SASDGE4: Mixed lineage leukemia protein-1 complex, MLL1-WDR5-ASH2L-RBBP5(2-480)

Basic information

Entry

Database: SASBDB / ID: SASDGE4

Sample

Mixed lineage leukemia protein-1 complex, MLL1-WDR5-ASH2L-RBBP5(2-480)

• Histone-lysine N-methyltransferase 2A (protein), MLL1KMT2A, Homo sapiens
• WD repeat-containing protein 5 (protein), WDR5, Homo sapiens
• Set1/Ash2 histone methyltransferase complex subunit ASH2 (protein), ASH2L, Homo sapiens
• Retinoblastoma-binding protein 5 (protein), RBBP5, Homo sapiens

Function / homology

Function:

protein-cysteine methyltransferase activity / response to potassium ion / [histone H3]-lysine4 N-methyltransferase / histone H3K4 monomethyltransferase activity / unmethylated CpG binding / histone H3K4 trimethyltransferase activity / negative regulation of DNA methylation-dependent heterochromatin formation / regulation of short-term neuronal synaptic plasticity / MLL3/4 complex / Set1C/COMPASS complex / MLL1/2 complex / ATAC complex / definitive hemopoiesis / NSL complex / histone H3K4 methyltransferase activity / T-helper 2 cell differentiation / : / Cardiogenesis / embryonic hemopoiesis / anterior/posterior pattern specification / exploration behavior / histone methyltransferase complex / regulation of tubulin deacetylation / : / Formation of WDR5-containing histone-modifying complexes / regulation of cell division / minor groove of adenine-thymine-rich DNA binding / membrane depolarization / MLL1 complex / regulation of embryonic development / histone acetyltransferase complex / negative regulation of fibroblast proliferation / homeostasis of number of cells within a tissue / positive regulation of gluconeogenesis / spleen development / transcription initiation-coupled chromatin remodeling / cellular response to transforming growth factor beta stimulus / methylated histone binding / Transferases; Transferring one-carbon groups; Methyltransferases / post-embryonic development / skeletal system development / gluconeogenesis / Deactivation of the beta-catenin transactivating complex / Formation of the beta-catenin:TCF transactivating complex / circadian regulation of gene expression / protein modification process / lysine-acetylated histone binding / visual learning / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / mitotic spindle / PKMTs methylate histone lysines / RMTs methylate histone arginines / Activation of anterior HOX genes in hindbrain development during early embryogenesis / response to estrogen / Transcriptional regulation of granulopoiesis / Neddylation / RUNX1 regulates transcription of genes involved in differentiation of HSCs / HATs acetylate histones / histone binding / fibroblast proliferation / protein-containing complex assembly / transcription cis-regulatory region binding / regulation of cell cycle / apoptotic process / DNA damage response / chromatin binding / nucleolus / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / zinc ion binding / nucleoplasm / identical protein binding / nucleus / cytosol

Domain/homology:

Retinoblastoma-binding protein 5/Swd1 / KMT2A, ePHD domain / KMT2A, PHD domain 1 / KMT2A, PHD domain 2 / KMT2A, PHD domain 3 / Methyltransferase, trithorax / : / FY-rich, N-terminal / F/Y-rich N-terminus / PHD-like zinc-binding domain / FYR domain FYRN motif profile. / "FY-rich" domain, N-terminal region / FY-rich, C-terminal / F/Y rich C-terminus / FYR domain FYRC motif profile. / "FY-rich" domain, C-terminal region / CXXC zinc finger domain / Zinc finger, CXXC-type / Zinc finger CXXC-type profile. / Cysteine-rich motif following a subset of SET domains / Post-SET domain / Post-SET domain profile. / SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain / SET domain superfamily / SET domain / SET domain profile. / SET domain / Extended PHD (ePHD) domain / Extended PHD (ePHD) domain profile. / PHD-finger / Zinc finger PHD-type signature. / Zinc finger PHD-type profile. / Zinc finger, PHD-finger / Zinc finger, PHD-type / PHD zinc finger / Zinc finger, FYVE/PHD-type / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily / G-protein beta WD-40 repeat / Zinc finger, RING/FYVE/PHD-type / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily

Component:

WD repeat-containing protein 5 / Histone-lysine N-methyltransferase 2A / Retinoblastoma-binding protein 5 / Isoform 3 of Set1/Ash2 histone methyltransferase complex subunit ASH2

• Biological species: Homo sapiens (human)
• Citation: Journal: Nucleic Acids Res / Year: 2019; Title: The internal interaction in RBBP5 regulates assembly and activity of MLL1 methyltransferase complex.; Authors: Jianming Han / Tingting Li / Yanjing Li / Muchun Li / Xiaoman Wang / Chao Peng / Chen Su / Na Li / Yiwen Li / Ying Xu / Yong Chen / ; Abstract: The Mixed Lineage Leukemia protein 1 (MLL1) plays an essential role in the maintenance of the histone H3 lysine 4 (H3K4) methylation status for gene expression during differentiation and development. The methyltransferase activity of MLL1 is regulated by three conserved core subunits, WDR5, RBBP5 and ASH2L. Here, we determined the structure of human RBBP5 and demonstrated its role in the assembly and regulation of the MLL1 complex. We identified an internal interaction between the WD40 propeller and the C-terminal distal region in RBBP5, which assisted the maintenance of the compact conformation of the MLL1 complex. We also discovered a vertebrate-specific motif in the C-terminal distal region of RBBP5 that contributed to nucleosome recognition and methylation of nucleosomes by the MLL1 complex. Our results provide new insights into functional conservation and evolutionary plasticity of the scaffold protein RBBP5 in the regulation of KMT2-family methyltransferase complexes.

Contact author

• Jianming Han (Shanghai Institue of Biochemistry and Cell biology, Chinese Academy of Sciences)

Models

Sample

• Sample: Name: Mixed lineage leukemia protein-1 complex, MLL1-WDR5-ASH2L-RBBP5(2-480); Specimen concentration: 2 mg/ml / Entity id: 1862 / 1863 / 1864 / 1865
• Buffer: Name: 300 mM NaCl, 25mM Tris-HCl, 4% glycerol, 1 mM TCEP / pH: 8 / Comment: degassing treatment

Entity #1862

Name: MLL1KMT2A / Type: protein / Description: Histone-lysine N-methyltransferase 2A / Formula weight: 24.927 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: Q03164
Sequence:

NEPPLNPHGS ARAEVHLRKS AFDMFNFLAS KHRQPPEYNP NDEEEEEVQL KSARRATSMD LPMPMRFRHL KKTSKEAVGV YRSPIHGRGL FCKRNIDAGE MVIEYAGNVI RSIQTDKREK YYDSKGIGCY MFRIDDSEVV DATMHGNAAR FINHSCEPNC YSRVINIDGQ KHIVIFAMRK IYRGEELTYD YKFPIEDASN KLPCNCGAKK CRKFLN

Entity #1863

Name: WDR5 / Type: protein / Description: WD repeat-containing protein 5 / Formula weight: 34.26 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: P61964
Sequence:

ATQSKPTPVK PNYALKFTLA GHTKAVSSVK FSPNGEWLAS SSADKLIKIW GAYDGKFEKT ISGHKLGISD VAWSSDSNLL VSASDDKTLK IWDVSSGKCL KTLKGHSNYV FCCNFNPQSN LIVSGSFDES VRIWDVKTGK CLKTLPAHSD PVSAVHFNRD GSLIVSSSYD GLCRIWDTAS GQCLKTLIDD DNPPVSFVKF SPNGKYILAA TLDNTLKLWD YSKGKCLKTY TGHKNEKYCI FANFSVTGGK WIVSGSEDNL VYIWNLQTKE IVQKLQGHTD VVISTACHPT ENIIASAALE NDKTIKLWKS DC

Entity #1864

Name: ASH2L / Type: protein
Description: Set1/Ash2 histone methyltransferase complex subunit ASH2
Formula weight: 60.207 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: Q9UBL3-3
Sequence:

MDTQAGSVDE ENGRQLGEVE LQCGICTKWF TADTFGIDTS SCLPFMTNYS FHCNVCHHSG NTYFLRKQAN LKEMCLSALA NLTWQSRTQD EHPKTMFSKD KDIIPFIDKY WECMTTRQRP GKMTWPNNIV KTMSKERDVF LVKEHPDPGS KDPEEDYPKF GLLDQDLSNI GPAYDNQKQS SAVSTSGNLN GGIAAGSSGK GRGAKRKQQD GGTTGTTKKA RSDPLFSAQR LPPHGYPLEH PFNKDGYRYI LAEPDPHAPD PEKLELDCWA GKPIPGDLYR ACLYERVLLA LHDRAPQLKI SDDRLTVVGE KGYSMVRASH GVRKGAWYFE ITVDEMPPDT AARLGWSQPL GNLQAPLGYD KFSYSWRSKK GTKFHQSIGK HYSSGYGQGD VLGFYINLPE DTETAKSLPD TYKDKALIKF KSYLYFEEKD FVDKAEKSLK QTPHSEIIFY KNGVNQGVAY KDIFEGVYFP AISLYKSCTV SINFGPCFKY PPKDLTYRPM SDMGWGAVVE HTLADVLYHV ETEVDGRRSP PWEP

Entity #1865

Name: RBBP5 / Type: protein / Description: Retinoblastoma-binding protein 5 / Formula weight: 52.962 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: Q15291
Sequence:

NLELLESFGQ NYPEEADGTL DCISMALTCT FNRWGTLLAV GCNDGRIVIW DFLTRGIAKI ISAHIHPVCS LCWSRDGHKL VSASTDNIVS QWDVLSGDCD QRFRFPSPIL KVQYHPRDQN KVLVCPMKSA PVMLTLSDSK HVVLPVDDDS DLNVVASFDR RGEYIYTGNA KGKILVLKTD SQDLVASFRV TTGTSNTTAI KSIEFARKGS CFLINTADRI IRVYDGREIL TCGRDGEPEP MQKLQDLVNR TPWKKCCFSG DGEYIVAGSA RQHALYIWEK SIGNLVKILH GTRGELLLDV AWHPVRPIIA SISSGVVSIW AQNQVENWSA FAPDFKELDE NVEYEERESE FDIEDEDKSE PEQTGADAAE DEEVDVTSVD PIAAFCSSDE ELEDSKALLY LPIAPEVEDP EENPYGPPPD AVQTSLMDEG ASSEKKRQSS ADGSQPPKKK PKTTNIELQG VPNDEVHPLL GVKGDGKSK

Experimental information

• Beam: Instrument name: Shanghai Synchrotron Radiation Facility (SSRF) BL19U2; City: Shanghai / 国: China / Type of source: X-ray synchrotronSynchrotron / Wavelength: 0.0918 Å / Dist. spec. to detc.: 2.415 mm
• Detector: Name: Pilatus 1M / Type: Dectris / Pixsize x: 172 mm

Scan

Title: Mixed lineage leukemia protein-1 complex, MLL1-WDR5-ASH2L-RBBP5(2-480)
Measurement date: Jun 22, 2019 / Storage temperature: 10 °C / Cell temperature: 10 °C / Exposure time: 1 sec. / Number of frames: 20 / Unit: 1/A /

	Min	Max
Q	0.0077	0.4732

Distance distribution function P(R)

Sofotware P(R): GNOM 4.6 / Number of points: 454 /

	Min	Max
Q	0.007969	0.4729
P(R) point	1	454
R	0	152.5

Result

Type of curve: single_conc /

	Experimental	Porod
MW	158.4 kDa	-
Volume	-	256 nm3

	P(R)	Guinier	Guinier error
Forward scattering, I0	0.06605	0.0669	0.00023
Radius of gyration, Rg	4.96 nm	4.983 nm	0.062

	Min	Max
D	-	15.25
Guinier point	5	36