Q9UHB7 (AFF4_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 80.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | 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 names |
| ||||||
| Organism | Homo sapiens (Human) | ||||||
| Taxonomic identifier | 9606 [NCBI] | ||||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1163 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | May play a role in transcriptional regulation By similarity. |
| Subunit structure | Component of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor b (P-TEFb). |
| Subcellular location | |
| Tissue specificity | Ubiquitously expressed. Strongly expressed in heart, placenta, skeletal muscle, pancreas and to a lower extent in brain. Ref.1 Ref.2 |
| Developmental stage | Expressed in fetal heart, lung, brain and to a lower extent liver. Ref.1 |
| Post-translational modification | Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 |
| Involvement in disease | Note=A chromosomal aberration involving AFF4 is found in acute lymphoblastic leukemia (ALL). Insertion ins(5;11)(q31;q13q23) that forms a MLL-AFF4 fusion protein. |
| Sequence similarities | Belongs to the AF4 family. |
| Sequence caution | The sequence AAI00288.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence. The sequence BAD92784.1 differs from that shown. Reason: Erroneous initiation. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Transcription Transcription regulation |
| Cellular component | Nucleus |
| Coding sequence diversity | Alternative splicing Chromosomal rearrangement Polymorphism |
| Disease | Proto-oncogene |
| PTM | Acetylation Phosphoprotein |
| Technical term | Complete proteome Direct protein sequencing Reference proteome |
| Gene Ontology (GO) | |
| Biological process | transcription from RNA polymerase II promoter Traceable author statement. Source: ProtInc |
| Cellular component | mitochondrion Inferred from direct assay. Source: HPA nucleolusInferred from direct assay. Source: HPA |
| Molecular function | protein binding Inferred from physical interaction. Source: IntAct sequence-specific DNA binding transcription factor activityTraceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| CCNT1 | O60563 | 5 | EBI-395282,EBI-2479671 | |
| MLLT1 | Q03111 | 8 | EBI-395282,EBI-1384215 | |
| MLLT3 | P42568 | 4 | EBI-395282,EBI-716132 |
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q9UHB7-1) 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. | ||||||
| Isoform 2 (identifier: Q9UHB7-2) The sequence of this isoform differs from the canonical sequence as follows: 880-900: EKAPSSSSNCPPSAPTLDSSK → VKCWGPGAFENHSTCHVTFPG 901-1163: Missing. | ||||||
| Isoform 3 (identifier: Q9UHB7-3) The sequence of this isoform differs from the canonical sequence as follows: 351-353: ESQ → VSK 354-1163: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1163 | 1163 | AF4/FMR2 family member 4 | PRO_0000239393 | |||||
Regions | |||||||||
| Compositional bias | 102 – 461 | 360 | Ser-rich | ||||||
| Compositional bias | 836 – 899 | 64 | Ser-rich | ||||||
Sites | |||||||||
| Site | 350 – 351 | 2 | Breakpoint for insertion to form MLL-AFF4 fusion protein | ||||||
Amino acid modifications | |||||||||
| Modified residue | 31 | 1 | Phosphoserine Ref.14 | ||||||
| Modified residue | 32 | 1 | Phosphoserine Ref.11 Ref.14 | ||||||
| Modified residue | 79 | 1 | N6-acetyllysine Ref.16 | ||||||
| Modified residue | 124 | 1 | Phosphoserine Ref.11 | ||||||
| Modified residue | 178 | 1 | Phosphoserine Ref.14 | ||||||
| Modified residue | 210 | 1 | Phosphoserine Ref.14 | ||||||
| Modified residue | 212 | 1 | Phosphoserine Ref.11 | ||||||
| Modified residue | 222 | 1 | Phosphoserine Ref.11 | ||||||
| Modified residue | 387 | 1 | Phosphoserine Ref.8 Ref.12 | ||||||
| Modified residue | 388 | 1 | Phosphoserine Ref.8 Ref.12 | ||||||
| Modified residue | 389 | 1 | Phosphoserine Ref.8 Ref.12 | ||||||
| Modified residue | 392 | 1 | Phosphoserine Ref.8 Ref.12 | ||||||
| Modified residue | 487 | 1 | Phosphoserine Ref.11 Ref.13 | ||||||
| Modified residue | 491 | 1 | Phosphoserine Ref.13 | ||||||
| Modified residue | 499 | 1 | Phosphoserine Ref.9 | ||||||
| Modified residue | 514 | 1 | Phosphoserine Ref.11 | ||||||
| Modified residue | 528 | 1 | Phosphothreonine Ref.11 | ||||||
| Modified residue | 549 | 1 | Phosphoserine Ref.8 Ref.11 Ref.14 | ||||||
| Modified residue | 599 | 1 | Phosphoserine Ref.11 | ||||||
| Modified residue | 617 | 1 | Phosphoserine Ref.14 | ||||||
| Modified residue | 668 | 1 | Phosphotyrosine Ref.14 | ||||||
| Modified residue | 671 | 1 | Phosphoserine Ref.14 | ||||||
| Modified residue | 674 | 1 | Phosphothreonine Ref.10 | ||||||
| Modified residue | 694 | 1 | Phosphoserine Ref.11 Ref.12 Ref.14 | ||||||
| Modified residue | 703 | 1 | Phosphoserine Ref.8 Ref.11 Ref.12 Ref.13 Ref.14 | ||||||
| Modified residue | 706 | 1 | Phosphoserine Ref.8 Ref.11 Ref.12 Ref.13 Ref.14 | ||||||
| Modified residue | 712 | 1 | Phosphotyrosine Ref.12 | ||||||
| Modified residue | 814 | 1 | Phosphoserine Ref.11 Ref.14 | ||||||
| Modified residue | 836 | 1 | Phosphoserine Ref.11 Ref.14 | ||||||
| Modified residue | 1043 | 1 | Phosphoserine Ref.11 Ref.12 Ref.13 Ref.14 | ||||||
| Modified residue | 1055 | 1 | Phosphoserine Ref.11 Ref.12 Ref.13 Ref.14 | ||||||
| Modified residue | 1058 | 1 | Phosphoserine Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 | ||||||
| Modified residue | 1062 | 1 | Phosphoserine Ref.12 Ref.13 | ||||||
Natural variations | |||||||||
| Alternative sequence | 351 – 353 | 3 | ESQ → VSK in isoform 3. | VSP_019218 | |||||
| Alternative sequence | 354 – 1163 | 810 | Missing in isoform 3. | VSP_019219 | |||||
| Alternative sequence | 880 – 900 | 21 | EKAPS…LDSSK → VKCWGPGAFENHSTCHVTFP G in isoform 2. | VSP_019220 | |||||
| Alternative sequence | 901 – 1163 | 263 | Missing in isoform 2. | VSP_019221 | |||||
| Natural variant | 136 | 1 | T → P. Corresponds to variant rs34527550 [ dbSNP | Ensembl ]. | VAR_053003 | |||||
| Natural variant | 757 | 1 | S → T Found in a clear cell renal carcinoma case; somatic mutation. Ref.18 | VAR_064693 | |||||
Experimental info | |||||||||
| Sequence conflict | 264 | 1 | E → G in AAM00184. Ref.2 | ||||||
| Sequence conflict | 359 | 1 | T → I in AAM00184. Ref.2 | ||||||
| Sequence conflict | 383 | 1 | D → G in AAM00184. Ref.2 | ||||||
| Sequence conflict | 445 | 1 | E → G in AAM00184. Ref.2 | ||||||
| Sequence conflict | 870 | 1 | K → R in AAF28915. Ref.7 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "AF5q31, a newly identified AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia with ins(5;11)(q31;q13q23)." Taki T., Kano H., Taniwaki M., Sako M., Yanagisawa M., Hayashi Y. Proc. Natl. Acad. Sci. U.S.A. 96:14535-14540(1999) [PubMed: 10588740] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHROMOSOMAL TRANSLOCATION WITH MLL, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Tissue: Placenta. |
| [2] | "MCEF, the newest member of the AF4 family of transcription factors involved in leukemia, is a positive transcription elongation factor-b-associated protein." Estable M.C., Naghavi M.H., Kato H., Xiao H., Qin J., Vahlne A., Roeder R.G. J. Biomed. Sci. 9:234-245(2002) [PubMed: 12065898] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 111-122, IDENTIFICATION IN PTEF-B COMPLEX, TISSUE SPECIFICITY, SUBCELLULAR LOCATION. Tissue: Fetal brain. |
| [3] | Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain. |
| [4] | "The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. Rubin E.M.Nature 431:268-274(2004) [PubMed: 15372022] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | 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. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-363 (ISOFORMS 1/2). Tissue: Blood, Brain and Skin. |
| [7] | "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. Chen Z.Genome Res. 10:1546-1560(2000) [PubMed: 11042152] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 788-1163 (ISOFORM 2). Tissue: Umbilical cord blood. |
| [8] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-387; SER-388; SER-389; SER-392; SER-549; SER-703 AND SER-706, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [9] | "ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-499, MASS SPECTROMETRY. Tissue: Embryonic kidney. |
| [10] | "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-674, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [11] | "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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32; SER-124; SER-212; SER-222; SER-487; SER-514; THR-528; SER-549; SER-599; SER-694; SER-703; SER-706; SER-814; SER-836; SER-1043; SER-1055 AND SER-1058, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [12] | "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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-387; SER-388; SER-389; SER-392; SER-694; SER-703; SER-706; TYR-712; SER-1043; SER-1055; SER-1058 AND SER-1062, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [13] | "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-487; SER-491; SER-703; SER-706; SER-1043; SER-1055; SER-1058 AND SER-1062, MASS SPECTROMETRY. Tissue: Embryonic kidney. |
| [14] | "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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31; SER-32; SER-178; SER-210; SER-549; SER-617; TYR-668; SER-671; SER-694; SER-703; SER-706; SER-814; SER-836; SER-1043; SER-1055 AND SER-1058, MASS SPECTROMETRY. |
| [15] | "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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1058, MASS SPECTROMETRY. Tissue: Leukemic T-cell. |
| [16] | "Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-79, MASS SPECTROMETRY. |
| [17] | "Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. |
| [18] | "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma." Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M. Futreal P.A.Nature 469:539-542(2011) [PubMed: 21248752] [Abstract] Cited for: VARIANT THR-757. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | 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. |
| IPI | IPI00004344. IPI00383219. IPI00658213. |
| RefSeq | NP_055238.1. NM_014423.3. |
| UniGene | Hs.519313. Hs.664840. |
3D structure databases | |
| ProteinModelPortal | Q9UHB7. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q9UHB7. 14 interactions. |
| MINT | MINT-1469196. |
| STRING | Q9UHB7. |
PTM databases | |
| PhosphoSite | Q9UHB7. |
Polymorphism databases | |
| DMDM | 74720814. |
Proteomic databases | |
| PeptideAtlas | Q9UHB7. |
| PRIDE | Q9UHB7. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000265343; ENSP00000265343; ENSG00000072364. ENST00000378595; ENSP00000367858; ENSG00000072364. |
| GeneID | 27125. |
| KEGG | hsa:27125. |
| UCSC | uc003kyd.1. human. uc003kye.1. human. uc003kyf.2. human. |
Organism-specific databases | |
| CTD | 27125. |
| GeneCards | GC05M132211. |
| H-InvDB | HIX0005164. |
| HGNC | HGNC:17869. AFF4. |
| HPA | HPA023690. |
| MIM | 604417. gene. |
| neXtProt | NX_Q9UHB7. |
| PharmGKB | PA142672641. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG18665. |
| GeneTree | ENSGT00530000063217. |
| HOGENOM | HBG715005. |
| HOVERGEN | HBG004189. |
| InParanoid | Q9UHB7. |
| OMA | TEHLKNS. |
| OrthoDB | EOG4CC40N. |
| PhylomeDB | Q9UHB7. |
Gene expression databases | |
| ArrayExpress | Q9UHB7. |
| Bgee | Q9UHB7. |
| CleanEx | HS_AFF4. |
| Genevestigator | Q9UHB7. |
| GermOnline | ENSG00000072364. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR007797. TF_AF4/FMR2. [Graphical view] |
| KO | K15185. |
| PANTHER | PTHR10528. AF-4. 1 hit. |
| Pfam | PF05110. AF-4. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| NextBio | 49830. |
| SOURCE | Search... |
Entry information
| Entry name | AFF4_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9UHB7 Secondary accession number(s): B2RP19 Q9P0E4 | ||||||||
| Entry 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. | ||||||||
Relevant documents
| Human chromosome 5 Human chromosome 5: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with