Reviewed, UniProtKB/Swiss-Prot O75533 (SF3B1_HUMAN)

Names and origin

Protein names

Recommended name:
    Splicing factor 3B subunit 1
Alternative name(s):
    Pre-mRNA-splicing factor SF3b 155 kDa subunit
      Short name=SF3b155
    Spliceosome-associated protein 155
      Short name=SAP 155

Gene names

Name:	SF3B1
Synonyms:	SAP155

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	1304 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Subunit of the splicing factor SF3B required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA. May also be involved in the assembly of the 'E' complex. Belongs also to the minor U12-dependent spliceosome, which is involved in the splicing of rare class of nuclear pre-mRNA intron.
Subunit structure	Identified in the spliceosome C complex, at least composed of AQR, ASCC3L1, C19orf29, CDC40, CDC5L, CRNKL1, DDX23, DDX41, DDX48, DDX5, DGCR14, DHX35, DHX38, DHX8, EFTUD2, FRG1, GPATC1, HNRPA1, HNRPA2B1, HNRPA3, HNRPC, HNRPF, HNRPH1, HNRPK, HNRPM, HNRPR, HNRPU, KIAA1160, KIAA1604, LSM2, LSM3, MAGOH, MORG1, PABPC1, PLRG1, PNN, PPIE, PPIL1, PPIL3, PPWD1, PRPF19, PRPF4B, PRPF6, PRPF8, RALY, RBM22, RBM8A, RBMX, SART1, SF3A1, SF3A2, SF3A3, SF3B1, SF3B2, SF3B3, SFRS1, SKIV2L2, SNRPA1, SNRPB, SNRPB2, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, SNW1, SRRM1, SRRM2, SYF2, SYNCRIP, TFIP11, THOC4, U2AF1, WDR57, XAB2 and ZCCHC8. Component of splicing factor SF3B which is composed of at least eight subunits; SF3B1/SAP155/SF3B155, SF3B2/SAP145/SF3B155, SF3B3/SAP130/SF3B130, SF3B4/SAP49/SF3B49, SF3B14A, PHF5A/SF3B14B, SF3B10 and SF3B125. SF3B associates with the splicing factor SF3A and a 12S RNA unit to form the U2 small nuclear ribonucleoproteins complex (U2 snRNP). SF3B1 interacts directly with the splicing factor U2AF. Phosphorylated form interacts with PPP1R8. Ref.4 Ref.5
Subcellular location	Nucleus speckle. Note= During mitosis, transiently dispersed from the nuclear speckles to the cytoplasm.
Post-translational modification	Phosphorylated. Phosphorylation occurs concomitantly with the splicing catalytic steps. Phosphorylation on Thr-244, Thr-248 and Thr-313 by cyclin-dependent kinases promotes interaction with PPP1R8 during mitosis. Ref.5 Ref.1 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14
Sequence similarities	Belongs to the SF3B1 family. Contains 11 HEAT repeats.

Ontologies

Keywords
Biological process	mRNA processing mRNA splicing
Cellular component	Nucleus Spliceosome
Domain	Repeat
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	nuclear mRNA splicing, via spliceosome Ref.1 Non-traceable author statement. Source: UniProtKB
Cellular component	nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell spliceosome Ref.1 Non-traceable author statement. Source: UniProtKB
Molecular function	RNA splicing factor activity, transesterification mechanism Ref.1 Non-traceable author statement. Source: UniProtKB protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATG12	O94817	1	EBI-876542,EBI-746742
BRF2	Q9HAW0	1	EBI-876542,EBI-1055224
GSK3B	P49841	1	EBI-876542,EBI-373586
HDAC3	O15379	1	EBI-876542,EBI-607682
PUF60	Q9UHX1	1	EBI-876542,EBI-1053259
RNPS1	Q15287	1	EBI-876542,EBI-395959
SMNDC1	O75940	1	EBI-876542,EBI-1052641
SNRPN	P63162	1	EBI-876542,EBI-712493
WDR57	Q96DI7	1	EBI-876542,EBI-538492
YWHAZ	P63104	1	EBI-876542,EBI-347088

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1304

1304

Splicing factor 3B subunit 1

PRO_0000174323

Regions

Repeat

529 – 568

40

HEAT 1

Repeat

569 – 603

35

HEAT 2

Repeat

604 – 641

38

HEAT 3

Repeat

643 – 677

35

HEAT 4

Repeat

680 – 718

39

HEAT 5

Repeat

763 – 801

39

HEAT 6

Repeat

843 – 881

39

HEAT 7

Repeat

1010 – 1048

39

HEAT 8

Repeat

1052 – 1090

39

HEAT 9

Repeat

1122 – 1160

39

HEAT 10

Repeat

1163 – 1201

39

HEAT 11

Region

223 – 491

269

Interaction with PPP1R8

Amino acid modifications

Modified residue

129

1

Phosphoserine Ref.14

Modified residue

142

1

Phosphothreonine Ref.11 Ref.14

Modified residue

194

1

Phosphoserine Ref.14

Modified residue

207

1

Phosphothreonine Ref.10 Ref.14

Modified residue

211

1

Phosphothreonine Ref.9 Ref.10 Ref.13 Ref.14

Modified residue

223

1

Phosphothreonine Ref.9 Ref.11 Ref.12 Ref.14

Modified residue

227

1

Phosphothreonine Ref.12 Ref.14

Modified residue

235

1

Phosphothreonine Ref.8 Ref.14

Modified residue

244

1

Phosphothreonine Ref.5 Ref.11

Modified residue

248

1

Phosphothreonine Probable

Modified residue

257

1

Phosphothreonine Ref.12

Modified residue

261

1

Phosphothreonine Ref.12

Modified residue

267

1

Phosphothreonine Ref.12

Modified residue

296

1

Phosphothreonine Ref.9

Modified residue

299

1

Phosphothreonine Ref.9 Ref.12

Modified residue

313

1

Phosphothreonine Probable

Modified residue

316

1

Phosphothreonine Ref.9

Modified residue

326

1

Phosphothreonine Ref.9 Ref.10 Ref.14

Modified residue

328

1

Phosphothreonine Ref.10 Ref.14

Modified residue

332

1

Phosphoserine Ref.14

Modified residue

344

1

Phosphoserine Ref.7

Modified residue

350

1

Phosphothreonine Ref.7

Modified residue

354

1

Phosphothreonine Ref.7 Ref.13

Modified residue

432

1

Phosphothreonine Ref.12

Modified residue

488

1

Phosphoserine Ref.13 Ref.14

Experimental info

Mutagenesis

223

1

T → A: No effect on interaction with PPP1R8 Ref.5

Mutagenesis

227

1

T → A: No effect on interaction with PPP1R8 Ref.5

Mutagenesis

235

1

T → A: No effect on interaction with PPP1R8 Ref.5

Mutagenesis

244

1

T → A: Slight inhibition of interaction with PPP1R8 Ref.5

Mutagenesis

248

1

T → A: Slight inhibition of interaction with PPP1R8 Ref.5

Mutagenesis

257

1

T → A: No effect on interaction with PPP1R8 Ref.5

Mutagenesis

261

1

T → A: Slight inhibition of interaction with PPP1R8 Ref.5

Mutagenesis

267

1

T → A: No effect on interaction with PPP1R8 Ref.5

Mutagenesis

273

1

T → A: No effect on interaction with PPP1R8 Ref.5

Mutagenesis

278

1

T → A: No effect on interaction with PPP1R8 Ref.5

Mutagenesis

296

1

T → A: No effect on interaction with PPP1R8 Ref.5

Mutagenesis

303

1

T → A: No effect on interaction with PPP1R8 Ref.5

Mutagenesis

313

1

T → A: No effect on interaction with PPP1R8 Ref.5

Secondary structure

1

.

.

.

.

.

.

.

1304

Helix Strand Turn

Details...

Helix

380 – 395

16

Helix

401 – 405

5

Beta strand

410 – 414

5

Sequences

	Sequence		Length	Mass (Da)
	O75533-1 [UniParc]. Last modified August 1, 1999. Version 2. Checksum: 40DB21A6209165A7	FASTA	1,304	145,815
	10 20 30 40 50 60 MAKIAKTHED IEAQIREIQG KKAALDEAQG VGLDSTGYYD QEIYGGSDSR FAGYVTSIAA 70 80 90 100 110 120 TELEDDDDDY SSSTSLLGQK KPGYHAPVAL LNDIPQSTEQ YDPFAEHRPP KIADREDEYK 130 140 150 160 170 180 KHRRTMIISP ERLDPFADGG KTPDPKMNVR TYMDVMREQH LTKEEREIRQ QLAEKAKAGE 190 200 210 220 230 240 LKVVNGAAAS QPPSKRKRRW DQTADQTPGA TPKKLSSWDQ AETPGHTPSL RWDETPGRAK 250 260 270 280 290 300 GSETPGATPG SKIWDPTPSH TPAGAATPGR GDTPGHATPG HGGATSSARK NRWDETPKTE 310 320 330 340 350 360 RDTPGHGSGW AETPRTDRGG DSIGETPTPG ASKRKSRWDE TPASQMGGST PVLTPGKTPI 370 380 390 400 410 420 GTPAMNMATP TPGHIMSMTP EQLQAWRWER EIDERNRPLS DEELDAMFPE GYKVLPPPAG 430 440 450 460 470 480 YVPIRTPARK LTATPTPLGG MTGFHMQTED RTMKSVNDQP SGNLPFLKPD DIQYFDKLLV 490 500 510 520 530 540 DVDESTLSPE EQKERKIMKL LLKIKNGTPP MRKAALRQIT DKAREFGAGP LFNQILPLLM 550 560 570 580 590 600 SPTLEDQERH LLVKVIDRIL YKLDDLVRPY VHKILVVIEP LLIDEDYYAR VEGLEIISNL 610 620 630 640 650 660 AKAAGLATMI STMRPDIDNM DEYVRNTTAR AFAVVASALG IPSLLPFLKA VCKSKKSWQA 670 680 690 700 710 720 RHTGIKIVQQ IAILMGCAIL PHLRSLVEII EHGLVDEQQK VRTISALAIA ALAEAATPYG 730 740 750 760 770 780 IESFDSVLKP LWKGIRQHRG KGLAAFLKAI GYLIPLMDAE YANYYTREVM LILIREFQSP 790 800 810 820 830 840 DEEMKKIVLK VVKQCCGTDG VEANYIKTEI LPPFFKHFWQ HRMALDRRNY RQLVDTTVEL 850 860 870 880 890 900 ANKVGAAEII SRIVDDLKDE AEQYRKMVME TIEKIMGNLG AADIDHKLEE QLIDGILYAF 910 920 930 940 950 960 QEQTTEDSVM LNGFGTVVNA LGKRVKPYLP QICGTVLWRL NNKSAKVRQQ AADLISRTAV 970 980 990 1000 1010 1020 VMKTCQEEKL MGHLGVVLYE YLGEEYPEVL GSILGALKAI VNVIGMHKMT PPIKDLLPRL 1030 1040 1050 1060 1070 1080 TPILKNRHEK VQENCIDLVG RIADRGAEYV SAREWMRICF ELLELLKAHK KAIRRATVNT 1090 1100 1110 1120 1130 1140 FGYIAKAIGP HDVLATLLNN LKVQERQNRV CTTVAIAIVA ETCSPFTVLP ALMNEYRVPE 1150 1160 1170 1180 1190 1200 LNVQNGVLKS LSFLFEYIGE MGKDYIYAVT PLLEDALMDR DLVHRQTASA VVQHMSLGVY 1210 1220 1230 1240 1250 1260 GFGCEDSLNH LLNYVWPNVF ETSPHVIQAV MGALEGLRVA IGPCRMLQYC LQGLFHPARK 1270 1280 1290 1300 VRDVYWKIYN SIYIGSQDAL IAHYPRIYND DKNTYIRYEL DYIL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Phosphorylation of spliceosomal protein SAP 155 coupled with splicing catalysis." Wang C., Chua K., Seghezzi W., Lees E., Gozani O., Reed R. Genes Dev. 12:1409-1414(1998) [PubMed: 9585501] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION.
[2]	Yu W., Gibbs R.A. Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1011-1304. Tissue: Brain.
[3]	"Functional association of U2 snRNP with the ATP-independent spliceosomal complex E." Das R., Zhou Z., Reed R. Mol. Cell 5:779-787(2000) [PubMed: 10882114] [Abstract] Cited for: CHARACTERIZATION OF THE SPLICEOSOME.
[4]	"Characterization of novel SF3b and 17S U2 snRNP proteins, including a human Prp5p homologue and an SF3b DEAD-box protein." Will C.L., Urlaub H., Achsel T., Gentzel M., Wilm M., Luehrmann R. EMBO J. 21:4978-4988(2002) [PubMed: 12234937] [Abstract] Cited for: SUBUNIT.
[5]	"Phosphorylation-dependent interaction between the splicing factors SAP155 and NIPP1." Boudrez A., Beullens M., Waelkens E., Stalmans W., Bollen M. J. Biol. Chem. 277:31834-31841(2002) [PubMed: 12105215] [Abstract] Cited for: INTERACTION WITH PPP1R8, PHOSPHORYLATION AT THR-244; THR-248 AND THR-313, MUTAGENESIS OF THR-223; THR-227; THR-235; THR-244; THR-248; THR-257; THR-261; THR-267; THR-273; THR-278; THR-296; THR-303 AND THR-313.
[6]	"Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis." Jurica M.S., Licklider L.J., Gygi S.P., Grigorieff N., Moore M.J. RNA 8:426-439(2002) [PubMed: 11991638] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE SPICEOSOMAL C COMPLEX.
[7]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-344; THR-350 AND THR-354, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"Global phosphoproteome of HT-29 human colon adenocarcinoma cells." Kim J.-E., Tannenbaum S.R., White F.M. J. Proteome Res. 4:1339-1346(2005) [PubMed: 16083285] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-235, MASS SPECTROMETRY.
[9]	"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 THR-211; THR-223; THR-296; THR-299; THR-316 AND THR-326, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-207; THR-211; THR-326 AND THR-328, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-142; THR-223 AND THR-244, MASS SPECTROMETRY. Tissue: Epithelium.
[12]	"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-223; THR-227; THR-257; THR-261; THR-267; THR-299 AND THR-432, MASS SPECTROMETRY.
[13]	"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 THR-211; THR-354 AND SER-488, MASS SPECTROMETRY.
[14]	"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-129; THR-142; SER-194; THR-207; THR-211; THR-223; THR-227; THR-235; THR-326; THR-328; SER-332 AND SER-488, MASS SPECTROMETRY.
[15]	"NMR solution structure of the human spliceosomal protein complex p14-SF3B155." RIKEN structural genomics initiative (RSGI) Submitted (JAN-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 379-424.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF054284 mRNA. Translation: AAC97189.1.
AF070540 mRNA. Translation: AAC28633.1.

UniGene

Hs.632554

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2F9D	X-ray	2.50	P/Q	373-415	[»]
2F9J	X-ray	3.00	P/Q	381-415	[»]
2FHO	NMR	-	A	379-424	[»]

SMR

O75533. Positions 379-424.

ModBase

Search...

Protein-protein interaction databases

IntAct

O75533. 16 interactions.

PTM databases

PhosphoSite

O75533.

Proteomic databases

PRIDE

O75533.

Genome annotation databases