AF9_MOUSE
ID AF9_MOUSE Reviewed; 569 AA.
AC A2AM29; Q8VDR6; Q99MK4;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Protein AF-9;
DE AltName: Full=Myeloid/lymphoid or mixed-lineage leukemia translocated to chromosome 3 protein homolog;
GN Name=Mllt3; Synonyms=Af9;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary tumor;
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 [MRNA] OF 10-569, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND INTERACTION WITH CBX8.
RC STRAIN=Swiss Webster / NIH;
RX PubMed=11439343; DOI=10.1038/sj.onc.1204478;
RA Hemenway C.S., de Erkenez A.C., Gould G.C.D.;
RT "The polycomb protein MPc3 interacts with AF9, an MLL fusion partner in
RT t(9;11)(p22;q23) acute leukemias.";
RL Oncogene 20:3798-3805(2001).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-413, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. Specifically recognizes and
CC binds acylated histone H3, with a preference for histone H3 that is
CC crotonylated. Crotonylation marks active promoters and enhancers and
CC confers resistance to transcriptional repressors. Recognizes and binds
CC histone H3 crotonylated at 'Lys-9' (H3K9cr), and with slightly lower
CC affinity histone H3 crotonylated at 'Lys-18' (H3K18cr). Also recognizes
CC and binds histone H3 acetylated and butyrylated at 'Lys-9' (H3K9ac and
CC H3K9bu, respectively), but with lower affinity than crotonylated
CC histone H3. In the SEC complex, MLLT3 is required to recruit the
CC complex to crotonylated histones. Recruitment of the SEC complex to
CC crotonylated histones promotes recruitment of DOT1L on active chromatin
CC to deposit histone H3 'Lys-79' methylation (H3K79me). Plays a key role
CC in hematopoietic stem cell (HSC) maintenance by preserving, rather than
CC confering, HSC stemness. Acts by binding to the transcription start
CC site of active genes in HSCs and sustaining level of H3K79me2, probably
CC by recruiting DOT1L. {ECO:0000250|UniProtKB:P42568}.
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) (By similarity). Interacts with
CC BCOR (By similarity). Interacts with CBX8 (PubMed:11439343). Interacts
CC with ALKBH4 (By similarity). {ECO:0000250|UniProtKB:P42568,
CC ECO:0000269|PubMed:11439343}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00376,
CC ECO:0000269|PubMed:11439343}. Chromosome
CC {ECO:0000250|UniProtKB:P42568}. Note=Colocalizes with acylated histone
CC H3. H3 Colocalizes with histone H3 crotonylated at 'Lys-18' (H3K18cr).
CC {ECO:0000250|UniProtKB:P42568}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Strong expression in the
CC spleen. {ECO:0000269|PubMed:11439343}.
CC -!- DOMAIN: The YEATS domain specifically recognizes and binds acylated
CC histones, with a marked preference for histones that are crotonylated.
CC Also binds histone H3 acetylated at 'Lys-9' (H3K9ac), but with lower
CC affinity. Binds crotonylated lysine through a non-canonical pi-pi-pi
CC stacking mechanism. The YEATS domain also binds DNA.
CC {ECO:0000250|UniProtKB:P42568}.
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DR EMBL; AL806533; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL831756; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL929524; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC021420; AAH21420.1; -; mRNA.
DR EMBL; AF333960; AAK28536.1; -; mRNA.
DR CCDS; CCDS38796.1; -.
DR RefSeq; NP_081602.3; NM_027326.3.
DR AlphaFoldDB; A2AM29; -.
DR BMRB; A2AM29; -.
DR SMR; A2AM29; -.
DR BioGRID; 213873; 9.
DR DIP; DIP-60099N; -.
DR IntAct; A2AM29; 4.
DR STRING; 10090.ENSMUSP00000077232; -.
DR iPTMnet; A2AM29; -.
DR PhosphoSitePlus; A2AM29; -.
DR SwissPalm; A2AM29; -.
DR EPD; A2AM29; -.
DR jPOST; A2AM29; -.
DR MaxQB; A2AM29; -.
DR PaxDb; A2AM29; -.
DR PeptideAtlas; A2AM29; -.
DR PRIDE; A2AM29; -.
DR ProteomicsDB; 285560; -.
DR Antibodypedia; 1068; 294 antibodies from 29 providers.
DR DNASU; 70122; -.
DR Ensembl; ENSMUST00000078090; ENSMUSP00000077232; ENSMUSG00000028496.
DR GeneID; 70122; -.
DR KEGG; mmu:70122; -.
DR UCSC; uc008tmp.1; mouse.
DR CTD; 4300; -.
DR MGI; MGI:1917372; Mllt3.
DR VEuPathDB; HostDB:ENSMUSG00000028496; -.
DR eggNOG; KOG3149; Eukaryota.
DR GeneTree; ENSGT00940000155903; -.
DR HOGENOM; CLU_036086_0_0_1; -.
DR InParanoid; A2AM29; -.
DR OMA; MSKEPKA; -.
DR OrthoDB; 727038at2759; -.
DR PhylomeDB; A2AM29; -.
DR TreeFam; TF314586; -.
DR Reactome; R-MMU-112382; Formation of RNA Pol II elongation complex.
DR Reactome; R-MMU-674695; RNA Polymerase II Pre-transcription Events.
DR Reactome; R-MMU-75955; RNA Polymerase II Transcription Elongation.
DR BioGRID-ORCS; 70122; 11 hits in 73 CRISPR screens.
DR ChiTaRS; Mllt3; mouse.
DR PRO; PR:A2AM29; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; A2AM29; protein.
DR Bgee; ENSMUSG00000028496; Expressed in embryonic post-anal tail and 277 other tissues.
DR ExpressionAtlas; A2AM29; baseline and differential.
DR Genevisible; A2AM29; MM.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0035267; C:NuA4 histone acetyltransferase complex; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0032783; C:super elongation complex; IBA:GO_Central.
DR GO; GO:0008023; C:transcription elongation factor complex; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042393; F:histone binding; ISS:UniProtKB.
DR GO; GO:0070577; F:lysine-acetylated histone binding; ISS:UniProtKB.
DR GO; GO:0140030; F:modification-dependent protein binding; ISS:UniProtKB.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:MGI.
DR GO; GO:0006338; P:chromatin remodeling; IBA:GO_Central.
DR GO; GO:0010467; P:gene expression; IDA:MGI.
DR GO; GO:0060218; P:hematopoietic stem cell differentiation; ISS:UniProtKB.
DR GO; GO:0016573; P:histone acetylation; IBA:GO_Central.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:2000096; P:positive regulation of Wnt signaling pathway, planar cell polarity pathway; ISO:MGI.
DR GO; GO:1902275; P:regulation of chromatin organization; ISS:UniProtKB.
DR GO; GO:2000035; P:regulation of stem cell division; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007379; P:segment specification; IMP:MGI.
DR Gene3D; 2.60.40.1970; -; 1.
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 Activator; Chromosome; DNA-binding; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..569
FT /note="Protein AF-9"
FT /id="PRO_0000305124"
FT DOMAIN 1..138
FT /note="YEATS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00376"
FT REGION 137..476
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 296..301
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 266..280
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..305
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 324..355
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 374..404
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 415..429
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 442..462
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 289
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42568"
FT MOD_RES 295
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42568"
FT MOD_RES 413
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 420
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42568"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42568"
FT CROSSLNK 340
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P42568"
FT CONFLICT 157
FT /note="S -> G (in Ref. 3; AAK28536)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="S -> G (in Ref. 3; AAK28536)"
FT /evidence="ECO:0000305"
FT CONFLICT 172
FT /note="S -> N (in Ref. 3; AAK28536)"
FT /evidence="ECO:0000305"
FT CONFLICT 176
FT /note="S -> G (in Ref. 3; AAK28536)"
FT /evidence="ECO:0000305"
FT CONFLICT 179..190
FT /note="Missing (in Ref. 2; AAH21420)"
FT /evidence="ECO:0000305"
FT CONFLICT 352
FT /note="M -> T (in Ref. 2; AAH21420)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 569 AA; 63375 MW; 120A0604B13675EC CRC64;
MASSCAVQVK LELGHRAQVR KKPTVEGFTH DWMVFVRGPE HSNIQHFVEK VVFHLHESFP
RPKRVCKDPP YKVEESGYAG FILPIEVYFK NKEEPKKVRF DYDLFLHLEG HPPVNHLRCE
KLTFNNPTED FRRKLLKAGG DPNRSIHTSS SSSSSSSSSS SSSSSSSSSS SSSSSSSSSS
SSSSSSSSSS TSFSKPHKLM KEHKEKPSKD SREHKSAFKE PSRDHNKSSK DSSKKPKENK
PLKEEKIVPK MAFKEPKPMS KEPKADSNLL TVTSGQQDKK APSKRPPASD SEELSAKKRK
KSSSEALFKS FSSAPPLILT CSADKKQIKD KSHVKMGKVK IESETSEKKK SMLPPFDDIV
DPNDSDVEEN MSSKSDSEQP SPASSSSSSS SSFTPSQTRQ QGPLRSIMKD LHSDDNEEES
DEAEDNDNDS EMERPVNRGG SRSRRVSLSD GSDSESSSAS SPLHHEPPPP LLKTNNNQIL
EVKSPIKQSK SDKQIKNGEC DKAYLDELVE LHRRLMTLRE RHILQQIVNL IEETGHFHIT
NTTFDFDLCS LDKTTVRKLQ SYLETSGTS
