ID:CENPA_HUMAN DESCRIPTION: RecName: Full=Histone H3-like centromeric protein A; AltName: Full=Centromere autoantigen A; AltName: Full=Centromere protein A; Short=CENP-A; FUNCTION: Histone H3-like variant which exclusively replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore. Required for recruitment and assembly of kinetochore proteins, mitotic progression and chromosome segregation. May serve as an epigenetic mark that propagates centromere identity through replication and cell division. The CENPA-H4 heterotetramer can bind DNA by itself (in vitro). SUBUNIT: Forms a nucleosome-like histone octamer containing two molecules each of H2A, H2B, CENPA and H4 assembled in one CENPA-H4 heterotetramer and two H2A-H2B heterodimers. Nucleosomes containing CENPA also contain histone H2A variants such as macroH2A H2AFY and H2A.Z/H2AFZ. The CENPA-H4 heterotetramer is more compact and structurally more rigid than corresponding H3-H4 heterotetramers. Heterotrimer composed of HJURP, CENPA and histone H4, where HJURP interacts with the dimer formed by CENPA and histone H4 and prevents tetramerization of CENPA and H4. Component of the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and MLF1IP/CENPU. Interacts (via CATD domain) with HJURP; the interaction is direct and is required for its localization to centromeres. Interacts with CENPC, CENPN and CENPT; interaction is direct. Interacts directly with herpes virus HSV-1 ICP0 protein. Part of a centromere complex consisting of CENPA, CENPT and CENPW. INTERACTION: P62805:HIST2H4B; NbExp=4; IntAct=EBI-1751979, EBI-302023; Q8NCD3:HJURP; NbExp=14; IntAct=EBI-1751979, EBI-719429; SUBCELLULAR LOCATION: Nucleus. Chromosome, centromere, kinetochore. Note=Localizes exclusively in the kinetochore domain of centromeres. Occupies a compact domain at the inner kinetochore plate stretching across 2 thirds of the length of the constriction but encompassing only one third of the constriction width and height. DOMAIN: The CATD (CENPA targeting domain) region is responsible for the more compact structure of nucleosomes containing CENPA and is necessary and sufficient to mediate the localization into centromeres. PTM: Ubiquitinated (Probable). Interaction with herpes virus HSV-1 ICP0 protein, leads to its degradation by the proteasome pathway. PTM: Phosphorylation of Ser-7 by AURKA and AURKB during prophase is required for localization of AURKA and AURKB at inner centromere and is essential for kinetochore function. Initial phosphorylation during prophase is mediated by AURKA and is maintained by AURKB. PTM: Poly-ADP-ribosylated by PARP1 (By similarity). MISCELLANEOUS: Antibodies against CENPA are present in sera from patients with autoimmune diseases that developed autoantibodies against centrosomal proteins. SIMILARITY: Belongs to the histone H3 family.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P49450
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BC011013 - Homo sapiens centromere protein A, mRNA (cDNA clone IMAGE:4286607), **** WARNING: chimeric clone ****. U14518 - Human centromere protein-A (CENP-A) mRNA, complete cds. BC000881 - Homo sapiens centromere protein A, mRNA (cDNA clone MGC:5165 IMAGE:3461992), complete cds. JD148475 - Sequence 129499 from Patent EP1572962. JD382053 - Sequence 363077 from Patent EP1572962. BC002703 - Homo sapiens centromere protein A, mRNA (cDNA clone MGC:3892 IMAGE:3626578), complete cds. JD127768 - Sequence 108792 from Patent EP1572962. CU674442 - Synthetic construct Homo sapiens gateway clone IMAGE:100017911 5' read CENPA mRNA. HQ448742 - Synthetic construct Homo sapiens clone IMAGE:100072188; CCSB002737_02 centromere protein A (CENPA) gene, encodes complete protein. JF432571 - Synthetic construct Homo sapiens clone IMAGE:100073806 centromere protein A (CENPA) gene, encodes complete protein. KJ890897 - Synthetic construct Homo sapiens clone ccsbBroadEn_00291 CENPA gene, encodes complete protein. KJ890898 - Synthetic construct Homo sapiens clone ccsbBroadEn_00292 CENPA gene, encodes complete protein. BT007246 - Homo sapiens centromere protein A, 17kDa mRNA, complete cds. JD385354 - Sequence 366378 from Patent EP1572962. JD174291 - Sequence 155315 from Patent EP1572962. JD313921 - Sequence 294945 from Patent EP1572962. JD273204 - Sequence 254228 from Patent EP1572962. JD082333 - Sequence 63357 from Patent EP1572962. JD466412 - Sequence 447436 from Patent EP1572962. JD172975 - Sequence 153999 from Patent EP1572962. JD448985 - Sequence 430009 from Patent EP1572962. JD224953 - Sequence 205977 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein P49450 (Reactome details) participates in the following event(s):
R-HSA-141409 Mad1 binds kinetochore R-HSA-375302 Kinetochore capture of astral microtubules R-HSA-5666129 CDC42:GTP recruits DIAPH2-2 to kinetochores R-HSA-5666169 Kinetochore capture of astral microtubules is positively regulated by CDC42:GTP:p-S196-DIAPH2-2 R-HSA-141431 MAD2 associates with the Mad1 kinetochore complex R-HSA-141439 Release of activated MAD2 from kinetochores R-HSA-2467811 Separation of sister chromatids R-HSA-2467809 ESPL1 (Separase) cleaves centromeric cohesin R-HSA-5666160 AURKB phosphorylates DIAPH2-2 at kinetochores R-HSA-606326 HJURP:CENPA complex localizes to the centromere R-HSA-141422 MAD2 converted to an inhibitory state via interaction with Mad1 R-HSA-1638821 PP2A-B56 dephosphorylates centromeric cohesin R-HSA-1638803 Phosphorylation of cohesin by PLK1 at centromeres R-HSA-2468287 CDK1 phosphorylates CDCA5 (Sororin) at centromeres R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal R-HSA-68877 Mitotic Prometaphase R-HSA-5663220 RHO GTPases Activate Formins R-HSA-2500257 Resolution of Sister Chromatid Cohesion R-HSA-2467813 Separation of Sister Chromatids R-HSA-141424 Amplification of signal from the kinetochores R-HSA-68886 M Phase R-HSA-195258 RHO GTPase Effectors R-HSA-606279 Deposition of new CENPA-containing nucleosomes at the centromere R-HSA-68882 Mitotic Anaphase R-HSA-69618 Mitotic Spindle Checkpoint R-HSA-69278 Cell Cycle (Mitotic) R-HSA-194315 Signaling by Rho GTPases R-HSA-774815 Nucleosome assembly R-HSA-2555396 Mitotic Metaphase and Anaphase R-HSA-69620 Cell Cycle Checkpoints R-HSA-1640170 Cell Cycle R-HSA-162582 Signal Transduction R-HSA-73886 Chromosome Maintenance