CDC26_HUMAN
ID CDC26_HUMAN Reviewed; 85 AA.
AC Q8NHZ8;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Anaphase-promoting complex subunit CDC26;
DE AltName: Full=Anaphase-promoting complex subunit 12;
DE Short=APC12;
DE AltName: Full=Cell division cycle protein 26 homolog;
GN Name=CDC26; Synonyms=ANAPC12, C9orf17;
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], AND IDENTIFICATION IN THE APC/C COMPLEX.
RX PubMed=10922056; DOI=10.1073/pnas.97.16.8973;
RA Gmachl M., Gieffers C., Podtelejnikov A.V., Mann M., Peters J.-M.;
RT "The RING-H2 finger protein APC11 and the E2 enzyme UBC4 are sufficient to
RT ubiquitinate substrates of the anaphase-promoting complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:8973-8978(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, 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 OF THE APC/C.
RX PubMed=18485873; DOI=10.1016/j.cell.2008.04.012;
RA Jin L., Williamson A., Banerjee S., Philipp I., Rape M.;
RT "Mechanism of ubiquitin-chain formation by the human anaphase-promoting
RT complex.";
RL Cell 133:653-665(2008).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42 AND SER-82, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP STRUCTURE BY ELECTRON MICROSCOPY OF THE APC/C.
RX PubMed=16364912; DOI=10.1016/j.molcel.2005.11.008;
RA Dube P., Herzog F., Gieffers C., Sander B., Riedel D., Mueller S.A.,
RA Engel A., Peters J.-M., Stark H.;
RT "Localization of the coactivator Cdh1 and the cullin subunit Apc2 in a
RT cryo-electron microscopy model of vertebrate APC/C.";
RL Mol. Cell 20:867-879(2005).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-29 IN COMPLEX WITH CDC16.
RX PubMed=19668213; DOI=10.1038/nsmb.1645;
RA Wang J., Dye B.T., Rajashankar K.R., Kurinov I., Schulman B.A.;
RT "Insights into anaphase promoting complex TPR subdomain assembly from a
RT CDC26-APC6 structure.";
RL Nat. Struct. Mol. Biol. 16:987-989(2009).
RN [12]
RP STRUCTURE BY ELECTRON MICROSCOPY (7.4 ANGSTROMS) OF THE APC/C, AND SUBUNIT.
RX PubMed=25043029; DOI=10.1038/nature13543;
RA Chang L., Zhang Z., Yang J., McLaughlin S.H., Barford D.;
RT "Molecular architecture and mechanism of the anaphase-promoting complex.";
RL Nature 513:388-393(2014).
RN [13] {ECO:0007744|PDB:4UI9, ECO:0007744|PDB:5A31}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF APC/C, AND SUBUNIT.
RX PubMed=26083744; DOI=10.1038/nature14471;
RA Chang L., Zhang Z., Yang J., McLaughlin S.H., Barford D.;
RT "Atomic structure of the APC/C and its mechanism of protein
RT ubiquitination.";
RL Nature 522:450-454(2015).
CC -!- FUNCTION: Component of the anaphase promoting complex/cyclosome
CC (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls
CC progression through mitosis and the G1 phase of the cell cycle. The
CC APC/C complex acts by mediating ubiquitination and subsequent
CC degradation of target proteins: it mainly mediates the formation of
CC 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the
CC formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. May
CC recruit the E2 ubiquitin-conjugating enzymes to the complex.
CC {ECO:0000269|PubMed:18485873}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: V-shaped homodimer. Interacts with CDC16. The mammalian APC/C
CC is composed at least of 14 distinct subunits ANAPC1, ANAPC2,
CC CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10,
CC ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a
CC complex of at least 19 chains with a combined molecular mass of around
CC 1.2 MDa; APC/C interacts with FZR1 and FBXO5.
CC {ECO:0000269|PubMed:10922056, ECO:0000269|PubMed:19668213,
CC ECO:0000269|PubMed:25043029, ECO:0000269|PubMed:26083744}.
CC -!- INTERACTION:
CC Q8NHZ8; P54253: ATXN1; NbExp=3; IntAct=EBI-2555941, EBI-930964;
CC Q8NHZ8; Q13042: CDC16; NbExp=15; IntAct=EBI-2555941, EBI-994830;
CC Q8NHZ8; Q13042-1: CDC16; NbExp=5; IntAct=EBI-2555941, EBI-15798699;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the CDC26 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF503918; AAM34207.1; -; mRNA.
DR EMBL; AL449305; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC042534; AAH42534.1; -; mRNA.
DR EMBL; BC066300; AAH66300.1; -; mRNA.
DR CCDS; CCDS6790.1; -.
DR RefSeq; NP_644815.1; NM_139286.3.
DR RefSeq; XP_016870062.1; XM_017014573.1.
DR RefSeq; XP_016870063.1; XM_017014574.1.
DR RefSeq; XP_016870064.1; XM_017014575.1.
DR PDB; 3HYM; X-ray; 2.80 A; A/C/E/G/I/K=1-29.
DR PDB; 4UI9; EM; 3.60 A; G/W=1-85.
DR PDB; 5A31; EM; 4.30 A; G/W=1-85.
DR PDB; 5G04; EM; 4.00 A; G/W=1-85.
DR PDB; 5G05; EM; 3.40 A; G/W=1-85.
DR PDB; 5KHR; EM; 6.10 A; G/W=1-85.
DR PDB; 5KHU; EM; 4.80 A; G/W=1-85.
DR PDB; 5L9T; EM; 6.40 A; G/W=1-85.
DR PDB; 5L9U; EM; 6.40 A; G/W=1-85.
DR PDB; 5LCW; EM; 4.00 A; G/W=1-85.
DR PDB; 6Q6G; EM; 3.20 A; G/W=1-85.
DR PDB; 6Q6H; EM; 3.20 A; G/W=1-85.
DR PDB; 6TLJ; EM; 3.80 A; G/W=1-85.
DR PDB; 6TM5; EM; 3.90 A; G/W=1-85.
DR PDB; 6TNT; EM; 3.78 A; G/W=1-85.
DR PDB; 7QE7; EM; 2.90 A; G/W=1-85.
DR PDBsum; 3HYM; -.
DR PDBsum; 4UI9; -.
DR PDBsum; 5A31; -.
DR PDBsum; 5G04; -.
DR PDBsum; 5G05; -.
DR PDBsum; 5KHR; -.
DR PDBsum; 5KHU; -.
DR PDBsum; 5L9T; -.
DR PDBsum; 5L9U; -.
DR PDBsum; 5LCW; -.
DR PDBsum; 6Q6G; -.
DR PDBsum; 6Q6H; -.
DR PDBsum; 6TLJ; -.
DR PDBsum; 6TM5; -.
DR PDBsum; 6TNT; -.
DR PDBsum; 7QE7; -.
DR AlphaFoldDB; Q8NHZ8; -.
DR SMR; Q8NHZ8; -.
DR BioGRID; 128878; 50.
DR ComplexPortal; CPX-1860; Anaphase-Promoting core complex.
DR DIP; DIP-48551N; -.
DR IntAct; Q8NHZ8; 39.
DR MINT; Q8NHZ8; -.
DR STRING; 9606.ENSP00000363322; -.
DR iPTMnet; Q8NHZ8; -.
DR PhosphoSitePlus; Q8NHZ8; -.
DR BioMuta; CDC26; -.
DR DMDM; 74751322; -.
DR EPD; Q8NHZ8; -.
DR jPOST; Q8NHZ8; -.
DR MassIVE; Q8NHZ8; -.
DR MaxQB; Q8NHZ8; -.
DR PaxDb; Q8NHZ8; -.
DR PeptideAtlas; Q8NHZ8; -.
DR PRIDE; Q8NHZ8; -.
DR ProteomicsDB; 73794; -.
DR TopDownProteomics; Q8NHZ8; -.
DR Antibodypedia; 44232; 106 antibodies from 21 providers.
DR DNASU; 246184; -.
DR Ensembl; ENST00000374206.4; ENSP00000363322.3; ENSG00000176386.9.
DR GeneID; 246184; -.
DR KEGG; hsa:246184; -.
DR MANE-Select; ENST00000374206.4; ENSP00000363322.3; NM_139286.4; NP_644815.1.
DR UCSC; uc004bgw.4; human.
DR CTD; 246184; -.
DR DisGeNET; 246184; -.
DR GeneCards; CDC26; -.
DR HGNC; HGNC:17839; CDC26.
DR HPA; ENSG00000176386; Low tissue specificity.
DR MIM; 614533; gene.
DR neXtProt; NX_Q8NHZ8; -.
DR OpenTargets; ENSG00000176386; -.
DR PharmGKB; PA25974; -.
DR VEuPathDB; HostDB:ENSG00000176386; -.
DR eggNOG; ENOG502S5GK; Eukaryota.
DR GeneTree; ENSGT00390000008457; -.
DR HOGENOM; CLU_190086_0_0_1; -.
DR InParanoid; Q8NHZ8; -.
DR OMA; HKSREQM; -.
DR OrthoDB; 1612963at2759; -.
DR PhylomeDB; Q8NHZ8; -.
DR TreeFam; TF101057; -.
DR PathwayCommons; Q8NHZ8; -.
DR Reactome; R-HSA-141430; Inactivation of APC/C via direct inhibition of the APC/C complex.
DR Reactome; R-HSA-174048; APC/C:Cdc20 mediated degradation of Cyclin B.
DR Reactome; R-HSA-174084; Autodegradation of Cdh1 by Cdh1:APC/C.
DR Reactome; R-HSA-174154; APC/C:Cdc20 mediated degradation of Securin.
DR Reactome; R-HSA-174178; APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
DR Reactome; R-HSA-174184; Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
DR Reactome; R-HSA-176407; Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase.
DR Reactome; R-HSA-176408; Regulation of APC/C activators between G1/S and early anaphase.
DR Reactome; R-HSA-176409; APC/C:Cdc20 mediated degradation of mitotic proteins.
DR Reactome; R-HSA-176412; Phosphorylation of the APC/C.
DR Reactome; R-HSA-179409; APC-Cdc20 mediated degradation of Nek2A.
DR Reactome; R-HSA-2467813; Separation of Sister Chromatids.
DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-HSA-68867; Assembly of the pre-replicative complex.
DR Reactome; R-HSA-69017; CDK-mediated phosphorylation and removal of Cdc6.
DR Reactome; R-HSA-8853884; Transcriptional Regulation by VENTX.
DR Reactome; R-HSA-9687136; Aberrant regulation of mitotic exit in cancer due to RB1 defects.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q8NHZ8; -.
DR SIGNOR; Q8NHZ8; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 246184; 473 hits in 1047 CRISPR screens.
DR ChiTaRS; CDC26; human.
DR EvolutionaryTrace; Q8NHZ8; -.
DR GenomeRNAi; 246184; -.
DR Pharos; Q8NHZ8; Tbio.
DR PRO; PR:Q8NHZ8; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q8NHZ8; protein.
DR Bgee; ENSG00000176386; Expressed in calcaneal tendon and 103 other tissues.
DR ExpressionAtlas; Q8NHZ8; baseline and differential.
DR Genevisible; Q8NHZ8; HS.
DR GO; GO:0005680; C:anaphase-promoting complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0031145; P:anaphase-promoting complex-dependent catabolic process; IC:ComplexPortal.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0070979; P:protein K11-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0051445; P:regulation of meiotic cell cycle; IC:ComplexPortal.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0030071; P:regulation of mitotic metaphase/anaphase transition; IEA:InterPro.
DR DisProt; DP01453; -.
DR InterPro; IPR018860; APC_suCDC26.
DR PANTHER; PTHR28579; PTHR28579; 1.
DR Pfam; PF10471; ANAPC_CDC26; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Cell division; Coiled coil; Mitosis; Nucleus;
KW Phosphoprotein; Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..85
FT /note="Anaphase-promoting complex subunit CDC26"
FT /id="PRO_0000271194"
FT REGION 30..85
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 7..38
FT /evidence="ECO:0000255"
FT COMPBIAS 71..85
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT HELIX 14..16
FT /evidence="ECO:0007829|PDB:3HYM"
FT HELIX 17..25
FT /evidence="ECO:0007829|PDB:3HYM"
SQ SEQUENCE 85 AA; 9777 MW; 134970EE68F0142C CRC64;
MLRRKPTRLE LKLDDIEEFE NIRKDLETRK KQKEDVEVVG GSDGEGAIGL SSDPKSREQM
INDRIGYKPQ PKPNNRSSQF GSLEF
