Q9UPS6 (SET1B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone-lysine N-methyltransferase SETD1B
EC=2.1.1.43

Alternative name(s):
Lysine N-methyltransferase 2G
SET domain-containing protein 1B
Short name=hSET1B

Gene names

Name:	SETD1B
Synonyms:	KIAA1076, KMT2G, SET1B

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	1923 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Histone methyltransferase that specifically methylates 'Lys-4' of histone H3, when part of the SET1 histone methyltransferase (HMT) complex, but not if the neighboring 'Lys-9' residue is already methylated. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. The non-overalpping localization with SETD1A suggests that SETD1A and SETD1B make non-redundant contributions to the epigenetic control of chromatin structure and gene expression. Specifically tri-methylates 'Lys-4' of histone H3 in vitro.
Catalytic activity	S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. Ref.3
Subunit structure	Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30. Interacts with HCFC1 and ASH2L/ASH2. Interacts (via the RRM domain) with WDR82. Interacts (via the RRM domain) with hyperphosphorylated C-terminal domain (CTD) of RNA polymerase II large subunit (POLR2A) only in the presence of WDR82. Binds specifically to CTD heptad repeats phosphorylated on 'Ser-5' of each heptad. Ref.3 Ref.4 Ref.5
Subcellular location	Nucleus speckle. Chromosome. Note: Localizes to a largely non-overlapping set of euchromatic nuclear speckles with SETD1A, suggesting that SETD1A and SET1B each bind to a unique set of target genes. Ref.3
Sequence similarities	Contains 1 post-SET domain. Contains 1 RRM (RNA recognition motif) domain. Contains 1 SET domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Chromosome Nucleus
Ligand	RNA-binding S-adenosyl-L-methionine
Molecular function	Activator Chromatin regulator Methyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	histone H3-K4 methylation Inferred from direct assay Ref.3. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Set1C/COMPASS complex Inferred from direct assay Ref.4Ref.5. Source: UniProtKB chromosome Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW histone-lysine N-methyltransferase activity Inferred from electronic annotation. Source: EC nucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1923

1923

Histone-lysine N-methyltransferase SETD1B

PRO_0000316993

Regions

Domain

93 – 181

89

RRM

Domain

1783 – 1905

123

SET

Domain

1907 – 1923

17

Post-SET

Compositional bias

366 – 1628

1263

Pro-rich

Compositional bias

989 – 1269

281

Glu-rich

Compositional bias

1062 – 1095

34

Asp-rich

Amino acid modifications

Modified residue

1616

1

Phosphoserine Ref.7

Modified residue

1620

1

Phosphoserine Ref.7

Secondary structure

1

.

.

.

1923

Helix Strand Turn

Details...

Helix

1704 – 1707

4

Sequences

	Sequence		Length	Mass (Da)
	Q9UPS6 [UniParc]. Last modified February 5, 2008. Version 2. Checksum: 057CD0948D670243	FASTA	1,923	208,732
	10 20 30 40 50 60 MENSHPPHHH HQQPPPQPGP SGERRNHHWR SYKLMIDPAL KKGHHKLYRY DGQHFSLAMS 70 80 90 100 110 120 SNRPVEIVED PRVVGIWTKN KELELSVPKF KIDEFYVGPV PPKQVTFAKL NDNIRENFLR 130 140 150 160 170 180 DMCKKYGEVE EVEILYNPKT KKHLGIAKVV FATVRGAKDA VQHLHSTSVM GNIIHVELDT 190 200 210 220 230 240 KGETRMRFYE LLVTGRYTPQ TLPVGELDAV SPIVNETLQL SDALKRLKDG GLSAGCGSGS 250 260 270 280 290 300 SSVTPNSGGT PFSQDTAYSS CRLDTPNSYG QGTPLTPRLG TPFSQDSSYS SRQPTPSYLF 310 320 330 340 350 360 SQDPAVTFKA RRHESKFTDA YNRRHEHHYV HNSPAVTAVA GATAAFRGSS DLPFGAVGGT 370 380 390 400 410 420 GGSSGPPFKA QPQDSATFAH TPPPAQATPA PGFKSAFSPY QTPVAHFPPP PEEPTATAAF 430 440 450 460 470 480 GARDSGEFRR APAPPPLPPA EPLAKEKPGT PPGPPPPDTN SMELGGRPTF GWSPEPCDSP 490 500 510 520 530 540 GTPTLESSPA GPEKPHDSLD SRIEMLLKEQ RTKLLFLREP DSDTELQMEG SPISSSSSQL 550 560 570 580 590 600 SPLAPFGTNS QPGFRGPTPP SSRPSSTGLE DISPTPLPDS DEDEELDLGL GPRPPPEPGP 610 620 630 640 650 660 PDPAGLLSQT AEVALDLVGD RTPTSEKMDE GQQSSGEDME ISDDEMPSAP ITSADCPKPM 670 680 690 700 710 720 VVTPGAAAVA APSVLAPTLP LPPPPGFPPL PPPPPPPPPQ PGFPMPPPLP PPPPPPPPAH 730 740 750 760 770 780 PAVTVPPPPL PAPPGVPPPP ILPPLPPFPP GLFPVMQVDM SHVLGGQWGG MPMSFQMQTQ 790 800 810 820 830 840 VLSRLMTGQG ACPYPPFMAA AAAAASAGLQ FVNLPPYRGP FSLSNSGPGR GQHWPPLPKF 850 860 870 880 890 900 DPSVPPPGYM PRQEDPHKAT VDGVLLVVLK ELKAIMKRDL NRKMVEVVAF RAFDEWWDKK 910 920 930 940 950 960 ERMAKASLTP VKSGEHKDED RPKPKDRIAS CLLESWGKGE GLGYEGLGLG IGLRGAIRLP 970 980 990 1000 1010 1020 SFKVKRKEPP DTTSSGDQKR LRPSTSVDEE DEESERERDR DMADTPCELA KRDPKGVGVR 1030 1040 1050 1060 1070 1080 RRPARPLELD SGGEEDEKES LSEEQESTEE EEEAEEEEEE EDDDDDDSDD RDESENDDED 1090 1100 1110 1120 1130 1140 TALSEASEKD EGDSDEEETV SIVTSKAEAT SSSESSESSE FESSSESSPS SSEDEEEVVA 1150 1160 1170 1180 1190 1200 REEEEEEEEE EMVAEESMAS AGPEDFEQDG EEAALAPGAP AVDSLGMEEE VDIETEAVAP 1210 1220 1230 1240 1250 1260 EERPSMLDEP PLPVGVEEPA DSREPPEEPG LSQEGAMLLS PEPPAKEVEA RPPLSPERAP 1270 1280 1290 1300 1310 1320 EHDLEVEPEP PMMLPLPLQP PLPPPRPPRP PSPPPEPETT DASHPSVPPE PLAEDHPPHT 1330 1340 1350 1360 1370 1380 PGLCGSLAKS QSTETVPATP GGEPPLSGGS SGLSLSSPQV PGSPFSYPAP SPSLSSGGLP 1390 1400 1410 1420 1430 1440 RTPGRDFSFT PTFSEPSGPL LLPVCPLPTG RRDERSGPLA SPVLLETGLP LPLPLPLPLP 1450 1460 1470 1480 1490 1500 LALPAVLRAQ ARAPTPLPPL LPAPLASCPP PMKRKPGRPR RSPPSMLSLD GPLVRPPAGA 1510 1520 1530 1540 1550 1560 ALGRELLLLP GQPQTPVFPS THDPRTVTLD FRNAGIPAPP PPLPPQPPPP PPPPPVEPTK 1570 1580 1590 1600 1610 1620 LPFKELDNQW PSEAIPPGPR GRDEVTEEYM ELAKSRGPWR RPPKKRHEDL VPPAGSPELS 1630 1640 1650 1660 1670 1680 PPQPLFRPRS EFEEMTILYD IWNGGIDEED IRFLCVTYER LLQQDNGMDW LNDTLWVYHP 1690 1700 1710 1720 1730 1740 STSLSSAKKK KRDDGIREHV TGCARSEGFY TIDKKDKLRY LNSSRASTDE PPADTQGMSI 1750 1760 1770 1780 1790 1800 PAQPHASTRA GSERRSEQRR LLSSFTGSCD SDLLKFNQLK FRKKKLKFCK SHIHDWGLFA 1810 1820 1830 1840 1850 1860 MEPIAADEMV IEYVGQNIRQ VIADMREKRY EDEGIGSSYM FRVDHDTIID ATKCGNFARF 1870 1880 1890 1900 1910 1920 INHSCNPNCY AKVITVESQK KIVIYSKQHI NVNEEITYDY KFPIEDVKIP CLCGSENCRG TLN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:197-205(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1120-1923. Tissue: Brain.
[3]	"Identification and characterization of the human Set1B histone H3-Lys4 methyltransferase complex." Lee J.-H., Tate C.M., You J.-S., Skalnik D.G. J. Biol. Chem. 282:13419-13428(2007) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME ACTIVITY, SUBCELLULAR LOCATION, IDENTIFICATION IN THE SET1 COMPLEX.
[4]	"Wdr82 is a C-terminal domain-binding protein that recruits the Setd1A Histone H3-Lys4 methyltransferase complex to transcription start sites of transcribed human genes." Lee J.H., Skalnik D.G. Mol. Cell. Biol. 28:609-618(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN SET1 COMPLEX, INTERACTION WITH WDR82; ASH2L AND POLR2A.
[5]	"Molecular regulation of H3K4 trimethylation by Wdr82, a component of human Set1/COMPASS." Wu M., Wang P.F., Lee J.S., Martin-Brown S., Florens L., Washburn M., Shilatifard A. Mol. Cell. Biol. 28:7337-7344(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN SET1 COMPLEX.
[6]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[7]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1616 AND SER-1620, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AC084018 Genomic DNA. No translation available.
AB028999 mRNA. Translation: BAA83028.1.

IPI

IPI00165459.

RefSeq

NP_055863.1. NM_015048.1.

UniGene

Hs.507122.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3UVO	X-ray	2.20	B	1702-1712	[»]
4ES0	X-ray	1.82	C	1698-1711	[»]

ProteinModelPortal

Q9UPS6.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000267197.

PTM databases

PhosphoSite

Q9UPS6.

Polymorphism databases

DMDM

166977692.

Proteomic databases

PaxDb

Q9UPS6.

PRIDE

Q9UPS6.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000267197; ENSP00000267197; ENSG00000139718.
ENST00000542440; ENSP00000442924; ENSG00000139718.

GeneID

23067.

KEGG

hsa:23067.

UCSC

uc001ubi.3. human.

Organism-specific databases

CTD

23067.

GeneCards

GC12P122243.

H-InvDB

HIX0011090.

HGNC

HGNC:29187. SETD1B.

HPA

HPA021667.

MIM

611055. gene.

neXtProt

NX_Q9UPS6.

PharmGKB

PA143485611.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2940.

HOGENOM

HOG000168216.

HOVERGEN

HBG055596.

InParanoid

Q9UPS6.

KO

K11422.

OMA

HHWRSYK.

OrthoDB

EOG4933HK.

Gene expression databases

Bgee

Q9UPS6.

CleanEx

HS_SETD1B.

Genevestigator

Q9UPS6.

Family and domain databases

Gene3D

3.30.70.330. 2 hits.

InterPro

IPR024657. COMPASS_Set1_N-SET.
IPR015722. Histone-lysine_MeTfrase.
IPR012677. Nucleotide-bd_a/b_plait.
IPR003616. Post-SET_dom.
IPR000504. RRM_dom.
IPR001214. SET_dom.
[Graphical view]

PANTHER

PTHR22884:SF10. PTHR22884:SF10. 1 hit.

Pfam

PF11764. N-SET. 1 hit.
PF00076. RRM_1. 1 hit.
PF00856. SET. 1 hit.
[Graphical view]

SMART

SM00508. PostSET. 1 hit.
SM00360. RRM. 1 hit.
SM00317. SET. 1 hit.
[Graphical view]

PROSITE

PS50868. POST_SET. 1 hit.
PS50102. RRM. 1 hit.
PS50280. SET. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

23067.

NextBio

44161.

SOURCE

Search...

Entry information

Entry name

SET1B_HUMAN

Accession

Primary (citable) accession number: Q9UPS6

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 5, 2008
Last sequence update:	February 5, 2008
Last modified:	May 1, 2013
This is version 87 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.