SET1B_HUMAN
ID SET1B_HUMAN Reviewed; 1966 AA.
AC Q9UPS6; F6MFW1;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 19-MAR-2014, sequence version 3.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Histone-lysine N-methyltransferase SETD1B;
DE EC=2.1.1.364 {ECO:0000269|PubMed:25561738};
DE AltName: Full=Lysine N-methyltransferase 2G;
DE AltName: Full=SET domain-containing protein 1B;
DE Short=hSET1B;
GN Name=SETD1B; Synonyms=KIAA1076, KMT2G, SET1B;
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), INTERACTION WITH RBM15, AND
RP MUTAGENESIS OF LEU-577 AND ASP-579.
RX PubMed=22927943; DOI=10.1371/journal.pone.0042965;
RA Lee J.H., Skalnik D.G.;
RT "Rbm15-Mkl1 interacts with the Setd1b histone H3-Lys4 methyltransferase via
RT a SPOC domain that is required for cytokine-independent proliferation.";
RL PLoS ONE 7:E42965-E42965(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1163-1966 (ISOFORM 1/2).
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND IDENTIFICATION IN
RP THE SET1 COMPLEX.
RX PubMed=17355966; DOI=10.1074/jbc.m609809200;
RA Lee J.-H., Tate C.M., You J.-S., Skalnik D.G.;
RT "Identification and characterization of the human Set1B histone H3-Lys4
RT methyltransferase complex.";
RL J. Biol. Chem. 282:13419-13428(2007).
RN [5]
RP IDENTIFICATION IN SET1 COMPLEX, AND INTERACTION WITH WDR82; ASH2L AND
RP POLR2A.
RX PubMed=17998332; DOI=10.1128/mcb.01356-07;
RA Lee J.H., Skalnik D.G.;
RT "Wdr82 is a C-terminal domain-binding protein that recruits the Setd1A
RT Histone H3-Lys4 methyltransferase complex to transcription start sites of
RT transcribed human genes.";
RL Mol. Cell. Biol. 28:609-618(2008).
RN [6]
RP IDENTIFICATION IN SET1 COMPLEX.
RX PubMed=18838538; DOI=10.1128/mcb.00976-08;
RA Wu M., Wang P.F., Lee J.S., Martin-Brown S., Florens L., Washburn M.,
RA Shilatifard A.;
RT "Molecular regulation of H3K4 trimethylation by Wdr82, a component of human
RT Set1/COMPASS.";
RL Mol. Cell. Biol. 28:7337-7344(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1659, 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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-986; SER-994 AND SER-1031,
RP 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 [10]
RP IDENTIFICATION IN SET1B COMPLEX.
RX PubMed=23508102; DOI=10.1128/mcb.01742-12;
RA van Nuland R., Smits A.H., Pallaki P., Jansen P.W., Vermeulen M.,
RA Timmers H.T.;
RT "Quantitative dissection and stoichiometry determination of the human
RT SET1/MLL histone methyltransferase complexes.";
RL Mol. Cell. Biol. 33:2067-2077(2013).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1335, AND IDENTIFICATION BY
RP 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 [12]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF ASN-1905.
RX PubMed=25561738; DOI=10.1074/jbc.m114.627646;
RA Shinsky S.A., Monteith K.E., Viggiano S., Cosgrove M.S.;
RT "Biochemical reconstitution and phylogenetic comparison of human SET1
RT family core complexes involved in histone methylation.";
RL J. Biol. Chem. 290:6361-6375(2015).
RN [13]
RP INVOLVEMENT IN IDDSELD.
RX PubMed=31110234; DOI=10.1038/s10038-019-0617-1;
RA Den K., Kato M., Yamaguchi T., Miyatake S., Takata A., Mizuguchi T.,
RA Miyake N., Mitsuhashi S., Matsumoto N.;
RT "A novel de novo frameshift variant in SETD1B causes epilepsy.";
RL J. Hum. Genet. 64:821-827(2019).
RN [14] {ECO:0007744|PDB:4ES0}
RP X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 1741-1754 IN COMPLEX WITH WDR5,
RP INTERACTION WITH WDR5, AND MOTIF WIN.
RX PubMed=22665483; DOI=10.1074/jbc.m112.364125;
RA Dharmarajan V., Lee J.H., Patel A., Skalnik D.G., Cosgrove M.S.;
RT "Structural basis for WDR5 interaction (Win) motif recognition in human
RT SET1 family histone methyltransferases.";
RL J. Biol. Chem. 287:27275-27289(2012).
RN [15] {ECO:0007744|PDB:3UVO}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 1745-1755 IN COMPLEX WITH WDR5,
RP INTERACTION WITH WDR5, AND MOTIF WIN.
RX PubMed=22266653; DOI=10.1093/nar/gkr1235;
RA Zhang P., Lee H., Brunzelle J.S., Couture J.F.;
RT "The plasticity of WDR5 peptide-binding cleft enables the binding of the
RT SET1 family of histone methyltransferases.";
RL Nucleic Acids Res. 40:4237-4246(2012).
RN [16]
RP VARIANTS IDDSELD TRP-1885 AND CYS-1902, AND INVOLVEMENT IN IDDSELD.
RX PubMed=29322246; DOI=10.1007/s00439-017-1863-y;
RA Hiraide T., Nakashima M., Yamoto K., Fukuda T., Kato M., Ikeda H.,
RA Sugie Y., Aoto K., Kaname T., Nakabayashi K., Ogata T., Matsumoto N.,
RA Saitsu H.;
RT "De novo variants in SETD1B are associated with intellectual disability,
RT epilepsy and autism.";
RL Hum. Genet. 137:95-104(2018).
RN [17]
RP VARIANTS IDDSELD TRP-1885 AND CYS-1902.
RX PubMed=31685013; DOI=10.1186/s13148-019-0749-3;
RA Krzyzewska I.M., Maas S.M., Henneman P., Lip K.V.D., Venema A.,
RA Baranano K., Chassevent A., Aref-Eshghi E., van Essen A.J., Fukuda T.,
RA Ikeda H., Jacquemont M., Kim H.G., Labalme A., Lewis S.M.E., Lesca G.,
RA Madrigal I., Mahida S., Matsumoto N., Rabionet R., Rajcan-Separovic E.,
RA Qiao Y., Sadikovic B., Saitsu H., Sweetser D.A., Alders M.,
RA Mannens M.M.A.M.;
RT "A genome-wide DNA methylation signature for SETD1B-related syndrome.";
RL Clin. Epigenetics 11:156-156(2019).
RN [18]
RP VARIANT IDDSELD GLY-129.
RX PubMed=31440728; DOI=10.1002/epi4.12339;
RA Hiraide T., Hattori A., Ieda D., Hori I., Saitoh S., Nakashima M.,
RA Saitsu H.;
RT "De novo variants in SETD1B cause intellectual disability, autism spectrum
RT disorder, and epilepsy with myoclonic absences.";
RL Epilepsia Open 4:476-481(2019).
RN [19]
RP VARIANTS IDDSELD 978-GLN--ASN-1966 DEL; 1322-GLN--ASN-1966 DEL AND
RP LEU-1945.
RX PubMed=32546566; DOI=10.1136/jmedgenet-2019-106756;
RG CAUSES Study;
RG EPGEN Study;
RA Roston A., Evans D., Gill H., McKinnon M., Isidor B., Cogne B.,
RA Mwenifumbo J., van Karnebeek C., An J., Jones S.J.M., Farrer M., Demos M.,
RA Connolly M., Gibson W.T.;
RT "SETD1B-associated neurodevelopmental disorder.";
RL J. Med. Genet. 58:196-204(2021).
CC -!- FUNCTION: Histone methyltransferase that catalyzes methyl group
CC transfer from S-adenosyl-L-methionine to the epsilon-amino group of
CC 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism
CC (PubMed:25561738, PubMed:17355966). Part of chromatin remodeling
CC machinery, forms H3K4me1, H3K4me2 and H3K4me3 methylation marks at
CC active chromatin sites where transcription and DNA repair take place
CC (PubMed:25561738, PubMed:17355966). Plays an essential role in
CC regulating the transcriptional programming of multipotent hematopoietic
CC progenitor cells and lymphoid lineage specification during
CC hematopoiesis (By similarity). {ECO:0000250|UniProtKB:Q8CFT2,
CC ECO:0000269|PubMed:17355966, ECO:0000269|PubMed:25561738}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine = H(+) +
CC N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:60264, Rhea:RHEA-COMP:15543, Rhea:RHEA-COMP:15547,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.364;
CC Evidence={ECO:0000269|PubMed:25561738};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60265;
CC Evidence={ECO:0000305|PubMed:25561738};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine
CC = H(+) + N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60268, Rhea:RHEA-COMP:15540, Rhea:RHEA-
CC COMP:15543, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:61929, ChEBI:CHEBI:61976;
CC Evidence={ECO:0000269|PubMed:17355966, ECO:0000269|PubMed:25561738};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60269;
CC Evidence={ECO:0000305|PubMed:17355966, ECO:0000305|PubMed:25561738};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-
CC methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(4)-[histone H3]
CC + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:60272, Rhea:RHEA-
CC COMP:15537, Rhea:RHEA-COMP:15540, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961,
CC ChEBI:CHEBI:61976; Evidence={ECO:0000269|PubMed:17355966,
CC ECO:0000269|PubMed:25561738};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60273;
CC Evidence={ECO:0000305|PubMed:17355966, ECO:0000305|PubMed:25561738};
CC -!- SUBUNIT: Component of the SET1B/COMPASS complex composed of the
CC catalytic subunit SETD1A, WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1,
CC HCFC1, DPY30 homotrimer and BOD1 (PubMed:23508102, PubMed:17355966,
CC PubMed:18838538). Forms a core complex with the evolutionary conserved
CC subcomplex WRAD composed of WDR5, RBBP5, ASH2L/ASH2 and DPY30 subunits;
CC WRAD differentially stimulates the methyltransferase activity
CC (PubMed:25561738). Interacts with HCFC1 and ASH2L/ASH2
CC (PubMed:17998332). Interacts (via the RRM domain) with WDR82
CC (PubMed:17998332). Interacts (via the RRM domain) with
CC hyperphosphorylated C-terminal domain (CTD) of RNA polymerase II large
CC subunit (POLR2A) only in the presence of WDR82 (PubMed:17998332). Binds
CC specifically to CTD heptad repeats phosphorylated on 'Ser-5' of each
CC heptad. Interacts with RBM15 (PubMed:22927943). Interacts (via WIN
CC motif) with WDR5 (PubMed:22665483, PubMed:22266653).
CC {ECO:0000269|PubMed:17355966, ECO:0000269|PubMed:17998332,
CC ECO:0000269|PubMed:18838538, ECO:0000269|PubMed:22927943,
CC ECO:0000269|PubMed:23508102, ECO:0000269|PubMed:25561738}.
CC -!- INTERACTION:
CC Q9UPS6-2; Q9UBL3-3: ASH2L; NbExp=2; IntAct=EBI-16197836, EBI-16130425;
CC -!- SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000269|PubMed:17355966}.
CC Chromosome {ECO:0000269|PubMed:17355966}. Note=Localizes to a largely
CC non-overlapping set of euchromatic nuclear speckles with SETD1A,
CC suggesting that SETD1A and SET1B each bind to a unique set of target
CC genes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UPS6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UPS6-2; Sequence=VSP_053875, VSP_053876;
CC -!- DISEASE: Intellectual developmental disorder with seizures and language
CC delay (IDDSELD) [MIM:619000]: An autosomal dominant neurodevelopmental
CC disorder characterized by mild to profound intellectual development
CC impairment, speech and language delay, and seizures. Autism and anxiety
CC are common features. Facial dysmorphism, tapering fingers, and
CC pigmentary skin changes may also be observed.
CC {ECO:0000269|PubMed:29322246, ECO:0000269|PubMed:31110234,
CC ECO:0000269|PubMed:31440728, ECO:0000269|PubMed:31685013,
CC ECO:0000269|PubMed:32546566}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR EMBL; JF813787; AEG67286.1; -; mRNA.
DR EMBL; AC079360; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC084018; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB028999; BAA83028.1; -; mRNA.
DR CCDS; CCDS86338.1; -. [Q9UPS6-1]
DR RefSeq; NP_055863.1; NM_015048.1.
DR RefSeq; XP_005253915.1; XM_005253858.4.
DR RefSeq; XP_006719359.1; XM_006719296.3. [Q9UPS6-1]
DR PDB; 3UVO; X-ray; 2.20 A; B=1745-1755.
DR PDB; 4ES0; X-ray; 1.82 A; C=1741-1754.
DR PDBsum; 3UVO; -.
DR PDBsum; 4ES0; -.
DR AlphaFoldDB; Q9UPS6; -.
DR SMR; Q9UPS6; -.
DR BioGRID; 116702; 66.
DR ComplexPortal; CPX-7111; Histone-lysine N-methyltransferase complex, SET1B variant.
DR CORUM; Q9UPS6; -.
DR DIP; DIP-61947N; -.
DR ELM; Q9UPS6; -.
DR IntAct; Q9UPS6; 19.
DR MINT; Q9UPS6; -.
DR STRING; 9606.ENSP00000442924; -.
DR BindingDB; Q9UPS6; -.
DR ChEMBL; CHEMBL4105837; -.
DR GlyGen; Q9UPS6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UPS6; -.
DR PhosphoSitePlus; Q9UPS6; -.
DR BioMuta; SETD1B; -.
DR DMDM; 166977692; -.
DR EPD; Q9UPS6; -.
DR jPOST; Q9UPS6; -.
DR MassIVE; Q9UPS6; -.
DR MaxQB; Q9UPS6; -.
DR PaxDb; Q9UPS6; -.
DR PeptideAtlas; Q9UPS6; -.
DR PRIDE; Q9UPS6; -.
DR ProteomicsDB; 85430; -. [Q9UPS6-1]
DR Antibodypedia; 9774; 121 antibodies from 26 providers.
DR Ensembl; ENST00000542440.5; ENSP00000442924.1; ENSG00000139718.12. [Q9UPS6-2]
DR Ensembl; ENST00000604567.6; ENSP00000474253.1; ENSG00000139718.12. [Q9UPS6-1]
DR Ensembl; ENST00000619791.1; ENSP00000481531.1; ENSG00000139718.12. [Q9UPS6-1]
DR GeneID; 23067; -.
DR MANE-Select; ENST00000604567.6; ENSP00000474253.1; NM_001353345.2; NP_001340274.1.
DR UCSC; uc021rfg.2; human. [Q9UPS6-1]
DR CTD; 23067; -.
DR DisGeNET; 23067; -.
DR GeneCards; SETD1B; -.
DR HGNC; HGNC:29187; SETD1B.
DR HPA; ENSG00000139718; Low tissue specificity.
DR MalaCards; SETD1B; -.
DR MIM; 611055; gene.
DR MIM; 619000; phenotype.
DR neXtProt; NX_Q9UPS6; -.
DR OpenTargets; ENSG00000139718; -.
DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability.
DR PharmGKB; PA143485611; -.
DR VEuPathDB; HostDB:ENSG00000139718; -.
DR eggNOG; KOG1080; Eukaryota.
DR GeneTree; ENSGT00940000154575; -.
DR HOGENOM; CLU_001226_0_0_1; -.
DR InParanoid; Q9UPS6; -.
DR OMA; RMPIEEC; -.
DR OrthoDB; 1234689at2759; -.
DR PhylomeDB; Q9UPS6; -.
DR TreeFam; TF106436; -.
DR BioCyc; MetaCyc:HS13795-MON; -.
DR PathwayCommons; Q9UPS6; -.
DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR SignaLink; Q9UPS6; -.
DR SIGNOR; Q9UPS6; -.
DR BioGRID-ORCS; 23067; 100 hits in 1096 CRISPR screens.
DR GenomeRNAi; 23067; -.
DR Pharos; Q9UPS6; Tbio.
DR PRO; PR:Q9UPS6; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9UPS6; protein.
DR Bgee; ENSG00000139718; Expressed in blood vessel layer and 203 other tissues.
DR ExpressionAtlas; Q9UPS6; baseline and differential.
DR Genevisible; Q9UPS6; HS.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0035097; C:histone methyltransferase complex; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0048188; C:Set1C/COMPASS complex; IDA:UniProtKB.
DR GO; GO:0042800; F:histone methyltransferase activity (H3-K4 specific); IEA:InterPro.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; TAS:Reactome.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0044648; P:histone H3-K4 dimethylation; IDA:CACAO.
DR GO; GO:0051568; P:histone H3-K4 methylation; IDA:UniProtKB.
DR GO; GO:0097692; P:histone H3-K4 monomethylation; IDA:CACAO.
DR GO; GO:0080182; P:histone H3-K4 trimethylation; IDA:CACAO.
DR CDD; cd12549; RRM_Set1B; 1.
DR Gene3D; 2.170.270.10; -; 1.
DR Gene3D; 3.30.70.330; -; 1.
DR IDEAL; IID00402; -.
DR InterPro; IPR024657; COMPASS_Set1_N-SET.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR003616; Post-SET_dom.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR InterPro; IPR044570; Set1-like.
DR InterPro; IPR034468; Set1B_RRM.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR InterPro; IPR037842; SETD1B.
DR PANTHER; PTHR45814; PTHR45814; 1.
DR PANTHER; PTHR45814:SF1; PTHR45814:SF1; 1.
DR Pfam; PF11764; N-SET; 1.
DR Pfam; PF00076; RRM_1; 1.
DR Pfam; PF00856; SET; 1.
DR SMART; SM01291; N-SET; 1.
DR SMART; SM00508; PostSET; 1.
DR SMART; SM00360; RRM; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS50868; POST_SET; 1.
DR PROSITE; PS50102; RRM; 1.
DR PROSITE; PS50280; SET; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Chromatin regulator;
KW Chromosome; Coiled coil; Disease variant; Epilepsy;
KW Intellectual disability; Methyltransferase; Nucleus; Phosphoprotein;
KW Reference proteome; RNA-binding; S-adenosyl-L-methionine; Transcription;
KW Transcription regulation; Transferase.
FT CHAIN 1..1966
FT /note="Histone-lysine N-methyltransferase SETD1B"
FT /id="PRO_0000316993"
FT DOMAIN 93..181
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 1827..1944
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT DOMAIN 1950..1966
FT /note="Post-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 235..302
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 357..660
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 675..719
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 963..1462
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1501..1541
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1555..1606
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1636..1668
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1767..1800
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1173..1204
FT /evidence="ECO:0000255"
FT MOTIF 1745..1750
FT /note="WDR5 interaction motif (WIN)"
FT /evidence="ECO:0000269|PubMed:22266653,
FT ECO:0000269|PubMed:22665483"
FT COMPBIAS 366..382
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 431..461
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 493..525
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 527..573
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 676..719
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 998..1041
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1042..1064
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1069..1088
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1103..1141
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1146..1171
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1172..1198
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1294..1311
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1313..1359
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1501..1516
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1578..1603
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1636..1655
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1767..1789
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1943
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT MOD_RES 986
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 994
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1031
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1265
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CFT2"
FT MOD_RES 1283
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CFT2"
FT MOD_RES 1335
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1659
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 1663
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CFT2"
FT VAR_SEQ 1043..1068
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_053875"
FT VAR_SEQ 1088..1104
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_053876"
FT VARIANT 129
FT /note="V -> G (in IDDSELD)"
FT /evidence="ECO:0000269|PubMed:31440728"
FT /id="VAR_084717"
FT VARIANT 978..1966
FT /note="Missing (in IDDSELD)"
FT /evidence="ECO:0000269|PubMed:32546566"
FT /id="VAR_084718"
FT VARIANT 1322..1966
FT /note="Missing (in IDDSELD)"
FT /evidence="ECO:0000269|PubMed:32546566"
FT /id="VAR_084719"
FT VARIANT 1885
FT /note="R -> W (in IDDSELD)"
FT /evidence="ECO:0000269|PubMed:29322246,
FT ECO:0000269|PubMed:31685013"
FT /id="VAR_084720"
FT VARIANT 1902
FT /note="R -> C (in IDDSELD)"
FT /evidence="ECO:0000269|PubMed:29322246,
FT ECO:0000269|PubMed:31685013"
FT /id="VAR_084721"
FT VARIANT 1945
FT /note="F -> L (in IDDSELD)"
FT /evidence="ECO:0000269|PubMed:32546566"
FT /id="VAR_084722"
FT MUTAGEN 577
FT /note="L->A: Abolishes interaction with RBM15."
FT /evidence="ECO:0000269|PubMed:22927943"
FT MUTAGEN 579
FT /note="D->A: Abolishes interaction with RBM15."
FT /evidence="ECO:0000269|PubMed:22927943"
FT MUTAGEN 1905
FT /note="N->A: Abolishes interaction with S-adenosyl-L-
FT methionine."
FT /evidence="ECO:0000269|PubMed:25561738"
FT HELIX 1747..1750
FT /evidence="ECO:0007829|PDB:4ES0"
SQ SEQUENCE 1966 AA; 212803 MW; 164F81BC84EAD2C2 CRC64;
MENSHPPHHH HQQPPPQPGP SGERRNHHWR SYKLMIDPAL KKGHHKLYRY DGQHFSLAMS
SNRPVEIVED PRVVGIWTKN KELELSVPKF KIDEFYVGPV PPKQVTFAKL NDNIRENFLR
DMCKKYGEVE EVEILYNPKT KKHLGIAKVV FATVRGAKDA VQHLHSTSVM GNIIHVELDT
KGETRMRFYE LLVTGRYTPQ TLPVGELDAV SPIVNETLQL SDALKRLKDG GLSAGCGSGS
SSVTPNSGGT PFSQDTAYSS CRLDTPNSYG QGTPLTPRLG TPFSQDSSYS SRQPTPSYLF
SQDPAVTFKA RRHESKFTDA YNRRHEHHYV HNSPAVTAVA GATAAFRGSS DLPFGAVGGT
GGSSGPPFKA QPQDSATFAH TPPPAQATPA PGFKSAFSPY QTPVAHFPPP PEEPTATAAF
GARDSGEFRR APAPPPLPPA EPLAKEKPGT PPGPPPPDTN SMELGGRPTF GWSPEPCDSP
GTPTLESSPA GPEKPHDSLD SRIEMLLKEQ RTKLLFLREP DSDTELQMEG SPISSSSSQL
SPLAPFGTNS QPGFRGPTPP SSRPSSTGLE DISPTPLPDS DEDEELDLGL GPRPPPEPGP
PDPAGLLSQT AEVALDLVGD RTPTSEKMDE GQQSSGEDME ISDDEMPSAP ITSADCPKPM
VVTPGAAAVA APSVLAPTLP LPPPPGFPPL PPPPPPPPPQ PGFPMPPPLP PPPPPPPPAH
PAVTVPPPPL PAPPGVPPPP ILPPLPPFPP GLFPVMQVDM SHVLGGQWGG MPMSFQMQTQ
VLSRLMTGQG ACPYPPFMAA AAAAASAGLQ FVNLPPYRGP FSLSNSGPGR GQHWPPLPKF
DPSVPPPGYM PRQEDPHKAT VDGVLLVVLK ELKAIMKRDL NRKMVEVVAF RAFDEWWDKK
ERMAKASLTP VKSGEHKDED RPKPKDRIAS CLLESWGKGE GLGYEGLGLG IGLRGAIRLP
SFKVKRKEPP DTTSSGDQKR LRPSTSVDEE DEESERERDR DMADTPCELA KRDPKGVGVR
RRPARPLELD SGGEEDEKES LSASSSSSAS SSSGSSTTSP SSSASDKEEE QESTEEEEEA
EEEEEEEVPR SQLSSSSTSS TSDKDDDDDD SDDRDESEND DEDTALSEAS EKDEGDSDEE
ETVSIVTSKA EATSSSESSE SSEFESSSES SPSSSEDEEE VVAREEEEEE EEEEMVAEES
MASAGPEDFE QDGEEAALAP GAPAVDSLGM EEEVDIETEA VAPEERPSML DEPPLPVGVE
EPADSREPPE EPGLSQEGAM LLSPEPPAKE VEARPPLSPE RAPEHDLEVE PEPPMMLPLP
LQPPLPPPRP PRPPSPPPEP ETTDASHPSV PPEPLAEDHP PHTPGLCGSL AKSQSTETVP
ATPGGEPPLS GGSSGLSLSS PQVPGSPFSY PAPSPSLSSG GLPRTPGRDF SFTPTFSEPS
GPLLLPVCPL PTGRRDERSG PLASPVLLET GLPLPLPLPL PLPLALPAVL RAQARAPTPL
PPLLPAPLAS CPPPMKRKPG RPRRSPPSML SLDGPLVRPP AGAALGRELL LLPGQPQTPV
FPSTHDPRTV TLDFRNAGIP APPPPLPPQP PPPPPPPPVE PTKLPFKELD NQWPSEAIPP
GPRGRDEVTE EYMELAKSRG PWRRPPKKRH EDLVPPAGSP ELSPPQPLFR PRSEFEEMTI
LYDIWNGGID EEDIRFLCVT YERLLQQDNG MDWLNDTLWV YHPSTSLSSA KKKKRDDGIR
EHVTGCARSE GFYTIDKKDK LRYLNSSRAS TDEPPADTQG MSIPAQPHAS TRAGSERRSE
QRRLLSSFTG SCDSDLLKFN QLKFRKKKLK FCKSHIHDWG LFAMEPIAAD EMVIEYVGQN
IRQVIADMRE KRYEDEGIGS SYMFRVDHDT IIDATKCGNF ARFINHSCNP NCYAKVITVE
SQKKIVIYSK QHINVNEEIT YDYKFPIEDV KIPCLCGSEN CRGTLN
