NHP6A/YPR052C Summary Help

Standard Name NHP6A 1
Systematic Name YPR052C
Feature Type ORF, Verified
Description High-mobility group (HMG) protein; binds to and remodels nucleosomes; involved in recruiting FACT and other chromatin remodelling complexes to chromosomes; functionally redundant with Nhp6Bp; required for transcriptional initiation fidelity of some tRNA genes; homologous to mammalian HMGB1 and HMGB2; NHP6A has a paralog, NHP6B, that arose from the whole genome duplication; protein abundance increases in response to DNA replication stress (2, 3, 4, 5, 6, 7, 8, 9 and see Summary Paragraph)
Name Description Non-Histone Protein 10
Chromosomal Location
ChrXVI:665974 to 665693 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All NHP6A GO evidence and references
  View Computational GO annotations for NHP6A
Molecular Function
Manually curated
High-throughput
Biological Process
Manually curated
Cellular Component
Manually curated
Targets 36 genes
Regulators 6 genes
Resources
Classical genetics
null
overexpression
Large-scale survey
null
overexpression
Resources
192 total interaction(s) for 135 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 12
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 6
  • Biochemical Activity: 1
  • Co-localization: 1
  • Co-purification: 1
  • PCA: 34
  • Reconstituted Complex: 2
  • Two-hybrid: 2

Genetic Interactions
  • Dosage Lethality: 2
  • Dosage Rescue: 15
  • Negative Genetic: 42
  • Phenotypic Enhancement: 9
  • Phenotypic Suppression: 9
  • Positive Genetic: 11
  • Synthetic Growth Defect: 26
  • Synthetic Lethality: 13
  • Synthetic Rescue: 5

Resources
Expression Summary
histogram
Resources
Length (a.a.) 93
Molecular Weight (Da) 10,802
Isoelectric Point (pI) 10.58
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXVI:665974 to 665693 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..282 665974..665693 2011-02-03 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 SGDIDS000006256
SUMMARY PARAGRAPH for NHP6A

NHP6A and NHP6B encode highly homologous proteins, each containing a single High Mobility Group (HMG) B domain, that are involved in modulation of chromatin structure (reviewed in 7). Though the short amino termini differ, they are 89 percent identical over the 90 amino acid core HMG B domain. Single null mutants in either nhp6a or nhp6b are viable with no phenotype, but the double knockout exhibits a slow growth phenotype at 30 degrees C and is inviable at 38 degrees C (2). Where both proteins have been assayed individually in vitro, slight differences are sometimes observed (e.g., see 11), but most biochemical experiments have been done only with purified Nhp6a protein. The two proteins are considered functionally equivalent and are collectively referred to as Nhp6.

Numerous genetic interactions, both synthetic lethality/sickness in combination with mutations in known chromatin remodelers (including FACT, Swi/Snf, RSC, Ssn6p, and Spt6p) and suppression of mutations by overexpression of Nhp6, indicate a role for Nhp6 in modulation of chromatin structure (reviewed in 7). These proteins are abundant, with approximately one molecule of Nhp6Ap present for every one to two nucleosomes, and one tenth as much Nhp6Bp (2), consistent with the observed 3-10 fold difference in mRNA levels (1). Nhp6 binds to DNA without sequence specificity, bending it sharply (12). Nhp6Ap binds directly to nucleosomes (13), loosening, or "remodelling", the structure of the core nucleosome (6, 3). The role of Nhp6 in the context of the yeast FACT complex (comprised of Spt16p and Pob3p) is the best characterized of its many interactions with chromatin remodelling activities (reviewed in 7). Unlike mammalian FACT, where one of the subunits contains an HMB domain, yeast FACT does not, instead relying on the external HMG domain of Nhp6 to localize it to chromatin where it contributes to the structural remodelling of the nucleosome begun by the binding of Nhp6 alone. However, the role of Nhp6 is not limited to its involvement with the FACT complex; it may serve to localize a number of different chromatin remodelling activities to the appropropriate places within the chromatin. Nhp6 activity contributes to the formation and correct placement of preinitiation complexes (PICs) for certain genes transcribed by either RNA polymerase II or RNA polymerase III, including the essential U6 snRNA (encoded by snR6 and transcribed by RNAP III), though it is possible that this is an indirect effect of the chromatin remodelling activities of Nhp6 (reviewed in 7). Nhp6 is also implicated in DNA repair, both as part of the FACT complex (14) and independently of FACT as well. In vitro, Nhp6Ap and the MutS-alpha complex, composed of Msh2p and Msh6p, colocalize with DNA containing mismatches (15).

In mammals the High Mobility Group B proteins encoded by HMGB1 and HMGB2 (originally called HMG1 and HMG2) are abundant and play important roles in the assembly of nucleoprotein complexes in processes including transcription, DNA repair, and V(D)J recombination. NHP6A and NHP6B appear to be the functional equivalents of HMGB1 and HMGB2. However, the mammalian proteins contain two repeats of the HMG domain and an acidic C-terminal tail, while the yeast proteins contain only a single HMG domain and no tail (reviewed in 8).

Last updated: 2010-03-30 Contact SGD

References cited on this page View Complete Literature Guide for NHP6A
1) Kolodrubetz D and Burgum A  (1990) Duplicated NHP6 genes of Saccharomyces cerevisiae encode proteins homologous to bovine high mobility group protein 1. J Biol Chem 265(6):3234-9
2) Paull TT, et al.  (1996) Yeast HMG proteins NHP6A/B potentiate promoter-specific transcriptional activation in vivo and assembly of preinitiation complexes in vitro. Genes Dev 10(21):2769-81
3) Rhoades AR, et al.  (2004) Structural features of nucleosomes reorganized by yeast FACT and its HMG box component, Nhp6. Mol Cell Biol 24(9):3907-17
4) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
5) Kassavetis GA and Steiner DF  (2006) Nhp6 is a transcriptional initiation fidelity factor for RNA polymerase III transcription in vitro and in vivo. J Biol Chem 281(11):7445-51
6) Xin H, et al.  (2009) yFACT induces global accessibility of nucleosomal DNA without H2A-H2B displacement. Mol Cell 35(3):365-76
7) Stillman DJ  (2010) Nhp6: A small but powerful effector of chromatin structure in Saccharomyces cerevisiae. Biochim Biophys Acta 1799(1-2):175-180
8) Thomas JO  (2001) HMG1 and 2: architectural DNA-binding proteins. Biochem Soc Trans 29(Pt 4):395-401
9) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
10) Kolodrubetz D, et al.  (1988) Amino-terminal sequence of a Saccharomyces cerevisiae nuclear protein, NHP6, shows significant identity to bovine HMG1. FEBS Lett 238(1):175-9
11) Braglia P, et al.  (2007) Requirement of Nhp6 Proteins for Transcription of a Subset of tRNA Genes and Heterochromatin Barrier Function in Saccharomyces cerevisiae. Mol Cell Biol 27(5):1545-57
12) Paull TT and Johnson RC  (1995) DNA looping by Saccharomyces cerevisiae high mobility group proteins NHP6A/B. Consequences for nucleoprotein complex assembly and chromatin condensation. J Biol Chem 270(15):8744-54
13) Ruone S, et al.  (2003) Multiple Nhp6 molecules are required to recruit Spt16-Pob3 to form yFACT complexes and to reorganize nucleosomes. J Biol Chem 278(46):45288-95
14) Vandemark AP, et al.  (2006) The structure of the yFACT Pob3-M domain, its interaction with the DNA replication factor RPA, and a potential role in nucleosome deposition. Mol Cell 22(3):363-74
15) Labazi M, et al.  (2009) Modulation of the DNA-binding activity of Saccharomyces cerevisiae MSH2-MSH6 complex by the high-mobility group protein NHP6A, in vitro. Nucleic Acids Res 37(22):7581-9
16) Zhu C, et al.  (2009) High-resolution DNA-binding specificity analysis of yeast transcription factors. Genome Res 19(4):556-66