General information | DisProt: | DP00501 | Name: | PC4 protein | Synonym(s): | Q6IBA2_HUMAN
SUB1 homolog (S. cerevisiae)
SUB1 homolog (S. cerevisiae), isoform CRA_a
cDNA, FLJ92014, highly similar to Homo sapiens SUB1 homolog (S. cerevisiae) (SUB1), mRNA
Positive cofactor 4
| First appeared in release: | Release 3.2 (05/26/2006) | UniProt: | Q6IBA2 | UniGene: | Hs.229641 | SwissProt: | Q6IBA2_HUMAN | TrEMBL: | | NCBI (GI): | 74721952 | Source organism: | Homo sapiens (Human) | Sequence length: | 127 | Percent disordered: | 47% | Homologues: | |
Native sequence |
10 20 30 40 50 60 | | | | | | MPKSKELVSS SSSGSDSDSE VDKKLKRKKQ VAPEKPVKKQ KTGETSRALS SSKQSSSSRD - 60 DNMFQIGKMR YVSVRDFKGK VLIDIREYWM DPEGEMKPGR KGISLNPEQW SQLKEQISDI - 120 DDAVRKL
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Functional narrative |
Cofactors mediate interactions between the general transcription machinery and DNA-bound activators to enhance or repress transcription. The transcriptional human positive cofactor 4 (PC4), mediates activator-dependent transcription by increasing the recruitment of the GTFs and probably also RNA polymerase II through concerted interactions with the basal transcription machinery. Because PC4 stimulates activation of RNA polymerase II transcription by a wide variety of transactivation domains [herpes simplex virion protein 16 (VP16), AH, CTF, SP1, E1a, IE, and NF-kappaB], representing all major classes of transactivation domains (such as acidic, proline rich, or glutamine rich), it is considered to be a general cofactor. The ability to mediate activator-dependent transcription has been correlated to its capability to bind double-stranded DNA. Contrary to transcriptional activation, PC4 has been shown to repress transcription under specific conditions depending upon the interaction with melted dsDNA. The inhibitory activity can be attenuated by the combined effects of TATA-box binding protein (TBP)-associated factors (TAFIIs), transcription factor II (TFII)H, and a preassembled RNA polymerase II holoenzyme. The helicase activity of ERCC3 (also referred to as XPB), present in TFIIH, is probably crucial for alleviation of PC4-mediated repression. Accordingly, the foremost function of PC4 could actually be to repress transcription until PIC assembly is complete, because TFIIH is generally believed to be the last factor to enter the PIC. Apart from its role in PIC stabilization and transcription regulation, PC4 is possibly involved in mRNA processing through the interaction with the polyadenylation factor CstF-64, DNA replication by interactions with the replication factor RPA, and tumor suppression by interactions with the breast- and ovarian-specific tumor suppressor protein BRCA1 and the proline- and glutamine-rich activation domains of AP-2.
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Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
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Region 1 | Type: | Disordered | Name: | PC4ntd (amino-terminal half of PC4) | Location: | 1 - 60 | Length: | 60 | Region sequence: |
MPKSKELVSSSSSGSDSDSEVDKKLKRKKQVAPEKPVKKQKTGETSRALSSSKQSSSSRD
| Modification type: | Fragment
Native
| PDB: | | Structural/functional type: | Function arises from the disordered state | Functional classes: | Modification site
Molecular recognition effectors
Molecular assembly
| Functional subclasses: | Phosphorylation
Acetylation
Autoregulatory
Transactivation (transcriptional activation)
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (298 K; pH: 5.6; 0.2-1 mM protein; 50 mM KCl, 50 mM phosphate, Complete protease inhibitor, glycine; HSQC, NOESY and TOCSY)
| References:
- Jonker HR, Wechselberger RW, Boelens R, Kaptein R, Folkers GE. "The Intrinsically Unstructured Domain of PC4 Modulates the Activity of the Structured Core through Inter- and Intramolecular Interactions." Biochemistry. 2006; 45(15): 5067-81. PubMed: 16605275
| Comments:
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References |
- Werten S, Moras D. "A global transcription cofactor bound to juxtaposed strands of unwound DNA." Nat Struct Mol Biol. 2006; 13(2): 181-2. PubMed: 16415882
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Comments |
Additional UniGene ID: Hs.644972
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