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Protein

AF4/FMR2 family member 4

Gene

AFF4

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

Functioni

Key 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. In the SEC complex, AFF4 acts as a central scaffold that recruits other factors through direct interactions with ELL proteins (ELL, ELL2 or ELL3) and the P-TEFb complex. In case of infection by HIV-1 virus, the SEC complex is recruited by the viral Tat protein to stimulate viral gene expression.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei350 – 351Breakpoint for insertion to form KMT2A/MLL1-AFF4 fusion protein2

GO - Molecular functioni

  • DNA-binding transcription factor activity Source: ProtInc

GO - Biological processi

Keywordsi

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
SIGNORiQ9UHB7

Names & Taxonomyi

Protein namesi
Recommended name:
AF4/FMR2 family member 4
Alternative name(s):
ALL1-fused gene from chromosome 5q31 protein
Short name:
Protein AF-5q31
Major CDK9 elongation factor-associated protein
Gene namesi
Name:AFF4
Synonyms:AF5Q31, MCEF
ORF Names:HSPC092
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000072364.12
HGNCiHGNC:17869 AFF4
MIMi604417 gene
neXtProtiNX_Q9UHB7

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

Nucleus

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving AFF4 is found in acute lymphoblastic leukemia (ALL). Insertion ins(5;11)(q31;q13q23) that forms a KMT2A/MLL1-AFF4 fusion protein.
CHOPS syndrome (CHOPS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by cognitive impairment, coarse facies, heart defects, obesity, pulmonary involvement, short stature, and skeletal dysplasia.
See also OMIM:616368
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073790254T → A in CHOPS. 1 PublicationCorresponds to variant dbSNP:rs786205233EnsemblClinVar.1
Natural variantiVAR_073791254T → S in CHOPS. 1 PublicationCorresponds to variant dbSNP:rs786205679EnsemblClinVar.1
Natural variantiVAR_073792258R → W in CHOPS. 1 PublicationCorresponds to variant dbSNP:rs786205680EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Dwarfism, Obesity, Proto-oncogene

Organism-specific databases

DisGeNETi27125
MalaCardsiAFF4
MIMi616368 phenotype
OpenTargetsiENSG00000072364
PharmGKBiPA142672641

Polymorphism and mutation databases

BioMutaiAFF4
DMDMi74720814

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002393931 – 1163AF4/FMR2 family member 4Add BLAST1163

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei120PhosphoserineCombined sources1
Modified residuei212PhosphoserineCombined sources1
Modified residuei387PhosphoserineCombined sources1
Modified residuei388PhosphoserineCombined sources1
Modified residuei389PhosphoserineCombined sources1
Modified residuei392PhosphoserineCombined sources1
Modified residuei487PhosphoserineCombined sources1
Modified residuei490PhosphoserineBy similarity1
Modified residuei491PhosphoserineBy similarity1
Modified residuei549PhosphoserineCombined sources1
Cross-linki583Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei671PhosphoserineCombined sources1
Modified residuei674PhosphothreonineCombined sources1
Modified residuei680PhosphoserineCombined sources1
Modified residuei694PhosphoserineCombined sources1
Modified residuei703PhosphoserineCombined sources1
Modified residuei706PhosphoserineCombined sources1
Modified residuei712PhosphotyrosineCombined sources1
Modified residuei814PhosphoserineCombined sources1
Modified residuei822N6-acetyllysineBy similarity1
Modified residuei836PhosphoserineCombined sources1
Modified residuei1043PhosphoserineCombined sources1
Modified residuei1055PhosphoserineCombined sources1
Modified residuei1058PhosphoserineCombined sources1
Modified residuei1062PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9UHB7
PaxDbiQ9UHB7
PeptideAtlasiQ9UHB7
PRIDEiQ9UHB7
ProteomicsDBi84300
84301 [Q9UHB7-2]
84302 [Q9UHB7-3]

PTM databases

iPTMnetiQ9UHB7
PhosphoSitePlusiQ9UHB7

Expressioni

Tissue specificityi

Ubiquitously expressed. Strongly expressed in heart, placenta, skeletal muscle, pancreas and to a lower extent in brain.2 Publications

Developmental stagei

Expressed in fetal heart, lung, brain and to a lower extent liver.1 Publication

Gene expression databases

BgeeiENSG00000072364 Expressed in 210 organ(s), highest expression level in metanephros
CleanExiHS_AFF4
ExpressionAtlasiQ9UHB7 baseline and differential
GenevisibleiQ9UHB7 HS

Organism-specific databases

HPAiHPA023690
HPA029634

Interactioni

Subunit structurei

Interacts with ELL3; the interaction is direct (By similarity). Interacts with ELL2; the interaction is direct and leads to stabilize ELL2 and prevent ELL2 ubiquitination and degradation. 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). Interacts with ELL.By similarity5 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi118016, 48 interactors
CORUMiQ9UHB7
ELMiQ9UHB7
IntActiQ9UHB7, 29 interactors
MINTiQ9UHB7
STRINGi9606.ENSP00000265343

Structurei

Secondary structure

11163
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9UHB7
SMRiQ9UHB7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi102 – 461Ser-richAdd BLAST360
Compositional biasi836 – 899Ser-richAdd BLAST64

Sequence similaritiesi

Belongs to the AF4 family.Curated

Phylogenomic databases

eggNOGiENOG410IGJB Eukaryota
ENOG410XRXU LUCA
GeneTreeiENSGT00530000063217
HOVERGENiHBG004189
InParanoidiQ9UHB7
KOiK15185
OMAiLIKYTMK
OrthoDBiEOG091G0KKW
PhylomeDBiQ9UHB7
TreeFamiTF326216

Family and domain databases

InterProiView protein in InterPro
IPR007797 TF_AF4/FMR2
PANTHERiPTHR10528 PTHR10528, 1 hit
PfamiView protein in Pfam
PF05110 AF-4, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9UHB7-1) [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
MNREDRNVLR MKERERRNQE IQQGEDAFPP SSPLFAEPYK VTSKEDKLSS
60 70 80 90 100
RIQSMLGNYD EMKDFIGDRS IPKLVAIPKP TVPPSADEKS NPNFFEQRHG
110 120 130 140 150
GSHQSSKWTP VGPAPSTSQS QKRSSGLQSG HSSQRTSAGS SSGTNSSGQR
160 170 180 190 200
HDRESYNNSG SSSRKKGQHG SEHSKSRSSS PGKPQAVSSL NSSHSRSHGN
210 220 230 240 250
DHHSKEHQRS KSPRDPDANW DSPSRVPFSS GQHSTQSFPP SLMSKSNSML
260 270 280 290 300
QKPTAYVRPM DGQESMEPKL SSEHYSSQSH GNSMTELKPS SKAHLTKLKI
310 320 330 340 350
PSQPLDASAS GDVSCVDEIL KEMTHSWPPP LTAIHTPCKT EPSKFPFPTK
360 370 380 390 400
ESQQSNFGTG EQKRYNPSKT SNGHQSKSML KDDLKLSSSE DSDGEQDCDK
410 420 430 440 450
TMPRSTPGSN SEPSHHNSEG ADNSRDDSSS HSGSESSSGS DSESESSSSD
460 470 480 490 500
SEANEPSQSA SPEPEPPPTN KWQLDNWLNK VNPHKVSPAS SVDSNIPSSQ
510 520 530 540 550
GYKKEGREQG TGNSYTDTSG PKETSSATPG RDSKTIQKGS ESGRGRQKSP
560 570 580 590 600
AQSDSTTQRR TVGKKQPKKA EKAAAEEPRG GLKIESETPV DLASSMPSSR
610 620 630 640 650
HKAATKGSRK PNIKKESKSS PRPTAEKKKY KSTSKSSQKS REIIETDTSS
660 670 680 690 700
SDSDESESLP PSSQTPKYPE SNRTPVKPSS VEEEDSFFRQ RMFSPMEEKE
710 720 730 740 750
LLSPLSEPDD RYPLIVKIDL NLLTRIPGKP YKETEPPKGE KKNVPEKHTR
760 770 780 790 800
EAQKQASEKV SNKGKRKHKN EDDNRASESK KPKTEDKNSA GHKPSSNRES
810 820 830 840 850
SKQSAAKEKD LLPSPAGPVP SKDPKTEHGS RKRTISQSSS LKSSSNSNKE
860 870 880 890 900
TSGSSKNSSS TSKQKKTEGK TSSSSKEVKE KAPSSSSNCP PSAPTLDSSK
910 920 930 940 950
PRRTKLVFDD RNYSADHYLQ EAKKLKHNAD ALSDRFEKAV YYLDAVVSFI
960 970 980 990 1000
ECGNALEKNA QESKSPFPMY SETVDLIKYT MKLKNYLAPD ATAADKRLTV
1010 1020 1030 1040 1050
LCLRCESLLY LRLFKLKKEN ALKYSKTLTE HLKNSYNNSQ APSPGLGSKA
1060 1070 1080 1090 1100
VGMPSPVSPK LSPGNSGNYS SGASSASASG SSVTIPQKIH QMAASYVQVT
1110 1120 1130 1140 1150
SNFLYATEIW DQAEQLSKEQ KEFFAELDKV MGPLIFNASI MTDLVRYTRQ
1160
GLHWLRQDAK LIS
Length:1,163
Mass (Da):127,459
Last modified:May 1, 2000 - v1
Checksum:i474E1906B8832AC1
GO
Isoform 2 (identifier: Q9UHB7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     880-900: EKAPSSSSNCPPSAPTLDSSK → VKCWGPGAFENHSTCHVTFPG
     901-1163: Missing.

Show »
Length:900
Mass (Da):98,205
Checksum:iA7C5BAE4A45086AE
GO
Isoform 3 (identifier: Q9UHB7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     351-353: ESQ → VSK
     354-1163: Missing.

Show »
Length:353
Mass (Da):38,823
Checksum:iF7811E19E60C9A92
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JCE0C9JCE0_HUMAN
AF4/FMR2 family member 4
AFF4
148Annotation score:
H7C319H7C319_HUMAN
AF4/FMR2 family member 4
AFF4
171Annotation score:

Sequence cautioni

The sequence AAI00288 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated
The sequence BAD92784 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti264E → G in AAM00184 (PubMed:12065898).Curated1
Sequence conflicti359T → I in AAM00184 (PubMed:12065898).Curated1
Sequence conflicti383D → G in AAM00184 (PubMed:12065898).Curated1
Sequence conflicti445E → G in AAM00184 (PubMed:12065898).Curated1
Sequence conflicti870K → R in AAF28915 (PubMed:11042152).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_053003136T → P. Corresponds to variant dbSNP:rs34527550Ensembl.1
Natural variantiVAR_073790254T → A in CHOPS. 1 PublicationCorresponds to variant dbSNP:rs786205233EnsemblClinVar.1
Natural variantiVAR_073791254T → S in CHOPS. 1 PublicationCorresponds to variant dbSNP:rs786205679EnsemblClinVar.1
Natural variantiVAR_073792258R → W in CHOPS. 1 PublicationCorresponds to variant dbSNP:rs786205680EnsemblClinVar.1
Natural variantiVAR_064693757S → T Found in a clear cell renal carcinoma case; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_019218351 – 353ESQ → VSK in isoform 3. 1 Publication3
Alternative sequenceiVSP_019219354 – 1163Missing in isoform 3. 1 PublicationAdd BLAST810
Alternative sequenceiVSP_019220880 – 900EKAPS…LDSSK → VKCWGPGAFENHSTCHVTFP G in isoform 2. 2 PublicationsAdd BLAST21
Alternative sequenceiVSP_019221901 – 1163Missing in isoform 2. 2 PublicationsAdd BLAST263

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF197927 mRNA Translation: AAF18981.1
AF213987 mRNA Translation: AAM00184.2
AB209547 mRNA Translation: BAD92784.1 Different initiation.
AC004500 Genomic DNA No translation available.
CH471062 Genomic DNA Translation: EAW62305.1
BC063007 mRNA Translation: AAH63007.1
BC100287 mRNA Translation: AAI00288.1 Sequence problems.
BC137226 mRNA Translation: AAI37227.1
AF161355 mRNA Translation: AAF28915.1
CCDSiCCDS4164.1 [Q9UHB7-1]
RefSeqiNP_055238.1, NM_014423.3 [Q9UHB7-1]
XP_005272020.1, XM_005271963.4 [Q9UHB7-1]
UniGeneiHs.519313
Hs.664840

Genome annotation databases

EnsembliENST00000265343; ENSP00000265343; ENSG00000072364 [Q9UHB7-1]
ENST00000378595; ENSP00000367858; ENSG00000072364 [Q9UHB7-2]
GeneIDi27125
KEGGihsa:27125
UCSCiuc003kyd.4 human [Q9UHB7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF197927 mRNA Translation: AAF18981.1
AF213987 mRNA Translation: AAM00184.2
AB209547 mRNA Translation: BAD92784.1 Different initiation.
AC004500 Genomic DNA No translation available.
CH471062 Genomic DNA Translation: EAW62305.1
BC063007 mRNA Translation: AAH63007.1
BC100287 mRNA Translation: AAI00288.1 Sequence problems.
BC137226 mRNA Translation: AAI37227.1
AF161355 mRNA Translation: AAF28915.1
CCDSiCCDS4164.1 [Q9UHB7-1]
RefSeqiNP_055238.1, NM_014423.3 [Q9UHB7-1]
XP_005272020.1, XM_005271963.4 [Q9UHB7-1]
UniGeneiHs.519313
Hs.664840

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4IMYX-ray2.94G/H/I2-73[»]
4OGRX-ray3.00C/G/L2-73[»]
4OR5X-ray2.90E/J32-69[»]
5JW9X-ray2.00A301-351[»]
5L1ZX-ray5.90C32-67[»]
ProteinModelPortaliQ9UHB7
SMRiQ9UHB7
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118016, 48 interactors
CORUMiQ9UHB7
ELMiQ9UHB7
IntActiQ9UHB7, 29 interactors
MINTiQ9UHB7
STRINGi9606.ENSP00000265343

PTM databases

iPTMnetiQ9UHB7
PhosphoSitePlusiQ9UHB7

Polymorphism and mutation databases

BioMutaiAFF4
DMDMi74720814

Proteomic databases

EPDiQ9UHB7
PaxDbiQ9UHB7
PeptideAtlasiQ9UHB7
PRIDEiQ9UHB7
ProteomicsDBi84300
84301 [Q9UHB7-2]
84302 [Q9UHB7-3]

Protocols and materials databases

DNASUi27125
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265343; ENSP00000265343; ENSG00000072364 [Q9UHB7-1]
ENST00000378595; ENSP00000367858; ENSG00000072364 [Q9UHB7-2]
GeneIDi27125
KEGGihsa:27125
UCSCiuc003kyd.4 human [Q9UHB7-1]

Organism-specific databases

CTDi27125
DisGeNETi27125
EuPathDBiHostDB:ENSG00000072364.12
GeneCardsiAFF4
HGNCiHGNC:17869 AFF4
HPAiHPA023690
HPA029634
MalaCardsiAFF4
MIMi604417 gene
616368 phenotype
neXtProtiNX_Q9UHB7
OpenTargetsiENSG00000072364
PharmGKBiPA142672641
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGJB Eukaryota
ENOG410XRXU LUCA
GeneTreeiENSGT00530000063217
HOVERGENiHBG004189
InParanoidiQ9UHB7
KOiK15185
OMAiLIKYTMK
OrthoDBiEOG091G0KKW
PhylomeDBiQ9UHB7
TreeFamiTF326216

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
SIGNORiQ9UHB7

Miscellaneous databases

ChiTaRSiAFF4 human
GenomeRNAii27125
PROiPR:Q9UHB7
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000072364 Expressed in 210 organ(s), highest expression level in metanephros
CleanExiHS_AFF4
ExpressionAtlasiQ9UHB7 baseline and differential
GenevisibleiQ9UHB7 HS

Family and domain databases

InterProiView protein in InterPro
IPR007797 TF_AF4/FMR2
PANTHERiPTHR10528 PTHR10528, 1 hit
PfamiView protein in Pfam
PF05110 AF-4, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiAFF4_HUMAN
AccessioniPrimary (citable) accession number: Q9UHB7
Secondary accession number(s): B2RP19
, B7WPD2, Q498B2, Q59FB3, Q6P592, Q8TDR1, Q9P0E4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 13, 2006
Last sequence update: May 1, 2000
Last modified: October 10, 2018
This is version 148 of the entry and version 1 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, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
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