Summary: Centromere protein H (CENP-H)
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CENPH Edit Wikipedia article
|, centromere protein H|
Centromere and kinetochore proteins play a critical role in centromere structure, kinetochore formation, and sister chromatid separation. The protein encoded by this gene colocalizes with inner kinetochore plate proteins CENP-A and CENP-C in both interphase and metaphase. CENP-H is required for the localisation of CENP-C, but not CENP-A, to the centromere. However, it may be involved in the incorporation of newly synthesised CENP-A into centromeres via its interaction with the CENP-A/CENP-HI complex. CENP-H localizes outside of centromeric heterochromatin, where CENP-B is localized, and inside the kinetochore corona, where CENP-E is localized during prometaphase. It is thought that this protein can bind to itself, as well as to CENP-A, CENP-B or CENP-C. Multimers of the protein localize constitutively to the inner kinetochore plate and play an important role in the organization and function of the active centromere-kinetochore complex. CENP-H contains a coiled-coil structure and a nuclear localisation signal.
CENP-H shows sequence similarity to the Schizosaccharomyces pombe kinetochore protein Fta3 which is a subunit of the Sim4 complex. This complex is required for loading the DASH complex onto the kinetochore via interaction with dad1. Fta2, Fta3 and Fta4 associate with the central core and inner repeat region of the centromere.
Other Protein Interactions
- GRCh38: Ensembl release 89: ENSG00000153044 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000045273 - 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.
- Sugata N, Li S, Earnshaw WC, Yen TJ, Yoda K, Masumoto H, Munekata E, Warburton PE, Todokoro K (Jan 2001). "Human CENP-H multimers colocalize with CENP-A and CENP-C at active centromere--kinetochore complexes". Hum Mol Genet. 9 (19): 2919â€“26. doi:10.1093/hmg/9.19.2919. PMID 11092768.
- Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M (Nov 2004). "A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1". Nat Cell Biol. 6 (11): 1135â€“41. doi:10.1038/ncb1187. PMID 15502821.
- "Entrez Gene: CENPH centromere protein H".
- Fukagawa, T.; Mikami, Y.; Nishihashi, A.; Regnier, V.; Haraguchi, T.; Hiraoka, Y.; Sugata, N.; Todokoro, K.; Brown, W.; Ikemura, T. (2001). "CENP-H, a constitutive centromere component, is required for centromere targeting of CENP-C in vertebrate cells". The EMBO Journal. 20 (16): 4603â€“4617. doi:10.1093/emboj/20.16.4603. PMC 125570. PMID 11500386.
- Sugata N, Munekata E, Todokoro K (September 1999). "Characterization of a novel kinetochore protein, CENP-H". J. Biol. Chem. 274 (39): 27343â€“6. doi:10.1074/jbc.274.39.27343. PMID 10488063.
- Guo XZ, Zhang G, Wang JY, Liu WL, Wang F, Dong JQ, Xu LH, Cao JY, Song LB, Zeng MS (2008). "Prognostic relevance of Centromere protein H expression in esophageal carcinoma". BMC Cancer. 8: 233. doi:10.1186/1471-2407-8-233. PMC 2535782. PMID 18700042.
- Liao WT, Song LB, Zhang HZ, Zhang X, Zhang L, Liu WL, Feng Y, Guo BH, Mai HQ, Cao SM, Li MZ, Qin HD, Zeng YX, Zeng MS (January 2007). "Centromere protein H is a novel prognostic marker for nasopharyngeal carcinoma progression and overall patient survival". Clin. Cancer Res. 13 (2 Pt 1): 508â€“14. doi:10.1158/1078-0432.CCR-06-1512. PMID 17255272.
- Liu X, McLeod I, Anderson S, Yates JR, He X (August 2005). "Molecular analysis of kinetochore architecture in fission yeast". EMBO J. 24 (16): 2919â€“30. doi:10.1038/sj.emboj.7600762. PMC 1187945. PMID 16079914.
- Prieto C, De Las Rivas J (July 2006). "APID: Agile Protein Interaction DataAnalyzer". Nucleic Acids Res. 34 (Web Server issue): W298â€“302. doi:10.1093/nar/gkl128. PMC 1538863. PMID 16845013. Archived from the original on 2010-04-09.
- Human CENPH genome location and CENPH gene details page in the UCSC Genome Browser.
- Human PMF1 genome location and PMF1 gene details page in the UCSC Genome Browser.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899â€“903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Saffery R, Sumer H, Hassan S, et al. (2003). "Transcription within a functional human centromere". Mol. Cell. 12 (2): 509â€“16. doi:10.1016/S1097-2765(03)00279-X. PMID 14536089.
- Obuse C, Yang H, Nozaki N, et al. (2004). "Proteomics analysis of the centromere complex from HeLa interphase cells: UV-damaged DNA binding protein 1 (DDB-1) is a component of the CEN-complex, while BMI-1 is transiently co-localized with the centromeric region in interphase". Genes Cells. 9 (2): 105â€“20. doi:10.1111/j.1365-2443.2004.00705.x. PMID 15009096.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121â€“7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Mikami Y, Hori T, Kimura H, Fukagawa T (2005). "The functional region of CENP-H interacts with the Nuf2 complex that localizes to centromere during mitosis". Mol. Cell. Biol. 25 (5): 1958â€“70. doi:10.1128/MCB.25.5.1958-1970.2005. PMC 549355. PMID 15713649.
- Tomonaga T, Matsushita K, Ishibashi M, et al. (2005). "Centromere protein H is up-regulated in primary human colorectal cancer and its overexpression induces aneuploidy". Cancer Res. 65 (11): 4683â€“9. doi:10.1158/0008-5472.CAN-04-3613. PMID 15930286.
- Foltz DR, Jansen LE, Black BE, et al. (2006). "The human CENP-A centromeric nucleosome-associated complex". Nat. Cell Biol. 8 (5): 458â€“69. doi:10.1038/ncb1397. PMID 16622419.
- Okada M, Cheeseman IM, Hori T, et al. (2006). "The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres". Nat. Cell Biol. 8 (5): 446â€“57. doi:10.1038/ncb1396. PMID 16622420.
- Izuta H, Ikeno M, Suzuki N, et al. (2006). "Comprehensive analysis of the ICEN (Interphase Centromere Complex) components enriched in the CENP-A chromatin of human cells". Genes Cells. 11 (6): 673â€“84. doi:10.1111/j.1365-2443.2006.00969.x. PMID 16716197.
- Orthaus S, Ohndorf S, Diekmann S (2006). "RNAi knockdown of human kinetochore protein CENP-H". Biochem. Biophys. Res. Commun. 348 (1): 36â€“46. doi:10.1016/j.bbrc.2006.06.187. PMID 16875666.
- Liao WT, Song LB, Zhang HZ, et al. (2007). "Centromere protein H is a novel prognostic marker for nasopharyngeal carcinoma progression and overall patient survival". Clin. Cancer Res. 13 (2 Pt 1): 508â€“14. doi:10.1158/1078-0432.CCR-06-1512. PMID 17255272.
- Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
|This article on a gene on human chromosome 5 is a stub. You can help Wikipedia by expanding it.|
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Centromere protein H (CENP-H) Provide feedback
This family consists of several eukaryotic centromere protein H (CENP-H) sequences. Macromolecular centromere-kinetochore complex plays a critical role in sister chromatid separation, but its complete protein composition as well as its precise dynamic function during mitosis has not yet been clearly determined. CENP-H contains a coiled-coil structure and a nuclear localisation signal. CENP-H is specifically and constitutively localised in kinetochores throughout the cell cycle. CENP-H may play a role in kinetochore organisation and function throughout the cell cycle . This the C-terminus of the region, which is conserved from fungi to humans.
Fukagawa T, Mikami Y, Nishihashi A, Regnier V, Haraguchi T, Hiraoka Y, Sugata N, Todokoro K, Brown W, Ikemura T; , EMBO J 2001;20:4603-4617.: CENP-H, a constitutive centromere component, is required for centromere targeting of CENP-C in vertebrate cells. PUBMED:11500386 EPMC:11500386
Internal database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR008426
Chromosome segregation in eukaryotes requires the kinetochore, a multi-protein structure that assembles on centromeric DNA, and which acts to link chromosomes to spindle microtubules. Kinetochore structure and composition is highly conserved among vertebrates. The inner kinetochore is essential for kinetochore assembly, and is involved in chromosome segregation via regulation of the spindle. Inner kinetochore components include the multi-subunit CENP-H/I complex, which may function, in part, in directing centromere protein A (CENP-A) deposition to centromeres, where CENP-A is a centromere-specific histone H3 variant required for the organisation of centromeric chromatin during interphase. The CENP-H/I complex contains three functional classes of proteins [PUBMED:16622420, PUBMED:18094054]:
- CENP-H class (includes CENP-H, -I, -K, -L)
- CENP-M class (includes CENP-M)
- CENP-O class (includes CENP-O, -P, -Q, -R, -50)
CENP-H is required for the localisation of CENP-C, but not CENP-A, to the centromere. However, it may be involved in the incorporation of newly synthesised CENP-A into centromeres via its interaction with the CENP-A/CENP-HI complex. CENP-H contains a coiled-coil structure and a nuclear localisation signal. CENP-H is specifically and constitutively localised in kinetochores throughout the cell cycle, and may play a role in kinetochore organisation and function throughout the cell cycle [PUBMED:10488063].PUBMED:16079914].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||kinetochore (GO:0000776)|
|Biological process||kinetochore assembly (GO:0051382)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
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We make a range of alignments for each Pfam-A family:
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- alignment generated by searching the UniProtKB sequence database using the family HMM
- alignment generated by searching the NCBI sequence database using the family HMM
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You can see the alignments as HTML or in three different sequence viewers:
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Seed source:||Pfam-B_8705 (release 8.0)|
|Number in seed:||80|
|Number in full:||405|
|Average length of the domain:||115.30 aa|
|Average identity of full alignment:||27 %|
|Average coverage of the sequence by the domain:||46.78 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||12|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
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The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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