P42568 (AF9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	MLLT3
Synonyms:	AF9, YEATS3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	568 AA.
Sequence status	Complete.
Protein existence	Evidence 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 CBX8. Ref.4 Ref.5 Ref.10 Ref.11
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 MLL/HRX. The result is a rogue activator protein.
Sequence similarities	Contains 1 YEATS domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Chromosomal rearrangement
Disease	Proto-oncogene
Molecular function	Activator
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	anterior/posterior pattern specification Inferred from electronic annotation. Source: Compara negative regulation of canonical Wnt receptor signaling pathway Inferred from direct assay PubMed 19591803. Source: MGI positive regulation of Wnt receptor signaling pathway, planar cell polarity pathway Inferred from genetic interaction PubMed 19591803. Source: MGI regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW segment specification Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AFF4	Q9UHB7	4	EBI-716132,EBI-395282

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 568

568

Protein AF-9

PRO_0000215921

Regions

Domain

8 – 112

105

YEATS

Motif

295 – 300

6

Nuclear localization signal Potential

Compositional bias

149 – 194

46

Poly-Ser

Compositional bias

383 – 391

9

Poly-Ser

Compositional bias

466 – 469

4

Poly-Pro

Sites

Site

375

1

MLL fusion point (in acute myeloid leukemia patient CO)

Site

481

1

MLL fusion point (in acute myeloid leukemia patient F1)

Amino acid modifications

Modified residue

288

1

Phosphoserine Ref.7

Modified residue

294

1

Phosphoserine Ref.6 Ref.7

Modified residue

412

1

Phosphoserine Ref.9

Modified residue

419

1

Phosphoserine Ref.9

Modified residue

429

1

Phosphoserine Ref.9

Modified residue

483

1

Phosphoserine Ref.6 Ref.7 Ref.12

Experimental info

Sequence conflict

6

1

A → S in AAA58361. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

568

Helix Strand Turn

Details...

Helix

504 – 515

12

Helix

523 – 531

9

Beta strand

536 – 538

3

Beta strand

543 – 545

3

Turn

547 – 549

3

Helix

552 – 561

10

Sequences

	Sequence		Length	Mass (Da)
	P42568 [UniParc]. Last modified November 25, 2008. Version 2. Checksum: 0A020B7FB34132F9	FASTA	568	63,351
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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]	"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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI01015721.

PIR

I39411.

RefSeq

NP_004520.2. NM_004529.2.

UniGene

Hs.591085.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2LM0	NMR	-	A	490-568	[»]

ProteinModelPortal

P42568.

ModBase

Search...

Protein-protein interaction databases

IntAct

P42568. 17 interactions.

MINT

MINT-1389464.

STRING

9606.ENSP00000369695.

PTM databases

PhosphoSite

P42568.

Polymorphism databases

DMDM

215273971.

Proteomic databases

PaxDb

P42568.

PRIDE

P42568.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000380338; ENSP00000369695; ENSG00000171843.

GeneID

4300.

KEGG

hsa:4300.

UCSC

uc003zoe.2. human.

Organism-specific databases

CTD

4300.

GeneCards

GC09M020334.

HGNC

HGNC:7136. MLLT3.

HPA

HPA001824.

MIM

159558. gene.

neXtProt

NX_P42568.

PharmGKB

PA30852.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5033.

HOVERGEN

HBG004191.

InParanoid

P42568.

KO

K15187.

OrthoDB

EOG45756W.

PhylomeDB

P42568.

Gene expression databases

ArrayExpress

P42568.

Bgee

P42568.

CleanEx

HS_MLLT3.

Genevestigator

P42568.

GermOnline

ENSG00000171843. Homo sapiens.

Family and domain databases

InterPro

IPR005033. YEATS.
[Graphical view]

PANTHER

PTHR23195. PTHR23195. 1 hit.

Pfam

PF03366. YEATS. 1 hit.
[Graphical view]

PROSITE

PS51037. YEATS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

4300.

NextBio

16927.

SOURCE

Search...

Entry information

Entry name

AF9_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 106 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.