cnp1 (SpCENP-A / CENP-A homolog) — review notes

UniProt: Q9Y812 (CENPA_SCHPO); PomBase SPBC1105.17; synonym sim2. 120 aa, histone H3 family.

Summary of function

Cnp1 is the fission-yeast CENP-A: the centromere-specific histone H3 variant that replaces canonical H3 in
centromeric (CENP-A) nucleosomes restricted to the central core/inner-repeat (cnt/imr) "central domain" of all
three centromeres. It epigenetically defines centromere identity, is the structural foundation of subkinetochore
chromatin, and is required for kinetochore assembly and accurate chromosome segregation.

Key evidence

• Essential CENP-A function / kinetochore / segregation; localizes to nonrepetitive inner centromere; Mis6-dependent:
  PMID:10864871
  UniProt FUNCTION (from PMID:10864871): "Required for recruitment and assembly of kinetochore proteins, mitotic progression and chromosome segregation. May serve as an epigenetic mark that propagates centromere identity"

• Restricted to central core (cnt/imr), not flanking repeats; domain structure:
  PMID:11553715
  PMID:11553715

• CENP-A nucleosome / replaces H3 / structural constituent; H3:H4 ratio plasticity:
  PMID:17677001
  PMID:17677001
  PMID:17677001

• CENP-A nucleosome composition (two H4 per particle, H3 absent from central domain):
  PMID:26275423
  PMID:26275423

• Biphasic (S and G2) deposition, essential for kinetochore formation:
  PMID:18077559
  PMID:18077559

• Scm3 is the CENP-A receptor/assembly factor (IPI with scm3/sim1 = SPAPB1A10.02):
  PMID:19217404
  PMID:19217404

• Sim3 (NASP) escort binds CENP-A NTD (IPI with sim3 = SPBC577.15c):
  PMID:29194511

• Mis6 dependence (IPI WITH=SPAC1687.20c = mis6):
  PMID:10864871

• Meiotic kinetochore - Cnp1 (Mis6-like group) remains at centromere throughout meiosis (condensed chromosome centromeric region IDA):
  PMID:17035632

• Centromere clustering at nuclear envelope; Cnp1 used as centromere marker (IDA chromatin/condensed chromosome):
  PMID:23166349

• Teb1 controls histone levels and centromeric Cnp1 incorporation (Cnp1 IDA chromatin):
  PMID:23314747

• Pcs1/Mde4 localize to central core (IPI WITH=Q9Y738; merotely prevention):
  PMID:17627824

• Mis12/Ppe1 kinetochore (IPI WITH=Q9Y738; PMID:12773390): Mis12 is independent of CENP-A pathway, but both reside in central centromere; physical interaction recorded by IntAct.
  PMID:12773390

Annotation review notes

• Core MF: structural constituent of chromatin (GO:0030527) — ACCEPT (IBA + IEA). This is the principal MF.
• nucleosomal DNA binding (GO:0031492) IBA — ACCEPT/keep non-core; centromeric DNA binding (GO:0019237 ISM) — keep as non-core (sequence non-specific; CENP-A deposition is sequence-independent per PMID:17677001). DNA binding (GO:0003677) IEA — general parent, MARK_AS_OVER_ANNOTATED / keep non-core.
• protein heterodimerization activity (GO:0046982) IEA InterPro — heterotetramer with H4 (CENP-A-H4), so heterodimerization is supported; keep non-core.
• protein binding (GO:0005515) bare — uninformative; MARK_AS_OVER_ANNOTATED across the IPI rows (mis6, sim3, scm3, Pcs1/Mde4/Mis12). Better captured by specific assembly/structural terms.
• CC: CENP-A containing nucleosome (GO:0043505), nucleosome (GO:0000786), CENP-A containing chromatin (GO:0061638), chromosome centromeric core domain (GO:0034506), chromosome centromeric region (GO:0000775), condensed chromosome centromeric region (GO:0000779), kinetochore (GO:0000776), chromatin (GO:0000785) — all ACCEPT (well supported). nucleus (GO:0005634) — broad but correct; keep non-core.
• BP: CENP-A containing chromatin assembly (GO:0034080) IMP — ACCEPT core. kinetochore assembly (GO:0051382) IBA — ACCEPT core. heterochromatin formation (GO:0031507) IBA — MARK_AS_OVER_ANNOTATED (Cnp1 occupies central core, NOT flanking heterochromatin; Swi6/Clr4 do heterochromatin). mitotic metaphase chromosome alignment (GO:0007080) IBA — KEEP_AS_NON_CORE (downstream consequence). chromatin organization (GO:0006325) IEA ARBA — general parent, KEEP_AS_NON_CORE.