11
  • cerebellar granule cell CL0001031
    CSI 2.58
    rCSI 3.79%
    PRS 66.79
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 2.39
    rCSI 20.66%
    PRS 69.16
  • diffuse bipolar 1 cell CL4033027
    CSI 2.31
    rCSI 17.35%
    PRS 65.93
  • skeletal muscle satellite cell CL0000594
    CSI 2.23
    rCSI 6.52%
    PRS 88.72
  • erythrocyte CL0000232
    CSI 2.23
    rCSI 5.06%
    PRS 75.52
  • regular atrial cardiac myocyte CL0002129
    CSI 2.09
    rCSI 6.72%
    PRS 71.25
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 2.06
    rCSI 6.35%
    PRS 79.42
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.95
    rCSI 2.36%
    PRS 56.39
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 1.89
    rCSI 2.68%
    PRS 70.34
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 1.72
    rCSI 18.25%
    PRS 70.74
  • intestinal crypt stem cell of colon CL0009043
    CSI 1.64
    rCSI 12.34%
    PRS 86.01
  • OFF-bipolar cell CL0000750
    CSI 1.61
    rCSI 2.2%
    PRS 77.65
  • diffuse bipolar 3b cell CL4033030
    CSI 1.52
    rCSI 10.08%
    PRS 69.53
  • helper T cell CL0000912
    CSI 1.51
    rCSI 2.14%
    PRS 75.06
  • pancreatic PP cell CL0002275
    CSI 1.43
    rCSI 5.7%
    PRS 83.03
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.37
    rCSI 3.69%
    PRS 79.8
  • type L enteroendocrine cell CL0002279
    CSI 1.34
    rCSI 2.52%
    PRS 83.89
  • stromal cell of ovary CL0002132
    CSI 1
    rCSI 2.75%
    PRS 82.62
  • enteroendocrine cell of colon CL0009042
    CSI 0.67
    rCSI 3.15%
    PRS 85.38
  • colon goblet cell CL0009039
    CSI 0.65
    rCSI 1.55%
    PRS 80.9
  • GABAergic interneuron CL0011005
    CSI 0.38
    rCSI 5.93%
    PRS 76.39
  • paneth cell of colon CL0009009
    CSI 0.34
    rCSI 3.35%
    PRS 85.61
  • central nervous system neuron CL2000029
    CSI 0.27
    rCSI 2%
    PRS 60.85

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 [PROX1](/details-gene/5629) (prospero homeobox 1) is a protein-coding gene located on chromosome 1q32.3 that encodes a key homeobox transcription factor. This protein is fundamentally involved in embryonic development and cell fate determination across multiple organ systems. Functional annotations highlight its critical roles in the development of the nervous system, including the brain and retina ([Brain development](/details-go/GO:0007420)), the liver ([Liver development](/details-go/GO:0001889)), the pancreas ([Pancreas development](/details-go/GO:0031016)), and the lymphatic system ([Lymphangiogenesis](/details-go/GO:0001946)). Expression data reveals that **Overall**, [PROX1](/details-gene/5629) shows highly significant expression in specific neuronal populations, such as [VIP GABAergic cortical interneuron](/details-cell/CL4023016) and [retina horizontal cell](/details-cell/CL0000745), as well as in [hepatocyte](/details-cell/CL0000182)s, underscoring its role in maintaining the identity and function of these specialized cells. Clinically, it is associated with developmental processes and its dysregulation is implicated in cancer ([Link](https://doi.org/10.1007/s10555-012-9390-8)), with an OMIM entry of [601546](https://omim.org/entry/601546). ## Cellular Roles and Expression Landscape The expression profile of [PROX1](/details-gene/5629) indicates a highly specific role in terminally differentiated cells across distinct tissues. Its significance is most pronounced in three primary domains: 1. **Central Nervous System and Retina:** [PROX1](/details-gene/5629) is a defining marker for several specialized neuronal subtypes. It has the highest significance in cortical interneurons, including [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 39.66) and [sncg GABAergic cortical interneuron](/details-cell/CL4023015) (CSI: 37.71). Furthermore, it is a key determinant in the retina, with high significance scores in [retina horizontal cell](/details-cell/CL0000745) (CSI: 33.65), [rod bipolar cell](/details-cell/CL0000751) (CSI: 31.90), and [ON-bipolar cell](/details-cell/CL0000749) (CSI: 28.10). This specific expression pattern is consistent with its annotated roles in [Brain development](/details-go/GO:0007420) and [Embryonic retina morphogenesis in camera-type eye](/details-go/GO:0060059). 2. **Hepatic System:** The gene is highly significant in [hepatocyte](/details-cell/CL0000182)s (CSI: 22.23), including subpopulations like [midzonal region hepatocyte](/details-cell/CL0019028) and [centrilobular region hepatocyte](/details-cell/CL0019029). This aligns with its well-established function in [Liver development](/details-go/GO:0001889) and [Hepatocyte differentiation](/details-go/GO:0070365). 3. **Glandular and Epithelial Tissues:** [PROX1](/details-gene/5629) also shows notable significance in secretory cells such as [intestine goblet cell](/details-cell/CL0019031) (CSI: 14.39) and endocrine cells like [pancreatic A cell](/details-cell/CL0000171) (CSI: 13.00), suggesting a role in the development and function of these specialized cell types within the digestive system. ## Pathways and Molecular Function [PROX1](/details-gene/5629) functions as a sequence-specific transcription factor, as indicated by its molecular function annotations, including [Dna-binding transcription factor activity, rna polymerase ii-specific](/details-go/GO:0000981) and [Rna polymerase ii cis-regulatory region sequence-specific dna binding](/details-go/GO:0000978). It operates primarily within the [Nucleus](/details-go/GO:0005634), where it binds to [Chromatin](/details-go/GO:0000785) to regulate gene expression. Its biological roles are extensive and often involve cell fate specification and differentiation. The most prominent developmental pathway it governs is [Lymphangiogenesis](/details-go/GO:0001946), where it is considered a master regulator of [Lymphatic endothelial cell differentiation](/details-go/GO:0060836). In addition to its roles in neuronal and hepatic development, [PROX1](/details-gene/5629) is also implicated in regulating cell proliferation, exhibiting context-dependent effects with annotations for both [Negative regulation of cell population proliferation](/details-go/GO:0008285) and [Positive regulation of cell population proliferation](/details-go/GO:0008284). This duality suggests it plays a crucial role in balancing growth and differentiation signals during development and tissue homeostasis. Furthermore, studies indicate it can modulate the activity of other transcription factors, such as retinoic acid-related orphan receptors, adding another layer to its regulatory complexity ([Link](https://doi.org/10.1093/nar/gkt447)). ## Research Directions The specific expression pattern and multifaceted functions of [PROX1](/details-gene/5629) suggest several avenues for future research. **Proposed Hypotheses:** 1. Given its high significance in multiple distinct subtypes of retinal and cortical neurons, [PROX1](/details-gene/5629) likely functions as a terminal selector gene that establishes and maintains the transcriptional identity of these cells. We hypothesize that **[PROX1](/details-gene/5629) interacts with different sets of co-regulatory proteins in each neuronal subtype to drive the expression of unique gene batteries responsible for their specialized morphologies and functions.** 2. Considering its role in both [Hepatocyte differentiation](/details-go/GO:0070365) and [Negative regulation of cell population proliferation](/details-go/GO:0008285), combined with its known dysregulation in cancer ([Link](https://doi.org/10.1007/s10555-012-9390-8)), we hypothesize that **loss of [PROX1](/details-gene/5629) expression in mature [hepatocyte](/details-cell/CL0000182)s is a critical event that permits cellular dedifferentiation and uncontrolled proliferation, thereby promoting the initiation of hepatocellular carcinoma.** **Experimental Approach:** To test the second hypothesis regarding its tumor-suppressive role in the liver, a conditional knockout mouse model could be employed. Specifically, *Prox1fl/fl* mice could be crossed with *Alb-CreERT2* mice to allow for tamoxifen-inducible deletion of [PROX1](/details-gene/5629) specifically in adult [hepatocyte](/details-cell/CL0000182)s. Following gene deletion, these mice, alongside control littermates, would be challenged with a liver carcinogen (e.g., diethylnitrosamine). Tumor burden, progression, and cellular differentiation status would be assessed via histology, immunohistochemistry for proliferation (Ki67) and differentiation markers, and transcriptomic analysis (RNA-seq) of liver tissue. **Therapeutic Potential:** As a transcription factor, [PROX1](/details-gene/5629) itself is a challenging direct drug target. However, its role as a potential tumor suppressor suggests that therapeutic strategies aimed at **activation** or **reactivation** of its expression or function could be beneficial in cancers where it is silenced, such as hepatocellular carcinoma. This could potentially be achieved through epigenetic therapies (e.g., using histone deacetylase inhibitors or demethylating agents) to restore its endogenous expression or by developing small molecules that stabilize the PROX1 protein or promote its transcriptional activity. Its highly specific expression profile suggests that targeting its downstream pathways may offer a therapeutic window with limited off-target effects in non-expressing tissues.

Genular Protein ID: 1257423890

Symbol: PROX1_HUMAN

Name: Prospero homeobox protein 1

UniProtKB Accession Codes:

Q92786 A6NK29 A8K2B1 Q5SW76 Q8TB91

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 76 Gene3D 1 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 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 3 SIGNOR 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: 8812486

Title: Structure and chromosomal localization of the human homeobox gene Prox 1.

PubMed ID: 8812486

DOI: 10.1006/geno.1996.0392

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: 22733308

Title: Transcription factor PROX1: its role in development and cancer.

PubMed ID: 22733308

DOI: 10.1007/s10555-012-9390-8

PubMed ID: 23723244

Title: Prospero-related homeobox 1 (Prox1) functions as a novel modulator of retinoic acid-related orphan receptors alpha- and gamma-mediated transactivation.

PubMed ID: 23723244

DOI: 10.1093/nar/gkt447

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

PubMed ID: 25755297

Title: System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel small ubiquitin-like modified target proteins and acceptor lysines relevant for genome stability.

PubMed ID: 25755297

DOI: 10.1074/mcp.o114.044792

PubMed ID: 22733734

Title: Determination of solution structures of proteins up to 40 kDa using CS-Rosetta with sparse NMR data from deuterated samples.

PubMed ID: 22733734

DOI: 10.1073/pnas.1203013109

Sequence Information:

  • Length: 737
  • Mass: 83203
  • Checksum: D243CEB421B313CA
  • Sequence:
    • MPDHDSTALL SRQTKRRRVD IGVKRTVGTA SAFFAKARAT FFSAMNPQGS EQDVEYSVVQ 
HADGEKSNVL RKLLKRANSY EDAMMPFPGA TIISQLLKNN MNKNGGTEPS FQASGLSSTG 
SEVHQEDICS NSSRDSPPEC LSPFGRPTMS QFDMDRLCDE HLRAKRARVE NIIRGMSHSP 
SVALRGNENE REMAPQSVSP RESYRENKRK QKLPQQQQQS FQQLVSARKE QKREERRQLK 
QQLEDMQKQL RQLQEKFYQI YDSTDSENDE DGNLSEDSMR SEILDARAQD SVGRSDNEMC 
ELDPGQFIDR ARALIREQEM AENKPKREGN NKERDHGPNS LQPEGKHLAE TLKQELNTAM 
SQVVDTVVKV FSAKPSRQVP QVFPPLQIPQ ARFAVNGENH NFHTANQRLQ CFGDVIIPNP 
LDTFGNVQMA SSTDQTEALP LVVRKNSSDQ SASGPAAGGH HQPLHQSPLS ATTGFTTSTF 
RHPFPLPLMA YPFQSPLGAP SGSFSGKDRA SPESLDLTRD TTSLRTKMSS HHLSHHPCSP 
AHPPSTAEGL SLSLIKSECG DLQDMSEISP YSGSAMQEGL SPNHLKKAKL MFFYTRYPSS 
NMLKTYFSDV KFNRCITSQL IKWFSNFREF YYIQMEKYAR QAINDGVTST EELSITRDCE 
LYRALNMHYN KANDFEVPER FLEVAQITLR EFFNAIIAGK DVDPSWKKAI YKVICKLDSE 
VPEIFKSPNC LQELLHE