TO6BL_HUMAN
ID TO6BL_HUMAN Reviewed; 577 AA.
AC Q8N6T0; Q9H677;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-MAY-2016, sequence version 3.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Type 2 DNA topoisomerase 6 subunit B-like {ECO:0000250|UniProtKB:J3QMY9};
DE AltName: Full=Type 2 DNA topoisomerase VI subunit B-like {ECO:0000250|UniProtKB:J3QMY9};
DE Short=TOPOVIBL {ECO:0000250|UniProtKB:J3QMY9};
GN Name=TOP6BL {ECO:0000303|PubMed:26917764};
GN Synonyms=C11orf80 {ECO:0000312|HGNC:HGNC:26197};
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 16-577 (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=18160775; DOI=10.1159/000109612;
RA Debacker K., Winnepenninckx B., Longman C., Colgan J., Tolmie J.,
RA Murray R., van Luijk R., Scheers S., Fitzpatrick D., Kooy F.;
RT "The molecular basis of the folate-sensitive fragile site FRA11A at
RT 11q13.";
RL Cytogenet. Genome Res. 119:9-14(2007).
RN [5]
RP IDENTIFICATION (ISOFORM 3).
RX PubMed=26917764; DOI=10.1126/science.aad5309;
RA Robert T., Nore A., Brun C., Maffre C., Crimi B., Bourbon H.M.,
RA de Massy B.;
RT "The TopoVIB-Like protein family is required for meiotic DNA double-strand
RT break formation.";
RL Science 351:943-949(2016).
RN [6]
RP VARIANT HYDM4 PRO-401, INVOLVEMENT IN HYDM4, AND TISSUE SPECIFICITY.
RX PubMed=30388401; DOI=10.1016/j.ajhg.2018.10.007;
RA Nguyen N.M.P., Ge Z.J., Reddy R., Fahiminiya S., Sauthier P., Bagga R.,
RA Sahin F.I., Mahadevan S., Osmond M., Breguet M., Rahimi K., Lapensee L.,
RA Hovanes K., Srinivasan R., Van den Veyver I.B., Sahoo T., Ao A.,
RA Majewski J., Taketo T., Slim R.;
RT "Causative mutations and mechanism of androgenetic hydatidiform moles.";
RL Am. J. Hum. Genet. 103:740-751(2018).
CC -!- FUNCTION: [Isoform 3]: Component of a topoisomerase 6 complex
CC specifically required for meiotic recombination. Together with SPO11,
CC mediates DNA cleavage that forms the double-strand breaks (DSB) that
CC initiate meiotic recombination. The complex promotes relaxation of
CC negative and positive supercoiled DNA and DNA decatenation through
CC cleavage and ligation cycles. {ECO:0000250|UniProtKB:J3QMY9}.
CC -!- SUBUNIT: [Isoform 3]: Heterotetramer of SPO11 and 2 TOP6BL chains.
CC Interacts with SPO11. {ECO:0000250|UniProtKB:J3QMY9}.
CC -!- SUBCELLULAR LOCATION: Chromosome {ECO:0000250|UniProtKB:J3QMY9}.
CC Note=Localizes to meiotic chromosomes. {ECO:0000250|UniProtKB:J3QMY9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=3;
CC IsoId=Q8N6T0-1; Sequence=Displayed;
CC Name=1;
CC IsoId=Q8N6T0-4; Sequence=VSP_058330, VSP_058331;
CC Name=2;
CC IsoId=Q8N6T0-5; Sequence=VSP_058331, VSP_058332;
CC -!- TISSUE SPECIFICITY: Detected in lung, spleen,colon and in skeletal
CC muscle. Expressed in the ovaries, Fallopian tubes and uterus
CC (PubMed:30388401). {ECO:0000269|PubMed:18160775,
CC ECO:0000269|PubMed:30388401}.
CC -!- DOMAIN: [Isoform 3]: Despite a weak sequence similarity, retains most
CC of the structural features of the ancestral archaeal Top6B subunit (AC
CC O05207), including the transducer domain that interacts with the SPO11
CC subunit and the ATP-binding fold, also named GHKL fold.
CC {ECO:0000250|UniProtKB:J3QMY9}.
CC -!- DISEASE: Hydatidiform mole, recurrent, 4 (HYDM4) [MIM:618432]: A
CC disorder characterized by excessive trophoblast development that
CC produces a growing mass of tissue inside the uterus at the beginning of
CC a pregnancy. It leads to abnormal pregnancies with no embryo, and
CC cystic degeneration of the chorionic villi.
CC {ECO:0000269|PubMed:30388401}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Expansion of a polymorphic CGG repeat within the 5'-UTR
CC of this gene may be the cause of folate-sensitive fragile site FRA11A.
CC The expansion is identified in the 15-year-old proband with
CC intellectual disability as well as in phenotypically normal members of
CC the family. {ECO:0000269|PubMed:18160775}.
CC -!- MISCELLANEOUS: [Isoform 1]: Contains a signal peptide sequence at
CC position 1-23. {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the TOP6B-like family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH28240.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB15387.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AP000485; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001157; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC028240; AAH28240.1; ALT_INIT; mRNA.
DR EMBL; AK026184; BAB15387.1; ALT_INIT; mRNA.
DR CCDS; CCDS53664.1; -. [Q8N6T0-4]
DR RefSeq; NP_001289013.1; NM_001302084.1.
DR RefSeq; NP_078926.3; NM_024650.3. [Q8N6T0-4]
DR AlphaFoldDB; Q8N6T0; -.
DR BioGRID; 122822; 1.
DR STRING; 9606.ENSP00000354227; -.
DR iPTMnet; Q8N6T0; -.
DR PhosphoSitePlus; Q8N6T0; -.
DR BioMuta; C11orf80; -.
DR DMDM; 519668662; -.
DR EPD; Q8N6T0; -.
DR MassIVE; Q8N6T0; -.
DR PeptideAtlas; Q8N6T0; -.
DR PRIDE; Q8N6T0; -.
DR ProteomicsDB; 72226; -. [Q8N6T0-1]
DR Antibodypedia; 52536; 16 antibodies from 8 providers.
DR DNASU; 79703; -.
DR Ensembl; ENST00000360962.10; ENSP00000354227.7; ENSG00000173715.18.
DR GeneID; 79703; -.
DR KEGG; hsa:79703; -.
DR UCSC; uc021qmd.2; human. [Q8N6T0-1]
DR CTD; 79703; -.
DR DisGeNET; 79703; -.
DR GeneCards; C11orf80; -.
DR HGNC; HGNC:26197; C11orf80.
DR HPA; ENSG00000173715; Tissue enhanced (skin).
DR MalaCards; C11orf80; -.
DR MIM; 616109; gene.
DR MIM; 618432; phenotype.
DR neXtProt; NX_Q8N6T0; -.
DR Orphanet; 254688; Complete hydatidiform mole.
DR PharmGKB; PA162377704; -.
DR VEuPathDB; HostDB:ENSG00000173715; -.
DR eggNOG; ENOG502S5QP; Eukaryota.
DR InParanoid; Q8N6T0; -.
DR OrthoDB; 1458907at2759; -.
DR TreeFam; TF337039; -.
DR PathwayCommons; Q8N6T0; -.
DR BioGRID-ORCS; 79703; 13 hits in 1063 CRISPR screens.
DR ChiTaRS; C11orf80; human.
DR GenomeRNAi; 79703; -.
DR Pharos; Q8N6T0; Tdark.
DR PRO; PR:Q8N6T0; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q8N6T0; protein.
DR Bgee; ENSG00000173715; Expressed in skin of abdomen and 107 other tissues.
DR ExpressionAtlas; Q8N6T0; baseline and differential.
DR Genevisible; Q8N6T0; HS.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0042138; P:meiotic DNA double-strand break formation; ISS:UniProtKB.
DR GO; GO:0007131; P:reciprocal meiotic recombination; ISS:UniProtKB.
DR InterPro; IPR028040; TopoVIB-like.
DR PANTHER; PTHR14652; PTHR14652; 1.
DR Pfam; PF15091; DUF4554; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromosome; Disease variant; Meiosis;
KW Reference proteome.
FT CHAIN 1..577
FT /note="Type 2 DNA topoisomerase 6 subunit B-like"
FT /id="PRO_0000296622"
FT REGION 463..551
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 470..484
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 488..506
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1
FT /note="M -> MGSRCRAWAWTRAWALAEFQARAEEGAAAAAAAAGGYPSTGRCRCSL
FT RGM (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_058330"
FT VAR_SEQ 56
FT /note="T -> TRWSLTLLPRPECSGAVSAHCNLHLPGSSDSHASVPRVAGITDAHHH
FT AWLIM (in isoform 1 and isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_058331"
FT VAR_SEQ 387..423
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_058332"
FT VARIANT 401
FT /note="S -> P (in HYDM4; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30388401"
FT /id="VAR_082606"
SQ SEQUENCE 577 AA; 64047 MW; 4CA7E34C0E212484 CRC64;
MEGTAVAVFE ILRFLIIHWK CDIDVSKGAL LEGQLVISIE GLNSKHQANA LHCVTTVASA
GSLFGGMVLK KFLKEIQSIL PGISAKLTWT SEEGSYSQDM TGVTPFQMIF EVDEKPRTLM
TDCLVIKHFL RKIIMVHPKV RFHFSVKVNG ILSTEIFGVE NEPTLNLGNG IALLVDSQHY
VRPNFGTIES HCSRIHPVLG HPVMLFIPED VAGMDLLGEL ILTPAAALCP SPKVSSNQLN
RISSVSIFLY GPLGLPLILS TWEQPMTTFF KDTSSLVDWK KYHLCMIPNL DLNLDRDLVL
PDVSYQVESS EEDQSQTMDP QGQTLLLFLF VDFHSAFPVQ QMEIWGVYTL LTTHLNAILV
ESHSVVQGSI QFTVDKVLEQ HHQAAKAQQK LQASLSVAVN SIMSILTGST RSSFRKMCLQ
TLQAADTQEF RTKLHKVFRE ITQHQFLHHC SCEVKQQLTL EKKDSAQGTE DAPDNSSLEL
LADTSGQAEN KRLKRGSPRI EEMRALRSAR APSPSEAAPR RPEATAAPLT PRGREHREAH
GRALAPGRAS LGSRLEDVLW LQEVSNLSEW LSPSPGP
