| Structural highlights
1j2x is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | ,
| | Gene: | RAP74 (Homo sapiens) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[CTDP1_HUMAN] Defects in CTDP1 are a cause of congenital cataracts facial dysmorphism and neuropathy syndrome (CCFDN) [MIM:604168]. CCFDN is an autosomal recessive developmental disorder that occurs in an endogamous group of Vlax Roma (Gypsies). The syndrome is characterized by a complex clinical phenotype with seemingly unrelated features involving multiple organs and systems. Developmental abnormalities include congenital cataracts and microcorneae, hypomyelination of the peripheral nervous system, impaired physical growth, delayed early motor and intellectual development, facial dysmorphism and hypogonadism. Central nervous system involvement, with cerebral and spinal cord atrophy, may be the result of disrupted development with superimposed degenerative changes. Affected individuals are prone to severe rhabdomyolysis after viral infections and to serious complications related to general anesthesia (such as pulmonary edema and epileptic seizures).[1]
Function
[T2FA_HUMAN] TFIIF is a general transcription initiation factor that binds to RNA polymerase II and helps to recruit it to the initiation complex in collaboration with TFIIB. It promotes transcription elongation.[2] [CTDP1_HUMAN] Processively dephosphorylates 'Ser-2' and 'Ser-5' of the heptad repeats YSPTSPS in the C-terminal domain of the largest RNA polymerase II subunit. This promotes the activity of RNA polymerase II. Plays a role in the exit from mitosis by dephosphorylating crucial mitotic substrates (USP44, CDC20 and WEE1) that are required for M-phase-promoting factor (MPF)/CDK1 inactivation.[3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
After mRNA transcription termination in eukaryotes, the hyperphosphorylated form of RNA polymerase II (pol II0) must be recycled by TFIIF-associating C-terminal domain phosphatase (FCP1), the phosphatase responsible for dephosphorylating the C-terminal domain of the largest polymerase subunit. Transcription factor (TF)-IIF stimulates the activity of FCP1, and the RNA polymerase II-associating protein 74 subunit of TFIIF forms a complex with FCP1 in both human and yeast. Here, we report a cocrystal structure of the winged-helix domain of human RNA polymerase II-associating protein 74 bound to the alpha-helical C terminus of human FCP1 (residues 944-961). These results illustrate the molecular mechanism by which TFIIF efficiently recruits FCP1 to the pol II transcription machinery for recycling of the polymerase.
Molecular mechanism of recruitment of TFIIF- associating RNA polymerase C-terminal domain phosphatase (FCP1) by transcription factor IIF.,Kamada K, Roeder RG, Burley SK Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2296-9. Epub 2003 Feb 18. PMID:12591941[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Varon R, Gooding R, Steglich C, Marns L, Tang H, Angelicheva D, Yong KK, Ambrugger P, Reinhold A, Morar B, Baas F, Kwa M, Tournev I, Guerguelcheva V, Kremensky I, Lochmuller H, Mullner-Eidenbock A, Merlini L, Neumann L, Burger J, Walter M, Swoboda K, Thomas PK, von Moers A, Risch N, Kalaydjieva L. Partial deficiency of the C-terminal-domain phosphatase of RNA polymerase II is associated with congenital cataracts facial dysmorphism neuropathy syndrome. Nat Genet. 2003 Oct;35(2):185-9. Epub 2003 Sep 21. PMID:14517542 doi:10.1038/ng1243
- ↑ Rossignol M, Keriel A, Staub A, Egly JM. Kinase activity and phosphorylation of the largest subunit of TFIIF transcription factor. J Biol Chem. 1999 Aug 6;274(32):22387-92. PMID:10428810
- ↑ Visconti R, Palazzo L, Della Monica R, Grieco D. Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit. Nat Commun. 2012 Jun 12;3:894. doi: 10.1038/ncomms1886. PMID:22692537 doi:10.1038/ncomms1886
- ↑ Kamada K, Roeder RG, Burley SK. Molecular mechanism of recruitment of TFIIF- associating RNA polymerase C-terminal domain phosphatase (FCP1) by transcription factor IIF. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2296-9. Epub 2003 Feb 18. PMID:12591941 doi:http://dx.doi.org/10.1073/pnas.262798199
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