Details for: CENPE

Gene ID: 1062

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: CENPE

Ensembl ID: ENSG00000138778

Description: centromere protein E

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • innate lymphoid cell CL0001065
    CSI 12.13
    rCSI 25.04%
    PRS 85.37
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 9.4
    rCSI 10.85%
    PRS 83.86
  • large pre-B-II cell CL0000957
    CSI 9.19
    rCSI 26.22%
    PRS 90.98
  • epithelial cell of lung CL0000082
    CSI 7.95
    rCSI 6.59%
    PRS 91.81
  • common dendritic progenitor CL0001029
    CSI 7.39
    rCSI 9.27%
    PRS 95.22
  • transit amplifying cell of small intestine CL0009012
    CSI 5.4
    rCSI 23.69%
    PRS 93.93
  • neural crest cell CL0011012
    CSI 5.16
    rCSI 4.08%
    PRS 84.32
  • precursor B cell CL0000817
    CSI 4.87
    rCSI 4.27%
    PRS 94.39
  • pro-B cell CL0000826
    CSI 4.08
    rCSI 3.38%
    PRS 92.04
  • mesodermal cell CL0000222
    CSI 4.02
    rCSI 4.83%
    PRS 89.91
  • plasmablast CL0000980
    CSI 4.02
    rCSI 3.16%
    PRS 93.08
  • promonocyte CL0000559
    CSI 3.89
    rCSI 6.67%
    PRS 92.75
  • glutamatergic neuron CL0000679
    CSI 3.82
    rCSI 7.85%
    PRS 79.7
  • goblet cell CL0000160
    CSI 3.79
    rCSI 3.58%
    PRS 88.91
  • erythrocyte CL0000232
    CSI 3.55
    rCSI 8.04%
    PRS 89.19
  • enteric smooth muscle cell CL0002504
    CSI 3.03
    rCSI 4.33%
    PRS 91.08
  • glioblast CL0000030
    CSI 2.68
    rCSI 4.28%
    PRS 83.79
  • common myeloid progenitor CL0000049
    CSI 2.56
    rCSI 2.07%
    PRS 92
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.54
    rCSI 2.59%
    PRS 95.38
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.45
    rCSI 2.12%
    PRS 92.89
  • ependymal cell CL0000065
    CSI 2.39
    rCSI 4.85%
    PRS 73.95
  • fraction A pre-pro B cell CL0002045
    CSI 2.37
    rCSI 2.71%
    PRS 94.54
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.21
    rCSI 2.84%
    PRS 87.44
  • myeloid lineage restricted progenitor cell CL0000839
    CSI 2.18
    rCSI 11.26%
    PRS 97.37
  • mesenchymal cell CL0008019
    CSI 2.17
    rCSI 5.51%
    PRS 86.14
  • granulocyte CL0000094
    CSI 2.11
    rCSI 3.23%
    PRS 94.47
  • promyelocyte CL0000836
    CSI 1.93
    rCSI 2.78%
    PRS 92.9
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.93
    rCSI 1.74%
    PRS 89.61
  • primitive red blood cell CL0002355
    CSI 1.9
    rCSI 10.24%
    PRS 92.5
  • germinal center B cell CL0000844
    CSI 1.78
    rCSI 5.31%
    PRS 94.03
  • transit amplifying cell CL0009010
    CSI 1.6
    rCSI 2.45%
    PRS 94.08
  • erythroblast CL0000765
    CSI 1.56
    rCSI 4.13%
    PRS 91.71
  • placental villous trophoblast CL2000060
    CSI 1.43
    rCSI 2.2%
    PRS 89.21
  • neural progenitor cell CL0011020
    CSI 1.12
    rCSI 4.93%
    PRS 80.67
  • erythroid progenitor cell CL0000038
    CSI 0.44
    rCSI 2.49%
    PRS 92.85
  • mesenchymal stem cell CL0000134
    CSI 0.42
    rCSI 4.64%
    PRS 92.76
  • pluripotent stem cell CL0002248
    CSI 0.2
    rCSI 6.09%
    PRS 95.36

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 [CENPE](/details-gene/1062) (centromere protein E) is a protein-coding gene located on chromosome 4q24. It encodes a kinesin-like motor protein that is essential for the proper segregation of chromosomes during cell division. As a key component of the kinetochore, [CENPE](/details-gene/1062) plays a critical role in capturing and stabilizing microtubule attachments, aligning chromosomes at the metaphase plate, and satisfying the mitotic spindle checkpoint [Link](https://doi.org/10.1038/359536a0). Its expression is a hallmark of cellular proliferation, with the highest significance observed in rapidly dividing cell populations, including hematopoietic progenitors such as [innate lymphoid cell](/details-cell/CL0001065) and [large pre-B-II cell](/details-cell/CL0000957), as well as other progenitor lineages like [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338). Dysregulation of [CENPE](/details-gene/1062) is associated with mitotic errors and aneuploidy, implicating it in developmental disorders and carcinogenesis. Clinical significance is noted under OMIM entry [117143](https://omim.org/entry/117143). ## Cellular Roles and Expression Landscape The expression profile of [CENPE](/details-gene/1062) strongly indicates its function as a central regulator of mitosis in highly proliferative cells. **Overall**, the gene shows the highest significance in various progenitor and transit-amplifying cell populations, reflecting its necessity for rapid cell division and tissue expansion. Functionally, these top-expressing cells can be grouped into several key categories: * **Hematopoietic and Immune Progenitors:** [CENPE](/details-gene/1062) is a particularly strong marker in developing immune cells, including [innate lymphoid cell](/details-cell/CL0001065) (CSI: 12.13), [large pre-B-II cell](/details-cell/CL0000957) (CSI: 9.19), [common dendritic progenitor](/details-cell/CL0001029) (CSI: 7.39), [precursor B cell](/details-cell/CL0000817) (CSI: 4.87), [pro-B cell](/details-cell/CL0000826) (CSI: 4.08), [plasmablast](/details-cell/CL0000980) (CSI: 4.02), and [promonocyte](/details-cell/CL0000559) (CSI: 3.89). This pattern suggests a critical role for [CENPE](/details-gene/1062) in the clonal expansion phases of lymphopoiesis and myelopoiesis. * **Neural and Developmental Progenitors:** High significance is also noted in [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338) (CSI: 9.40) and [neural crest cell](/details-cell/CL0011012) (CSI: 5.16), consistent with its role in the extensive cell division required for nervous system development. * **Epithelial and Mesodermal Progenitors:** The gene is significantly expressed in [epithelial cell of lung](/details-cell/CL0000082) (CSI: 7.95), [transit amplifying cell of small intestine](/details-cell/CL0009012) (CSI: 5.40), and [mesodermal cell](/details-cell/CL0000222) (CSI: 4.02), highlighting its importance in tissues characterized by high cellular turnover and regeneration. The consistent enrichment of [CENPE](/details-gene/1062) in these diverse, actively dividing cell types solidifies its identity as a fundamental component of the cell division machinery rather than a lineage-specific marker. ## Pathways and Molecular Function The molecular functions of [CENPE](/details-gene/1062) are intrinsically linked to the mechanics of cell division, as detailed by its functional annotations. It operates primarily as a plus-end directed microtubule motor protein ([GO:0003777](https://www.ebi.ac.uk/QuickGO/term/GO:0003777)) that binds directly to both kinetochores ([GO:0043515](https://www.ebi.ac.uk/QuickGO/term/GO:0043515)) and microtubules ([GO:0008017](https://www.ebi.ac.uk/QuickGO/term/GO:0008017)) [Link](https://doi.org/10.1083/jcb.143.1.49). This activity is ATP-dependent ([GO:0005524](https://www.ebi.ac.uk/QuickGO/term/GO:0005524)) and essential for multiple stages of mitosis. Its biological roles are centered on ensuring chromosomal fidelity: * **Chromosome Congression and Alignment:** [CENPE](/details-gene/1062) is crucial for the [attachment of mitotic spindle microtubules to kinetochore](/details-go/GO:0051315) and the subsequent transport of chromosomes to the equatorial plane, a process known as [mitotic metaphase chromosome alignment](/details-go/GO:0007080) [Link](https://doi.org/10.1016/j.cub.2013.06.040). * **Spindle Assembly Checkpoint (SAC):** The protein is a key component of the [Mitotic Spindle Checkpoint](/details-reactome/R-HSA-69618), a surveillance mechanism that prevents the onset of anaphase until all chromosomes are properly attached to the spindle. This is reflected in its involvement in the [amplification of signal from the kinetochores](/details-reactome/R-HSA-141424). * **Chromosome Segregation:** Following checkpoint satisfaction, [CENPE](/details-gene/1062) contributes to the orderly [separation of sister chromatids](/details-reactome/R-HSA-2467813) and [chromosome segregation](/details-go/GO:0007059). These functions place [CENPE](/details-gene/1062) as a central node in Reactome pathways such as [M phase](/details-reactome/R-HSA-68886), [Cell Cycle, Mitotic](/details-reactome/R-HSA-69278), and [Mitotic Prometaphase](/details-reactome/R-HSA-68877). Its interactions with other mitotic proteins, including CENP-F, BUBR1, SKAP, and NUF2, further underscore its integral role in the complex protein machinery governing mitosis [Link](https://doi.org/10.1083/jcb.143.1.49), [Link](https://doi.org/10.1074/jbc.m111.277194), [Link](https://doi.org/10.1074/jbc.m609026200). ## Research Directions Given its fundamental role in cell proliferation, [CENPE](/details-gene/1062) is a subject of intense interest, particularly in the context of cancer, where uncontrolled cell division is a defining feature. Based on the available data, several testable hypotheses can be proposed: 1. **Inhibition of [CENPE](/details-gene/1062) will selectively induce mitotic catastrophe in cancer cells with high proliferative indices, making it an effective therapeutic target for hematological malignancies and solid tumors derived from rapidly renewing tissues.** The high expression in progenitor cells like [large pre-B-II cell](/details-cell/CL0000957) and [epithelial cell of lung](/details-cell/CL0000082) suggests that cancers originating from these lineages would be particularly vulnerable. 2. **Beyond its canonical mitotic role, [CENPE](/details-gene/1062) may have specialized functions that support the rapid, demand-driven expansion of specific immune populations, such as [innate lymphoid cell](/details-cell/CL0001065).** Disruption of [CENPE](/details-gene/1062) function in these cells could lead to impaired immune responses, suggesting a potential role in immunodeficiency or as a target for immunomodulation. **Proposed Experimental Approach:** To test the first hypothesis regarding its therapeutic potential, a multi-faceted approach could be employed. A specific small-molecule inhibitor of the [CENPE](/details-gene/1062) motor domain (e.g., GSK-923295) could be applied to a panel of cancer cell lines exhibiting high [CENPE](/details-gene/1062) expression (e.g., acute lymphoblastic leukemia, lung adenocarcinoma) alongside non-transformed, quiescent primary cells as controls. The primary endpoints would be to assess for mitotic arrest using flow cytometry for DNA content (propidium iodide staining), quantify apoptosis via Annexin V/7-AAD staining, and visualize chromosomal misalignment and spindle defects using high-resolution immunofluorescence microscopy for α-tubulin and DNA. A successful outcome would show a significant increase in G2/M-arrested and apoptotic cells specifically in the cancer cell lines, with minimal effect on the quiescent controls. **Therapeutic Potential:** [CENPE](/details-gene/1062) represents a highly attractive therapeutic target. As a kinesin motor, it is an enzyme with a druggable ATP-binding pocket, making it amenable to small molecule **inhibition**. Its expression is largely restricted to actively dividing cells, offering a therapeutic window to target proliferative cancer cells while potentially sparing most healthy, non-dividing tissues. Therefore, inhibitors of [CENPE](/details-gene/1062) hold significant promise as anti-mitotic agents for cancer therapy, either as monotherapy or in combination with other cytotoxic drugs.

Genular Protein ID: 3139227939

Symbol: CENPE_HUMAN

Name: Centromere-associated protein E

UniProtKB Accession Codes:

Q02224 A6NKY9 A8K2U7 Q4LE75

Database IDs:

AGR 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 1 ChEMBL 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EMBL 5 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 34 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PDB 5 PDBsum 5 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 9 RefSeq 2 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 1406971

Title: CENP-E is a putative kinetochore motor that accumulates just before mitosis.

PubMed ID: 1406971

DOI: 10.1038/359536a0

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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 7889940

Title: Mitotic HeLa cells contain a CENP-E-associated minus end-directed microtubule motor.

PubMed ID: 7889940

DOI: 10.1002/j.1460-2075.1995.tb07073.x

PubMed ID: 9763420

Title: Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1.

PubMed ID: 9763420

DOI: 10.1083/jcb.143.1.49

PubMed ID: 10852915

Title: Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules.

PubMed ID: 10852915

DOI: 10.1074/jbc.m003469200

PubMed ID: 15297875

Title: Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation.

PubMed ID: 15297875

DOI: 10.1038/sj.emboj.7600347

PubMed ID: 17535814

Title: Human NUF2 interacts with centromere-associated protein E and is essential for a stable spindle microtubule-kinetochore attachment.

PubMed ID: 17535814

DOI: 10.1074/jbc.m609026200

PubMed ID: 18460473

Title: Septin 7 interacts with centromere-associated protein E and is required for its kinetochore localization.

PubMed ID: 18460473

DOI: 10.1074/jbc.m710591200

PubMed ID: 18374647

Title: SUMO-2/3 modification and binding regulate the association of CENP-E with kinetochores and progression through mitosis.

PubMed ID: 18374647

DOI: 10.1016/j.molcel.2008.01.013

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19625775

Title: Defects in chromosome congression and mitotic progression in KIF18A-deficient cells are partly mediated through impaired functions of CENP-E.

PubMed ID: 19625775

DOI: 10.4161/cc.8.16.9366

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22110139

Title: CENP-E kinesin interacts with SKAP protein to orchestrate accurate chromosome segregation in mitosis.

PubMed ID: 22110139

DOI: 10.1074/jbc.m111.277194

PubMed ID: 23891108

Title: Lateral to end-on conversion of chromosome-microtubule attachment requires kinesins CENP-E and MCAK.

PubMed ID: 23891108

DOI: 10.1016/j.cub.2013.06.040

PubMed ID: 23186163

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

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 23955301

Title: Kinetochore kinesin CENP-E is a processive bi-directional tracker of dynamic microtubule tips.

PubMed ID: 23955301

DOI: 10.1038/ncb2831

PubMed ID: 24748105

Title: Mutations in CENPE define a novel kinetochore-centromeric mechanism for microcephalic primordial dwarfism.

PubMed ID: 24748105

DOI: 10.1007/s00439-014-1443-3

PubMed ID: 26321640

Title: CTCF recruits centromeric protein CENP-E to the pericentromeric/centromeric regions of chromosomes through unusual CTCF-binding sites.

PubMed ID: 26321640

DOI: 10.1016/j.celrep.2015.08.005

PubMed ID: 25918224

Title: TRAMM/TrappC12 plays a role in chromosome congression, kinetochore stability, and CENP-E recruitment.

PubMed ID: 25918224

DOI: 10.1083/jcb.201501090

PubMed ID: 25395579

Title: Chromosome congression is promoted by CENP-Q- and CENP-E-dependent pathways.

PubMed ID: 25395579

DOI: 10.1242/jcs.163659

PubMed ID: 25743205

Title: Chromokinesin Kid and kinetochore kinesin CENP-E differentially support chromosome congression without end-on attachment to microtubules.

PubMed ID: 25743205

DOI: 10.1038/ncomms7447

PubMed ID: 25908662

Title: Mitosis. Microtubule detyrosination guides chromosomes during mitosis.

PubMed ID: 25908662

DOI: 10.1126/science.aaa5175

PubMed ID: 15236970

Title: Crystal structure of the motor domain of the human kinetochore protein CENP-E.

PubMed ID: 15236970

DOI: 10.1016/j.jmb.2004.05.053

Sequence Information:

  • Length: 2701
  • Mass: 316415
  • Checksum: 4BC59C2EF0B02D88
  • Sequence:
    • MAEEGAVAVC VRVRPLNSRE ESLGETAQVY WKTDNNVIYQ VDGSKSFNFD RVFHGNETTK 
NVYEEIAAPI IDSAIQGYNG TIFAYGQTAS GKTYTMMGSE DHLGVIPRAI HDIFQKIKKF 
PDREFLLRVS YMEIYNETIT DLLCGTQKMK PLIIREDVNR NVYVADLTEE VVYTSEMALK 
WITKGEKSRH YGETKMNQRS SRSHTIFRMI LESREKGEPS NCEGSVKVSH LNLVDLAGSE 
RAAQTGAAGV RLKEGCNINR SLFILGQVIK KLSDGQVGGF INYRDSKLTR ILQNSLGGNA 
KTRIICTITP VSFDETLTAL QFASTAKYMK NTPYVNEVST DEALLKRYRK EIMDLKKQLE 
EVSLETRAQA MEKDQLAQLL EEKDLLQKVQ NEKIENLTRM LVTSSSLTLQ QELKAKRKRR 
VTWCLGKINK MKNSNYADQF NIPTNITTKT HKLSINLLRE IDESVCSESD VFSNTLDTLS 
EIEWNPATKL LNQENIESEL NSLRADYDNL VLDYEQLRTE KEEMELKLKE KNDLDEFEAL 
ERKTKKDQEM QLIHEISNLK NLVKHAEVYN QDLENELSSK VELLREKEDQ IKKLQEYIDS 
QKLENIKMDL SYSLESIEDP KQMKQTLFDA ETVALDAKRE SAFLRSENLE LKEKMKELAT 
TYKQMENDIQ LYQSQLEAKK KMQVDLEKEL QSAFNEITKL TSLIDGKVPK DLLCNLELEG 
KITDLQKELN KEVEENEALR EEVILLSELK SLPSEVERLR KEIQDKSEEL HIITSEKDKL 
FSEVVHKESR VQGLLEEIGK TKDDLATTQS NYKSTDQEFQ NFKTLHMDFE QKYKMVLEEN 
ERMNQEIVNL SKEAQKFDSS LGALKTELSY KTQELQEKTR EVQERLNEME QLKEQLENRD 
STLQTVEREK TLITEKLQQT LEEVKTLTQE KDDLKQLQES LQIERDQLKS DIHDTVNMNI 
DTQEQLRNAL ESLKQHQETI NTLKSKISEE VSRNLHMEEN TGETKDEFQQ KMVGIDKKQD 
LEAKNTQTLT ADVKDNEIIE QQRKIFSLIQ EKNELQQMLE SVIAEKEQLK TDLKENIEMT 
IENQEELRLL GDELKKQQEI VAQEKNHAIK KEGELSRTCD RLAEVEEKLK EKSQQLQEKQ 
QQLLNVQEEM SEMQKKINEI ENLKNELKNK ELTLEHMETE RLELAQKLNE NYEEVKSITK 
ERKVLKELQK SFETERDHLR GYIREIEATG LQTKEELKIA HIHLKEHQET IDELRRSVSE 
KTAQIINTQD LEKSHTKLQE EIPVLHEEQE LLPNVKEVSE TQETMNELEL LTEQSTTKDS 
TTLARIEMER LRLNEKFQES QEEIKSLTKE RDNLKTIKEA LEVKHDQLKE HIRETLAKIQ 
ESQSKQEQSL NMKEKDNETT KIVSEMEQFK PKDSALLRIE IEMLGLSKRL QESHDEMKSV 
AKEKDDLQRL QEVLQSESDQ LKENIKEIVA KHLETEEELK VAHCCLKEQE ETINELRVNL 
SEKETEISTI QKQLEAINDK LQNKIQEIYE KEEQFNIKQI SEVQEKVNEL KQFKEHRKAK 
DSALQSIESK MLELTNRLQE SQEEIQIMIK EKEEMKRVQE ALQIERDQLK ENTKEIVAKM 
KESQEKEYQF LKMTAVNETQ EKMCEIEHLK EQFETQKLNL ENIETENIRL TQILHENLEE 
MRSVTKERDD LRSVEETLKV ERDQLKENLR ETITRDLEKQ EELKIVHMHL KEHQETIDKL 
RGIVSEKTNE ISNMQKDLEH SNDALKAQDL KIQEELRIAH MHLKEQQETI DKLRGIVSEK 
TDKLSNMQKD LENSNAKLQE KIQELKANEH QLITLKKDVN ETQKKVSEME QLKKQIKDQS 
LTLSKLEIEN LNLAQKLHEN LEEMKSVMKE RDNLRRVEET LKLERDQLKE SLQETKARDL 
EIQQELKTAR MLSKEHKETV DKLREKISEK TIQISDIQKD LDKSKDELQK KIQELQKKEL 
QLLRVKEDVN MSHKKINEME QLKKQFEAQN LSMQSVRMDN FQLTKKLHES LEEIRIVAKE 
RDELRRIKES LKMERDQFIA TLREMIARDR QNHQVKPEKR LLSDGQQHLT ESLREKCSRI 
KELLKRYSEM DDHYECLNRL SLDLEKEIEF QKELSMRVKA NLSLPYLQTK HIEKLFTANQ 
RCSMEFHRIM KKLKYVLSYV TKIKEEQHES INKFEMDFID EVEKQKELLI KIQHLQQDCD 
VPSRELRDLK LNQNMDLHIE EILKDFSESE FPSIKTEFQQ VLSNRKEMTQ FLEEWLNTRF 
DIEKLKNGIQ KENDRICQVN NFFNNRIIAI MNESTEFEER SATISKEWEQ DLKSLKEKNE 
KLFKNYQTLK TSLASGAQVN PTTQDNKNPH VTSRATQLTT EKIRELENSL HEAKESAMHK 
ESKIIKMQKE LEVTNDIIAK LQAKVHESNK CLEKTKETIQ VLQDKVALGA KPYKEEIEDL 
KMKLVKIDLE KMKNAKEFEK EISATKATVE YQKEVIRLLR ENLRRSQQAQ DTSVISEHTD 
PQPSNKPLTC GGGSGIVQNT KALILKSEHI RLEKEISKLK QQNEQLIKQK NELLSNNQHL 
SNEVKTWKER TLKREAHKQV TCENSPKSPK VTGTASKKKQ ITPSQCKERN LQDPVPKESP 
KSCFFDSRSK SLPSPHPVRY FDNSSLGLCP EVQNAGAESV DSQPGPWHAS SGKDVPECKT 
Q