Details for: CENPK

Gene ID: 64105

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: CENPK

Ensembl ID: ENSG00000123219

Description: centromere protein K

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 13.74
    rCSI 12.52%
    PRS 96.79
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 8.8
    rCSI 10.16%
    PRS 82.45
  • pro-B cell CL0000826
    CSI 6.61
    rCSI 5.47%
    PRS 91.04
  • large pre-B-II cell CL0000957
    CSI 5.18
    rCSI 14.79%
    PRS 90.42
  • multi-ciliated epithelial cell CL0005012
    CSI 4.94
    rCSI 4.93%
    PRS 83.83
  • double negative thymocyte CL0002489
    CSI 4.05
    rCSI 2.82%
    PRS 96.71
  • glioblast CL0000030
    CSI 4.03
    rCSI 6.44%
    PRS 82.14
  • transit amplifying cell of colon CL0009011
    CSI 3.99
    rCSI 4.69%
    PRS 89.73
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 3.66
    rCSI 2.78%
    PRS 97.47
  • intestine goblet cell CL0019031
    CSI 3.43
    rCSI 3.04%
    PRS 87.1
  • melanocyte of skin CL1000458
    CSI 3.39
    rCSI 4.62%
    PRS 60.02
  • hematopoietic stem cell CL0000037
    CSI 3.35
    rCSI 2.23%
    PRS 91.12
  • neural crest cell CL0011012
    CSI 3.27
    rCSI 2.58%
    PRS 82.16
  • group 3 innate lymphoid cell CL0001071
    CSI 3.17
    rCSI 2.38%
    PRS 93
  • naive T cell CL0000898
    CSI 3.15
    rCSI 2.19%
    PRS 97.49
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 3
    rCSI 2.02%
    PRS 97.22
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.84
    rCSI 2.57%
    PRS 88.36
  • erythrocyte CL0000232
    CSI 2.79
    rCSI 6.34%
    PRS 88.14
  • forebrain radial glial cell CL0013000
    CSI 2.73
    rCSI 8.76%
    PRS 89.42
  • mature T cell CL0002419
    CSI 2.58
    rCSI 2.01%
    PRS 96.97
  • erythroid progenitor cell CL0000038
    CSI 2.58
    rCSI 14.78%
    PRS 91.82
  • radial glial cell CL0000681
    CSI 2.52
    rCSI 3.5%
    PRS 88.11
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.44
    rCSI 2.49%
    PRS 94.65
  • early lymphoid progenitor CL0000936
    CSI 2.34
    rCSI 2.06%
    PRS 92.79
  • common myeloid progenitor CL0000049
    CSI 2.27
    rCSI 1.84%
    PRS 91.03
  • enteric smooth muscle cell CL0002504
    CSI 2.22
    rCSI 3.17%
    PRS 89.83
  • ciliated epithelial cell CL0000067
    CSI 2.22
    rCSI 1.95%
    PRS 80.71
  • intestinal epithelial cell CL0002563
    CSI 2.21
    rCSI 2.31%
    PRS 87.25
  • fraction A pre-pro B cell CL0002045
    CSI 2.15
    rCSI 2.46%
    PRS 94.03
  • promonocyte CL0000559
    CSI 2.13
    rCSI 3.64%
    PRS 92.04
  • lymphoid lineage restricted progenitor cell CL0000838
    CSI 2.09
    rCSI 8.13%
    PRS 97.53
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.08
    rCSI 2.67%
    PRS 86.06
  • granulocyte monocyte progenitor cell CL0000557
    CSI 1.99
    rCSI 1.72%
    PRS 91.8
  • blood vessel endothelial cell CL0000071
    CSI 1.8
    rCSI 3.74%
    PRS 87.84
  • mesodermal cell CL0000222
    CSI 1.79
    rCSI 2.15%
    PRS 88.37
  • common dendritic progenitor CL0001029
    CSI 1.74
    rCSI 2.18%
    PRS 94.57
  • promyelocyte CL0000836
    CSI 1.69
    rCSI 2.44%
    PRS 92.07
  • erythroid lineage cell CL0000764
    CSI 1.63
    rCSI 10.47%
    PRS 92.73
  • extravillous trophoblast CL0008036
    CSI 1.5
    rCSI 1.85%
    PRS 88.04
  • mesenchymal cell CL0008019
    CSI 1.49
    rCSI 3.79%
    PRS 84.43
  • placental villous trophoblast CL2000060
    CSI 1.43
    rCSI 2.21%
    PRS 87.84
  • primitive red blood cell CL0002355
    CSI 1.25
    rCSI 6.73%
    PRS 91.83
  • neural progenitor cell CL0011020
    CSI 1.16
    rCSI 5.11%
    PRS 79.05
  • basal cell of epidermis CL0002187
    CSI 1.05
    rCSI 1.87%
    PRS 60.59
  • colon goblet cell CL0009039
    CSI 1.05
    rCSI 2.49%
    PRS 91.55
  • mature alpha-beta T cell CL0000791
    CSI 0.96
    rCSI 3.46%
    PRS 97.99
  • deuterosomal cell CL4033044
    CSI 0.95
    rCSI 3.22%
    PRS 84.73
  • erythroblast CL0000765
    CSI 0.94
    rCSI 2.48%
    PRS 91.08
  • transit amplifying cell of small intestine CL0009012
    CSI 0.89
    rCSI 3.89%
    PRS 93.14
  • pluripotent stem cell CL0002248
    CSI 0.4
    rCSI 11.96%
    PRS 94.49
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 0.37
    rCSI 1.84%
    PRS 96.58

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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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 [CENPK](/details-gene/64105) (Centromere Protein K) is a protein-coding gene located on chromosome 5q12.3. It is a critical component of the inner kinetochore, a multiprotein complex that assembles on centromeric DNA. The primary function of [CENPK](/details-gene/64105) is to ensure proper chromosome segregation during mitosis. It plays a vital role in kinetochore assembly and the mitotic spindle checkpoint, processes fundamental to cell division ([Link](https://doi.org/10.1091/mbc.e07-10-1051)). Consistent with this role, its expression is most significant in highly proliferative cell populations. **Overall**, its expression profile shows the highest significance in immune cells undergoing clonal expansion, such as [effector memory CD8-positive, alpha-beta T cells](/details-cell/CL0000913), and various progenitor cells, including [neuroblasts](/details-cell/CL0000338) and [pro-B cells](/details-cell/CL0000826). ## Cellular Roles and Expression Landscape The expression pattern of [CENPK](/details-gene/64105) strongly correlates with cellular proliferation. An analysis of its **Overall** expression significance reveals a distinct enrichment in actively dividing cell types across different lineages. The most significant expression is observed in the immune system, particularly in lymphocytes known for rapid expansion, including [effector memory CD8-positive, alpha-beta T cell](/details-cell/CL0000913) (CSI: 13.74) and various B cell precursors like [pro-B cell](/details-cell/CL0000826) (CSI: 6.61) and [large pre-B-II cell](/details-cell/CL0000957) (CSI: 5.18). This suggests that [CENPK](/details-gene/64105) is a key workhorse supporting the mitotic machinery required for immune responses. Beyond the hematopoietic system, [CENPK](/details-gene/64105) is also a significant marker for other proliferative populations. These include neural precursors like [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338) (CSI: 8.80), cancer cells such as [glioblast](/details-cell/CL0000030) (CSI: 4.03), and tissue-specific stem/progenitor cells like [transit amplifying cell of colon](/details-cell/CL0009011) (CSI: 3.99) and [hematopoietic stem cell](/details-cell/CL0000037) (CSI: 3.35). This broad but specific expression profile in proliferating cells underscores its fundamental role in cell division rather than in the differentiated function of any particular cell lineage. ## Pathways and Molecular Function Functionally, [CENPK](/details-gene/64105) is integral to the maintenance of genomic stability during cell division. It is a core component of the [inner kinetochore](/details-ontology/GO0000939), where it forms part of the CENP-H/I/K complex ([Link](https://doi.org/10.1091/mbc.e07-10-1051), [Link](https://doi.org/10.1007/s11427-009-0050-3)). This complex is essential for the recruitment of other kinetochore proteins and the proper attachment of microtubules to chromosomes. Gene Ontology annotations confirm its role in biological processes such as [chromosome segregation](/details-ontology/GO0007059), [kinetochore assembly](/details-ontology/GO0051382), and [mitotic sister chromatid segregation](/details-ontology/GO0000070). Its molecular function is primarily related to [protein binding](/details-ontology/GO0005515), reflecting its role as a scaffold within the kinetochore complex. Reactome pathway analysis provides a more detailed view of its involvement in the [cell cycle](/details-reactome/R-HSA-1640170), particularly during [M phase](/details-reactome/R-HSA-68886). [CENPK](/details-gene/64105) is implicated in crucial regulatory networks, including the [mitotic spindle checkpoint](/details-reactome/R-HSA-69618) and the process of [separation of sister chromatids](/details-reactome/R-HSA-2467813). These pathways ensure that mitosis does not proceed until every chromosome is correctly attached to the spindle, preventing aneuploidy. ## Research Directions The specific enrichment of [CENPK](/details-gene/64105) in proliferative cells, including cancer cells like [glioblast](/details-cell/CL0000030), highlights its potential as a biomarker and therapeutic target in oncology. Its fundamental role in mitosis makes it a critical node for investigation in diseases characterized by uncontrolled cell division. Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis:** The downregulation of [CENPK](/details-gene/64105) expression is a necessary prerequisite for cellular exit from the cell cycle and the initiation of terminal differentiation in progenitor populations like [hematopoietic stem cells](/details-cell/CL0000037). 2. **Hypothesis:** In [effector memory CD8-positive, alpha-beta T cells](/details-cell/CL0000913), [CENPK](/details-gene/64105) mRNA is maintained at a poised state, allowing for rapid protein translation and entry into the cell cycle upon secondary antigen encounter, thereby facilitating a swift memory response. **Experimental Proposal:** To test the second hypothesis regarding its role in T cell memory, one could perform a targeted knockdown of [CENPK](/details-gene/64105) in isolated human [effector memory CD8-positive, alpha-beta T cells](/details-cell/CL0000913) using lentiviral-mediated shRNA. These modified cells, along with control cells, would then be stimulated *in vitro* with their cognate peptide-MHC complexes. Proliferation could be quantitatively measured using a dye dilution assay (e.g., CFSE), while effector function could be assessed by measuring cytokine production (e.g., IFN-gamma) via ELISA or intracellular staining. A significant reduction in proliferation in the knockdown group would support the hypothesis that [CENPK](/details-gene/64105) is essential for the rapid clonal expansion characteristic of a memory immune response. **Therapeutic Potential:** Given its critical role in mitosis and high expression in cancer cells, [CENPK](/details-gene/64105) represents a potential target for anti-cancer therapies. The therapeutic strategy would focus on **inhibition**. As an intracellular protein within the nucleus, it is not readily targetable by antibodies. Therefore, the development of small molecule inhibitors that disrupt its binding to other kinetochore components could be a viable approach. However, a significant challenge would be managing on-target toxicity in healthy, highly proliferative tissues such as the bone marrow ([hematopoietic stem cell](/details-cell/CL0000037)) and intestinal epithelium ([transit amplifying cell of colon](/details-cell/CL0009011)).

Genular Protein ID: 1910365840

Symbol: CENPK_HUMAN

Name: Centromere protein K

UniProtKB Accession Codes:

Q9BS16 Q9H4L0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 EMDB 8 Ensembl 3 ExpressionAtlas 1 GO 7 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 9 PDBsum 9 PRO 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 Reactome 7 RefSeq 6 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8950979

Title: Fusion of the MLL gene with two different genes, AF-6 and AF-5alpha, by a complex translocation involving chromosomes 5, 6, 8 and 11 in infant leukemia.

PubMed ID: 8950979

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: 16716197

Title: Comprehensive analysis of the ICEN (Interphase Centromere Complex) components enriched in the CENP-A chromatin of human cells.

PubMed ID: 16716197

DOI: 10.1111/j.1365-2443.2006.00969.x

PubMed ID: 16622420

Title: The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres.

PubMed ID: 16622420

DOI: 10.1038/ncb1396

PubMed ID: 16622419

Title: The human CENP-A centromeric nucleosome-associated complex.

PubMed ID: 16622419

DOI: 10.1038/ncb1397

PubMed ID: 18045986

Title: KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly in vertebrates.

PubMed ID: 18045986

DOI: 10.1091/mbc.e07-10-1051

PubMed ID: 19381461

Title: CENP-K and CENP-H may form coiled-coils in the kinetochores.

PubMed ID: 19381461

DOI: 10.1007/s11427-009-0050-3

Sequence Information:

  • Length: 269
  • Mass: 31655
  • Checksum: D59737D32D221A84
  • Sequence:
    • MNQEDLDPDS TTDVGDVTNT EEELIRECEE MWKDMEECQN KLSLIGTETL TDSNAQLSLL 
IMQVKCLTAE LSQWQKKTPE TIPLTEDVLI TLGKEEFQKL RQDLEMVLST KESKNEKLKE 
DLEREQRWLD EQQQIMESLN VLHSELKNKV ETFSESRIFN ELKTKMLNIK EYKEKLLSTL 
GEFLEDHFPL PDRSVKKKKK NIQESSVNLI TLHEMLEILI NRLFDVPHDP YVKISDSFWP 
PYVELLLRNG IALRHPEDPT RIRLEAFHQ

Genular Protein ID: 3289216

Symbol: D6RHD3_HUMAN

Name: N/A

UniProtKB Accession Codes:

D6RHD3

Database IDs:

ARBA 7 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 2 ExpressionAtlas 1 GO 3 GeneTree 1 HGNC 1 InterPro 1 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 2 Pfam 1 Proteomes 2 ProteomicsDB 2 RefSeq 2 SAM 1 SMR 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

Sequence Information:

  • Length: 239
  • Mass: 28246
  • Checksum: E86D69EE5F24DE84
  • Sequence:
    • MWKDMEECQN KLSLIGTETL TDSNAQLSLL IMQVKCLTAE LSQWQKKTPE TIPLTEDVLI 
TLGKEEFQKL RQDLEMVLST KESKNEKLKE DLEREQRWLD EQQQIMESLN VLHSELKNKV 
ETFSESRIFN ELKTKMLNIK EYKEKLLSTL GEFLEDHFPL PDRSVKKKKK NIQESSVNLI 
TLHEMLEILI NRLFDVPHDP YVKISDSFWP PYVELLLRNG IALRHPEDPT RIRLEAFHQ