Kinetochore-associated protein 1 (KNTC1)
The protein contains 2209 amino acids for an estimated molecular weight of 250749 Da.
Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. Required for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores (PubMed:11146660, PubMed:11590237, PubMed:15824131). Its function related to the spindle assembly machinery is proposed to depend on its association in the mitotic RZZ complex. (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs7968222 | |
| dbSNP:rs17883249 | |
| dbSNP:rs35315099 | |
| dbSNP:rs7310898 | |
| dbSNP:rs11837038 |
Biological Process
Cell division
Mitotic cell cycle checkpoint signaling
Mitotic spindle assembly checkpoint signaling
Mitotic spindle organization
Protein-containing complex assembly
Regulation of exit from mitosis
Cellular Component
Actin cytoskeleton
Condensed chromosome kinetochore
Cytosol
Kinetochore microtubule
Nucleus
Plasma membrane
RZZ complex
Spindle pole
Molecular Function
The reference OMIM entry for this protein is 607363
Kinetochore-associated protein 1; kntc1
Rough deal, drosophila, homolog of; rod
Kiaa0166
DESCRIPTION
KNTC1 is a homolog of the Drosophila 'rough deal' (Rod) protein, a component of the mitotic checkpoint surveillance mechanism. This complex prevents the onset of anaphase by elaborating an inhibitory signal until all chromosomes are properly attached and aligned on the spindle (Scaerou et al., 2001).CLONING
By randomly sequencing clones obtained from a human myeloid cell line, Nagase et al. (1996) cloned KNTC1, which they called KIAA0166. The deduced protein contains 2,209 amino acids. Northern blot analysis revealed low-to-moderate expression in all tissues tested, with highest expression in testis. By Western blot analysis of HeLa cells, Chan et al. (2000) found that KNTC1, which they called ROD, has a relative molecular mass close to the calculated molecular mass of 250 kD.GENE FUNCTION
By coimmunoprecipitation of HeLa cells, Chan et al. (2000) and Scaerou et al. (2001) determined that KNTC1 interacts with ZW10 (603954). Using a yeast 2-hybrid screen, Scaerou et al. (2001) localized the ZW10-binding region to the middle third of KNTC1. By immunofluorescence localization, Chan et al. (2000) found KNTC1 throughout the cytoplasm of cells at all mitotic stages. A fraction of the total pool was associated with kinetochores and the spindle during mitosis. KNTC1 initially concentrated at kinetochores during prometaphase. During metaphase, staining moved to the spindle fibers and prominently to the spindle poles. By late anaphase, KNTC1 was detected only at the spindle poles. KNTC1 colocalized with ZW10 at kinetochores at prometaphase. Using synchronized HeLa cells, Scaerou et al. (2001) found KNTC1 and ZW10 colocalized at kinetochores during prometaphase and metaphase, with the brightest staining for both proteins on the spindle near the poles. After late anaphase and telophase, ZW10 accumulated at the spindle midzone, while KNTC1 staining became prominent at the spindle poles. By injection of antibodies directed toward KNTC1 or ZW10 into HeLa cells shortly after their release from the G1/S boundary, Chan et al. (2000) found that anaphase cells contained lagging chromosomes and divided cells contained chromatin bridges. They concluded that both KNTC1 and ZW10 are essential components of the mitotic checkpoint.MAPPING
By analysis of human-rodent hybrid cell lines, Nagase et al. (1996) mapped the KNTC1 gene to chromosome 17. However, Gross (2011) mapped the KNTC1 gene to chromosome 12q24.31 based on an alignment of the KNTC1 sequence (GenBank GENBANK BC150278) with the genomic sequence (GRCh37). ... More on the omim web site
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 607363 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).