|Gene:||hupA||Accession Numbers: EG10466 (EcoCyc), b4000, ECK3992|
Component of: HU DNA-binding transcriptional dual regulator (extended summary available)
Gene Citations: [Kohno90]
Locations: cytosol, membrane
|Map Position: [4,198,304 -> 4,198,576] (90.49 centisomes)||Length: 273 bp / 90 aa|
Molecular Weight of Polypeptide: 9.535 kD (from nucleotide sequence)
Unification Links: ASAP:ABE-0013077 , CGSC:34243 , DIP:DIP-35892N , EchoBASE:EB0461 , EcoGene:EG10466 , EcoliWiki:b4000 , Mint:MINT-1244407 , ModBase:P0ACF0 , OU-Microarray:b4000 , PortEco:hupA , PR:PRO_000022941 , Pride:P0ACF0 , Protein Model Portal:P0ACF0 , RefSeq:NP_418428 , RegulonDB:EG10466 , SMR:P0ACF0 , String:511145.b4000 , UniProt:P0ACF0
Relationship Links: InterPro:IN-FAMILY:IPR000119 , InterPro:IN-FAMILY:IPR010992 , InterPro:IN-FAMILY:IPR020816 , InterPro:IN-FAMILY:IPR023630 , PDB:Structure:1MUL , PDB:Structure:2O97 , Pfam:IN-FAMILY:PF00216 , Prints:IN-FAMILY:PR01727 , Prosite:IN-FAMILY:PS00045 , Smart:IN-FAMILY:SM00411
|Biological Process:||GO:0006351 - transcription, DNA-templated
[Perez00, Aki97, Broyles86, RouviereYaniv79, Painbeni97, Lee01b, Delihas01]
GO:0006974 - cellular response to DNA damage stimulus [Khil02]
GO:0030261 - chromosome condensation [UniProtGOA11a]
|Molecular Function:||GO:0003677 - DNA binding
[UniProtGOA11a, GOA01, Azam99]
GO:0005515 - protein binding [Ramstein03, Chodavarapu11, Chodavarapu08, Chodavarapu08a, Butland05]
GO:0042802 - identical protein binding [Ramstein03]
|Cellular Component:||GO:0005829 - cytosol
GO:0016020 - membrane [Lasserre06]
|MultiFun Terms:||information transfer → protein related → nucleoproteins, basic proteins|
|information transfer → RNA related → Transcription related|
|regulation → type of regulation → transcriptional level|
|regulation → type of regulation → transcriptional level → activator|
|regulation → type of regulation → transcriptional level → repressor|
|Growth Medium||Growth?||T (°C)||O2||pH||Osm/L||Growth Observations|
|LB enriched||Yes||37||Aerobic||6.95||Yes [Gerdes03, Comment 1]|
|LB Lennox||Yes||37||Aerobic||7||Yes [Baba06, Comment 2]|
|M9 medium with 1% glycerol||Yes||37||Aerobic||7.2||0.35||Yes [Joyce06, Comment 3]|
|MOPS medium with 0.4% glucose||Yes||37||Aerobic||7.2||0.22||Yes [Baba06, Comment 2]|
Subunit of: HU DNA-binding transcriptional dual regulator
The HU protein is a small DNA-binding protein that is considered a global regulatory protein and shares properties with histones, which play an important role in nucleoid organization [Ali99, Azam99, Azam00, Dorman09] and regulation [Kar05, Lee01b, Oberto09, Aki97, Semsey04, Painbeni97].
HU is a heterodimer formed by an α-subunit and a β-subunit, which are encoded by the hupA and hupB genes, respectively [Kano87, Kano88, Laine80, Kohno90, Bonnefoy91], and are differentially stimulated during cold shock [Giangrossi02]. HU is a transcriptional dual regulator. HU-1 (HupB) and HU-2 (HupA) are closely related but differ by 28 residues, and they have a high content of hydrophobic residues represented mostly by alanine. There is no sequence homology between the proteins HU-1 and HU-2 compared to any of the five histones of different eukaryotes studied [Laine80].
HU forms high-affinity complexes with DNA containing sharp bends, kinks, branched and bulged structures, or single-strand breaks and loops [Bonnefoy94a, Castaing95, Lavoie96, Lyubchenko97, Pontiggia93].
Three dimeric forms exist in Escherichia coli: two homodimers, EcHUα2 and EcHUβ2, and a heterodimer, HUαβ [Ramstein03]. All these forms are in thermal equilibrium between two dimeric conformations (N2<-->I2) that vary in their secondary structure content [Garnier11].
Based on high-temperature molecular dynamics simulation and NMR experiments, information has been obtained about the structural and dynamic features at the atomic level for the N2<-->I2 thermal transition of the EcHUβ2 homodimer [Garnier11]. A 3D model has been proposed for the major I2 conformation of EcHUβ2 [Garnier11].
The crystal structure of the DNA-HUαβ complex has been resolved [Guo07a]. In the presence of poly(P), HupA is efficiently degraded by Lon [Kuroda06]. The presence of HU depends on the phase of growth [Ali99], and it is distributed uniformly in the nucleoid [Azam00]. Currently, no inducer for this regulator has been reported in the literature.
HU belongs to a family of DNA architectural proteins and acts mostly as a regulatory or accessory factor, stabilizing a correct nucleoprotein complex [Dame02, Sarkar07, Boubrik91]. For example, HU introduces negative supercoiling in covalently closed circular DNA in the presence of topoisomerase I [RouviereYaniv79a, Shindo92]. The HU protein has been shown to be involved in DNA replication [Jaffe97, Ryan02, Kano91] and the formation of transcription foci [Berger10], and it modulates the binding of IHF to oriC [Bonnefoy92a] and stabilizes the DnaA oligomer bound to oriC [Chodavarapu08a]. As another example, HU is required for the expression of σS factors [Balandina01]. Recently, Oberto et al. showed that HU also plays an important role in the regulation of many genes in response to environmental changes and adaptation to stress, including changes in osmolarity, acid stress, SOS induction, and anaerobiosis [Oberto09, Bi09].
HU binds DNA without sequence specificity and with low affinity, but at low concentrations HU induces bends and at high concentrations HU induces the formation of rigid filaments [Kamashev99, Bonnefoy91, Krolenko99, Azam99, Czapla08]. The binding of this protein is destabilized when the tension of the double helix increases [Xiao11].
The effects of HU protein enhancements on DNA flexibility and the cyclization rate have been determined, based on a Monte Carlo approach, by Czapla et al. [Czapla11].
DNA binding site length: 34 base-pairs
Symmetry: Inverted Repeat
|Sequence-Conflict||19 -> 32|
3/2/1998 (pkarp) Merged genes G119/b4000 and EG10466/hupA
10/20/97 Gene b4000 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10466; confirmed by SwissProt match.
Ali99: Ali Azam T, Iwata A, Nishimura A, Ueda S, Ishihama A (1999). "Growth phase-dependent variation in protein composition of the Escherichia coli nucleoid." J Bacteriol 181(20);6361-70. PMID: 10515926
Azam99: Azam TA, Ishihama A (1999). "Twelve species of the nucleoid-associated protein from Escherichia coli. Sequence recognition specificity and DNA binding affinity." J Biol Chem 274(46);33105-13. PMID: 10551881
Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554
Berger10: Berger M, Farcas A, Geertz M, Zhelyazkova P, Brix K, Travers A, Muskhelishvili G (2010). "Coordination of genomic structure and transcription by the main bacterial nucleoid-associated protein HU." EMBO Rep 11(1);59-64. PMID: 20010798
Bi09: Bi H, Sun L, Fukamachi T, Saito H, Kobayashi H (2009). "HU participates in expression of a specific set of genes required for growth and survival at acidic pH in Escherichia coli." Curr Microbiol 58(5);443-8. PMID: 19127382
Bonnefoy91: Bonnefoy E, Rouviere-Yaniv J (1991). "HU and IHF, two homologous histone-like proteins of Escherichia coli, form different protein-DNA complexes with short DNA fragments." EMBO J 10(3);687-96. PMID: 2001682
Boubrik91: Boubrik F, Bonnefoy E, Rouviere-Yaniv J (1991). "HU and IHF: similarities and differences. In Escherichia coli, the lack of HU is not compensated for by IHF." Res Microbiol 142(2-3);239-47. PMID: 1925023
Broyles86: Broyles SS, Pettijohn DE (1986). "Interaction of the Escherichia coli HU protein with DNA. Evidence for formation of nucleosome-like structures with altered DNA helical pitch." J Mol Biol 187(1);47-60. PMID: 3514923
Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043
Castaing95: Castaing B, Zelwer C, Laval J, Boiteux S (1995). "HU protein of Escherichia coli binds specifically to DNA that contains single-strand breaks or gaps." J Biol Chem 270(17);10291-6. PMID: 7730334
Chodavarapu08: Chodavarapu S, Gomez R, Vicente M, Kaguni JM (2008). "Escherichia coli Dps interacts with DnaA protein to impede initiation: a model of adaptive mutation." Mol Microbiol 67(6);1331-46. PMID: 18284581
Chodavarapu08a: Chodavarapu S, Felczak MM, Yaniv JR, Kaguni JM (2008). "Escherichia coli DnaA interacts with HU in initiation at the E. coli replication origin." Mol Microbiol 67(4);781-92. PMID: 18179598
Chodavarapu11: Chodavarapu S, Felczak MM, Kaguni JM (2011). "Two forms of ribosomal protein L2 of Escherichia coli that inhibit DnaA in DNA replication." Nucleic Acids Res 39(10);4180-91. PMID: 21288885
Czapla08: Czapla L, Swigon D, Olson WK (2008). "Effects of the nucleoid protein HU on the structure, flexibility, and ring-closure properties of DNA deduced from Monte Carlo simulations." J Mol Biol 382(2);353-70. PMID: 18586040
Czapla11: Czapla L, Peters JP, Rueter EM, Olson WK, Maher LJ (2011). "Understanding apparent DNA flexibility enhancement by HU and HMGB architectural proteins." J Mol Biol 409(2);278-89. PMID: 21459097
Garnier11: Garnier N, Loth K, Coste F, Augustyniak R, Nadan V, Damblon C, Castaing B (2011). "An alternative flexible conformation of the E. coli HUβ(2) protein: structural, dynamics, and functional aspects." Eur Biophys J 40(2);117-29. PMID: 20936276
Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938
Giangrossi02: Giangrossi M, Giuliodori AM, Gualerzi CO, Pon CL (2002). "Selective expression of the beta-subunit of nucleoid-associated protein HU during cold shock in Escherichia coli." Mol Microbiol 44(1);205-16. PMID: 11967080
Jaffe97: Jaffe A, Vinella D, D'Ari R (1997). "The Escherichia coli histone-like protein HU affects DNA initiation, chromosome partitioning via MukB, and cell division via MinCDE." J Bacteriol 179(11);3494-9. PMID: 9171392
Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394
Kano91: Kano Y, Ogawa T, Ogura T, Hiraga S, Okazaki T, Imamoto F (1991). "Participation of the histone-like protein HU and of IHF in minichromosomal maintenance in Escherichia coli." Gene 103(1);25-30. PMID: 1879696
Krolenko99: Krolenko EV, Kamashev DE, Balandina AV, Karpov VL, Rouviere-Yaniv J, Preobrazhenskaia OV (1999). "[Immunochemical detection of the histone-like bacterial protein Hu in covalently bound DNA-protein complexes, obtained in vitro and in vivo]." Mol Biol (Mosk) 33(3);442-6. PMID: 10519118
Kuroda06: Kuroda A, Nomura K, Takiguchi N, Kato J, Ohtake H (2006). "Inorganic polyphosphate stimulates lon-mediated proteolysis of nucleoid proteins in Escherichia coli." Cell Mol Biol (Noisy-le-grand) 52(4);23-9. PMID: 17543195
Laine78: Laine B, Sautiere P, Biserte G, Cohen-Solal M, Gros F, Rouviere-Yaniv J (1978). "The amino- and carboxy-terminal amino acid sequences of protein HU from Escherichia coli." FEBS Lett 89(1);116-20. PMID: 350619
Laine80: Laine B, Kmiecik D, Sautiere P, Biserte G, Cohen-Solal M (1980). "Complete amino-acid sequences of DNA-binding proteins HU-1 and HU-2 from Escherichia coli." Eur J Biochem 103(3);447-61. PMID: 6987059
Lasserre06: Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006). "A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis." Electrophoresis 27(16);3306-21. PMID: 16858726
Oberto09: Oberto J, Nabti S, Jooste V, Mignot H, Rouviere-Yaniv J (2009). "The HU regulon is composed of genes responding to anaerobiosis, acid stress, high osmolarity and SOS induction." PLoS ONE 4(2);e4367. PMID: 19194530
Painbeni97: Painbeni E, Caroff M, Rouviere-Yaniv J (1997). "Alterations of the outer membrane composition in Escherichia coli lacking the histone-like protein HU." Proc Natl Acad Sci U S A 94(13);6712-7. PMID: 9192630
Perez00: Perez N, Rehault M, Amouyal M (2000). "A functional assay in Escherichia coli to detect non-assisted interaction between galactose repressor dimers." Nucleic Acids Res 28(18);3600-4. PMID: 10982882
Ramstein03: Ramstein J, Hervouet N, Coste F, Zelwer C, Oberto J, Castaing B (2003). "Evidence of a thermal unfolding dimeric intermediate for the Escherichia coli histone-like HU proteins: thermodynamics and structure." J Mol Biol 331(1);101-21. PMID: 12875839
Ryan02: Ryan VT, Grimwade JE, Nievera CJ, Leonard AC (2002). "IHF and HU stimulate assembly of pre-replication complexes at Escherichia coli oriC by two different mechanisms." Mol Microbiol 46(1);113-24. PMID: 12366835
Sarkar07: Sarkar T, Vitoc I, Mukerji I, Hud NV (2007). "Bacterial protein HU dictates the morphology of DNA condensates produced by crowding agents and polyamines." Nucleic Acids Res 35(3);951-61. PMID: 17259223
Shindo92: Shindo H, Furubayashi A, Shimizu M, Miyake M, Imamoto F (1992). "Preferential binding of E.coli histone-like protein HU alpha to negatively supercoiled DNA." Nucleic Acids Res 20(7);1553-8. PMID: 1579448
Xiao11: Xiao B, Zhang H, Johnson RC, Marko JF (2011). "Force-driven unbinding of proteins HU and Fis from DNA quantified using a thermodynamic Maxwell relation." Nucleic Acids Res 39(13);5568-77. PMID: 21427084
Teramoto10: Teramoto J, Yamanishi Y, Magdy el-SH, Hasegawa A, Kori A, Nakajima M, Arai F, Fukuda T, Ishihama A (2010). "Single live-bacterial cell assay of promoter activity and regulation." Genes Cells 15(11);1111-22. PMID: 20964794
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