Details for: NMI

Gene ID: 9111

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: NMI

Ensembl ID: ENSG00000123609

Description: N-myc and STAT interactor

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 17.08
    rCSI 15.42%
    PRS 47.62
  • multi-ciliated epithelial cell CL0005012
    CSI 9.82
    rCSI 9.8%
    PRS 44.74
  • neural progenitor cell CL0011020
    CSI 8.24
    rCSI 36.23%
    PRS 43.35
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 7.48
    rCSI 5.04%
    PRS 62.63
  • epithelial cell of lung CL0000082
    CSI 7.02
    rCSI 5.82%
    PRS 49.61
  • hematopoietic stem cell CL0000037
    CSI 6.54
    rCSI 4.35%
    PRS 54.65
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 5.43
    rCSI 4.18%
    PRS 50.13
  • cerebral cortex endothelial cell CL1001602
    CSI 5.11
    rCSI 8.84%
    PRS 41.25
  • ciliated cell CL0000064
    CSI 5.11
    rCSI 8.27%
    PRS 48.69
  • erythroid progenitor cell CL0000038
    CSI 5.09
    rCSI 29.16%
    PRS 61.58
  • fraction A pre-pro B cell CL0002045
    CSI 4.5
    rCSI 5.15%
    PRS 72.76
  • club cell CL0000158
    CSI 4.38
    rCSI 6.42%
    PRS 49.08
  • placental villous trophoblast CL2000060
    CSI 4.18
    rCSI 6.47%
    PRS 48.65
  • CD4-positive, alpha-beta thymocyte CL0000810
    CSI 3.89
    rCSI 3.12%
    PRS 72.57
  • thymocyte CL0000893
    CSI 3.66
    rCSI 13.01%
    PRS 84.45
  • fibroblast of lung CL0002553
    CSI 3.6
    rCSI 3.35%
    PRS 50.54
  • naive T cell CL0000898
    CSI 3.49
    rCSI 2.43%
    PRS 64.81
  • fallopian tube secretory epithelial cell CL4030006
    CSI 3.47
    rCSI 3.34%
    PRS 51.15
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 3.21
    rCSI 9.2%
    PRS 69.78
  • lung macrophage CL1001603
    CSI 3.14
    rCSI 7.01%
    PRS 57.92
  • activated type II NK T cell CL0000931
    CSI 3.06
    rCSI 3.44%
    PRS 67.64
  • double negative thymocyte CL0002489
    CSI 2.99
    rCSI 2.08%
    PRS 60.82
  • secretory cell CL0000151
    CSI 2.87
    rCSI 2.99%
    PRS 51.32
  • CD14-positive monocyte CL0001054
    CSI 2.81
    rCSI 3.5%
    PRS 62.1
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 2.81
    rCSI 2.14%
    PRS 63.24
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 2.71
    rCSI 1.6%
    PRS 67.41
  • T-helper 17 cell CL0000899
    CSI 2.6
    rCSI 2.07%
    PRS 73.39
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.48
    rCSI 1.73%
    PRS 53.17
  • inflammatory macrophage CL0000863
    CSI 2.47
    rCSI 4.22%
    PRS 76.76
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.41
    rCSI 2.45%
    PRS 64.53
  • Kupffer cell CL0000091
    CSI 2.39
    rCSI 5.47%
    PRS 50.26
  • monocyte CL0000576
    CSI 2.28
    rCSI 4.13%
    PRS 70.04
  • non-classical monocyte CL0000875
    CSI 2.27
    rCSI 3.65%
    PRS 77
  • precursor B cell CL0000817
    CSI 2.26
    rCSI 1.98%
    PRS 60.89
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 2.23
    rCSI 1.6%
    PRS 64.6
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 2.18
    rCSI 2.85%
    PRS 64.58
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 2.09
    rCSI 10.5%
    PRS 62.8
  • mature alpha-beta T cell CL0000791
    CSI 2.06
    rCSI 7.47%
    PRS 70.73
  • common lymphoid progenitor CL0000051
    CSI 2.06
    rCSI 2.75%
    PRS 73.49
  • myeloid leukocyte CL0000766
    CSI 2.05
    rCSI 1.89%
    PRS 51.87
  • CD8-positive, alpha-beta thymocyte CL0000811
    CSI 1.98
    rCSI 3.09%
    PRS 77.38
  • hematopoietic precursor cell CL0008001
    CSI 1.98
    rCSI 2.03%
    PRS 69.01
  • CD4-positive helper T cell CL0000492
    CSI 1.95
    rCSI 1.47%
    PRS 64.35
  • pro-B cell CL0000826
    CSI 1.93
    rCSI 1.6%
    PRS 52.34
  • early lymphoid progenitor CL0000936
    CSI 1.91
    rCSI 1.68%
    PRS 56.22
  • respiratory hillock cell CL4030023
    CSI 1.91
    rCSI 3.4%
    PRS 65.9
  • group 3 innate lymphoid cell CL0001071
    CSI 1.9
    rCSI 1.42%
    PRS 55.1
  • common myeloid progenitor CL0000049
    CSI 1.88
    rCSI 1.52%
    PRS 51.85
  • immature B cell CL0000816
    CSI 1.87
    rCSI 1.39%
    PRS 64.62
  • intermediate monocyte CL0002393
    CSI 1.84
    rCSI 2.77%
    PRS 53.62
  • colon epithelial cell CL0011108
    CSI 1.81
    rCSI 1.89%
    PRS 47.8
  • goblet cell CL0000160
    CSI 1.73
    rCSI 1.64%
    PRS 51.27
  • granulocyte CL0000094
    CSI 1.65
    rCSI 2.52%
    PRS 60.29
  • granulocyte monocyte progenitor cell CL0000557
    CSI 1.6
    rCSI 1.38%
    PRS 55.29
  • ionocyte CL0005006
    CSI 1.57
    rCSI 1.69%
    PRS 49.17
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.54
    rCSI 3.51%
    PRS 48.64
  • promyelocyte CL0000836
    CSI 1.5
    rCSI 2.17%
    PRS 60.8
  • intestine goblet cell CL0019031
    CSI 1.48
    rCSI 1.31%
    PRS 49.39
  • common dendritic progenitor CL0001029
    CSI 1.46
    rCSI 1.83%
    PRS 61.08
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 1.45
    rCSI 1.75%
    PRS 59
  • ependymal cell CL0000065
    CSI 1.45
    rCSI 2.93%
    PRS 32.17
  • extravillous trophoblast CL0008036
    CSI 1.43
    rCSI 1.77%
    PRS 46.69
  • dendritic cell, human CL0001056
    CSI 1.41
    rCSI 2.16%
    PRS 58.71
  • alveolar macrophage CL0000583
    CSI 1.4
    rCSI 2.31%
    PRS 56.39
  • lung ciliated cell CL1000271
    CSI 1.4
    rCSI 1.62%
    PRS 40.85
  • mononuclear phagocyte CL0000113
    CSI 1.39
    rCSI 3.06%
    PRS 55
  • ciliated epithelial cell CL0000067
    CSI 1.38
    rCSI 1.21%
    PRS 39.53
  • alternatively activated macrophage CL0000890
    CSI 1.33
    rCSI 1.67%
    PRS 64.21
  • professional antigen presenting cell CL0000145
    CSI 1.32
    rCSI 4.55%
    PRS 79.78
  • elicited macrophage CL0000861
    CSI 1.31
    rCSI 1.2%
    PRS 59.14
  • promonocyte CL0000559
    CSI 1.24
    rCSI 2.12%
    PRS 60.46
  • keratinocyte CL0000312
    CSI 1.19
    rCSI 0.99%
    PRS 55.87
  • erythroid lineage cell CL0000764
    CSI 1.18
    rCSI 7.58%
    PRS 71.69
  • transitional stage B cell CL0000818
    CSI 1
    rCSI 3.27%
    PRS 81.07
  • pancreatic ductal cell CL0002079
    CSI 0.98
    rCSI 1.9%
    PRS 53.11
  • syncytiotrophoblast cell CL0000525
    CSI 0.93
    rCSI 2.68%
    PRS 67.35
  • mammary gland epithelial cell CL0002327
    CSI 0.89
    rCSI 3.13%
    PRS 65.44
  • hematopoietic multipotent progenitor cell CL0000837
    CSI 0.89
    rCSI 2.14%
    PRS 69.52
  • CD8-positive, alpha-beta cytotoxic T cell CL0000794
    CSI 0.87
    rCSI 1.04%
    PRS 71.45
  • mature B cell CL0000785
    CSI 0.76
    rCSI 0.66%
    PRS 61.16
  • CD8-alpha-alpha-positive, alpha-beta intraepithelial T cell CL0000915
    CSI 0.74
    rCSI 3.39%
    PRS 83.08
  • megakaryocyte CL0000556
    CSI 0.7
    rCSI 3.02%
    PRS 66.1
  • endothelial cell of placenta CL0009092
    CSI 0.67
    rCSI 3.31%
    PRS 62.46
  • Hofbauer cell CL3000001
    CSI 0.66
    rCSI 1.24%
    PRS 61.34
  • megakaryocyte progenitor cell CL0000553
    CSI 0.65
    rCSI 11.93%
    PRS 83.35
  • myeloid lineage restricted progenitor cell CL0000839
    CSI 0.52
    rCSI 2.69%
    PRS 74.4
  • large pre-B-II cell CL0000957
    CSI 0.52
    rCSI 1.48%
    PRS 64.73
  • myelocyte CL0002193
    CSI 0.5
    rCSI 3.29%
    PRS 81.37
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 0.49
    rCSI 2.96%
    PRS 73.81
  • eosinophil CL0000771
    CSI 0.38
    rCSI 2.52%
    PRS 80.5
  • lymphoid lineage restricted progenitor cell CL0000838
    CSI 0.34
    rCSI 1.34%
    PRS 71.56
  • cytotoxic T cell CL0000910
    CSI 0.19
    rCSI 1.1%
    PRS 62.11

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 [NMI](/details-gene/9111) (N-myc and STAT interactor) is a protein-coding gene located on chromosome 2q23.3 that functions as a critical adaptor protein in signal transduction, particularly within immune pathways. First identified as a partner of Myc proteins ([Link](https://pubmed.ncbi.nlm.nih.gov/8668343/)), its primary role involves modulating STAT-mediated signaling in response to cytokines like IL-2 and interferons ([Link](https://doi.org/10.1016/s0092-8674(00)80965-4)). Functionally, [NMI](/details-gene/9111) is deeply involved in the [innate immune response](/details-cell/GO:0045087) and [response to virus](/details-cell/GO:0009615), where it exhibits complex regulatory functions, including both positive and negative regulation of immune signaling cascades. Expression data indicate that **Overall**, [NMI](/details-gene/9111) shows the highest significance in progenitor cells, such as [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050), and in various epithelial cells, particularly [multi-ciliated epithelial cell](/details-cell/CL0005012), suggesting roles in both hematopoiesis and mucosal immunity. ## Cellular Roles and Expression Landscape The expression profile of [NMI](/details-gene/9111) highlights its importance across several distinct cellular contexts, primarily in progenitor and immune-related cell types. **Overall**, the gene demonstrates its highest significance in the [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 17.08), with notable expression in other progenitor populations including [neural progenitor cell](/details-cell/CL0011020) and [hematopoietic stem cell](/details-cell/CL0000037). This pattern suggests a potential role for [NMI](/details-gene/9111) in the regulation of cell proliferation and differentiation during development and hematopoiesis, which is consistent with its annotated function in the [negative regulation of cell population proliferation](/details-cell/GO:0008285). Beyond progenitor cells, [NMI](/details-gene/9111) is a significant gene in various epithelial and immune cells. It is highly expressed in [multi-ciliated epithelial cell](/details-cell/CL0005012) and [epithelial cell of lung](/details-cell/CL0000082), which aligns with its established role in responding to viral pathogens at mucosal surfaces. Its relevance extends to the adaptive and innate immune systems, with significant expression in [central memory CD8-positive, alpha-beta T cell](/details-cell/CL0000907), [CD14-low, CD16-positive monocyte](/details-cell/CL0002396), and developing [thymocyte](/details-cell/CL0000893). This widespread significance across immune lineages underscores its role as a key modulator of cytokine and interferon signaling pathways that are fundamental to immune cell function. ## Pathways and Molecular Function [NMI](/details-gene/9111) functions primarily as a signaling adaptor protein, reflected by its molecular function annotations including [protein binding](/details-cell/GO:0005515) and [identical protein binding](/details-cell/GO:0042802). Its biological activities are concentrated in the regulation of the immune system. It is a known component of the [cell surface receptor signaling pathway via jak-stat](/details-cell/GO:0007259), where it interacts with STAT proteins to modulate transcriptional responses to interferons and interleukins ([Link](https://doi.org/10.1016/s0092-8674(00)80965-4)). The gene plays a dual role in immune regulation. It is involved in the [positive regulation of inflammatory response](/details-cell/GO:0050729) and can act as a damage-associated molecular pattern (DAMP) to promote inflammation upon cellular stress ([Link](https://doi.org/10.1038/s41467-017-00930-9)). Conversely, it also participates in the homeostatic control of immunity through [negative regulation of innate immune response](/details-cell/GO:0045824), specifically by downregulating the production of type I interferons ([negative regulation of interferon-alpha production](/details-cell/GO:0032687) and [negative regulation of interferon-beta production](/details-cell/GO:0032688)). This regulatory complexity is highlighted by its involvement in ubiquitin-mediated protein regulation, such as [protein k48-linked ubiquitination](/details-cell/GO:0070936). Reactome pathway analysis further reinforces its role in host-pathogen interactions, with significant enrichment in pathways related to [viral infection pathways](/details-cell/R-HSA-9824446), including specific annotations for [Sars-cov infections](/details-cell/R-HSA-9679506). ## Research Directions The functional dichotomy of [NMI](/details-gene/9111) as both a promoter and an inhibitor of immune responses, combined with its specific expression patterns, presents several avenues for future research. **Proposed Hypotheses:** 1. Given its high significance in [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) and its role in [negative regulation of cell population proliferation](/details-cell/GO:0008285), [NMI](/details-gene/9111) may function as a critical checkpoint protein that governs the transition from proliferation to differentiation during erythropoiesis and megakaryopoiesis by modulating STAT5 signaling. 2. Based on its high expression in [epithelial cell of lung](/details-cell/CL0000082) and its documented involvement in antiviral pathways ([response to virus](/details-cell/GO:0009615)), [NMI](/details-gene/9111) likely acts as a key host factor in lung epithelial cells that fine-tunes the local interferon response to respiratory viruses, where its dysregulation could contribute to either uncontrolled viral replication or excessive inflammation. **Experimental Approach:** To test the second hypothesis regarding the role of [NMI](/details-gene/9111) in the lung, a compelling experiment would be to use CRISPR-Cas9 to generate an [NMI](/details-gene/9111) knockout in a human lung epithelial cell line (e.g., A549 or Calu-3). These knockout cells, along with wild-type controls, could be infected with a relevant respiratory virus, such as influenza A virus or SARS-CoV-2. The impact of [NMI](/details-gene/9111) deletion on the antiviral response could be assessed by measuring viral titers over time and quantifying the expression of key interferon-stimulated genes (ISGs) and pro-inflammatory cytokines using RNA-seq and ELISA. This would clarify whether [NMI](/details-gene/9111) primarily suppresses or enhances the epithelial antiviral state. **Therapeutic Potential:** As an intracellular signaling adaptor, [NMI](/details-gene/9111) presents a challenging but potentially valuable therapeutic target. Its dual function complicates strategy; however, its role in negatively regulating type I interferon production suggests that *inhibition* of [NMI](/details-gene/9111) function could be a viable host-directed therapy to boost antiviral immunity during acute infections. Conversely, in hyper-inflammatory conditions like cytokine release syndrome or severe COVID-19, where [NMI](/details-gene/9111) might contribute to inflammation as a DAMP, inhibiting its activity or extracellular release could have therapeutic benefits. Developing small molecule inhibitors or biologics that disrupt its key protein-protein interactions (e.g., with STATs or IFP35) would be the most likely path toward clinical application.

Genular Protein ID: 2533727068

Symbol: NMI_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q13287 B5BU69 Q53TI8 Q8WTW2 Q9BVE5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 1 ExpressionAtlas 1 GO 22 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 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 Reactome 1 RefSeq 3 SIGNOR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8668343

Title: Isolation and characterization of Nmi, a novel partner of Myc proteins.

PubMed ID: 8668343

PubMed ID: 19054851

Title: Human protein factory for converting the transcriptome into an in vitro-expressed proteome.

PubMed ID: 19054851

DOI: 10.1038/nmeth.1273

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

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: 9781816

Title: Interferon-induced upregulation and cytoplasmic localization of Myc-interacting protein Nmi.

PubMed ID: 9781816

DOI: 10.1089/jir.1998.18.767

PubMed ID: 9989503

Title: Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling.

PubMed ID: 9989503

DOI: 10.1016/s0092-8674(00)80965-4

PubMed ID: 10779520

Title: Interferon-alpha induces nmi-IFP35 heterodimeric complex formation that is affected by the phosphorylation of IFP35.

PubMed ID: 10779520

DOI: 10.1074/jbc.m003177200

PubMed ID: 10950963

Title: Interferon-inducible Myc/STAT-interacting protein Nmi associates with IFP 35 into a high molecular mass complex and inhibits proteasome-mediated degradation of IFP 35.

PubMed ID: 10950963

DOI: 10.1074/jbc.m006975200

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 23186163

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

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 26342464

Title: Trim21 regulates Nmi-IFI35 complex-mediated inhibition of innate antiviral response.

PubMed ID: 26342464

DOI: 10.1016/j.virol.2015.08.013

PubMed ID: 29038465

Title: NMI and IFP35 serve as proinflammatory DAMPs during cellular infection and injury.

PubMed ID: 29038465

DOI: 10.1038/s41467-017-00930-9

PubMed ID: 29350881

Title: Interferon-induced protein 35 inhibits endothelial cell proliferation, migration and re-endothelialization of injured arteries by inhibiting the nuclear factor-kappa B pathway.

PubMed ID: 29350881

DOI: 10.1111/apha.13037

PubMed ID: 29377960

Title: Human cytomegalovirus UL23 inhibits transcription of interferon-gamma stimulated genes and blocks antiviral interferon-gamma responses by interacting with human N-myc interactor protein.

PubMed ID: 29377960

DOI: 10.1371/journal.ppat.1006867

Sequence Information:

  • Length: 307
  • Mass: 35057
  • Checksum: EC228BD0C9E643F1
  • Sequence:
    • MEADKDDTQQ ILKEHSPDEF IKDEQNKGLI DEITKKNIQL KKEIQKLETE LQEATKEFQI 
KEDIPETKMK FLSVETPEND SQLSNISCSF QVSSKVPYEI QKGQALITFE KEEVAQNVVS 
MSKHHVQIKD VNLEVTAKPV PLNSGVRFQV YVEVSKMKIN VTEIPDTLRE DQMRDKLELS 
FSKSRNGGGE VDRVDYDRQS GSAVITFVEI GVADKILKKK EYPLYINQTC HRVTVSPYTE 
IHLKKYQIFS GTSKRTVLLT GMEGIQMDEE IVEDLINIHF QRAKNGGGEV DVVKCSLGQP 
HIAYFEE