Ki-67 (protein)

MKI67
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1R21, 2AFF
Identifiers
Aliases	MKI67, marker of proliferation Ki-67, KIA, MIB-, MIB-1, PPP1R105
External IDs	OMIM: 176741; MGI: 106035; HomoloGene: 1814; GeneCards: MKI67; OMA:MKI67 - orthologs
Gene location (Human)
Chr.	Chromosome 10 (human)
End	128,126,423 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	135,318,090 bp
RNA expression pattern
	Top expressed in
	ventricular zone; ; ganglionic eminence; ; bone marrow cells; ; gonad; ; trabecular bone; ; tendon of biceps brachii; ; thymus; ; stromal cell of endometrium; ; mucosa of transverse colon; ; testicle;
	Top expressed in
	fetal liver hematopoietic progenitor cell; ; tibiofemoral joint; ; human fetus; ; Paneth cell; ; genital tubercle; ; vas deferens; ; hair follicle; ; primitive streak; ; tail of embryo; ; efferent ductule;
	More reference expression data
	n/a
Gene ontology
Molecular function	nucleotide binding; protein C-terminus binding; protein binding; ATP binding; DNA binding; RNA binding;
Cellular component	cytoplasm; membrane; chromosome; nucleolus; chromosome, centromeric region; nucleus; condensed chromosome; nuclear body;
Biological process	cellular response to heat; response to organic cyclic compound; DNA metabolic process; animal organ regeneration; hyaluronan metabolic process; cell cycle; regulation of chromosome segregation; cell population proliferation; regulation of mitotic nuclear division; regulation of chromatin organization; meiosis;
	Sources:Amigo / QuickGO
Orthologs
	4288
	17345
	ENSG00000148773
	ENSMUSG00000031004
	P46013
	E9PVX6
	NM_001145966; NM_002417
	NM_001081117
	NP_001139438; NP_002408
	NP_001074586
	Wikidata
View/Edit Human	View/Edit Mouse

Antigen KI-67 also known as Ki-67 or MKI67 is a protein that in humans is encoded by the MKI67 gene (antigen identified by monoclonal antibody Ki-67).^[5]^[6]^[7]

Function

Antigen KI-67 is a nuclear protein that is associated with and may be necessary for cellular proliferation. Furthermore, it is associated with ribosomal RNA transcription.^[7] Inactivation of antigen KI-67 leads to inhibition of ribosomal RNA synthesis.^[8]

Use as cell marker

The Ki-67 protein (also known as MKI67) is a cellular marker for proliferation.^[9] It is strictly associated with cell proliferation. During interphase, the Ki-67 antigen can be exclusively detected within the cell nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. Ki-67 protein is present during all active phases of the cell cycle (G₁, S, G₂, and mitosis), but is absent from resting cells (G₀).

Antibody labeling

Ki-67 is an excellent marker to determine the growth fraction of a given cell population. The fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) is often correlated with the clinical course of cancer. The best-studied examples in this context are carcinomas of the prostate, brain and the breast and nephroblastoma. For these types of tumors, the prognostic value for survival and tumor recurrence have repeatedly been proven in uni- and multivariate analysis.

MIB-1

Ki-67 and MIB-1 monoclonal antibodies are directed against different epitopes of the same proliferation-related antigen. Ki-67 and MIB1 may be used on fixed sections.^[10] MIB-1 is used in clinical applications to determine the Ki-67 labelling index. One of its primary advantages over the original Ki-67 antibody (and the reason why it has essentially supplanted the original antibody for clinical use) is that it can be used on formalin-fixed paraffin-embedded sections, after heat-mediated antigen retrieval (see next section below).

Original Ki-67 antibody

The Ki-67 protein was originally defined by the prototype monoclonal antibody Ki-67,^[11] which was generated by immunizing mice with nuclei of the Hodgkin lymphoma cell line L428. The name is derived from the city of origin (Kiel, Germany) and the number of the original clone in the 96-well plate.

Interactions

Ki-67 (protein) has been shown to interact with CBX3.^[12]

Additional images

Immunofluorescent antibody staining against neurofilament (green) and Ki-67 (red) in a mouse embryo 12.5 days after fertilization. The proliferating cells are in the ventricular zone in the neural tube and therefore colored red.
Protein Ki-67 in the human MCF-7 cells.

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000148773 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000031004 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: Antigen identified by monoclonal antibody Ki-67".
^ Schonk DM, Kuijpers HJ, van Drunen E, van Dalen CH, Geurts van Kessel AH, Verheijen R, Ramaekers FC (October 1989). "Assignment of the gene(s) involved in the expression of the proliferation-related Ki-67 antigen to human chromosome 10". Hum. Genet. 83 (3): 297–9. doi:10.1007/BF00285178. PMID 2571566.
^ ^a ^b Bullwinkel J, Baron-Lühr B, Lüdemann A, Wohlenberg C, Gerdes J, Scholzen T (March 2006). "Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells". J. Cell. Physiol. 206 (3): 624–35. doi:10.1002/jcp.20494. PMID 16206250.
^ Rahmanzadeh R, Hüttmann G, Gerdes J, Scholzen T (June 2007). "Chromophore-assisted light inactivation of pKi-67 leads to inhibition of ribosomal RNA synthesis". Cell Prolif. 40 (3): 422–30. doi:10.1111/j.1365-2184.2007.00433.x. PMID 17531085.
^ Scholzen T, Gerdes J (March 2000). "The Ki-67 protein: from the known and the unknown". J. Cell. Physiol. 182 (3): 311–22. doi:10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9. PMID 10653597.
^ Bánkfalvi A (November 2000). "Comparative methodological analysis of erbB-2/HER-2 gene dosage, chromosomal copy number and protein overexpression in breast carcinoma tissues for diagnostic use". Histopathology. 37 (5): 411–9. doi:10.1046/j.1365-2559.2000.00984.x. PMID 11119122.
^ Gerdes J, Schwab U, Lemke H, Stein H (1983). "Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation". Int. J. Cancer. 31 (1): 13–20. doi:10.1002/ijc.2910310104. PMID 6339421.
^ Kametaka, Ai; Takagi Masatoshi; Hayakawa Tomohiro; Haraguchi Tokuko; Hiraoka Yasushi; Yoneda Yoshihiro (Dec 2002). "Interaction of the chromatin compaction-inducing domain (LR domain) of Ki-67 antigen with HP1 proteins". Genes Cells. 7 (12). England: 1231–42. doi:10.1046/j.1365-2443.2002.00596.x. ISSN 1356-9597. PMID 12485163. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help)

External links

Ki-67+Antigen at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
http://www.pathologyoutlines.com/topic/stainski67.html

Template:PBB Controls

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000148773 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000031004 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: Antigen identified by monoclonal antibody Ki-67".

[pmid2571566-6] Schonk DM, Kuijpers HJ, van Drunen E, van Dalen CH, Geurts van Kessel AH, Verheijen R, Ramaekers FC (October 1989). "Assignment of the gene(s) involved in the expression of the proliferation-related Ki-67 antigen to human chromosome 10". Hum. Genet. 83 (3): 297–9. doi:10.1007/BF00285178. PMID 2571566.

[pmid16206250-7] Bullwinkel J, Baron-Lühr B, Lüdemann A, Wohlenberg C, Gerdes J, Scholzen T (March 2006). "Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells". J. Cell. Physiol. 206 (3): 624–35. doi:10.1002/jcp.20494. PMID 16206250.

[pmid17531085-8] Rahmanzadeh R, Hüttmann G, Gerdes J, Scholzen T (June 2007). "Chromophore-assisted light inactivation of pKi-67 leads to inhibition of ribosomal RNA synthesis". Cell Prolif. 40 (3): 422–30. doi:10.1111/j.1365-2184.2007.00433.x. PMID 17531085.

[pmid10653597-9] Scholzen T, Gerdes J (March 2000). "The Ki-67 protein: from the known and the unknown". J. Cell. Physiol. 182 (3): 311–22. doi:10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9. PMID 10653597.

[pmid11119122-10] Bánkfalvi A (November 2000). "Comparative methodological analysis of erbB-2/HER-2 gene dosage, chromosomal copy number and protein overexpression in breast carcinoma tissues for diagnostic use". Histopathology. 37 (5): 411–9. doi:10.1046/j.1365-2559.2000.00984.x. PMID 11119122.

[pmid6339421-11] Gerdes J, Schwab U, Lemke H, Stein H (1983). "Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation". Int. J. Cancer. 31 (1): 13–20. doi:10.1002/ijc.2910310104. PMID 6339421.

[pmid12485163-12] Kametaka, Ai; Takagi Masatoshi; Hayakawa Tomohiro; Haraguchi Tokuko; Hiraoka Yasushi; Yoneda Yoshihiro (Dec 2002). "Interaction of the chromatin compaction-inducing domain (LR domain) of Ki-67 antigen with HP1 proteins". Genes Cells. 7 (12). England: 1231–42. doi:10.1046/j.1365-2443.2002.00596.x. ISSN 1356-9597. PMID 12485163. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help)

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