AF9_HUMAN
ID AF9_HUMAN Reviewed; 568 AA.
AC P42568; B1AMQ2; B2R7B3; B7Z755; D3DRJ8; Q8IVB0;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Protein AF-9 {ECO:0000305};
DE AltName: Full=ALL1-fused gene from chromosome 9 protein {ECO:0000303|PubMed:10861294};
DE AltName: Full=Myeloid/lymphoid or mixed-lineage leukemia translocated to chromosome 3 protein {ECO:0000303|PubMed:16001262};
DE AltName: Full=YEATS domain-containing protein 3;
GN Name=MLLT3 {ECO:0000303|PubMed:16001262, ECO:0000312|HGNC:HGNC:7136};
GN Synonyms=AF9 {ECO:0000303|PubMed:10861294}, YEATS3;
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] (ISOFORM 1), AND CHROMOSOMAL TRANSLOCATION WITH
RP KMT2A.
RX PubMed=8506309; DOI=10.1073/pnas.90.10.4631;
RA Nakamura T., Alder H., Gu Y., Prasad R., Canaani O., Kamada N., Gale R.P.,
RA Lange B., Crist W.M., Nowell P.C., Croce C.M., Canaani E.;
RT "Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute
RT leukemia share sequence homology and/or common motifs.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:4631-4635(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Synovium;
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [6]
RP INTERACTION WITH BCOR.
RX PubMed=10898795;
RA Huynh K.D., Fischle W., Verdin E., Bardwell V.J.;
RT "BCoR, a novel corepressor involved in BCL-6 repression.";
RL Genes Dev. 14:1810-1823(2000).
RN [7]
RP CHROMOSOMAL TRANSLOCATION.
RX PubMed=10861294; DOI=10.1093/hmg/9.11.1671;
RA Strissel P.L., Strick R., Tomek R.J., Roe B.A., Rowley J.D.,
RA Zeleznik-Le N.J.;
RT "DNA structural properties of AF9 are similar to MLL and could act as
RT recombination hot spots resulting in MLL/AF9 translocations and
RT leukemogenesis.";
RL Hum. Mol. Genet. 9:1671-1679(2000).
RN [8]
RP INTERACTION WITH CBX8.
RX PubMed=11313972; DOI=10.1038/sj.onc.1204108;
RA Garcia-Cuellar M.P., Zilles O., Schreiner S.A., Birke M., Winkler T.H.,
RA Slany R.K.;
RT "The ENL moiety of the childhood leukemia-associated MLL-ENL oncoprotein
RT recruits human Polycomb 3.";
RL Oncogene 20:411-419(2001).
RN [9]
RP CHROMOSOMAL TRANSLOCATION.
RX PubMed=16001262; DOI=10.1007/s00439-005-0004-1;
RA Pramparo T., Grosso S., Messa J., Zatterale A., Bonaglia M.C., Chessa L.,
RA Balestri P., Rocchi M., Zuffardi O., Giorda R.;
RT "Loss-of-function mutation of the AF9/MLLT3 gene in a girl with neuromotor
RT development delay, cerebellar ataxia, and epilepsy.";
RL Hum. Genet. 118:76-81(2005).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-294 AND SER-483, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-288; SER-294 AND SER-483, AND
RP IDENTIFICATION BY 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 [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412 AND SER-419, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP FUNCTION, AND IDENTIFICATION IN THE SEC COMPLEX.
RX PubMed=20471948; DOI=10.1016/j.molcel.2010.04.013;
RA He N., Liu M., Hsu J., Xue Y., Chou S., Burlingame A., Krogan N.J.,
RA Alber T., Zhou Q.;
RT "HIV-1 Tat and host AFF4 recruit two transcription elongation factors into
RT a bifunctional complex for coordinated activation of HIV-1 transcription.";
RL Mol. Cell 38:428-438(2010).
RN [15]
RP FUNCTION, AND IDENTIFICATION IN THE SEC COMPLEX.
RX PubMed=20159561; DOI=10.1016/j.molcel.2010.01.026;
RA Lin C., Smith E.R., Takahashi H., Lai K.C., Martin-Brown S., Florens L.,
RA Washburn M.P., Conaway J.W., Conaway R.C., Shilatifard A.;
RT "AFF4, a component of the ELL/P-TEFb elongation complex and a shared
RT subunit of MLL chimeras, can link transcription elongation to leukemia.";
RL Mol. Cell 37:429-437(2010).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-483, AND IDENTIFICATION BY
RP 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 [17]
RP IDENTIFICATION IN THE SEC COMPLEX.
RX PubMed=22195968; DOI=10.1016/j.molcel.2011.12.008;
RA Smith E.R., Lin C., Garrett A.S., Thornton J., Mohaghegh N., Hu D.,
RA Jackson J., Saraf A., Swanson S.K., Seidel C., Florens L., Washburn M.P.,
RA Eissenberg J.C., Shilatifard A.;
RT "The little elongation complex regulates small nuclear RNA transcription.";
RL Mol. Cell 44:954-965(2011).
RN [18]
RP INTERACTION OF FUSION PROTEIN KMT2A-MLLT3 WITH MEN1.
RX PubMed=22936661; DOI=10.1182/blood-2012-05-429274;
RA Shi A., Murai M.J., He S., Lund G., Hartley T., Purohit T., Reddy G.,
RA Chruszcz M., Grembecka J., Cierpicki T.;
RT "Structural insights into inhibition of the bivalent menin-MLL interaction
RT by small molecules in leukemia.";
RL Blood 120:4461-4469(2012).
RN [19]
RP REVIEW ON THE SUPER ELONGATION COMPLEX.
RX PubMed=22895430; DOI=10.1038/nrm3417;
RA Luo Z., Lin C., Shilatifard A.;
RT "The super elongation complex (SEC) family in transcriptional control.";
RL Nat. Rev. Mol. Cell Biol. 13:543-547(2012).
RN [20]
RP INTERACTION WITH ALKBH4.
RX PubMed=23145062; DOI=10.1371/journal.pone.0049045;
RA Bjornstad L.G., Meza T.J., Otterlei M., Olafsrud S.M., Meza-Zepeda L.A.,
RA Falnes P.O.;
RT "Human ALKBH4 interacts with proteins associated with transcription.";
RL PLoS ONE 7:E49045-E49045(2012).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-294 AND SER-483, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 [22]
RP INTERACTION OF FUSION PROTEIN KMT2A-MLLT3 WITH PSIP1 AND MEN1.
RX PubMed=25305204; DOI=10.1182/blood-2014-01-550079;
RA Murai M.J., Pollock J., He S., Miao H., Purohit T., Yokom A., Hess J.L.,
RA Muntean A.G., Grembecka J., Cierpicki T.;
RT "The same site on the integrase-binding domain of lens epithelium-derived
RT growth factor is a therapeutic target for MLL leukemia and HIV.";
RL Blood 124:3730-3737(2014).
RN [23]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-339, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [24]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-339, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [25]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=31776511; DOI=10.1038/s41586-019-1790-2;
RA Calvanese V., Nguyen A.T., Bolan T.J., Vavilina A., Su T., Lee L.K.,
RA Wang Y., Lay F.D., Magnusson M., Crooks G.M., Kurdistani S.K.,
RA Mikkola H.K.A.;
RT "MLLT3 governs human haematopoietic stem-cell self-renewal and
RT engraftment.";
RL Nature 576:281-286(2019).
RN [26] {ECO:0007744|PDB:2LM0}
RP STRUCTURE BY NMR OF 490-568 IN COMPLEX WITH AFF1.
RX PubMed=23260655; DOI=10.1016/j.str.2012.11.011;
RA Leach B.I., Kuntimaddi A., Schmidt C.R., Cierpicki T., Johnson S.A.,
RA Bushweller J.H.;
RT "Leukemia fusion target AF9 is an intrinsically disordered transcriptional
RT regulator that recruits multiple partners via coupled folding and
RT binding.";
RL Structure 21:176-183(2013).
RN [27] {ECO:0007744|PDB:4TMP}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1-138 IN COMPLEX WITH H3K9AC
RP PEPTIDE, FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF PHE-28;
RP HIS-56; SER-58; PHE-59; GLY-77; TYR-78; PHE-81 AND ASP-103.
RX PubMed=25417107; DOI=10.1016/j.cell.2014.09.049;
RA Li Y., Wen H., Xi Y., Tanaka K., Wang H., Peng D., Ren Y., Jin Q.,
RA Dent S.Y., Li W., Li H., Shi X.;
RT "AF9 YEATS domain links histone acetylation to DOT1L-mediated H3K79
RT methylation.";
RL Cell 159:558-571(2014).
RN [28] {ECO:0007744|PDB:5HJB, ECO:0007744|PDB:5HJD}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 1-138 IN COMPLEX WITH H3K9CR
RP PEPTIDE, FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF PHE-28;
RP HIS-56; SER-58; PHE-59; GLY-77 AND TYR-78.
RX PubMed=27105114; DOI=10.1016/j.molcel.2016.03.028;
RA Li Y., Sabari B.R., Panchenko T., Wen H., Zhao D., Guan H., Wan L.,
RA Huang H., Tang Z., Zhao Y., Roeder R.G., Shi X., Allis C.D., Li H.;
RT "Molecular coupling of histone crotonylation and active transcription by
RT AF9 YEATS domain.";
RL Mol. Cell 62:181-193(2016).
RN [29] {ECO:0007744|PDB:2NDF, ECO:0007744|PDB:2NDG}
RP STRUCTURE BY NMR OF 1-138, FUNCTION, DOMAIN, AND MUTAGENESIS OF PHE-59 AND
RP TYR-78.
RX PubMed=27545619; DOI=10.1016/j.str.2016.05.023;
RA Zhang Q., Zeng L., Zhao C., Ju Y., Konuma T., Zhou M.M.;
RT "Structural insights into histone crotonyl-lysine recognition by the AF9
RT YEATS domain.";
RL Structure 24:1606-1612(2016).
RN [30] {ECO:0007744|PDB:5YYF}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1-138 IN COMPLEX WITH INHIBITOR,
RP FUNCTION, DOMAIN, AND ACTIVITY REGULATION.
RX PubMed=30374167; DOI=10.1038/s41589-018-0144-y;
RA Li X., Li X.M., Jiang Y., Liu Z., Cui Y., Fung K.Y., van der Beelen S.H.E.,
RA Tian G., Wan L., Shi X., Allis C.D., Li H., Li Y., Li X.D.;
RT "Structure-guided development of YEATS domain inhibitors by targeting pi-
RT pi-pi stacking.";
RL Nat. Chem. Biol. 14:1140-1149(2018).
RN [31] {ECO:0007744|PDB:6MIL, ECO:0007744|PDB:6MIM}
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 1-138 IN COMPLEX WITH H3K9CR
RP PEPTIDE, FUNCTION, DOMAIN, AND MUTAGENESIS OF 61-ARG--LYS-67; 78-TYR-ALA-79
RP AND TYR-78.
RX PubMed=30385749; DOI=10.1038/s41467-018-07072-6;
RA Klein B.J., Vann K.R., Andrews F.H., Wang W.W., Zhang J., Zhang Y.,
RA Beloglazkina A.A., Mi W., Li Y., Li H., Shi X., Kutateladze A.G.,
RA Strahl B.D., Liu W.R., Kutateladze T.G.;
RT "Structural insights into the pi-pi-pi stacking mechanism and DNA-binding
RT activity of the YEATS domain.";
RL Nat. Commun. 9:4574-4574(2018).
CC -!- FUNCTION: Chromatin reader component of the super elongation complex
CC (SEC), a complex required to increase the catalytic rate of RNA
CC polymerase II transcription by suppressing transient pausing by the
CC polymerase at multiple sites along the DNA (PubMed:20159561,
CC PubMed:20471948, PubMed:25417107, PubMed:27105114, PubMed:27545619).
CC Specifically recognizes and binds acylated histone H3, with a
CC preference for histone H3 that is crotonylated (PubMed:25417107,
CC PubMed:27105114, PubMed:27545619, PubMed:30374167, PubMed:30385749).
CC Crotonylation marks active promoters and enhancers and confers
CC resistance to transcriptional repressors (PubMed:25417107,
CC PubMed:27105114, PubMed:27545619). Recognizes and binds histone H3
CC crotonylated at 'Lys-9' (H3K9cr), and with slightly lower affinity
CC histone H3 crotonylated at 'Lys-18' (H3K18cr) (PubMed:27105114). Also
CC recognizes and binds histone H3 acetylated and butyrylated at 'Lys-9'
CC (H3K9ac and H3K9bu, respectively), but with lower affinity than
CC crotonylated histone H3 (PubMed:25417107, PubMed:27105114,
CC PubMed:30385749). In the SEC complex, MLLT3 is required to recruit the
CC complex to crotonylated histones (PubMed:27105114, PubMed:27545619).
CC Recruitment of the SEC complex to crotonylated histones promotes
CC recruitment of DOT1L on active chromatin to deposit histone H3 'Lys-79'
CC methylation (H3K79me) (PubMed:25417107). Plays a key role in
CC hematopoietic stem cell (HSC) maintenance by preserving, rather than
CC confering, HSC stemness (PubMed:31776511). Acts by binding to the
CC transcription start site of active genes in HSCs and sustaining level
CC of H3K79me2, probably by recruiting DOT1L (PubMed:31776511).
CC {ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948,
CC ECO:0000269|PubMed:25417107, ECO:0000269|PubMed:27105114,
CC ECO:0000269|PubMed:27545619, ECO:0000269|PubMed:30374167,
CC ECO:0000269|PubMed:30385749, ECO:0000269|PubMed:31776511}.
CC -!- ACTIVITY REGULATION: Crotonylated lysine binding is strongly inhibited
CC by the peptide XL-07i, carrying a 2-furancarbonyl side chain and capped
CC with a hydrophobic carboxybenzyl group (PubMed:30374167). XL-07i
CC targets the unique pi-pi-pi stacking interaction at the crotonylation
CC recognition site (PubMed:30374167). {ECO:0000269|PubMed:30374167}.
CC -!- SUBUNIT: Component of the super elongation complex (SEC), at least
CC composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb
CC complex and ELL (ELL, ELL2 or ELL3) (PubMed:20159561, PubMed:20471948,
CC PubMed:22195968, PubMed:23260655, PubMed:25417107). Interacts with BCOR
CC (PubMed:10898795). Interacts with CBX8 (PubMed:11313972). Interacts
CC with ALKBH4 (PubMed:23145062). {ECO:0000269|PubMed:10898795,
CC ECO:0000269|PubMed:11313972, ECO:0000269|PubMed:20159561,
CC ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:22195968,
CC ECO:0000269|PubMed:23145062, ECO:0000269|PubMed:23260655,
CC ECO:0000269|PubMed:25417107}.
CC -!- INTERACTION:
CC P42568; P51825: AFF1; NbExp=7; IntAct=EBI-716132, EBI-2610180;
CC P42568; Q9UHB7: AFF4; NbExp=4; IntAct=EBI-716132, EBI-395282;
CC P42568; Q9NXW9: ALKBH4; NbExp=5; IntAct=EBI-716132, EBI-8637516;
CC P42568; Q92624: APPBP2; NbExp=4; IntAct=EBI-716132, EBI-743771;
CC P42568; Q6W2J9-1: BCOR; NbExp=2; IntAct=EBI-716132, EBI-16028932;
CC P42568; Q9HC52: CBX8; NbExp=2; IntAct=EBI-716132, EBI-712912;
CC P42568; Q8TEK3: DOT1L; NbExp=6; IntAct=EBI-716132, EBI-2619253;
CC P42568; Q8IZU1: FAM9A; NbExp=4; IntAct=EBI-716132, EBI-8468186;
CC P42568; Q5JXC2: MIIP; NbExp=3; IntAct=EBI-716132, EBI-2801965;
CC P42568; Q5SQQ9-2: VAX1; NbExp=3; IntAct=EBI-716132, EBI-12227803;
CC P42568; Q7Z3I7: ZNF572; NbExp=3; IntAct=EBI-716132, EBI-10172590;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00376,
CC ECO:0000269|PubMed:27105114}. Chromosome {ECO:0000269|PubMed:25417107,
CC ECO:0000269|PubMed:27105114}. Note=Colocalizes with acylated histone H3
CC (PubMed:25417107, PubMed:27105114). Colocalizes with histone H3
CC crotonylated at 'Lys-18' (H3K18cr) (PubMed:27105114).
CC {ECO:0000269|PubMed:25417107, ECO:0000269|PubMed:27105114}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P42568-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P42568-2; Sequence=VSP_054924;
CC -!- TISSUE SPECIFICITY: Enriched in undifferentiated hematopoietic stem
CC cells in fetal liver, cord blood and bone marrow.
CC {ECO:0000269|PubMed:31776511}.
CC -!- DOMAIN: The YEATS domain specifically recognizes and binds acylated
CC histones, with a marked preference for histones that are crotonylated
CC (PubMed:27105114, PubMed:27545619). Also binds histone H3 acetylated at
CC 'Lys-9' (H3K9ac), but with lower affinity (PubMed:25417107,
CC PubMed:27105114). Binds crotonylated lysine through a non-canonical pi-
CC pi-pi stacking mechanism (PubMed:30374167, PubMed:30385749). The YEATS
CC domain also binds DNA (PubMed:30385749). {ECO:0000269|PubMed:25417107,
CC ECO:0000269|PubMed:27105114, ECO:0000269|PubMed:27545619,
CC ECO:0000269|PubMed:30374167, ECO:0000269|PubMed:30385749}.
CC -!- DISEASE: Note=A chromosomal aberration involving MLLT3 is associated
CC with acute leukemias. Translocation t(9;11)(p22;q23) with KMT2A/MLL1.
CC The result is a rogue activator protein. Fusion protein KMT2A-MLLT3
CC interacts with MEN1 and PSIP1 (PubMed:22936661, PubMed:25305204).
CC {ECO:0000269|PubMed:10861294, ECO:0000269|PubMed:22936661,
CC ECO:0000269|PubMed:25305204, ECO:0000269|PubMed:8506309}.
CC -!- DISEASE: Note=A chromosomal aberration involving MLLT3 was observed in
CC a patient with neuromotor development delay, cerebellar ataxia and
CC epilepsy. Translocation t(4;9)(q35;p22). {ECO:0000269|PubMed:16001262}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/AF9ID5.html";
CC ---------------------------------------------------------------------------
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DR EMBL; L13744; AAA58361.1; -; mRNA.
DR EMBL; AK301474; BAH13491.1; -; mRNA.
DR EMBL; AK312914; BAG35760.1; -; mRNA.
DR EMBL; AL354879; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL512635; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL513498; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL163193; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL627410; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471071; EAW58631.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58632.1; -; Genomic_DNA.
DR EMBL; BC036089; AAH36089.1; -; mRNA.
DR CCDS; CCDS6494.1; -. [P42568-1]
DR CCDS; CCDS69579.1; -. [P42568-2]
DR PIR; I39411; I39411.
DR RefSeq; NP_001273620.1; NM_001286691.1. [P42568-2]
DR RefSeq; NP_004520.2; NM_004529.3. [P42568-1]
DR PDB; 2LM0; NMR; -; A=490-568.
DR PDB; 2MV7; NMR; -; A=500-568.
DR PDB; 2N4Q; NMR; -; B=500-568.
DR PDB; 2NDF; NMR; -; A=1-138.
DR PDB; 2NDG; NMR; -; A=1-138.
DR PDB; 4TMP; X-ray; 2.30 A; A/C=1-138.
DR PDB; 5HJB; X-ray; 2.70 A; A=1-138.
DR PDB; 5HJD; X-ray; 2.81 A; A/C/E/G/K/N/Q/T=1-138.
DR PDB; 5YYF; X-ray; 1.90 A; A/C=1-138.
DR PDB; 6B7G; NMR; -; A=500-568.
DR PDB; 6L5Z; X-ray; 3.05 A; A=1-138.
DR PDB; 6LS6; X-ray; 2.20 A; A/B=1-138.
DR PDB; 6MIL; X-ray; 1.93 A; A/C=1-138.
DR PDB; 6MIM; X-ray; 2.52 A; A/C=1-138.
DR PDB; 7EIC; X-ray; 1.95 A; A/B=1-138.
DR PDB; 7EID; X-ray; 2.00 A; A/B=1-138.
DR PDBsum; 2LM0; -.
DR PDBsum; 2MV7; -.
DR PDBsum; 2N4Q; -.
DR PDBsum; 2NDF; -.
DR PDBsum; 2NDG; -.
DR PDBsum; 4TMP; -.
DR PDBsum; 5HJB; -.
DR PDBsum; 5HJD; -.
DR PDBsum; 5YYF; -.
DR PDBsum; 6B7G; -.
DR PDBsum; 6L5Z; -.
DR PDBsum; 6LS6; -.
DR PDBsum; 6MIL; -.
DR PDBsum; 6MIM; -.
DR PDBsum; 7EIC; -.
DR PDBsum; 7EID; -.
DR AlphaFoldDB; P42568; -.
DR BMRB; P42568; -.
DR SMR; P42568; -.
DR BioGRID; 110446; 86.
DR CORUM; P42568; -.
DR DIP; DIP-56409N; -.
DR IntAct; P42568; 52.
DR MINT; P42568; -.
DR STRING; 9606.ENSP00000369695; -.
DR BindingDB; P42568; -.
DR ChEMBL; CHEMBL4295761; -.
DR iPTMnet; P42568; -.
DR PhosphoSitePlus; P42568; -.
DR BioMuta; MLLT3; -.
DR DMDM; 215273971; -.
DR jPOST; P42568; -.
DR MassIVE; P42568; -.
DR MaxQB; P42568; -.
DR PaxDb; P42568; -.
DR PeptideAtlas; P42568; -.
DR PRIDE; P42568; -.
DR ProteomicsDB; 55517; -. [P42568-1]
DR ProteomicsDB; 6833; -.
DR Antibodypedia; 1068; 294 antibodies from 29 providers.
DR DNASU; 4300; -.
DR Ensembl; ENST00000380338.9; ENSP00000369695.4; ENSG00000171843.17. [P42568-1]
DR Ensembl; ENST00000630269.2; ENSP00000485996.1; ENSG00000171843.17. [P42568-2]
DR GeneID; 4300; -.
DR KEGG; hsa:4300; -.
DR MANE-Select; ENST00000380338.9; ENSP00000369695.4; NM_004529.4; NP_004520.2.
DR UCSC; uc003zoe.3; human. [P42568-1]
DR CTD; 4300; -.
DR DisGeNET; 4300; -.
DR GeneCards; MLLT3; -.
DR HGNC; HGNC:7136; MLLT3.
DR HPA; ENSG00000171843; Low tissue specificity.
DR MalaCards; MLLT3; -.
DR MIM; 159558; gene.
DR neXtProt; NX_P42568; -.
DR OpenTargets; ENSG00000171843; -.
DR Orphanet; 402017; Acute myeloid leukemia with t(9;11)(p22;q23).
DR PharmGKB; PA30852; -.
DR VEuPathDB; HostDB:ENSG00000171843; -.
DR eggNOG; KOG3149; Eukaryota.
DR GeneTree; ENSGT00940000155903; -.
DR InParanoid; P42568; -.
DR OMA; MSKEPKA; -.
DR PhylomeDB; P42568; -.
DR TreeFam; TF314586; -.
DR PathwayCommons; P42568; -.
DR Reactome; R-HSA-112382; Formation of RNA Pol II elongation complex.
DR Reactome; R-HSA-674695; RNA Polymerase II Pre-transcription Events.
DR Reactome; R-HSA-75955; RNA Polymerase II Transcription Elongation.
DR SignaLink; P42568; -.
DR SIGNOR; P42568; -.
DR BioGRID-ORCS; 4300; 22 hits in 1078 CRISPR screens.
DR ChiTaRS; MLLT3; human.
DR GeneWiki; MLLT3; -.
DR GenomeRNAi; 4300; -.
DR Pharos; P42568; Tchem.
DR PRO; PR:P42568; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P42568; protein.
DR Bgee; ENSG00000171843; Expressed in ganglionic eminence and 165 other tissues.
DR ExpressionAtlas; P42568; baseline and differential.
DR Genevisible; P42568; HS.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0035267; C:NuA4 histone acetyltransferase complex; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0032783; C:super elongation complex; IBA:GO_Central.
DR GO; GO:0008023; C:transcription elongation factor complex; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0070577; F:lysine-acetylated histone binding; IDA:UniProtKB.
DR GO; GO:0140030; F:modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl.
DR GO; GO:0006338; P:chromatin remodeling; IBA:GO_Central.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0060218; P:hematopoietic stem cell differentiation; IDA:UniProtKB.
DR GO; GO:0016573; P:histone acetylation; IBA:GO_Central.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:2000096; P:positive regulation of Wnt signaling pathway, planar cell polarity pathway; IGI:MGI.
DR GO; GO:1902275; P:regulation of chromatin organization; IMP:UniProtKB.
DR GO; GO:2000035; P:regulation of stem cell division; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007379; P:segment specification; IEA:Ensembl.
DR DisProt; DP01070; -.
DR Gene3D; 2.60.40.1970; -; 1.
DR IDEAL; IID00552; -.
DR InterPro; IPR040930; AF-9_AHD.
DR InterPro; IPR038704; YEAST_sf.
DR InterPro; IPR005033; YEATS.
DR PANTHER; PTHR23195; PTHR23195; 1.
DR Pfam; PF17793; AHD; 1.
DR Pfam; PF03366; YEATS; 1.
DR PROSITE; PS51037; YEATS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Chromosomal rearrangement;
KW Chromosome; DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein;
KW Proto-oncogene; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..568
FT /note="Protein AF-9"
FT /id="PRO_0000215921"
FT DOMAIN 1..138
FT /note="YEATS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00376"
FT REGION 78..80
FT /note="Histone H3K9cr binding"
FT /evidence="ECO:0000269|PubMed:27105114,
FT ECO:0000269|PubMed:30385749, ECO:0007744|PDB:5HJB,
FT ECO:0007744|PDB:5HJD, ECO:0007744|PDB:6MIL,
FT ECO:0007744|PDB:6MIM"
FT REGION 106..108
FT /note="Histone H3K9cr binding"
FT /evidence="ECO:0000269|PubMed:27105114,
FT ECO:0000269|PubMed:30385749, ECO:0007744|PDB:5HJB,
FT ECO:0007744|PDB:5HJD, ECO:0007744|PDB:6MIL,
FT ECO:0007744|PDB:6MIM"
FT REGION 137..475
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 295..300
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 143..195
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 196..262
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 282..304
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 323..354
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 373..403
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 414..428
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 441..461
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 58
FT /note="Histone H3K9cr binding"
FT /evidence="ECO:0000269|PubMed:27105114,
FT ECO:0000269|PubMed:30385749, ECO:0007744|PDB:5HJB,
FT ECO:0007744|PDB:5HJD, ECO:0007744|PDB:6MIL,
FT ECO:0007744|PDB:6MIM"
FT SITE 103
FT /note="Histone H3K9cr binding"
FT /evidence="ECO:0000269|PubMed:27105114,
FT ECO:0000269|PubMed:30385749, ECO:0007744|PDB:5HJB,
FT ECO:0007744|PDB:5HJD, ECO:0007744|PDB:6MIL,
FT ECO:0007744|PDB:6MIM"
FT SITE 375
FT /note="KMT2A/MLL1 fusion point (in acute myeloid leukemia
FT patient CO)"
FT /evidence="ECO:0000269|PubMed:8506309"
FT SITE 481
FT /note="KMT2A/MLL1 fusion point (in acute myeloid leukemia
FT patient F1)"
FT /evidence="ECO:0000269|PubMed:8506309"
FT MOD_RES 288
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 294
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:23186163"
FT MOD_RES 412
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 419
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT CROSSLNK 339
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..4
FT /note="MASS -> M (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054924"
FT MUTAGEN 28
FT /note="F->A: Decreased binding to crotonylated histone H3.
FT Decreased binding to acetylated histone H3."
FT /evidence="ECO:0000269|PubMed:25417107,
FT ECO:0000269|PubMed:27105114"
FT MUTAGEN 56
FT /note="H->A: Decreased binding to crotonylated histone H3.
FT Decreased binding to acetylated histone H3."
FT /evidence="ECO:0000269|PubMed:25417107,
FT ECO:0000269|PubMed:27105114"
FT MUTAGEN 58
FT /note="S->A: Decreased binding to crotonylated histone H3.
FT Decreased binding to acetylated histone H3."
FT /evidence="ECO:0000269|PubMed:25417107,
FT ECO:0000269|PubMed:27105114"
FT MUTAGEN 59
FT /note="F->A: Strongly decreased binding to crotonylated
FT histone H3. Decreased binding to acetylated histone H3."
FT /evidence="ECO:0000269|PubMed:25417107,
FT ECO:0000269|PubMed:27105114, ECO:0000269|PubMed:27545619"
FT MUTAGEN 61..67
FT /note="RPKRVCK->EPERVCE: Decreased DNA-binding."
FT /evidence="ECO:0000269|PubMed:30385749"
FT MUTAGEN 77
FT /note="G->A: Decreased binding to crotonylated histone H3.
FT Decreased binding to acetylated histone H3."
FT /evidence="ECO:0000269|PubMed:25417107,
FT ECO:0000269|PubMed:27105114"
FT MUTAGEN 78..79
FT /note="YA->WG: Binds equally well acetylated and
FT crotonylated histone H3."
FT /evidence="ECO:0000269|PubMed:30385749"
FT MUTAGEN 78
FT /note="Y->A: Strongly decreased binding to crotonylated
FT histone H3. Decreased binding to acetylated histone H3."
FT /evidence="ECO:0000269|PubMed:25417107,
FT ECO:0000269|PubMed:27105114, ECO:0000269|PubMed:27545619"
FT MUTAGEN 78
FT /note="Y->W: Does not affect ability to discriminate
FT between acetylated and crotonylated histone H3."
FT /evidence="ECO:0000269|PubMed:30385749"
FT MUTAGEN 81
FT /note="F->A: Decreased binding to acetylated histone H3."
FT /evidence="ECO:0000269|PubMed:25417107"
FT MUTAGEN 103
FT /note="D->A: Decreased binding to acetylated histone H3."
FT /evidence="ECO:0000269|PubMed:25417107"
FT CONFLICT 6
FT /note="A -> S (in Ref. 1; AAA58361 and 2; BAG35760)"
FT /evidence="ECO:0000305"
FT CONFLICT 173
FT /note="S -> G (in Ref. 5; AAH36089)"
FT /evidence="ECO:0000305"
FT CONFLICT 419
FT /note="S -> P (in Ref. 2; BAG35760)"
FT /evidence="ECO:0000305"
FT STRAND 6..19
FT /evidence="ECO:0007829|PDB:5YYF"
FT STRAND 30..37
FT /evidence="ECO:0007829|PDB:5YYF"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:5YYF"
FT TURN 45..47
FT /evidence="ECO:0007829|PDB:5YYF"
FT STRAND 48..54
FT /evidence="ECO:0007829|PDB:5YYF"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:5YYF"
FT STRAND 63..90
FT /evidence="ECO:0007829|PDB:5YYF"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:5YYF"
FT STRAND 97..104
FT /evidence="ECO:0007829|PDB:5YYF"
FT STRAND 114..126
FT /evidence="ECO:0007829|PDB:5YYF"
FT HELIX 129..135
FT /evidence="ECO:0007829|PDB:5YYF"
FT HELIX 504..515
FT /evidence="ECO:0007829|PDB:2LM0"
FT HELIX 523..531
FT /evidence="ECO:0007829|PDB:2LM0"
FT STRAND 536..538
FT /evidence="ECO:0007829|PDB:2LM0"
FT STRAND 543..545
FT /evidence="ECO:0007829|PDB:2LM0"
FT TURN 547..549
FT /evidence="ECO:0007829|PDB:2LM0"
FT HELIX 552..561
FT /evidence="ECO:0007829|PDB:2LM0"
SQ SEQUENCE 568 AA; 63351 MW; 0A020B7FB34132F9 CRC64;
MASSCAVQVK LELGHRAQVR KKPTVEGFTH DWMVFVRGPE HSNIQHFVEK VVFHLHESFP
RPKRVCKDPP YKVEESGYAG FILPIEVYFK NKEEPRKVRF DYDLFLHLEG HPPVNHLRCE
KLTFNNPTED FRRKLLKAGG DPNRSIHTSS SSSSSSSSSS SSSSSSSSSS SSSSSSSSSS
SSSSSSSSSS TSFSKPHKLM KEHKEKPSKD SREHKSAFKE PSRDHNKSSK ESSKKPKENK
PLKEEKIVPK MAFKEPKPMS KEPKPDSNLL TITSGQDKKA PSKRPPISDS EELSAKKRKK
SSSEALFKSF SSAPPLILTC SADKKQIKDK SHVKMGKVKI ESETSEKKKS TLPPFDDIVD
PNDSDVEENI SSKSDSEQPS PASSSSSSSS SFTPSQTRQQ GPLRSIMKDL HSDDNEEESD
EVEDNDNDSE MERPVNRGGS RSRRVSLSDG SDSESSSASS PLHHEPPPPL LKTNNNQILE
VKSPIKQSKS DKQIKNGECD KAYLDELVEL HRRLMTLRER HILQQIVNLI EETGHFHITN
TTFDFDLCSL DKTTVRKLQS YLETSGTS
