KEGG   PATHWAY: hsa03040
Entry
hsa03040                    Pathway                                
Name
Spliceosome - Homo sapiens (human)
Description
After transcription, eukaryotic mRNA precursors contain protein-coding exons and noncoding introns. In the following splicing, introns are excised and exons are joined by a macromolecular complex, the spliceosome. The standard spliceosome is made up of five small nuclear ribonucleoproteins (snRNPs), U1, U2, U4, U5, and U6 snRNPs, and several spliceosome-associated proteins (SAPs). Spliceosomes are not a simple stable complex, but a dynamic family of particles that assemble on the mRNA precursor and help fold it into a conformation that allows transesterification to proceed. Various spliceosome forms (e.g. A-, B- and C-complexes) have been identified.
Class
Genetic Information Processing; Transcription
Pathway map
hsa03040  Spliceosome
hsa03040

Network
nt06547  Spliceosome
  Element
N01963  Sm core assembly and 3 end processing of pre U1 snRNA
N01964  pre U1 snRNP import and U1 snRNP formation
N01968  Spliceosome assembly (E and A complex formation)
N01969  U4/U6-U5 snRNP fomation
N01970  Spliceosome assembly (B complex formation)
N01971  spliceosome activation
N01972  Spliceosome catalysis (branching)
N01993  Spliceosome catalysis (exon ligation)
N01994  Spliceosome disassembly
N01995  mRNA export to the cytoplasm
Drug
D11837  Zotatifin (USAN/INN)
D12345  Obefazimod (USAN)
Other DBs
GO: 0005681
PDB: 5O9Z 5Z56 6FF7 8I0W
Organism
Homo sapiens (human) [GN:hsa]
Gene
100534599  ISY1-RAB43; ISY1-RAB43 protein [KO:K12870]
10084  PQBP1; polyglutamine-binding protein 1 isoform 1 [KO:K12865]
101060301  HNRNPCL4; heterogeneous nuclear ribonucleoprotein C-like 4 [KO:K12884]
101447996  RNVU1-8; RNA, variant U1 small nuclear 8 [KO:K14276]
10189  ALYREF; THO complex subunit 4 [KO:K12881]
101954264  RNVU1-4; RNA, variant U1 small nuclear 4 [KO:K14276]
101954266  RNVU1-14; RNA, variant U1 small nuclear 14 [KO:K14276]
101954267  RNVU1-15; RNA, variant U1 small nuclear 15 [KO:K14276]
101954269  RNVU1-17; RNA, variant U1 small nuclear 17 [KO:K14276]
101954271  RNU6-9; RNA, U6 small nuclear 9 [KO:K14280]
101954272  RNVU1-3; RNA, variant U1 small nuclear 3 [KO:K14276]
101954273  RNVU1-1; RNA, variant U1 small nuclear 1 [KO:K14276]
101954275  RNU6-7; RNA, U6 small nuclear 7 [KO:K14280]
101954276  RNVU1-6; RNA, variant U1 small nuclear 6 [KO:K14276]
101954277  RNVU1-19; RNA, variant U1 small nuclear 19 [KO:K14276]
101954278  RNU6-8; RNA, U6 small nuclear 8 [KO:K14280]
10262  SF3B4; splicing factor 3B subunit 4 [KO:K12831]
102724594  U2AF1L5; splicing factor U2AF 35 kDa subunit-like protein isoform 1 [KO:K12836]
10285  SMNDC1; survival of motor neuron-related-splicing factor 30 [KO:K12839]
10286  BCAS2; pre-mRNA-splicing factor SPF27 [KO:K12861]
10291  SF3A1; splicing factor 3A subunit 1 [KO:K12825]
103625684  RNU6-2; RNA, U6 small nuclear 2 [KO:K14280]
10450  PPIE; peptidyl-prolyl cis-trans isomerase E isoform 1 [KO:K09564] [EC:5.2.1.8]
10465  PPIH; peptidyl-prolyl cis-trans isomerase H isoform 1 [KO:K09567] [EC:5.2.1.8]
10523  CHERP; calcium homeostasis endoplasmic reticulum protein isoform 2 [KO:K12841]
10569  SLU7; pre-mRNA-splicing factor SLU7 isoform b [KO:K12819]
10594  PRPF8; pre-mRNA-processing-splicing factor 8 [KO:K12856]
106480225  RNU2-63P; RNA, U2 small nuclear 63, pseudogene [KO:K14277]
10713  USP39; ubiquitin carboxyl-terminal hydrolase 39 isoform 1 [KO:K12847]
10772  SRSF10; serine/arginine-rich splicing factor 10 isoform 2 [KO:K12900]
10907  TXNL4A; thioredoxin-like protein 4A isoform 1 [KO:K12859]
10915  TCERG1; transcription elongation regulator 1 isoform 1 [KO:K12824]
10929  SRSF8; serine/arginine-rich splicing factor 8 [KO:K12891]
10946  SF3A3; splicing factor 3A subunit 3 isoform 1 [KO:K12827]
10992  SF3B2; splicing factor 3B subunit 2 [KO:K12829]
11017  SNRNP27; U4/U6.U5 small nuclear ribonucleoprotein 27 kDa protein [KO:K12846]
11157  LSM6; U6 snRNA-associated Sm-like protein LSm6 [KO:K12625]
11325  DDX42; ATP-dependent RNA helicase DDX42 [KO:K12835] [EC:5.6.2.7]
11338  U2AF2; splicing factor U2AF 65 kDa subunit isoform a [KO:K12837]
124900488  [KO:K14280]
124900516  [KO:K14278]
124900632  [KO:K14280]
124900883  [KO:K14280]
124900884  [KO:K14280]
124900885  [KO:K14280]
124900887  [KO:K14280]
124900915  [KO:K14277]
124901219  [KO:K14277]
124901224  [KO:K14278]
124901516  [KO:K14280]
124901518  [KO:K14280]
124901863  [KO:K14278]
124902331  [KO:K14280]
124902333  [KO:K14280]
124902335  [KO:K14280]
124902818  [KO:K14280]
124903091  [KO:K14280]
124903120  [KO:K14276]
124903275  [KO:K14280]
124903414  [KO:K14280]
124904107  [KO:K14280]
124904108  [KO:K14280]
124904109  [KO:K14280]
124904122  [KO:K14276]
124904135  [KO:K14277]
124904136  [KO:K14277]
124904137  [KO:K14277]
124904138  [KO:K14277]
124904139  [KO:K14277]
124904140  [KO:K14277]
124904141  [KO:K14277]
124904142  [KO:K14277]
124904143  [KO:K14277]
124904144  [KO:K14277]
124904145  [KO:K14277]
124904146  [KO:K14277]
124904147  [KO:K14277]
124904613  [KO:K14276]
124904616  RNVU1-28; RNA, variant U1 small nuclear 28 [KO:K14276]
124904619  RNVU1-31; RNA, variant U1 small nuclear 31 [KO:K14276]
124904621  RNVU1-27; RNA, variant U1 small nuclear 27 [KO:K14276]
124904624  RNVU1-26; U1 spliceosomal RNA [KO:K14276]
124904627  RNVU1-30; RNA, variant U1 small nuclear 30 [KO:K14276]
124904631  [KO:K14276]
124904634  [KO:K14276]
124904651  [KO:K14277]
124904694  [KO:K14280]
124904697  [KO:K14280]
124904706  [KO:K14280]
124904727  [KO:K14280]
124904986  [KO:K14280]
124905062  [KO:K14277]
124905168  [KO:K14280]
124905169  [KO:K14280]
124905264  [KO:K14280]
124905313  [KO:K14280]
124905321  [KO:K14276]
124905326  [KO:K14280]
124905327  [KO:K14280]
124905334  [KO:K14280]
124905519  [KO:K14280]
124905574  [KO:K14276]
124906338  [KO:K14280]
144983  HNRNPA1L2; heterogeneous nuclear ribonucleoprotein A1-like 2 [KO:K12741]
151903  CCDC12; coiled-coil domain-containing protein 12 isoform 2 [KO:K12871]
153527  ZMAT2; zinc finger matrin-type protein 2 [KO:K12848]
1655  DDX5; probable ATP-dependent RNA helicase DDX5 isoform a [KO:K12823] [EC:5.6.2.7]
1659  DHX8; ATP-dependent RNA helicase DHX8 isoform 1 [KO:K12818] [EC:5.6.2.6]
1665  DHX15; ATP-dependent RNA helicase DHX15 [KO:K12820] [EC:5.6.2.6]
199746  U2AF1L4; splicing factor U2AF 26 kDa subunit isoform 2 [KO:K12836]
220988  HNRNPA3; heterogeneous nuclear ribonucleoprotein A3 isoform a [KO:K12741]
22794  CASC3; protein CASC3 [KO:K14323]
22827  PUF60; poly(U)-binding-splicing factor PUF60 isoform a [KO:K12838]
22916  NCBP2; nuclear cap-binding protein subunit 2 isoform 1 [KO:K12883]
22938  SNW1; SNW domain-containing protein 1 isoform 2 [KO:K06063]
22985  ACIN1; apoptotic chromatin condensation inducer in the nucleus isoform 1 [KO:K12875]
23020  SNRNP200; U5 small nuclear ribonucleoprotein 200 kDa helicase [KO:K12854] [EC:5.6.2.6]
23350  U2SURP; U2 snRNP-associated SURP motif-containing protein isoform 1 [KO:K12842]
23450  SF3B3; splicing factor 3B subunit 3 [KO:K12830]
23451  SF3B1; splicing factor 3B subunit 1 isoform 1 [KO:K12828]
23658  LSM5; U6 snRNA-associated Sm-like protein LSm5 isoform a [KO:K12624]
24148  PRPF6; pre-mRNA-processing factor 6 [KO:K12855]
2521  FUS; RNA-binding protein FUS isoform 1 [KO:K13098]
25766  PRPF40B; pre-mRNA-processing factor 40 homolog B isoform 1 [KO:K12821]
25804  LSM4; U6 snRNA-associated Sm-like protein LSm4 isoform 1 [KO:K12623]
25949  SYF2; pre-mRNA-splicing factor SYF2 isoform 1 [KO:K12868]
26121  PRPF31; U4/U6 small nuclear ribonucleoprotein Prp31 [KO:K12844]
26827  RNU6-1; RNA, U6 small nuclear 1 [KO:K14280]
26828  RNU5F-1; RNA, U5F small nuclear 1 [KO:K14279]
26829  RNU5E-1; RNA, U5E small nuclear 1 [KO:K14279]
26830  RNU5D-1; RNA, U5D small nuclear 1 [KO:K14279]
26831  RNU5A-1; RNA, U5A small nuclear 1 [KO:K14279]
26832  RNU5B-1; RNA, U5B small nuclear 1 [KO:K14279]
26834  RNU4-2; RNA, U4 small nuclear 2 [KO:K14278]
26835  RNU4-1; RNA, U4 small nuclear 1 [KO:K14278]
26855  RNU2-2; RNA, U2 small nuclear 2 [KO:K14277]
26863  RNVU1-18; RNA, variant U1 small nuclear 18 [KO:K14276]
26864  RNVU1-7; RNA, variant U1 small nuclear 7 [KO:K14276]
26869  RNU1-3; RNA, U1 small nuclear 3 [KO:K14276]
26870  RNU1-2; RNA, U1 small nuclear 2 [KO:K14276]
26871  RNU1-1; RNA, U1 small nuclear 1 [KO:K14276]
27238  GPKOW; G-patch domain and KOW motifs-containing protein [KO:K13101]
27258  LSM3; U6 snRNA-associated Sm-like protein LSm3 [KO:K12622]
27316  RBMX; RNA-binding motif protein, X chromosome isoform 1 [KO:K12885]
27339  PRPF19; pre-mRNA-processing factor 19 [KO:K10599] [EC:2.3.2.27]
29896  TRA2A; transformer-2 protein homolog alpha isoform 1 [KO:K12897]
3178  HNRNPA1; heterogeneous nuclear ribonucleoprotein A1 isoform b [KO:K12741]
3183  HNRNPC; heterogeneous nuclear ribonucleoproteins C1/C2 isoform a [KO:K12884]
3190  HNRNPK; heterogeneous nuclear ribonucleoprotein K isoform b [KO:K12886]
3192  HNRNPU; heterogeneous nuclear ribonucleoprotein U isoform a [KO:K12888]
3303  HSPA1A; heat shock 70 kDa protein 1A [KO:K03283]
3304  HSPA1B; heat shock 70 kDa protein 1B [KO:K03283]
3305  HSPA1L; heat shock 70 kDa protein 1-like [KO:K03283]
3310  HSPA6; heat shock 70 kDa protein 6 [KO:K03283]
3312  HSPA8; heat shock cognate 71 kDa protein isoform 1 [KO:K03283]
343069  HNRNPCL1; heterogeneous nuclear ribonucleoprotein C-like 1 [KO:K12884]
392517  NCBP2L; nuclear cap-binding protein subunit 2-like [KO:K12883]
4116  MAGOH; protein mago nashi homolog [KO:K12877]
440563  HNRNPCL2; heterogeneous nuclear ribonucleoprotein C-like 2 [KO:K12884]
4670  HNRNPM; heterogeneous nuclear ribonucleoprotein M isoform a [KO:K12887]
4686  NCBP1; nuclear cap-binding protein subunit 1 isoform 1 [KO:K12882]
4809  SNU13; NHP2-like protein 1 [KO:K12845]
494115  RBMXL1; RNA binding motif protein, X-linked-like-1 [KO:K12885]
5093  PCBP1; poly(rC)-binding protein 1 [KO:K12889]
51340  CRNKL1; crooked neck-like protein 1 isoform a [KO:K12869]
51362  CDC40; pre-mRNA-processing factor 17 [KO:K12816]
51503  CWC15; spliceosome-associated protein CWC15 homolog [KO:K12863]
51634  RBMX2; RNA-binding motif protein, X-linked 2 [KO:K13107]
51639  SF3B6; splicing factor 3B subunit 6 [KO:K12833]
51645  PPIL1; peptidyl-prolyl cis-trans isomerase-like 1 [KO:K12733] [EC:5.2.1.8]
51690  LSM7; U6 snRNA-associated Sm-like protein LSm7 [KO:K12626]
51691  LSM8; LSM8 homolog, U6 small nuclear RNA associated [KO:K12627]
51729  WBP11; WW domain-binding protein 11 [KO:K12866]
5356  PLRG1; pleiotropic regulator 1 isoform 1 [KO:K12862]
54883  CWC25; pre-mRNA-splicing factor CWC25 homolog [KO:K28450]
55110  MAGOHB; protein mago nashi homolog 2 isoform 1 [KO:K12877]
55119  PRPF38B; pre-mRNA-splicing factor 38B isoform a [KO:K12850]
55660  PRPF40A; pre-mRNA-processing factor 40 homolog A isoform 2 [KO:K12821]
55696  RBM22; pre-mRNA-splicing factor RBM22 [KO:K12872]
55702  YJU2; splicing factor YJU2 [KO:K28527]
56259  CTNNBL1; beta-catenin-like protein 1 isoform 1 [KO:K12864]
56949  XAB2; pre-mRNA-splicing factor SYF1 [KO:K12867]
57187  THOC2; THO complex subunit 2 isoform 1 [KO:K12879]
57461  ISY1; pre-mRNA-splicing factor ISY1 homolog isoform 2 [KO:K12870]
57819  LSM2; U6 snRNA-associated Sm-like protein LSm2 [KO:K12621]
58517  RBM25; RNA-binding protein 25 [KO:K12822]
6060  RNU1-4; RNA, U1 small nuclear 4 [KO:K14276]
6063  RNVU1-2A; RNA, variant U1 small nuclear 2A [KO:K14276]
6066  RNU2-1; RNA, U2 small nuclear 1 [KO:K14277]
6100  RP9; retinitis pigmentosa 9 protein [KO:K19604]
6426  SRSF1; serine/arginine-rich splicing factor 1 isoform 1 [KO:K12890]
642659  HNRNPA1L3; heterogeneous nuclear ribonucleoprotein A1-like 3 [KO:K12741]
6427  SRSF2; serine/arginine-rich splicing factor 2 [KO:K12891]
6428  SRSF3; serine/arginine-rich splicing factor 3 [KO:K12892]
6429  SRSF4; serine/arginine-rich splicing factor 4 [KO:K12893]
6430  SRSF5; serine/arginine-rich splicing factor 5 isoform 1 [KO:K12893]
6431  SRSF6; serine/arginine-rich splicing factor 6 [KO:K12893]
6432  SRSF7; serine/arginine-rich splicing factor 7 isoform 1 [KO:K12896]
6434  TRA2B; transformer-2 protein homolog beta isoform 1 [KO:K12897]
649330  HNRNPCL3; heterogeneous nuclear ribonucleoprotein C-like 3 [KO:K12884]
6625  SNRNP70; U1 small nuclear ribonucleoprotein 70 kDa isoform 1 [KO:K11093]
6626  SNRPA; U1 small nuclear ribonucleoprotein A [KO:K11091]
6627  SNRPA1; U2 small nuclear ribonucleoprotein A' [KO:K11092]
6628  SNRPB; small nuclear ribonucleoprotein-associated proteins B and B' isoform B' [KO:K11086]
6629  SNRPB2; U2 small nuclear ribonucleoprotein B'' [KO:K11094]
6631  SNRPC; U1 small nuclear ribonucleoprotein C [KO:K11095]
6632  SNRPD1; small nuclear ribonucleoprotein Sm D1 isoform 1 [KO:K11087]
6633  SNRPD2; small nuclear ribonucleoprotein Sm D2 isoform 1 [KO:K11096]
6634  SNRPD3; small nuclear ribonucleoprotein Sm D3 [KO:K11088]
6635  SNRPE; small nuclear ribonucleoprotein E isoform 1 [KO:K11097]
6636  SNRPF; small nuclear ribonucleoprotein F isoform 1 [KO:K11098]
6637  SNRPG; small nuclear ribonucleoprotein G isoform a [KO:K11099]
7307  U2AF1; splicing factor U2AF 35 kDa subunit isoform a [KO:K12836]
7536  SF1; splicing factor 1 isoform 1 [KO:K13095]
7919  DDX39B; spliceosome RNA helicase DDX39B [KO:K12812] [EC:5.6.2.7]
79228  THOC6; THO complex subunit 6 isoform 1 [KO:K13175]
79753  SNIP1; smad nuclear-interacting protein 1 [KO:K13108]
80145  THOC7; THO complex subunit 7 isoform 1 [KO:K13176]
8175  SF3A2; splicing factor 3A subunit 2 [KO:K12826]
83443  SF3B5; splicing factor 3B subunit 5 [KO:K12832]
84321  THOC3; THO complex subunit 3 isoform 1 [KO:K12880]
8449  DHX16; pre-mRNA-splicing factor ATP-dependent RNA helicase DHX16 isoform 1 [KO:K12813] [EC:5.6.2.6]
84811  BUD13; BUD13 homolog isoform 1 [KO:K13106]
84844  PHF5A; PHD finger-like domain-containing protein 5A [KO:K12834]
84950  PRPF38A; pre-mRNA-splicing factor 38A [KO:K12849]
84991  RBM17; splicing factor 45 [KO:K12840]
8559  PRPF18; pre-mRNA-splicing factor 18 isoform 2 [KO:K12817]
8563  THOC5; THO complex subunit 5 [KO:K13174]
8683  SRSF9; serine/arginine-rich splicing factor 9 [KO:K21123]
8896  BUD31; protein BUD31 homolog [KO:K12873]
9092  SART1; U4/U6.U5 tri-snRNP-associated protein 1 [KO:K11984]
9128  PRPF4; U4/U6 small nuclear ribonucleoprotein Prp4 isoform 1 [KO:K12662]
9129  PRPF3; U4/U6 small nuclear ribonucleoprotein Prp3 isoform 1 [KO:K12843]
9343  EFTUD2; 116 kDa U5 small nuclear ribonucleoprotein component isoform a [KO:K12852]
9410  SNRNP40; U5 small nuclear ribonucleoprotein 40 kDa protein [KO:K12857]
9416  DDX23; probable ATP-dependent RNA helicase DDX23 [KO:K12858] [EC:5.6.2.7]
9716  AQR; RNA helicase aquarius [KO:K12874]
9775  EIF4A3; eukaryotic initiation factor 4A-III isoform 1 [KO:K13025] [EC:5.6.2.7]
9785  DHX38; pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 [KO:K12815] [EC:5.6.2.6]
9879  DDX46; probable ATP-dependent RNA helicase DDX46 isoform 2 [KO:K12811] [EC:5.6.2.7]
988  CDC5L; cell division cycle 5-like protein [KO:K12860]
9939  RBM8A; RNA-binding protein 8A [KO:K12876]
9984  THOC1; THO complex subunit 1 [KO:K12878]
Reference
PMID:19239890
  Authors
Wahl MC, Will CL, Luhrmann R
  Title
The spliceosome: design principles of a dynamic RNP machine.
  Journal
Cell 136:701-18 (2009)
DOI:10.1016/j.cell.2009.02.009
Reference
PMID:10978320
  Authors
Morris DP, Greenleaf AL
  Title
The splicing factor, Prp40, binds the phosphorylated carboxyl-terminal domain of RNA polymerase II.
  Journal
J Biol Chem 275:39935-43 (2000)
DOI:10.1074/jbc.M004118200
Reference
PMID:17537823
  Authors
Chen YI, Moore RE, Ge HY, Young MK, Lee TD, Stevens SW
  Title
Proteomic analysis of in vivo-assembled pre-mRNA splicing complexes expands the catalog of participating factors.
  Journal
Nucleic Acids Res 35:3928-44 (2007)
DOI:10.1093/nar/gkm347
Reference
PMID:19733268
  Authors
Ritchie DB, Schellenberg MJ, MacMillan AM
  Title
Spliceosome structure: piece by piece.
  Journal
Biochim Biophys Acta 1789:624-33 (2009)
DOI:10.1016/j.bbagrm.2009.08.010
Reference
PMID:28781166
  Authors
Bertram K, Agafonov DE, Dybkov O, Haselbach D, Leelaram MN, Will CL, Urlaub H, Kastner B, Luhrmann R, Stark H
  Title
Cryo-EM Structure of a Pre-catalytic Human Spliceosome Primed for Activation.
  Journal
Cell 170:701-713.e11 (2017)
DOI:10.1016/j.cell.2017.07.011
Reference
PMID:29360106
  Authors
Zhang X, Yan C, Zhan X, Li L, Lei J, Shi Y
  Title
Structure of the human activated spliceosome in three conformational states.
  Journal
Cell Res 28:307-322 (2018)
DOI:10.1038/cr.2018.14
Reference
PMID:29361316
  Authors
Haselbach D, Komarov I, Agafonov DE, Hartmuth K, Graf B, Dybkov O, Urlaub H, Kastner B, Luhrmann R, Stark H
  Title
Structure and Conformational Dynamics of the Human Spliceosomal B(act) Complex.
  Journal
Cell 172:454-464.e11 (2018)
DOI:10.1016/j.cell.2018.01.010
Reference
PMID:39068178
  Authors
Zhan X, Lu Y, Shi Y
  Title
Molecular basis for the activation of human spliceosome.
  Journal
Nat Commun 15:6348 (2024)
DOI:10.1038/s41467-024-50785-0
KO pathway
ko03040   

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