AFF4_HUMAN
ID AFF4_HUMAN Reviewed; 1163 AA.
AC Q9UHB7; B2RP19; B7WPD2; Q498B2; Q59FB3; Q6P592; Q8TDR1; Q9P0E4;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=AF4/FMR2 family member 4;
DE AltName: Full=ALL1-fused gene from chromosome 5q31 protein;
DE Short=Protein AF-5q31;
DE AltName: Full=Major CDK9 elongation factor-associated protein;
GN Name=AFF4; Synonyms=AF5Q31, MCEF; ORFNames=HSPC092;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHROMOSOMAL TRANSLOCATION WITH
RP KMT2A/MLL1, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Placenta;
RX PubMed=10588740; DOI=10.1073/pnas.96.25.14535;
RA Taki T., Kano H., Taniwaki M., Sako M., Yanagisawa M., Hayashi Y.;
RT "AF5q31, a newly identified AF4-related gene, is fused to MLL in infant
RT acute lymphoblastic leukemia with ins(5;11)(q31;q13q23).";
RL Proc. Natl. Acad. Sci. U.S.A. 96:14535-14540(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 111-122,
RP IDENTIFICATION IN P-TEFB COMPLEX, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Fetal brain;
RX PubMed=12065898; DOI=10.1007/bf02256070;
RA Estable M.C., Naghavi M.H., Kato H., Xiao H., Qin J., Vahlne A.,
RA Roeder R.G.;
RT "MCEF, the newest member of the AF4 family of transcription factors
RT involved in leukemia, is a positive transcription elongation factor-b-
RT associated protein.";
RL J. Biomed. Sci. 9:234-245(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 1-363 (ISOFORMS 1/2).
RC TISSUE=Blood, Brain, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 788-1163 (ISOFORM 2).
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-703 AND SER-706, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-674, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-549; SER-814; SER-1043 AND
RP SER-1055, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-387; SER-388; SER-389;
RP SER-392; SER-671; SER-694; SER-703; SER-706; TYR-712; SER-1043; SER-1055;
RP SER-1058 AND SER-1062, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-549; SER-671; SER-1043 AND
RP SER-1058, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1058, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [17]
RP FUNCTION, AND IDENTIFICATION IN THE SEC COMPLEX.
RX PubMed=20471948; DOI=10.1016/j.molcel.2010.04.013;
RA He N., Liu M., Hsu J., Xue Y., Chou S., Burlingame A., Krogan N.J.,
RA Alber T., Zhou Q.;
RT "HIV-1 Tat and host AFF4 recruit two transcription elongation factors into
RT a bifunctional complex for coordinated activation of HIV-1 transcription.";
RL Mol. Cell 38:428-438(2010).
RN [18]
RP FUNCTION, AND IDENTIFICATION IN THE SEC COMPLEX.
RX PubMed=20159561; DOI=10.1016/j.molcel.2010.01.026;
RA Lin C., Smith E.R., Takahashi H., Lai K.C., Martin-Brown S., Florens L.,
RA Washburn M.P., Conaway J.W., Conaway R.C., Shilatifard A.;
RT "AFF4, a component of the ELL/P-TEFb elongation complex and a shared
RT subunit of MLL chimeras, can link transcription elongation to leukemia.";
RL Mol. Cell 37:429-437(2010).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-814; SER-836 AND SER-1043,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP IDENTIFICATION IN THE SEC COMPLEX.
RX PubMed=22195968; DOI=10.1016/j.molcel.2011.12.008;
RA Smith E.R., Lin C., Garrett A.S., Thornton J., Mohaghegh N., Hu D.,
RA Jackson J., Saraf A., Swanson S.K., Seidel C., Florens L., Washburn M.P.,
RA Eissenberg J.C., Shilatifard A.;
RT "The little elongation complex regulates small nuclear RNA transcription.";
RL Mol. Cell 44:954-965(2011).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP INTERACTION WITH ELL2.
RX PubMed=22483617; DOI=10.1016/j.molcel.2012.03.007;
RA Liu M., Hsu J., Chan C., Li Z., Zhou Q.;
RT "The ubiquitin ligase Siah1 controls ELL2 stability and formation of super
RT elongation complexes to modulate gene transcription.";
RL Mol. Cell 46:325-334(2012).
RN [24]
RP REVIEW ON THE SUPER ELONGATION COMPLEX.
RX PubMed=22895430; DOI=10.1038/nrm3417;
RA Luo Z., Lin C., Shilatifard A.;
RT "The super elongation complex (SEC) family in transcriptional control.";
RL Nat. Rev. Mol. Cell Biol. 13:543-547(2012).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-120; SER-212; SER-487;
RP THR-674; SER-680; SER-703; SER-706; SER-814; SER-836; SER-1043 AND
RP SER-1058, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [26]
RP FUNCTION.
RX PubMed=23251033; DOI=10.1073/pnas.1216971110;
RA Chou S., Upton H., Bao K., Schulze-Gahmen U., Samelson A.J., He N.,
RA Nowak A., Lu H., Krogan N.J., Zhou Q., Alber T.;
RT "HIV-1 Tat recruits transcription elongation factors dispersed along a
RT flexible AFF4 scaffold.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E123-E131(2013).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-487 AND SER-706, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [28]
RP INVOLVEMENT IN CHOPS, AND VARIANTS CHOPS ALA-254; SER-254 AND TRP-258.
RX PubMed=25730767; DOI=10.1038/ng.3229;
RA Izumi K., Nakato R., Zhang Z., Edmondson A.C., Noon S., Dulik M.C.,
RA Rajagopalan R., Venditti C.P., Gripp K., Samanich J., Zackai E.H.,
RA Deardorff M.A., Clark D., Allen J.L., Dorsett D., Misulovin Z., Komata M.,
RA Bando M., Kaur M., Katou Y., Shirahige K., Krantz I.D.;
RT "Germline gain-of-function mutations in AFF4 cause a developmental syndrome
RT functionally linking the super elongation complex and cohesin.";
RL Nat. Genet. 47:338-344(2015).
RN [29]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-583, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [30]
RP VARIANT THR-757.
RX PubMed=21248752; DOI=10.1038/nature09639;
RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT PBRM1 in renal carcinoma.";
RL Nature 469:539-542(2011).
CC -!- FUNCTION: Key component of the super elongation complex (SEC), a
CC complex required to increase the catalytic rate of RNA polymerase II
CC transcription by suppressing transient pausing by the polymerase at
CC multiple sites along the DNA. In the SEC complex, AFF4 acts as a
CC central scaffold that recruits other factors through direct
CC interactions with ELL proteins (ELL, ELL2 or ELL3) and the P-TEFb
CC complex. In case of infection by HIV-1 virus, the SEC complex is
CC recruited by the viral Tat protein to stimulate viral gene expression.
CC {ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948,
CC ECO:0000269|PubMed:23251033}.
CC -!- SUBUNIT: Interacts with ELL3; the interaction is direct (By
CC similarity). Interacts with ELL2; the interaction is direct and leads
CC to stabilize ELL2 and prevent ELL2 ubiquitination and degradation.
CC Component of the super elongation complex (SEC), at least composed of
CC EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and
CC ELL (ELL, ELL2 or ELL3). Interacts with ELL. {ECO:0000250,
CC ECO:0000269|PubMed:12065898, ECO:0000269|PubMed:20159561,
CC ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:22195968,
CC ECO:0000269|PubMed:22483617}.
CC -!- INTERACTION:
CC Q9UHB7; P63010: AP2B1; NbExp=3; IntAct=EBI-395282, EBI-432924;
CC Q9UHB7; O60563: CCNT1; NbExp=6; IntAct=EBI-395282, EBI-2479671;
CC Q9UHB7; Q08379: GOLGA2; NbExp=3; IntAct=EBI-395282, EBI-618309;
CC Q9UHB7; Q03111: MLLT1; NbExp=8; IntAct=EBI-395282, EBI-1384215;
CC Q9UHB7; P42568: MLLT3; NbExp=4; IntAct=EBI-395282, EBI-716132;
CC Q9UHB7; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-395282, EBI-742948;
CC Q9UHB7; Q8IUQ4: SIAH1; NbExp=5; IntAct=EBI-395282, EBI-747107;
CC Q9UHB7; Q12933: TRAF2; NbExp=3; IntAct=EBI-395282, EBI-355744;
CC Q9UHB7; P04608: tat; Xeno; NbExp=4; IntAct=EBI-395282, EBI-6164389;
CC Q9UHB7-2; P63010: AP2B1; NbExp=3; IntAct=EBI-10261324, EBI-432924;
CC Q9UHB7-2; Q08379: GOLGA2; NbExp=3; IntAct=EBI-10261324, EBI-618309;
CC Q9UHB7-2; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-10261324, EBI-742948;
CC Q9UHB7-2; Q8IUQ4: SIAH1; NbExp=5; IntAct=EBI-10261324, EBI-747107;
CC Q9UHB7-2; Q12933: TRAF2; NbExp=3; IntAct=EBI-10261324, EBI-355744;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12065898}.
CC Note=Associates to transcriptionally active chromatin but not at snRNA
CC genes. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9UHB7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UHB7-2; Sequence=VSP_019220, VSP_019221;
CC Name=3;
CC IsoId=Q9UHB7-3; Sequence=VSP_019218, VSP_019219;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Strongly expressed in
CC heart, placenta, skeletal muscle, pancreas and to a lower extent in
CC brain. {ECO:0000269|PubMed:10588740, ECO:0000269|PubMed:12065898}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal heart, lung, brain and to a
CC lower extent liver. {ECO:0000269|PubMed:10588740}.
CC -!- DISEASE: Note=A chromosomal aberration involving AFF4 is found in acute
CC lymphoblastic leukemia (ALL). Insertion ins(5;11)(q31;q13q23) that
CC forms a KMT2A/MLL1-AFF4 fusion protein.
CC -!- DISEASE: CHOPS syndrome (CHOPS) [MIM:616368]: A syndrome characterized
CC by cognitive impairment, coarse facies, heart defects, obesity,
CC pulmonary involvement, short stature, and skeletal dysplasia.
CC {ECO:0000269|PubMed:25730767}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the AF4 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI00288.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=BAD92784.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/AF5q31ID230.html";
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DR EMBL; AF197927; AAF18981.1; -; mRNA.
DR EMBL; AF213987; AAM00184.2; -; mRNA.
DR EMBL; AB209547; BAD92784.1; ALT_INIT; mRNA.
DR EMBL; AC004500; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471062; EAW62305.1; -; Genomic_DNA.
DR EMBL; BC063007; AAH63007.1; -; mRNA.
DR EMBL; BC100287; AAI00288.1; ALT_SEQ; mRNA.
DR EMBL; BC137226; AAI37227.1; -; mRNA.
DR EMBL; AF161355; AAF28915.1; -; mRNA.
DR CCDS; CCDS4164.1; -. [Q9UHB7-1]
DR RefSeq; NP_055238.1; NM_014423.3. [Q9UHB7-1]
DR RefSeq; XP_005272020.1; XM_005271963.4. [Q9UHB7-1]
DR PDB; 4IMY; X-ray; 2.94 A; G/H/I=2-73.
DR PDB; 4OGR; X-ray; 3.00 A; C/G/L=2-73.
DR PDB; 4OR5; X-ray; 2.90 A; E/J=32-69.
DR PDB; 5JW9; X-ray; 2.00 A; A=301-351.
DR PDB; 5L1Z; X-ray; 5.90 A; C=32-67.
DR PDB; 6CYT; X-ray; 3.50 A; C=32-67.
DR PDB; 6K7P; X-ray; 2.40 A; A=902-1163.
DR PDB; 6KN5; X-ray; 2.20 A; A=899-1163.
DR PDB; 6R80; X-ray; 2.20 A; A=899-1163.
DR PDBsum; 4IMY; -.
DR PDBsum; 4OGR; -.
DR PDBsum; 4OR5; -.
DR PDBsum; 5JW9; -.
DR PDBsum; 5L1Z; -.
DR PDBsum; 6CYT; -.
DR PDBsum; 6K7P; -.
DR PDBsum; 6KN5; -.
DR PDBsum; 6R80; -.
DR AlphaFoldDB; Q9UHB7; -.
DR SMR; Q9UHB7; -.
DR BioGRID; 118016; 92.
DR CORUM; Q9UHB7; -.
DR ELM; Q9UHB7; -.
DR IntAct; Q9UHB7; 48.
DR MINT; Q9UHB7; -.
DR STRING; 9606.ENSP00000265343; -.
DR GlyGen; Q9UHB7; 4 sites, 1 O-linked glycan (4 sites).
DR iPTMnet; Q9UHB7; -.
DR PhosphoSitePlus; Q9UHB7; -.
DR BioMuta; AFF4; -.
DR DMDM; 74720814; -.
DR EPD; Q9UHB7; -.
DR jPOST; Q9UHB7; -.
DR MassIVE; Q9UHB7; -.
DR MaxQB; Q9UHB7; -.
DR PaxDb; Q9UHB7; -.
DR PeptideAtlas; Q9UHB7; -.
DR PRIDE; Q9UHB7; -.
DR ProteomicsDB; 84300; -. [Q9UHB7-1]
DR ProteomicsDB; 84301; -. [Q9UHB7-2]
DR ProteomicsDB; 84302; -. [Q9UHB7-3]
DR Antibodypedia; 14555; 267 antibodies from 31 providers.
DR DNASU; 27125; -.
DR Ensembl; ENST00000265343.10; ENSP00000265343.5; ENSG00000072364.13. [Q9UHB7-1]
DR Ensembl; ENST00000378595.7; ENSP00000367858.3; ENSG00000072364.13. [Q9UHB7-2]
DR GeneID; 27125; -.
DR KEGG; hsa:27125; -.
DR MANE-Select; ENST00000265343.10; ENSP00000265343.5; NM_014423.4; NP_055238.1.
DR UCSC; uc003kyd.4; human. [Q9UHB7-1]
DR CTD; 27125; -.
DR DisGeNET; 27125; -.
DR GeneCards; AFF4; -.
DR HGNC; HGNC:17869; AFF4.
DR HPA; ENSG00000072364; Low tissue specificity.
DR MalaCards; AFF4; -.
DR MIM; 604417; gene.
DR MIM; 616368; phenotype.
DR neXtProt; NX_Q9UHB7; -.
DR OpenTargets; ENSG00000072364; -.
DR Orphanet; 444077; Cognitive impairment-coarse facies-heart defects-obesity-pulmonary involvement-short stature-skeletal dysplasia syndrome.
DR PharmGKB; PA142672641; -.
DR VEuPathDB; HostDB:ENSG00000072364; -.
DR eggNOG; ENOG502QR32; Eukaryota.
DR GeneTree; ENSGT00950000182974; -.
DR HOGENOM; CLU_006484_0_0_1; -.
DR InParanoid; Q9UHB7; -.
DR OMA; SYSADHY; -.
DR OrthoDB; 558558at2759; -.
DR PhylomeDB; Q9UHB7; -.
DR TreeFam; TF326216; -.
DR PathwayCommons; Q9UHB7; -.
DR Reactome; R-HSA-112382; Formation of RNA Pol II elongation complex.
DR Reactome; R-HSA-674695; RNA Polymerase II Pre-transcription Events.
DR Reactome; R-HSA-75955; RNA Polymerase II Transcription Elongation.
DR SignaLink; Q9UHB7; -.
DR SIGNOR; Q9UHB7; -.
DR BioGRID-ORCS; 27125; 23 hits in 1094 CRISPR screens.
DR ChiTaRS; AFF4; human.
DR GenomeRNAi; 27125; -.
DR Pharos; Q9UHB7; Tbio.
DR PRO; PR:Q9UHB7; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9UHB7; protein.
DR Bgee; ENSG00000072364; Expressed in esophagus squamous epithelium and 188 other tissues.
DR ExpressionAtlas; Q9UHB7; baseline and differential.
DR Genevisible; Q9UHB7; HS.
DR GO; GO:0000791; C:euchromatin; ISS:UniProtKB.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0032783; C:super elongation complex; IBA:GO_Central.
DR GO; GO:0008023; C:transcription elongation factor complex; IDA:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0007286; P:spermatid development; IEA:Ensembl.
DR DisProt; DP01463; -.
DR InterPro; IPR007797; AF4/FMR2.
DR InterPro; IPR043640; AF4/FMR2_CHD.
DR InterPro; IPR043639; AF4_int.
DR PANTHER; PTHR10528; PTHR10528; 1.
DR Pfam; PF18876; AF-4_C; 1.
DR Pfam; PF18875; AF4_int; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chromosomal rearrangement;
KW Direct protein sequencing; Disease variant; Dwarfism; Isopeptide bond;
KW Nucleus; Obesity; Phosphoprotein; Proto-oncogene; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..1163
FT /note="AF4/FMR2 family member 4"
FT /id="PRO_0000239393"
FT REGION 1..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 76..312
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 324..904
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1034..1073
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..22
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 86..165
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 174..195
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 196..218
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 223..253
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 269..290
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 346..375
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 376..400
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 402..417
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 430..459
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 483..560
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 567..584
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 609..648
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 653..676
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 677..706
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 731..793
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 833..868
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 878..899
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1059..1073
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 350..351
FT /note="Breakpoint for insertion to form KMT2A/MLL1-AFF4
FT fusion protein"
FT MOD_RES 120
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 212
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 387
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 388
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 389
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 392
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 487
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ESC8"
FT MOD_RES 491
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ESC8"
FT MOD_RES 549
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 671
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 674
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 680
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 694
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 703
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 706
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 712
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 814
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 822
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9ESC8"
FT MOD_RES 836
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1043
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 1055
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976"
FT MOD_RES 1058
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1062
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT CROSSLNK 583
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 351..353
FT /note="ESQ -> VSK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019218"
FT VAR_SEQ 354..1163
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019219"
FT VAR_SEQ 880..900
FT /note="EKAPSSSSNCPPSAPTLDSSK -> VKCWGPGAFENHSTCHVTFPG (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:11042152, ECO:0000303|Ref.3"
FT /id="VSP_019220"
FT VAR_SEQ 901..1163
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11042152, ECO:0000303|Ref.3"
FT /id="VSP_019221"
FT VARIANT 136
FT /note="T -> P (in dbSNP:rs34527550)"
FT /id="VAR_053003"
FT VARIANT 254
FT /note="T -> A (in CHOPS; dbSNP:rs786205233)"
FT /evidence="ECO:0000269|PubMed:25730767"
FT /id="VAR_073790"
FT VARIANT 254
FT /note="T -> S (in CHOPS; dbSNP:rs786205679)"
FT /evidence="ECO:0000269|PubMed:25730767"
FT /id="VAR_073791"
FT VARIANT 258
FT /note="R -> W (in CHOPS; dbSNP:rs786205680)"
FT /evidence="ECO:0000269|PubMed:25730767"
FT /id="VAR_073792"
FT VARIANT 757
FT /note="S -> T (found in a clear cell renal carcinoma case;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21248752"
FT /id="VAR_064693"
FT CONFLICT 264
FT /note="E -> G (in Ref. 2; AAM00184)"
FT /evidence="ECO:0000305"
FT CONFLICT 359
FT /note="T -> I (in Ref. 2; AAM00184)"
FT /evidence="ECO:0000305"
FT CONFLICT 383
FT /note="D -> G (in Ref. 2; AAM00184)"
FT /evidence="ECO:0000305"
FT CONFLICT 445
FT /note="E -> G (in Ref. 2; AAM00184)"
FT /evidence="ECO:0000305"
FT CONFLICT 870
FT /note="K -> R (in Ref. 7; AAF28915)"
FT /evidence="ECO:0000305"
FT HELIX 4..18
FT /evidence="ECO:0007829|PDB:4IMY"
FT HELIX 47..56
FT /evidence="ECO:0007829|PDB:4OR5"
FT HELIX 59..62
FT /evidence="ECO:0007829|PDB:4OR5"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:4OR5"
FT HELIX 315..323
FT /evidence="ECO:0007829|PDB:5JW9"
FT HELIX 915..931
FT /evidence="ECO:0007829|PDB:6KN5"
FT HELIX 935..958
FT /evidence="ECO:0007829|PDB:6KN5"
FT HELIX 967..981
FT /evidence="ECO:0007829|PDB:6KN5"
FT HELIX 993..1017
FT /evidence="ECO:0007829|PDB:6KN5"
FT HELIX 1019..1032
FT /evidence="ECO:0007829|PDB:6KN5"
FT HELIX 1087..1116
FT /evidence="ECO:0007829|PDB:6KN5"
FT HELIX 1117..1120
FT /evidence="ECO:0007829|PDB:6KN5"
FT HELIX 1121..1131
FT /evidence="ECO:0007829|PDB:6KN5"
FT TURN 1136..1138
FT /evidence="ECO:0007829|PDB:6KN5"
FT HELIX 1141..1159
FT /evidence="ECO:0007829|PDB:6KN5"
SQ SEQUENCE 1163 AA; 127459 MW; 474E1906B8832AC1 CRC64;
MNREDRNVLR MKERERRNQE IQQGEDAFPP SSPLFAEPYK VTSKEDKLSS RIQSMLGNYD
EMKDFIGDRS IPKLVAIPKP TVPPSADEKS NPNFFEQRHG GSHQSSKWTP VGPAPSTSQS
QKRSSGLQSG HSSQRTSAGS SSGTNSSGQR HDRESYNNSG SSSRKKGQHG SEHSKSRSSS
PGKPQAVSSL NSSHSRSHGN DHHSKEHQRS KSPRDPDANW DSPSRVPFSS GQHSTQSFPP
SLMSKSNSML QKPTAYVRPM DGQESMEPKL SSEHYSSQSH GNSMTELKPS SKAHLTKLKI
PSQPLDASAS GDVSCVDEIL KEMTHSWPPP LTAIHTPCKT EPSKFPFPTK ESQQSNFGTG
EQKRYNPSKT SNGHQSKSML KDDLKLSSSE DSDGEQDCDK TMPRSTPGSN SEPSHHNSEG
ADNSRDDSSS HSGSESSSGS DSESESSSSD SEANEPSQSA SPEPEPPPTN KWQLDNWLNK
VNPHKVSPAS SVDSNIPSSQ GYKKEGREQG TGNSYTDTSG PKETSSATPG RDSKTIQKGS
ESGRGRQKSP AQSDSTTQRR TVGKKQPKKA EKAAAEEPRG GLKIESETPV DLASSMPSSR
HKAATKGSRK PNIKKESKSS PRPTAEKKKY KSTSKSSQKS REIIETDTSS SDSDESESLP
PSSQTPKYPE SNRTPVKPSS VEEEDSFFRQ RMFSPMEEKE LLSPLSEPDD RYPLIVKIDL
NLLTRIPGKP YKETEPPKGE KKNVPEKHTR EAQKQASEKV SNKGKRKHKN EDDNRASESK
KPKTEDKNSA GHKPSSNRES SKQSAAKEKD LLPSPAGPVP SKDPKTEHGS RKRTISQSSS
LKSSSNSNKE TSGSSKNSSS TSKQKKTEGK TSSSSKEVKE KAPSSSSNCP PSAPTLDSSK
PRRTKLVFDD RNYSADHYLQ EAKKLKHNAD ALSDRFEKAV YYLDAVVSFI ECGNALEKNA
QESKSPFPMY SETVDLIKYT MKLKNYLAPD ATAADKRLTV LCLRCESLLY LRLFKLKKEN
ALKYSKTLTE HLKNSYNNSQ APSPGLGSKA VGMPSPVSPK LSPGNSGNYS SGASSASASG
SSVTIPQKIH QMAASYVQVT SNFLYATEIW DQAEQLSKEQ KEFFAELDKV MGPLIFNASI
MTDLVRYTRQ GLHWLRQDAK LIS
