CENPX_HUMAN
ID CENPX_HUMAN Reviewed; 81 AA.
AC A8MT69; O00281; O00282; Q96DD4; Q96F51;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Centromere protein X;
DE Short=CENP-X;
DE AltName: Full=FANCM-associated histone fold protein 2 {ECO:0000303|PubMed:20347428};
DE AltName: Full=FANCM-interacting histone fold protein 2 {ECO:0000303|PubMed:20347429};
DE AltName: Full=Fanconi anemia-associated polypeptide of 10 kDa;
DE AltName: Full=Retinoic acid-inducible gene D9 protein homolog;
DE AltName: Full=Stimulated by retinoic acid gene 13 protein homolog;
GN Name=CENPX;
GN Synonyms=FAAP10, MHF2 {ECO:0000303|PubMed:20347428,
GN ECO:0000303|PubMed:20347429}, STRA13;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
RA Scott L.M., Collins S.J.;
RT "Nucleotide sequence of two human D9 transcripts.";
RL Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 2-81 (ISOFORM 3).
RC TISSUE=Placenta, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH CENPS.
RX PubMed=19620631; DOI=10.1083/jcb.200903100;
RA Amano M., Suzuki A., Hori T., Backer C., Okawa K., Cheeseman I.M.,
RA Fukagawa T.;
RT "The CENP-S complex is essential for the stable assembly of outer
RT kinetochore structure.";
RL J. Cell Biol. 186:173-182(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE FA CORE COMPLEX,
RP IDENTIFICATION IN THE BRAFT COMPLEX, INTERACTION WITH FANCM AND CENPS,
RP SUBCELLULAR LOCATION, DNA-BINDING, AND FUNCTION.
RX PubMed=20347428; DOI=10.1016/j.molcel.2010.01.039;
RA Yan Z., Delannoy M., Ling C., Daee D., Osman F., Muniandy P.A., Shen X.,
RA Oostra A.B., Du H., Steltenpool J., Lin T., Schuster B., Decaillet C.,
RA Stasiak A., Stasiak A.Z., Stone S., Hoatlin M.E., Schindler D.,
RA Woodcock C.L., Joenje H., Sen R., de Winter J.P., Li L., Seidman M.M.,
RA Whitby M.C., Myung K., Constantinousend A., Wang W.;
RT "A histone-fold complex and FANCM form a conserved DNA-remodeling complex
RT to maintain genome stability.";
RL Mol. Cell 37:865-878(2010).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE FA CORE COMPLEX,
RP INTERACTION WITH FANCM AND CENPS, SUBCELLULAR LOCATION, DNA-BINDING, AND
RP FUNCTION.
RX PubMed=20347429; DOI=10.1016/j.molcel.2010.01.036;
RA Singh T.R., Saro D., Ali A.M., Zheng X.-F., Du C., Killen M.W.,
RA Sachpatzidis A., Wahengbam K., Pierce A.J., Xiong Y., Sung P., Meetei A.R.;
RT "MHF1-MHF2, a histone-fold-containing protein complex, participates in the
RT Fanconi anemia pathway via FANCM.";
RL Mol. Cell 37:879-886(2010).
RN [7]
RP INTERACTION WITH CENPS; CENPT AND CEPNW.
RX PubMed=22304917; DOI=10.1016/j.cell.2011.11.061;
RA Nishino T., Takeuchi K., Gascoigne K.E., Suzuki A., Hori T., Oyama T.,
RA Morikawa K., Cheeseman I.M., Fukagawa T.;
RT "CENP-T-W-S-X forms a unique centromeric chromatin structure with a
RT histone-like fold.";
RL Cell 148:487-501(2012).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [9]
RP IDENTIFICATION IN THE CENP-T-W-S-X COMPLEX, SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=24522885; DOI=10.1098/rsob.130229;
RA Dornblut C., Quinn N., Monajambashi S., Prendergast L., van Vuuren C.,
RA Muench S., Deng W., Leonhardt H., Cardoso M.C., Hoischen C., Diekmann S.,
RA Sullivan K.F.;
RT "A CENP-S/X complex assembles at the centromere in S and G2 phases of the
RT human cell cycle.";
RL Open Biol. 4:130229-130229(2014).
CC -!- FUNCTION: DNA-binding component of the Fanconi anemia (FA) core
CC complex. Required for the normal activation of the FA pathway, leading
CC to monoubiquitination of the FANCI-FANCD2 complex in response to DNA
CC damage, cellular resistance to DNA cross-linking drugs, and prevention
CC of chromosomal breakage (PubMed:20347428, PubMed:20347429). In complex
CC with CENPS (MHF heterodimer), crucial cofactor for FANCM in both
CC binding and ATP-dependent remodeling of DNA. Stabilizes FANCM. In
CC complex with CENPS and FANCM (but not other FANC proteins), rapidly
CC recruited to blocked forks and promotes gene conversion at blocked
CC replication forks (PubMed:20347428, PubMed:20347429). In complex with
CC CENPS, CENPT and CENPW (CENP-T-W-S-X heterotetramer), involved in the
CC formation of a functional kinetochore outer plate, which is essential
CC for kinetochore-microtubule attachment and faithful mitotic progression
CC (PubMed:19620631). As a component of MHF and CENP-T-W-S-X complexes,
CC binds DNA and bends it to form a nucleosome-like structure
CC (PubMed:20347428, PubMed:20347429). DNA-binding function is fulfilled
CC in the presence of CENPS, with the following preference for DNA
CC substates: Holliday junction > double-stranded > splay arm > single-
CC stranded. Does not bind DNA on its own (PubMed:20347429).
CC {ECO:0000269|PubMed:19620631, ECO:0000269|PubMed:20347428,
CC ECO:0000269|PubMed:20347429}.
CC -!- SUBUNIT: Heterodimer with CENPX, sometimes called MHF; this interaction
CC stabilizes both partners (PubMed:19620631, PubMed:20347428,
CC PubMed:20347429, PubMed:24522885). MHF heterodimers can assemble to
CC form tetrameric structures (PubMed:22304917). MHF also coassemble with
CC CENPT-CENPW heterodimers at centromeres to form the tetrameric CENP-T-
CC W-S-X complex (PubMed:22304917, PubMed:24522885). Forms a discrete
CC complex with FANCM and CENPX, called FANCM-MHF; this interaction,
CC probably mediated by direct binding between CENPS and FANCM, leads to
CC synergistic activation of double-stranded DNA binding and strongly
CC stimulates FANCM-mediated DNA remodeling (PubMed:20347428,
CC PubMed:20347429). Recruited by FANCM to the Fanconi anemia (FA) core
CC complex, which consists of CENPS, CENPX, FANCA, FANCB, FANCC, FANCE,
CC FANCF, FANCG, FANCL, FANCM, FAAP24 and FAAP100. The FA core complex
CC associates with Bloom syndrome (BLM) complex, which consists of at
CC least BLM, DNA topoisomerase 3-alpha (TOP3A), RMI1/BLAP75, RPA1/RPA70
CC and RPA2/RPA32. The super complex between FA and BLM is called BRAFT
CC (PubMed:20347428, PubMed:20347429). {ECO:0000269|PubMed:19620631,
CC ECO:0000269|PubMed:20347428, ECO:0000269|PubMed:20347429,
CC ECO:0000269|PubMed:22304917, ECO:0000269|PubMed:24522885}.
CC -!- INTERACTION:
CC A8MT69; Q8N2Z9: CENPS; NbExp=6; IntAct=EBI-5529694, EBI-5529649;
CC A8MT69; Q04864: REL; NbExp=3; IntAct=EBI-5529694, EBI-307352;
CC A8MT69; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-5529694, EBI-2130429;
CC A8MT69-2; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-13128870, EBI-2130429;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19620631,
CC ECO:0000269|PubMed:24522885}. Chromosome, centromere
CC {ECO:0000269|PubMed:19620631, ECO:0000269|PubMed:24522885}. Chromosome,
CC centromere, kinetochore {ECO:0000269|PubMed:19620631,
CC ECO:0000269|PubMed:24522885}. Note=Assembly of CENPS and CENPX and its
CC partner subunits CENPT and CENPW at centromeres occurs through a
CC dynamic exchange mechanism. Although exchange is continuous in the cell
CC cycle, de novo assembly starts principally during mid-late S phase and
CC is complete by G2. CENPX being less stably bound at the kinetochore
CC than CENPS. {ECO:0000269|PubMed:19620631, ECO:0000269|PubMed:24522885}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=A8MT69-1; Sequence=Displayed;
CC Name=2; Synonyms=Variant A;
CC IsoId=A8MT69-2; Sequence=VSP_033948;
CC Name=3; Synonyms=Variant B;
CC IsoId=A8MT69-3; Sequence=VSP_033948, VSP_033949;
CC -!- DEVELOPMENTAL STAGE: Expression varies across the cell cycle, with
CC highest levels in S phase (at protein level). No statistically
CC significant changes at the transcript level.
CC {ECO:0000269|PubMed:24522885}.
CC -!- SIMILARITY: Belongs to the CENP-X/MHF2 family. {ECO:0000305}.
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DR EMBL; U95006; AAB53638.1; -; mRNA.
DR EMBL; U95007; AAB53639.1; -; mRNA.
DR EMBL; AC137723; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009571; AAH09571.1; -; mRNA.
DR EMBL; BC011610; AAH11610.1; -; mRNA.
DR CCDS; CCDS32772.1; -. [A8MT69-2]
DR CCDS; CCDS59302.1; -. [A8MT69-3]
DR CCDS; CCDS59303.1; -. [A8MT69-1]
DR RefSeq; NP_001257935.1; NM_001271006.1. [A8MT69-1]
DR RefSeq; NP_001257936.1; NM_001271007.1. [A8MT69-3]
DR RefSeq; NP_001317465.1; NM_001330536.1.
DR RefSeq; NP_659435.2; NM_144998.3. [A8MT69-2]
DR PDB; 4DRA; X-ray; 2.41 A; E/F/G/H=1-81.
DR PDB; 4DRB; X-ray; 2.63 A; J/K/L/M/N/O=1-81.
DR PDB; 4E44; X-ray; 2.10 A; B/D=1-81.
DR PDB; 4E45; X-ray; 2.00 A; B/D/G/I/L/N=1-81.
DR PDB; 4NDY; X-ray; 7.00 A; B/D/H/L/M/N/U/V/W/X=8-81.
DR PDB; 4NE1; X-ray; 6.50 A; B/D/H/L/M/N/U/V/W/X/Z/b/d/h/i/j/o/p/q/r=8-81.
DR PDB; 4NE3; X-ray; 1.80 A; B=8-81.
DR PDB; 4NE5; X-ray; 2.50 A; B/D/F/H=8-81.
DR PDB; 4NE6; X-ray; 2.10 A; B/D=8-81.
DR PDBsum; 4DRA; -.
DR PDBsum; 4DRB; -.
DR PDBsum; 4E44; -.
DR PDBsum; 4E45; -.
DR PDBsum; 4NDY; -.
DR PDBsum; 4NE1; -.
DR PDBsum; 4NE3; -.
DR PDBsum; 4NE5; -.
DR PDBsum; 4NE6; -.
DR AlphaFoldDB; A8MT69; -.
DR SMR; A8MT69; -.
DR BioGRID; 128376; 29.
DR ComplexPortal; CPX-5646; Kinetochore CCAN complex.
DR ComplexPortal; CPX-6266; Fanconi anemia FANCM-FAAP24-MHF anchoring complex.
DR CORUM; A8MT69; -.
DR IntAct; A8MT69; 9.
DR MINT; A8MT69; -.
DR STRING; 9606.ENSP00000376168; -.
DR GlyGen; A8MT69; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; A8MT69; -.
DR PhosphoSitePlus; A8MT69; -.
DR BioMuta; CENPX; -.
DR EPD; A8MT69; -.
DR jPOST; A8MT69; -.
DR MassIVE; A8MT69; -.
DR MaxQB; A8MT69; -.
DR PeptideAtlas; A8MT69; -.
DR PRIDE; A8MT69; -.
DR ProteomicsDB; 1998; -. [A8MT69-1]
DR ProteomicsDB; 1999; -. [A8MT69-2]
DR ProteomicsDB; 2000; -. [A8MT69-3]
DR TopDownProteomics; A8MT69-1; -. [A8MT69-1]
DR TopDownProteomics; A8MT69-2; -. [A8MT69-2]
DR Antibodypedia; 32957; 76 antibodies from 17 providers.
DR DNASU; 201254; -.
DR Ensembl; ENST00000306704.10; ENSP00000302951.6; ENSG00000169689.15. [A8MT69-2]
DR Ensembl; ENST00000392359.8; ENSP00000376168.3; ENSG00000169689.15. [A8MT69-1]
DR Ensembl; ENST00000580435.5; ENSP00000462015.1; ENSG00000169689.15. [A8MT69-3]
DR GeneID; 201254; -.
DR KEGG; hsa:201254; -.
DR MANE-Select; ENST00000392359.8; ENSP00000376168.3; NM_001271006.2; NP_001257935.1.
DR UCSC; uc002kdc.5; human. [A8MT69-1]
DR CTD; 201254; -.
DR DisGeNET; 201254; -.
DR GeneCards; CENPX; -.
DR HGNC; HGNC:11422; CENPX.
DR HPA; ENSG00000169689; Low tissue specificity.
DR MIM; 615128; gene.
DR neXtProt; NX_A8MT69; -.
DR OpenTargets; ENSG00000169689; -.
DR PharmGKB; PA36223; -.
DR VEuPathDB; HostDB:ENSG00000169689; -.
DR eggNOG; ENOG502S98G; Eukaryota.
DR GeneTree; ENSGT00390000002725; -.
DR HOGENOM; CLU_175684_0_0_1; -.
DR InParanoid; A8MT69; -.
DR OMA; AESEDCN; -.
DR OrthoDB; 1560521at2759; -.
DR PhylomeDB; A8MT69; -.
DR PathwayCommons; A8MT69; -.
DR Reactome; R-HSA-606279; Deposition of new CENPA-containing nucleosomes at the centromere.
DR Reactome; R-HSA-6783310; Fanconi Anemia Pathway.
DR SignaLink; A8MT69; -.
DR SIGNOR; A8MT69; -.
DR BioGRID-ORCS; 201254; 115 hits in 1071 CRISPR screens.
DR ChiTaRS; CENPX; human.
DR GenomeRNAi; 201254; -.
DR Pharos; A8MT69; Tbio.
DR PRO; PR:A8MT69; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; A8MT69; protein.
DR Bgee; ENSG00000169689; Expressed in mucosa of transverse colon and 190 other tissues.
DR ExpressionAtlas; A8MT69; baseline and differential.
DR Genevisible; A8MT69; HS.
DR GO; GO:0000785; C:chromatin; IDA:ComplexPortal.
DR GO; GO:0071821; C:FANCM-MHF complex; IDA:UniProtKB.
DR GO; GO:0043240; C:Fanconi anaemia nuclear complex; IDA:UniProtKB.
DR GO; GO:0000776; C:kinetochore; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0036297; P:interstrand cross-link repair; IDA:ComplexPortal.
DR GO; GO:0051382; P:kinetochore assembly; IEA:InterPro.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; TAS:UniProtKB.
DR GO; GO:0031297; P:replication fork processing; IMP:UniProtKB.
DR GO; GO:0000712; P:resolution of meiotic recombination intermediates; IMP:UniProtKB.
DR IDEAL; IID00424; -.
DR InterPro; IPR018552; CENP-X.
DR PANTHER; PTHR28680; PTHR28680; 1.
DR Pfam; PF09415; CENP-X; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Cell division;
KW Centromere; Chromosome; DNA damage; DNA repair; DNA-binding; Kinetochore;
KW Mitosis; Nucleus; Reference proteome.
FT CHAIN 1..81
FT /note="Centromere protein X"
FT /id="PRO_0000337180"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT VAR_SEQ 30..47
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.1"
FT /id="VSP_033948"
FT VAR_SEQ 73..77
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.1"
FT /id="VSP_033949"
FT CONFLICT 65
FT /note="V -> A (in Ref. 3; AAH09571)"
FT /evidence="ECO:0000305"
FT CONFLICT 73
FT /note="V -> L (in Ref. 1; AAB53638)"
FT /evidence="ECO:0000305"
FT HELIX 12..20
FT /evidence="ECO:0007829|PDB:4NE3"
FT HELIX 32..59
FT /evidence="ECO:0007829|PDB:4NE3"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:4NE3"
FT HELIX 67..80
FT /evidence="ECO:0007829|PDB:4NE3"
SQ SEQUENCE 81 AA; 8959 MW; 0BA47A4F0FFD2978 CRC64;
MEGAGAGSGF RKELVSRLLH LHFKDDKTKV SGDALQLMVE LLKVFVVEAA VRGVRQAQAE
DALRVDVDQL EKVLPQLLLD F
