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P42568 (AF9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:MLLT3
Synonyms:AF9, YEATS3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length568 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.10 Ref.11

Subunit structure

Component of the super elongation complex (SEC), at least composed of EAF1, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3). Interacts with BCOR. Interacts with ALKBH4 and CBX8. Ref.4 Ref.5 Ref.10 Ref.11 Ref.14

Subcellular location

Nucleus By similarity.

Involvement in disease

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.

Sequence similarities

Contains 1 YEATS domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

AFF4Q9UHB74EBI-716132,EBI-395282

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 568568Protein AF-9
PRO_0000215921

Regions

Domain8 – 112105YEATS
Motif295 – 3006Nuclear localization signal Potential
Compositional bias149 – 19446Poly-Ser
Compositional bias383 – 3919Poly-Ser
Compositional bias466 – 4694Poly-Pro

Sites

Site3751KMT2A/MLL1 fusion point (in acute myeloid leukemia patient CO)
Site4811KMT2A/MLL1 fusion point (in acute myeloid leukemia patient F1)

Amino acid modifications

Modified residue2881Phosphoserine Ref.7
Modified residue2941Phosphoserine Ref.6 Ref.7
Modified residue4121Phosphoserine Ref.9
Modified residue4191Phosphoserine Ref.9
Modified residue4291Phosphoserine Ref.9
Modified residue4831Phosphoserine Ref.6 Ref.7 Ref.12

Experimental info

Sequence conflict61A → S in AAA58361. Ref.1

Secondary structure

............. 568
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P42568 [UniParc].

Last modified November 25, 2008. Version 2.
Checksum: 0A020B7FB34132F9

FASTA56863,351
        10         20         30         40         50         60 
MASSCAVQVK LELGHRAQVR KKPTVEGFTH DWMVFVRGPE HSNIQHFVEK VVFHLHESFP 

        70         80         90        100        110        120 
RPKRVCKDPP YKVEESGYAG FILPIEVYFK NKEEPRKVRF DYDLFLHLEG HPPVNHLRCE 

       130        140        150        160        170        180 
KLTFNNPTED FRRKLLKAGG DPNRSIHTSS SSSSSSSSSS SSSSSSSSSS SSSSSSSSSS 

       190        200        210        220        230        240 
SSSSSSSSSS TSFSKPHKLM KEHKEKPSKD SREHKSAFKE PSRDHNKSSK ESSKKPKENK 

       250        260        270        280        290        300 
PLKEEKIVPK MAFKEPKPMS KEPKPDSNLL TITSGQDKKA PSKRPPISDS EELSAKKRKK 

       310        320        330        340        350        360 
SSSEALFKSF SSAPPLILTC SADKKQIKDK SHVKMGKVKI ESETSEKKKS TLPPFDDIVD 

       370        380        390        400        410        420 
PNDSDVEENI SSKSDSEQPS PASSSSSSSS SFTPSQTRQQ GPLRSIMKDL HSDDNEEESD 

       430        440        450        460        470        480 
EVEDNDNDSE MERPVNRGGS RSRRVSLSDG SDSESSSASS PLHHEPPPPL LKTNNNQILE 

       490        500        510        520        530        540 
VKSPIKQSKS DKQIKNGECD KAYLDELVEL HRRLMTLRER HILQQIVNLI EETGHFHITN 

       550        560 
TTFDFDLCSL DKTTVRKLQS YLETSGTS 

« Hide

References

« Hide 'large scale' references
[1]"Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs."
Nakamura T., Alder H., Gu Y., Prasad R., Canaani O., Kamada N., Gale R.P., Lange B., Crist W.M., Nowell P.C., Croce C.M., Canaani E.
Proc. Natl. Acad. Sci. U.S.A. 90:4631-4635(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"BCoR, a novel corepressor involved in BCL-6 repression."
Huynh K.D., Fischle W., Verdin E., Bardwell V.J.
Genes Dev. 14:1810-1823(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BCOR.
[5]"The ENL moiety of the childhood leukemia-associated MLL-ENL oncoprotein recruits human Polycomb 3."
Garcia-Cuellar M.P., Zilles O., Schreiner S.A., Birke M., Winkler T.H., Slany R.K.
Oncogene 20:411-419(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CBX8.
[6]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-294 AND SER-483, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-288; SER-294 AND SER-483, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412; SER-419 AND SER-429, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[10]"HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription."
He N., Liu M., Hsu J., Xue Y., Chou S., Burlingame A., Krogan N.J., Alber T., Zhou Q.
Mol. Cell 38:428-438(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN THE SEC COMPLEX.
[11]"AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia."
Lin C., Smith E.R., Takahashi H., Lai K.C., Martin-Brown S., Florens L., Washburn M.P., Conaway J.W., Conaway R.C., Shilatifard A.
Mol. Cell 37:429-437(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN THE SEC COMPLEX.
[12]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-483, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"The super elongation complex (SEC) family in transcriptional control."
Luo Z., Lin C., Shilatifard A.
Nat. Rev. Mol. Cell Biol. 13:543-547(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON THE SUPER ELONGATION COMPLEX.
[14]"Human ALKBH4 interacts with proteins associated with transcription."
Bjornstad L.G., Meza T.J., Otterlei M., Olafsrud S.M., Meza-Zepeda L.A., Falnes P.O.
PLoS ONE 7:E49045-E49045(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ALKBH4.
[15]"Leukemia fusion target AF9 is an intrinsically disordered transcriptional regulator that recruits multiple partners via coupled folding and binding."
Leach B.I., Kuntimaddi A., Schmidt C.R., Cierpicki T., Johnson S.A., Bushweller J.H.
Structure 21:176-183(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 490-568 IN COMPLEX WITH AFF1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L13744 mRNA. Translation: AAA58361.1.
AL512635, AL354879, AL513498 Genomic DNA. Translation: CAH70705.1.
AL354879, AL512635, AL513498 Genomic DNA. Translation: CAI14771.1.
CH471071 Genomic DNA. Translation: EAW58631.1.
CH471071 Genomic DNA. Translation: EAW58632.1.
PIRI39411.
RefSeqNP_004520.2. NM_004529.3.
UniGeneHs.317248.
Hs.591085.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2LM0NMR-A490-568[»]
ProteinModelPortalP42568.
SMRP42568. Positions 29-136, 460-568.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110446. 36 interactions.
DIPDIP-56409N.
IntActP42568. 18 interactions.
MINTMINT-1389464.
STRING9606.ENSP00000369695.

PTM databases

PhosphoSiteP42568.

Polymorphism databases

DMDM215273971.

Proteomic databases

PaxDbP42568.
PRIDEP42568.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000380338; ENSP00000369695; ENSG00000171843.
GeneID4300.
KEGGhsa:4300.
UCSCuc003zoe.2. human.

Organism-specific databases

CTD4300.
GeneCardsGC09M020334.
HGNCHGNC:7136. MLLT3.
HPAHPA001824.
MIM159558. gene.
neXtProtNX_P42568.
PharmGKBPA30852.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5033.
HOVERGENHBG004191.
InParanoidP42568.
KOK15187.
OMAPNRSVHT.
OrthoDBEOG71G9V5.
PhylomeDBP42568.
TreeFamTF314586.

Gene expression databases

ArrayExpressP42568.
BgeeP42568.
CleanExHS_MLLT3.
GenevestigatorP42568.

Family and domain databases

InterProIPR005033. YEATS.
[Graphical view]
PANTHERPTHR23195. PTHR23195. 1 hit.
PfamPF03366. YEATS. 1 hit.
[Graphical view]
PROSITEPS51037. YEATS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMLLT3.
GenomeRNAi4300.
NextBio16927.
PROP42568.
SOURCESearch...

Entry information

Entry nameAF9_HUMAN
AccessionPrimary (citable) accession number: P42568
Secondary accession number(s): B1AMQ2, D3DRJ8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 25, 2008
Last modified: March 19, 2014
This is version 113 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM