THP1/YOL072W Summary Help

Standard Name THP1 1
Systematic Name YOL072W
Alias BUD29 2
Feature Type ORF, Verified
Description Nuclear pore-associated protein; component of TREX-2 complex (Sac3p-Thp1p-Sus1p-Cdc31p) involved in transcription elongation and mRNA export from the nucleus; involved in post-transcriptional tethering of active genes to the nuclear periphery and to non-nascent mRNP; contains a PAM domain implicated in protein-protein binding (3, 4, 5, 6, 7 and see Summary Paragraph)
Name Description Tho2/Hpr1 Phenotype 1
Chromosomal Location
ChrXV:194970 to 196337 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All THP1 GO evidence and references
  View Computational GO annotations for THP1
Molecular Function
Manually curated
Biological Process
Manually curated
High-throughput
Cellular Component
Manually curated
Classical genetics
null
Large-scale survey
null
unspecified
Resources
255 total interaction(s) for 157 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 22
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 26
  • Biochemical Activity: 2
  • Co-crystal Structure: 1
  • Co-purification: 1
  • PCA: 1
  • Reconstituted Complex: 1

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Lethality: 1
  • Dosage Rescue: 1
  • Negative Genetic: 119
  • Phenotypic Enhancement: 1
  • Phenotypic Suppression: 1
  • Positive Genetic: 36
  • Synthetic Growth Defect: 14
  • Synthetic Lethality: 19
  • Synthetic Rescue: 6

Resources
Expression Summary
histogram
Resources
Length (a.a.) 455
Molecular Weight (Da) 52,678
Isoelectric Point (pI) 9
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXV:194970 to 196337 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2006-01-05 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1368 194970..196337 2006-01-05 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000005433
SUMMARY PARAGRAPH for THP1

Thp1p is an RNA-binding protein which forms the stable TREX-2 (TRanscription EXport) complex with Sac3p, Sus1p, and Cdc31p (3, 4, 8). TREX-2 is associated with the nuclear pore, is essential for nuclear mRNA export, and plays a role in mRNP biogenesis and genome maintenance (9, 8, 10, 11, 12, 13). TREX-2 functions by docking the mRNP to specific nucleoporins at the nuclear entrance of the nuclear pore complex (NPC) (3). TREX-2 components Sus1p and Cdc31p function synergistically to promote association of TREX-2 with the NPC, where it is anchored via the nucleoporin Nup1p (14, 13). The TREX-2 complex facilitates the repositioning and association of actively transcribing genes with nuclear pores -"gene gating"- that is central to integrating transcription, processing, and mRNA nuclear export (14).

TREX and TREX-2, the two main mRNA export complexes, are also required for efficient transcription-coupled repair (TCR) in yeast (15). Thp1p (TREX-2) and two other proteins previously shown to control transcription-associated recombination, Hpr1p and Tho2p (members of the THO complex), act in the same "pathway" connecting transcription elongation with the incidence of mitotic recombination (1). TREX-2, together with THO/TREX, defines a specific pathway connecting transcription elongation with export via an RNA-dependent dynamic process that provides a feedback mechanism for the control of transcription and the preservation of genetic integrity of transcribed DNA regions (11).

Sgf73p, a subunit of the SAGA histone acetyltransferase complex, mediates recruitment of Thp1p and Sac3p to SAGA and their stable interaction with Sus1p-Cdc31p to form TREX-2 and target it to the nuclear pore complex (16). Targeting of Thp1p to the nuclear pore complex is perturbed in cells mutant for SEM1, a component of the lid subcomplex of the regulatory subunit of the 26S proteasome (17).

Mutants disrupted for THP1 grow slowly, are cold-sensitive and sporulate with reduced efficiency (18). Deletion of THP1 also strongly stimulates recombination and impairs transcription (1, 4). sac3Delta confers a transcription defect and hyper-recombination phenotype identical to that of thp1Delta (4), and mutations in either Sac3p or Thp1p affect genome integrity and lead to strong mRNA export defects (3, 4, 19, 11). The poly(A)+ RNA-binding heterogeneous nuclear ribonucleoprotein Nab2p is a multicopy suppressor of the transcription and RNA export defects of thp1Delta cells (4). thp1Delta cells also exhibit diploid-specific sensitivity to doxorubicin (20).

Orthologs of Thp1p, the TREX-2 complex as a whole, and Nup1p, have been identified in Arabidopsis (13). Homologs of Thp1p have also been identified in Schizosaccharomyces pombe, Caenorhabditis elegans, Drosophila melanogaster, and Homo sapiens (1).

Last updated: 2010-06-07 Contact SGD

References cited on this page View Complete Literature Guide for THP1
1) Gallardo M and Aguilera A  (2001) A new hyperrecombination mutation identifies a novel yeast gene, THP1, connecting transcription elongation with mitotic recombination. Genetics 157(1):79-89
2) Ni L and Snyder M  (2001) A genomic study of the bipolar bud site selection pattern in Saccharomyces cerevisiae. Mol Biol Cell 12(7):2147-70
3) Fischer T, et al.  (2002) The mRNA export machinery requires the novel Sac3p-Thp1p complex to dock at the nucleoplasmic entrance of the nuclear pores. EMBO J 21(21):5843-52
4) Gallardo M, et al.  (2003) Nab2p and the Thp1p-Sac3p complex functionally interact at the interface between transcription and mRNA metabolism. J Biol Chem 278(26):24225-32
5) Ciccarelli FD, et al.  (2003) The PAM domain, a multi-protein complex-associated module with an all-alpha-helix fold. BMC Bioinformatics 4():64
6) Chekanova JA, et al.  (2008) Sus1, Sac3, and Thp1 mediate post-transcriptional tethering of active genes to the nuclear rim as well as to non-nascent mRNP. RNA 14(1):66-77
7) Tous C, et al.  (2011) A novel assay identifies transcript elongation roles for the Nup84 complex and RNA processing factors. EMBO J 30(10):1953-64
8) Fischer T, et al.  (2004) Yeast centrin Cdc31 is linked to the nuclear mRNA export machinery. Nat Cell Biol 6(9):840-8
9) Rodriguez-Navarro S, et al.  (2004) Sus1, a functional component of the SAGA histone acetylase complex and the nuclear pore-associated mRNA export machinery. Cell 116(1):75-86
10) Kohler A, et al.  (2006) The mRNA export factor Sus1 is involved in Spt/Ada/Gcn5 acetyltransferase-mediated H2B deubiquitinylation through its interaction with Ubp8 and Sgf11. Mol Biol Cell 17(10):4228-36
11) Gonzalez-Aguilera C, et al.  (2008) The THP1-SAC3-SUS1-CDC31 complex works in transcription elongation-mRNA export preventing RNA-mediated genome instability. Mol Biol Cell 19(10):4310-8
12) Klockner C, et al.  (2009) Mutational Uncoupling of the Role of Sus1 in Nuclear Pore Complex Targeting of an mRNA Export Complex and Histone H2B Deubiquitination. J Biol Chem 284(18):12049-56
13) Lu Q, et al.  (2010) Arabidopsis homolog of the yeast TREX-2 mRNA export complex: components and anchoring nucleoporin. Plant J 61(2):259-70
14) Jani D, et al.  (2009) Sus1, Cdc31, and the Sac3 CID region form a conserved interaction platform that promotes nuclear pore association and mRNA export. Mol Cell 33(6):727-37
15) Gaillard H, et al.  (2007) A new connection of mRNP biogenesis and export with transcription-coupled repair. Nucleic Acids Res 35(12):3893-906
16) Kohler A, et al.  (2008) Yeast Ataxin-7 links histone deubiquitination with gene gating and mRNA export. Nat Cell Biol 10(6):707-15
17) Faza MB, et al.  (2009) Sem1 is a functional component of the nuclear pore complex-associated messenger RNA export machinery. J Cell Biol 184(6):833-46
18) Iwanejko L, et al.  (1999) Disruption and functional analysis of six ORFs on chromosome XV: YOL117w, YOL115w ( TRF4), YOL114c, YOL112w ( MSB4), YOL111c and YOL072w. Yeast 15(14):1529-39
19) Thomsen R, et al.  (2008) General, rapid, and transcription-dependent fragmentation of nucleolar antigens in S. cerevisiae mRNA export mutants. RNA 14(4):706-16
20) Westmoreland TJ, et al.  (2009) Comparative genome-wide screening identifies a conserved doxorubicin repair network that is diploid specific in Saccharomyces cerevisiae. PLoS One 4(6):e5830