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Protein

Protein AF-9

Gene

MLLT3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Chromatin reader component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA (PubMed:20159561, PubMed:20471948, PubMed:25417107, PubMed:27105114, PubMed:27545619). Specifically recognizes and binds acylated histone H3, with a marked preference for histone H3 that is crotonylated (PubMed:25417107, PubMed:27105114, PubMed:27545619). Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:25417107, PubMed:27105114, PubMed:27545619). Recognizes and binds histone H3 crotonylated at 'Lys-9' (H3K9cr), and with slightly lower affinity histone H3 crotonylated at 'Lys-18' (H3K18cr) (PubMed:27105114). Also recognizes and binds histone H3 acetylated at 'Lys-9' (H3K9ac), but with lower affinity than crotonylated histone H3 (PubMed:25417107, PubMed:27105114). In the SEC complex, MLLT3 is required to recruit the complex to crotonylated histones (PubMed:27105114, PubMed:27545619).5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei58Histone H3K9crCombined sources1 Publication1
Binding sitei103Histone H3K9crCombined sources1 Publication1
Sitei375KMT2A/MLL1 fusion point (in acute myeloid leukemia patient CO)1 Publication1
Sitei481KMT2A/MLL1 fusion point (in acute myeloid leukemia patient F1)1 Publication1

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • histone binding Source: UniProtKB
  • lysine-acetylated histone binding Source: UniProtKB
  • modification-dependent protein binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionActivator
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-112382. Formation of RNA Pol II elongation complex.
R-HSA-674695. RNA Polymerase II Pre-transcription Events.
R-HSA-75955. RNA Polymerase II Transcription Elongation.
SIGNORiP42568.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein AF-9
Alternative name(s):
ALL1-fused gene from chromosome 9 protein
Myeloid/lymphoid or mixed-lineage leukemia translocated to chromosome 3 protein
YEATS domain-containing protein 3
Gene namesi
Name:MLLT3Imported
Synonyms:AF9, YEATS3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000171843.15.
HGNCiHGNC:7136. MLLT3.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving MLLT3 is associated with acute leukemias. Translocation t(9;11)(p22;q23) with KMT2A/MLL1. The result is a rogue activator protein.2 Publications
A chromosomal aberration involving MLLT3 was observed in a patient with neuromotor development delay, cerebellar ataxia and epilepsy. Translocation t(4;9)(q35;p22).1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi28F → A: Decreased binding to crotonylated histone H3. Decreased binding to acetylated histone H3. 2 Publications1
Mutagenesisi56H → A: Decreased binding to crotonylated histone H3. Decreased binding to acetylated histone H3. 2 Publications1
Mutagenesisi58S → A: Decreased binding to crotonylated histone H3. Decreased binding to acetylated histone H3. 2 Publications1
Mutagenesisi59F → A: Strongly decreased binding to crotonylated histone H3. Decreased binding to acetylated histone H3. 3 Publications1
Mutagenesisi77G → A: Decreased binding to crotonylated histone H3. Decreased binding to acetylated histone H3. 2 Publications1
Mutagenesisi78Y → A: Strongly decreased binding to crotonylated histone H3. Decreased binding to acetylated histone H3. 3 Publications1
Mutagenesisi81F → A: Decreased binding to acetylated histone H3. 1 Publication1
Mutagenesisi103D → A: Decreased binding to acetylated histone H3. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi4300.
MalaCardsiMLLT3.
OpenTargetsiENSG00000171843.
Orphaneti402017. 'Acute myeloid leukemia with t(9;11)(p22;q23)'.
PharmGKBiPA30852.

Polymorphism and mutation databases

DMDMi215273971.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002159211 – 568Protein AF-9Add BLAST568

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei288PhosphoserineCombined sources1
Modified residuei294PhosphoserineCombined sources1
Cross-linki339Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei412PhosphoserineCombined sources1
Modified residuei419PhosphoserineCombined sources1
Modified residuei483PhosphoserineCombined sources1

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP42568.
PaxDbiP42568.
PeptideAtlasiP42568.
PRIDEiP42568.

PTM databases

iPTMnetiP42568.
PhosphoSitePlusiP42568.

Expressioni

Gene expression databases

BgeeiENSG00000171843.
CleanExiHS_MLLT3.
ExpressionAtlasiP42568. baseline and differential.
GenevisibleiP42568. HS.

Organism-specific databases

HPAiHPA001824.

Interactioni

Subunit structurei

Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3) (PubMed:20159561, PubMed:20471948, PubMed:22195968, PubMed:23260655, PubMed:25417107). Interacts with BCOR (PubMed:10898795). Interacts with CBX8 (PubMed:11313972). Interacts with ALKBH4 (PubMed:23145062).8 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • histone binding Source: UniProtKB
  • lysine-acetylated histone binding Source: UniProtKB
  • modification-dependent protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110446. 61 interactors.
CORUMiP42568.
DIPiDIP-56409N.
IntActiP42568. 35 interactors.
MINTiMINT-1389464.
STRINGi9606.ENSP00000369695.

Structurei

Secondary structure

1568
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi3 – 19Combined sources17
Beta strandi30 – 37Combined sources8
Helixi39 – 41Combined sources3
Helixi44 – 46Combined sources3
Beta strandi48 – 54Combined sources7
Beta strandi59 – 61Combined sources3
Beta strandi63 – 90Combined sources28
Beta strandi92 – 94Combined sources3
Beta strandi97 – 104Combined sources8
Beta strandi114 – 126Combined sources13
Helixi129 – 137Combined sources9
Helixi504 – 515Combined sources12
Helixi523 – 531Combined sources9
Beta strandi536 – 538Combined sources3
Beta strandi543 – 545Combined sources3
Turni547 – 549Combined sources3
Helixi552 – 561Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LM0NMR-A490-568[»]
2MV7NMR-A500-568[»]
2N4QNMR-B500-568[»]
2NDFNMR-A1-138[»]
2NDGNMR-A1-138[»]
4TMPX-ray2.30A/C1-138[»]
5HJBX-ray2.70A1-138[»]
5HJDX-ray2.81A/C/E/G/K/N/Q/T1-138[»]
DisProtiDP01070.
ProteinModelPortaliP42568.
SMRiP42568.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini8 – 112YEATSPROSITE-ProRule annotationAdd BLAST105

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni78 – 80Histone H3K9cr bindingCombined sources1 Publication3
Regioni106 – 108Histone H3K9cr bindingCombined sources1 Publication3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi295 – 300Nuclear localization signalSequence analysis6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi149 – 194Poly-SerAdd BLAST46
Compositional biasi383 – 391Poly-Ser9
Compositional biasi466 – 469Poly-Pro4

Domaini

The YEATS domain specifically recognizes and binds acylated histones, with a marked preference histones that are crotonylated (PubMed:27105114, PubMed:27545619). Also binds histone H3 acetylated at 'Lys-9' (H3K9ac), but with lower affinity (PubMed:25417107, PubMed:27105114).3 Publications

Phylogenomic databases

eggNOGiKOG3149. Eukaryota.
COG5033. LUCA.
GeneTreeiENSGT00440000039936.
HOVERGENiHBG004191.
InParanoidiP42568.
KOiK15187.
OMAiMSKEPKS.
OrthoDBiEOG091G06LN.
PhylomeDBiP42568.
TreeFamiTF314586.

Family and domain databases

InterProiView protein in InterPro
IPR005033. YEATS.
PANTHERiPTHR23195. PTHR23195. 1 hit.
PfamiView protein in Pfam
PF03366. YEATS. 1 hit.
PROSITEiView protein in PROSITE
PS51037. YEATS. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P42568-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MASSCAVQVK LELGHRAQVR KKPTVEGFTH DWMVFVRGPE HSNIQHFVEK
60 70 80 90 100
VVFHLHESFP RPKRVCKDPP YKVEESGYAG FILPIEVYFK NKEEPRKVRF
110 120 130 140 150
DYDLFLHLEG HPPVNHLRCE KLTFNNPTED FRRKLLKAGG DPNRSIHTSS
160 170 180 190 200
SSSSSSSSSS SSSSSSSSSS SSSSSSSSSS SSSSSSSSSS TSFSKPHKLM
210 220 230 240 250
KEHKEKPSKD SREHKSAFKE PSRDHNKSSK ESSKKPKENK PLKEEKIVPK
260 270 280 290 300
MAFKEPKPMS KEPKPDSNLL TITSGQDKKA PSKRPPISDS EELSAKKRKK
310 320 330 340 350
SSSEALFKSF SSAPPLILTC SADKKQIKDK SHVKMGKVKI ESETSEKKKS
360 370 380 390 400
TLPPFDDIVD PNDSDVEENI SSKSDSEQPS PASSSSSSSS SFTPSQTRQQ
410 420 430 440 450
GPLRSIMKDL HSDDNEEESD EVEDNDNDSE MERPVNRGGS RSRRVSLSDG
460 470 480 490 500
SDSESSSASS PLHHEPPPPL LKTNNNQILE VKSPIKQSKS DKQIKNGECD
510 520 530 540 550
KAYLDELVEL HRRLMTLRER HILQQIVNLI EETGHFHITN TTFDFDLCSL
560
DKTTVRKLQS YLETSGTS
Length:568
Mass (Da):63,351
Last modified:November 25, 2008 - v2
Checksum:i0A020B7FB34132F9
GO
Isoform 2 (identifier: P42568-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MASS → M

Note: No experimental confirmation available.
Show »
Length:565
Mass (Da):63,106
Checksum:iE8D74987AC7356CC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6A → S in AAA58361 (PubMed:8506309).Curated1
Sequence conflicti6A → S in BAG35760 (PubMed:14702039).Curated1
Sequence conflicti173S → G in AAH36089 (PubMed:15489334).Curated1
Sequence conflicti419S → P in BAG35760 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0549241 – 4MASS → M in isoform 2. 1 Publication4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L13744 mRNA. Translation: AAA58361.1.
AK301474 mRNA. Translation: BAH13491.1.
AK312914 mRNA. Translation: BAG35760.1.
AL512635, AL354879, AL513498 Genomic DNA. Translation: CAH70705.1.
AL354879, AL512635, AL513498 Genomic DNA. Translation: CAI14771.1.
AL163193 Genomic DNA. No translation available.
AL627410 Genomic DNA. No translation available.
CH471071 Genomic DNA. Translation: EAW58631.1.
CH471071 Genomic DNA. Translation: EAW58632.1.
BC036089 mRNA. Translation: AAH36089.1.
CCDSiCCDS6494.1. [P42568-1]
CCDS69579.1. [P42568-2]
PIRiI39411.
RefSeqiNP_001273620.1. NM_001286691.1. [P42568-2]
NP_004520.2. NM_004529.3. [P42568-1]
UniGeneiHs.317248.
Hs.591085.

Genome annotation databases

EnsembliENST00000380338; ENSP00000369695; ENSG00000171843. [P42568-1]
ENST00000630269; ENSP00000485996; ENSG00000171843. [P42568-2]
GeneIDi4300.
KEGGihsa:4300.
UCSCiuc003zoe.3. human. [P42568-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement

Similar proteinsi

Entry informationi

Entry nameiAF9_HUMAN
AccessioniPrimary (citable) accession number: P42568
Secondary accession number(s): B1AMQ2
, B2R7B3, B7Z755, D3DRJ8, Q8IVB0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 25, 2008
Last modified: October 25, 2017
This is version 151 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references