ID MS3L1_HUMAN Reviewed; 521 AA. AC Q8N5Y2; A6NCU2; A6NHW8; A8K165; B4DUV8; B7Z227; Q9UG70; Q9Y5Z8; DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 27-MAR-2024, entry version 188. DE RecName: Full=Male-specific lethal 3 homolog; DE AltName: Full=Male-specific lethal-3 homolog 1; DE AltName: Full=Male-specific lethal-3 protein-like 1; DE Short=MSL3-like 1; GN Name=MSL3; Synonyms=MSL3L1; 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 ALTERNATIVE SPLICING (ISOFORM RP 2). RX PubMed=10395802; DOI=10.1006/geno.1999.5844; RA Prakash S.K., Van den Veyver I.B., Franco B., Volta M., Ballabio A., RA Zoghbi H.Y.; RT "Characterization of a novel chromo domain gene in Xp22.3 with homology to RT Drosophila msl-3."; RL Genomics 59:77-84(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 4; 5 AND 6), AND RP VARIANT THR-2. RC TISSUE=Amygdala, Brain, and Hepatoma; 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=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 283-521. RC TISSUE=Uterus; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [7] RP IDENTIFICATION OF MSL COMPLEX COMPONENTS, FUNCTION OF THE MSL COMPLEX, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=16227571; DOI=10.1128/mcb.25.21.9175-9188.2005; RA Smith E.R., Cayrou C., Huang R., Lane W.S., Cote J., Lucchesi J.C.; RT "A human protein complex homologous to the Drosophila MSL complex is RT responsible for the majority of histone H4 acetylation at lysine 16."; RL Mol. Cell. Biol. 25:9175-9188(2005). RN [8] RP ERRATUM OF PUBMED:16227571. RA Smith E.R., Cayrou C., Huang R., Lane W.S., Cote J., Lucchesi J.C.; RL Mol. Cell. Biol. 26:387-387(2006). RN [9] RP FUNCTION, AND IDENTIFICATION IN THE MSL COMPLEX. RX PubMed=16543150; DOI=10.1016/j.molcel.2006.02.007; RA Mendjan S., Taipale M., Kind J., Holz H., Gebhardt P., Schelder M., RA Vermeulen M., Buscaino A., Duncan K., Mueller J., Wilm M., RA Stunnenberg H.G., Saumweber H., Akhtar A.; RT "Nuclear pore components are involved in the transcriptional regulation of RT dosage compensation in Drosophila."; RL Mol. Cell 21:811-823(2006). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367; SER-407 AND SER-411, 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 [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-311; THR-405 AND SER-407, 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 [12] RP IDENTIFICATION IN THE MSL COMPLEX, AND FUNCTION OF THE MSL COMPLEX. RX PubMed=20018852; DOI=10.1074/jbc.c109.087981; RA Cai Y., Jin J., Swanson S.K., Cole M.D., Choi S.H., Florens L., RA Washburn M.P., Conaway J.W., Conaway R.C.; RT "Subunit composition and substrate specificity of a MOF-containing histone RT acetyltransferase distinct from the male-specific lethal (MSL) complex."; RL J. Biol. Chem. 285:4268-4272(2010). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367, 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 [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-400, 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 [15] RP FUNCTION IN MSL COMPLEX, AND INTERACTION WITH MSL1. RX PubMed=22547026; DOI=10.1038/cr.2012.72; RA Huang J., Wan B., Wu L., Yang Y., Dou Y., Lei M.; RT "Structural insight into the regulation of MOF in the male-specific lethal RT complex and the non-specific lethal complex."; RL Cell Res. 22:1078-1081(2012). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-311; SER-367 AND SER-400, AND RP IDENTIFICATION BY 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 [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 1-101 IN COMPLEX WITH DNA AND RP HISTONE H4, MUTAGENESIS OF HIS-55; TRP-59 AND ARG-65, AND FUNCTION. RX PubMed=20657587; DOI=10.1038/nsmb.1856; RA Kim D., Blus B.J., Chandra V., Huang P., Rastinejad F., Khorasanizadeh S.; RT "Corecognition of DNA and a methylated histone tail by the MSL3 RT chromodomain."; RL Nat. Struct. Mol. Biol. 17:1027-1029(2010). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 2-93, MUTAGENESIS OF TYR-31, AND RP FUNCTION. RX PubMed=20943666; DOI=10.1074/jbc.m110.134312; RA Moore S.A., Ferhatoglu Y., Jia Y., Al-Jiab R.A., Scott M.J.; RT "Structural and biochemical studies on the chromo-barrel domain of male RT specific lethal 3 (MSL3) reveal a binding preference for mono- or RT dimethyllysine 20 on histone H4."; RL J. Biol. Chem. 285:40879-40890(2010). RN [20] RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 167-517 IN COMPLEX WITH MSL1, RP FUNCTION IN MSL COMPLEX, AND INTERACTION WITH MSL1. RX PubMed=21217699; DOI=10.1038/nsmb.1960; RA Kadlec J., Hallacli E., Lipp M., Holz H., Sanchez-Weatherby J., Cusack S., RA Akhtar A.; RT "Structural basis for MOF and MSL3 recruitment into the dosage compensation RT complex by MSL1."; RL Nat. Struct. Mol. Biol. 18:142-149(2011). RN [21] RP VARIANTS MRXSBA 281-GLN--TYR-521 DEL; PRO-308; 346-GLN--TYR-521 DEL AND RP 458-ARG--TYR-521 DEL, INVOLVEMENT IN MRXSBA, CHARACTERIZATION OF VARIANT RP MRXSBA 346-GLN--TYR-521 DEL, INTERACTION WITH KAT8 AND MSL1, AND RP SUBCELLULAR LOCATION. RX PubMed=30224647; DOI=10.1038/s41588-018-0220-y; RG DDD Study; RA Basilicata M.F., Bruel A.L., Semplicio G., Valsecchi C.I.K., Aktas T., RA Duffourd Y., Rumpf T., Morton J., Bache I., Szymanski W.G., Gilissen C., RA Vanakker O., Ounap K., Mittler G., van der Burgt I., El Chehadeh S., RA Cho M.T., Pfundt R., Tan T.Y., Kirchhoff M., Menten B., Vergult S., RA Lindstrom K., Reis A., Johnson D.S., Fryer A., McKay V., Fisher R.B., RA Thauvin-Robinet C., Francis D., Roscioli T., Pajusalu S., Radtke K., RA Ganesh J., Brunner H.G., Wilson M., Faivre L., Kalscheuer V.M., RA Thevenon J., Akhtar A.; RT "De novo mutations in MSL3 cause an X-linked syndrome marked by impaired RT histone H4 lysine 16 acetylation."; RL Nat. Genet. 50:1442-1451(2018). CC -!- FUNCTION: Has a role in chromatin remodeling and transcriptional CC regulation (PubMed:20018852, PubMed:20657587, PubMed:20943666, CC PubMed:21217699, PubMed:30224647). Has a role in X inactivation CC (PubMed:21217699). Component of the MSL complex which is responsible CC for the majority of histone H4 acetylation at 'Lys-16' which is CC implicated in the formation of higher-order chromatin structure CC (PubMed:16227571, PubMed:20657587, PubMed:16543150, PubMed:30224647). CC Specifically recognizes histone H4 monomethylated at 'Lys-20' CC (H4K20Me1) in a DNA-dependent manner and is proposed to be involved in CC chromosomal targeting of the MSL complex (PubMed:20657587, CC PubMed:20943666). {ECO:0000269|PubMed:16227571, CC ECO:0000269|PubMed:16543150, ECO:0000269|PubMed:20018852, CC ECO:0000269|PubMed:20657587, ECO:0000269|PubMed:20943666, CC ECO:0000269|PubMed:21217699, ECO:0000269|PubMed:22547026, CC ECO:0000269|PubMed:30224647}. CC -!- SUBUNIT: Component of the MSL histone acetyltransferase complex at CC least composed of the KAT8/MOF, MSL1/hampin, MSL2 and MSL3 CC (PubMed:20018852, PubMed:20657587, PubMed:21217699, PubMed:22547026, CC PubMed:16543150). Interacts (via the MRG domain) with MSL1 and KAT8/MOF CC (PubMed:21217699, PubMed:30224647). {ECO:0000269|PubMed:16543150, CC ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:20657587, CC ECO:0000269|PubMed:21217699, ECO:0000269|PubMed:22547026, CC ECO:0000269|PubMed:30224647}. CC -!- INTERACTION: CC Q8N5Y2; O76024: WFS1; NbExp=3; IntAct=EBI-2560796, EBI-720609; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:30224647}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; CC IsoId=Q8N5Y2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8N5Y2-2; Sequence=VSP_007636, VSP_007637; CC Name=3; CC IsoId=Q8N5Y2-3; Sequence=VSP_043342; CC Name=4; CC IsoId=Q8N5Y2-4; Sequence=VSP_045652; CC Name=5; CC IsoId=Q8N5Y2-5; Sequence=VSP_045653, VSP_045654; CC Name=6; CC IsoId=Q8N5Y2-6; Sequence=VSP_055376, VSP_055377; CC -!- TISSUE SPECIFICITY: Expressed in many tissues including liver, CC pancreas, heart, lung, kidney, skeletal muscle, brain, and placenta, CC with highest expression in skeletal muscle and heart. CC -!- DISEASE: Basilicata-Akhtar syndrome (MRXSBA) [MIM:301032]: An X-linked CC syndrome characterized by intellectual disability, global developmental CC delay, progressive gait disturbance, poor or absent speech, facial CC dysmorphism, and mild distal skeletal anomalies. CC {ECO:0000269|PubMed:30224647}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: MSL3L1 gene undergoes X inactivation. 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; AF117065; AAD38499.1; -; mRNA. DR EMBL; AK025642; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK289780; BAF82469.1; -; mRNA. DR EMBL; AK294255; BAH11713.1; -; mRNA. DR EMBL; AK300814; BAG62470.1; -; mRNA. DR EMBL; AC004554; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471074; EAW98799.1; -; Genomic_DNA. DR EMBL; CH471074; EAW98801.1; -; Genomic_DNA. DR EMBL; BC031210; AAH31210.1; -; mRNA. DR EMBL; AL050178; CAB43308.1; -; mRNA. DR EMBL; AL713667; CAD28473.1; -; mRNA. DR CCDS; CCDS14147.1; -. [Q8N5Y2-1] DR CCDS; CCDS14148.1; -. [Q8N5Y2-5] DR CCDS; CCDS14149.1; -. [Q8N5Y2-4] DR CCDS; CCDS55369.1; -. [Q8N5Y2-3] DR CCDS; CCDS65213.1; -. [Q8N5Y2-6] DR PIR; T08795; T08795. DR RefSeq; NP_001180199.1; NM_001193270.2. [Q8N5Y2-3] DR RefSeq; NP_001269103.1; NM_001282174.1. [Q8N5Y2-6] DR RefSeq; NP_006791.2; NM_006800.3. [Q8N5Y2-4] DR RefSeq; NP_523352.1; NM_078628.1. [Q8N5Y2-5] DR RefSeq; NP_523353.2; NM_078629.3. [Q8N5Y2-1] DR RefSeq; XP_005274497.1; XM_005274440.2. DR PDB; 2Y0N; X-ray; 3.00 A; A/B/C/D=167-289, A/B/C/D=442-518. DR PDB; 3OA6; X-ray; 2.35 A; A/B=1-101. DR PDB; 3OB9; X-ray; 2.50 A; A/B/C/D/E=2-93. DR PDBsum; 2Y0N; -. DR PDBsum; 3OA6; -. DR PDBsum; 3OB9; -. DR AlphaFoldDB; Q8N5Y2; -. DR SMR; Q8N5Y2; -. DR BioGRID; 116143; 28. DR ComplexPortal; CPX-815; MSL histone acetyltransferase complex. DR CORUM; Q8N5Y2; -. DR DIP; DIP-56857N; -. DR IntAct; Q8N5Y2; 18. DR MINT; Q8N5Y2; -. DR STRING; 9606.ENSP00000312244; -. DR iPTMnet; Q8N5Y2; -. DR PhosphoSitePlus; Q8N5Y2; -. DR BioMuta; MSL3; -. DR DMDM; 32171482; -. DR EPD; Q8N5Y2; -. DR jPOST; Q8N5Y2; -. DR MassIVE; Q8N5Y2; -. DR MaxQB; Q8N5Y2; -. DR PaxDb; 9606-ENSP00000312244; -. DR PeptideAtlas; Q8N5Y2; -. DR ProteomicsDB; 1230; -. DR ProteomicsDB; 6399; -. DR ProteomicsDB; 72108; -. [Q8N5Y2-1] DR ProteomicsDB; 72109; -. [Q8N5Y2-2] DR ProteomicsDB; 72110; -. [Q8N5Y2-3] DR ProteomicsDB; 863; -. DR Pumba; Q8N5Y2; -. DR Antibodypedia; 23748; 150 antibodies from 21 providers. DR DNASU; 10943; -. DR Ensembl; ENST00000312196.10; ENSP00000312244.4; ENSG00000005302.19. [Q8N5Y2-1] DR Ensembl; ENST00000337339.7; ENSP00000338078.2; ENSG00000005302.19. [Q8N5Y2-5] DR Ensembl; ENST00000361672.6; ENSP00000354562.2; ENSG00000005302.19. [Q8N5Y2-6] DR Ensembl; ENST00000398527.7; ENSP00000381538.2; ENSG00000005302.19. [Q8N5Y2-3] DR Ensembl; ENST00000482871.6; ENSP00000498064.1; ENSG00000005302.19. [Q8N5Y2-4] DR Ensembl; ENST00000648013.1; ENSP00000497518.1; ENSG00000005302.19. [Q8N5Y2-4] DR Ensembl; ENST00000649078.1; ENSP00000498017.1; ENSG00000005302.19. [Q8N5Y2-4] DR Ensembl; ENST00000649271.1; ENSP00000496967.1; ENSG00000005302.19. [Q8N5Y2-4] DR Ensembl; ENST00000649602.1; ENSP00000498168.1; ENSG00000005302.19. [Q8N5Y2-4] DR Ensembl; ENST00000649649.1; ENSP00000497137.1; ENSG00000005302.19. [Q8N5Y2-6] DR Ensembl; ENST00000649685.1; ENSP00000497496.1; ENSG00000005302.19. [Q8N5Y2-6] DR Ensembl; ENST00000650215.1; ENSP00000496944.1; ENSG00000005302.19. [Q8N5Y2-6] DR Ensembl; ENST00000650628.1; ENSP00000496838.1; ENSG00000005302.19. [Q8N5Y2-4] DR GeneID; 10943; -. DR KEGG; hsa:10943; -. DR MANE-Select; ENST00000312196.10; ENSP00000312244.4; NM_078629.4; NP_523353.2. DR UCSC; uc004cuv.2; human. [Q8N5Y2-1] DR AGR; HGNC:7370; -. DR CTD; 10943; -. DR DisGeNET; 10943; -. DR GeneCards; MSL3; -. DR HGNC; HGNC:7370; MSL3. DR HPA; ENSG00000005302; Low tissue specificity. DR MalaCards; MSL3; -. DR MIM; 300609; gene. DR MIM; 301032; phenotype. DR neXtProt; NX_Q8N5Y2; -. DR OpenTargets; ENSG00000005302; -. DR PharmGKB; PA164723161; -. DR VEuPathDB; HostDB:ENSG00000005302; -. DR eggNOG; KOG3001; Eukaryota. DR GeneTree; ENSGT00950000182965; -. DR HOGENOM; CLU_039566_5_2_1; -. DR InParanoid; Q8N5Y2; -. DR OMA; DTEYAHL; -. DR OrthoDB; 2878816at2759; -. DR PhylomeDB; Q8N5Y2; -. DR TreeFam; TF323400; -. DR PathwayCommons; Q8N5Y2; -. DR Reactome; R-HSA-3214847; HATs acetylate histones. DR SignaLink; Q8N5Y2; -. DR SIGNOR; Q8N5Y2; -. DR BioGRID-ORCS; 10943; 27 hits in 784 CRISPR screens. DR ChiTaRS; MSL3; human. DR EvolutionaryTrace; Q8N5Y2; -. DR GenomeRNAi; 10943; -. DR Pharos; Q8N5Y2; Tbio. DR PRO; PR:Q8N5Y2; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q8N5Y2; Protein. DR Bgee; ENSG00000005302; Expressed in monocyte and 193 other cell types or tissues. DR ExpressionAtlas; Q8N5Y2; baseline and differential. DR GO; GO:0072487; C:MSL complex; IDA:UniProtKB. DR GO; GO:0035267; C:NuA4 histone acetyltransferase complex; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0046972; F:histone H4K16 acetyltransferase activity; IMP:UniProtKB. DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:ComplexPortal. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IMP:UniProtKB. DR CDD; cd18983; CBD_MSL3_like; 1. DR DisProt; DP01279; -. DR Gene3D; 2.30.30.140; -; 1. DR Gene3D; 1.10.274.30; MRG domain; 2. DR InterPro; IPR016197; Chromo-like_dom_sf. DR InterPro; IPR000953; Chromo/chromo_shadow_dom. DR InterPro; IPR008676; MRG. DR InterPro; IPR038217; MRG_C_sf. DR InterPro; IPR026541; MRG_dom. DR InterPro; IPR025995; Tudor-knot. DR PANTHER; PTHR10880; MORTALITY FACTOR 4-LIKE PROTEIN; 1. DR PANTHER; PTHR10880:SF15; MRG DOMAIN-CONTAINING PROTEIN; 1. DR Pfam; PF05712; MRG; 1. DR Pfam; PF11717; Tudor-knot; 1. DR SMART; SM00298; CHROMO; 1. DR SUPFAM; SSF54160; Chromo domain-like; 1. DR PROSITE; PS51640; MRG; 1. DR Genevisible; Q8N5Y2; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chromatin regulator; DNA-binding; KW Intellectual disability; Nucleus; Phosphoprotein; Reference proteome; KW Transcription; Transcription regulation. FT CHAIN 1..521 FT /note="Male-specific lethal 3 homolog" FT /id="PRO_0000080247" FT DOMAIN 13..71 FT /note="Tudor-knot" FT /evidence="ECO:0000255" FT DOMAIN 168..517 FT /note="MRG" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00972" FT REGION 114..166 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 290..440 FT /note="Required for the histone acetyltransferase activity FT of the MSL complex" FT REGION 298..409 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 139..153 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 298..332 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 334..357 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 358..381 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 309 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9WVG9" FT MOD_RES 311 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 367 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 400 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 405 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 407 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 411 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT VAR_SEQ 1..166 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045652" FT VAR_SEQ 1..59 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10395802" FT /id="VSP_007636" FT VAR_SEQ 1..34 FT /note="MSASEGMKFKFHSGEKVLCFEPDPTKARVLYDAK -> MSPSVRPGAGWAPV FT GRPGRPIQ (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043342" FT VAR_SEQ 1..6 FT /note="MSASEG -> MKMMKT (in isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055376" FT VAR_SEQ 7..155 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055377" FT VAR_SEQ 60..61 FT /note="NR -> MP (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10395802" FT /id="VSP_007637" FT VAR_SEQ 391..416 FT /note="KTPVHSRSSSPIPLTPSKEGSAVFAG -> SRFILGCPRPGRASVYFVFSQC FT QAWC (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045653" FT VAR_SEQ 417..521 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045654" FT VARIANT 2 FT /note="S -> T (in dbSNP:rs150938844)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_069061" FT VARIANT 199 FT /note="K -> Q (in dbSNP:rs1051595)" FT /id="VAR_048732" FT VARIANT 281..521 FT /note="Missing (in MRXSBA)" FT /evidence="ECO:0000269|PubMed:30224647" FT /id="VAR_082955" FT VARIANT 308 FT /note="L -> P (in MRXSBA; uncertain significance; FT dbSNP:rs1555906707)" FT /evidence="ECO:0000269|PubMed:30224647" FT /id="VAR_082956" FT VARIANT 346..521 FT /note="Missing (in MRXSBA; loss of interaction with MOF and FT MSL1)" FT /evidence="ECO:0000269|PubMed:30224647" FT /id="VAR_082957" FT VARIANT 458..521 FT /note="Missing (in MRXSBA)" FT /evidence="ECO:0000269|PubMed:30224647" FT /id="VAR_082958" FT MUTAGEN 31 FT /note="Y->A: Diminishes interaction with histone H4 FT monomethylated at 'Lys-20'(H4K20Me1)." FT /evidence="ECO:0000269|PubMed:20943666" FT MUTAGEN 55 FT /note="H->A: Diminishes DNA-binding; when associated with FT A-65." FT /evidence="ECO:0000269|PubMed:20657587" FT MUTAGEN 56 FT /note="F->A: Abolishes interaction with histone H4 FT monomethylated at 'Lys-20'(H4K20Me1)." FT MUTAGEN 59 FT /note="W->G: Diminishes DNA-binding." FT /evidence="ECO:0000269|PubMed:20657587" FT MUTAGEN 65 FT /note="R->A: Diminishes DNA-binding; when associated with FT A-55." FT /evidence="ECO:0000269|PubMed:20657587" FT CONFLICT 37 FT /note="D -> V (in Ref. 1; AAD38499)" FT /evidence="ECO:0000305" FT CONFLICT 346 FT /note="Q -> R (in Ref. 2; AK025642)" FT /evidence="ECO:0000305" FT CONFLICT 391 FT /note="K -> E (in Ref. 2; AK025642)" FT /evidence="ECO:0000305" FT STRAND 16..20 FT /evidence="ECO:0007829|PDB:3OA6" FT STRAND 30..42 FT /evidence="ECO:0007829|PDB:3OA6" FT STRAND 48..56 FT /evidence="ECO:0007829|PDB:3OA6" FT HELIX 61..63 FT /evidence="ECO:0007829|PDB:3OA6" FT STRAND 65..68 FT /evidence="ECO:0007829|PDB:3OA6" FT HELIX 69..71 FT /evidence="ECO:0007829|PDB:3OA6" FT STRAND 72..74 FT /evidence="ECO:0007829|PDB:3OA6" FT HELIX 77..91 FT /evidence="ECO:0007829|PDB:3OA6" FT HELIX 178..192 FT /evidence="ECO:0007829|PDB:2Y0N" FT HELIX 206..222 FT /evidence="ECO:0007829|PDB:2Y0N" FT HELIX 251..272 FT /evidence="ECO:0007829|PDB:2Y0N" FT HELIX 276..278 FT /evidence="ECO:0007829|PDB:2Y0N" FT HELIX 279..287 FT /evidence="ECO:0007829|PDB:2Y0N" FT HELIX 447..449 FT /evidence="ECO:0007829|PDB:2Y0N" FT HELIX 453..469 FT /evidence="ECO:0007829|PDB:2Y0N" FT HELIX 474..493 FT /evidence="ECO:0007829|PDB:2Y0N" FT HELIX 495..498 FT /evidence="ECO:0007829|PDB:2Y0N" FT HELIX 501..503 FT /evidence="ECO:0007829|PDB:2Y0N" SQ SEQUENCE 521 AA; 59824 MW; 6DFFB9E183D0CFB9 CRC64; MSASEGMKFK FHSGEKVLCF EPDPTKARVL YDAKIVDVIV GKDEKGRKIP EYLIHFNGWN RSWDRWAAED HVLRDTDENR RLQRKLARKA VARLRSTGRK KKRCRLPGVD SVLKGLPTEE KDENDENSLS SSSDCSENKD EEISEESDIE EKTEVKEEPE LQTRREMEER TITIEIPEVL KKQLEDDCYY INRRKRLVKL PCQTNIITIL ESYVKHFAIN AAFSANERPR HHHVMPHANM NVHYIPAEKN VDLCKEMVDG LRITFDYTLP LVLLYPYEQA QYKKVTSSKF FLPIKESATS TNRSQEELSP SPPLLNPSTP QSTESQPTTG EPATPKRRKA EPEALQSLRR STRHSANCDR LSESSASPQP KRRQQDTSAS MPKLFLHLEK KTPVHSRSSS PIPLTPSKEG SAVFAGFEGR RTNEINEVLS WKLVPDNYPP GDQPPPPSYI YGAQHLLRLF VKLPEILGKM SFSEKNLKAL LKHFDLFLRF LAEYHDDFFP ESAYVAACEA HYSTKNPRAI Y //