製品: Acetyl-Histone H3 (Lys9/14/18/23/27) Antibody
カタログ: AF4365
タンパク質の説明: Rabbit polyclonal antibody to Acetyl-Histone H3 (Lys9/14/18/23/27)
アプリケーション: WB IHC IF/ICC
反応性: Human, Mouse, Rat
予測: Bovine
分子量: 17kDa; 15kD(Calculated).
ユニプロット: P68431 | Q71DI3 | P84243
RRID: AB_2844627

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製品説明

ソース:
Rabbit
アプリケーション:
WB 1:500-1:2000, IF/ICC 1:100-1:500, IHC 1:50-1:200
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

反応性:
Human,Mouse,Rat
予測:
Bovine(100%)
クローナリティ:
Polyclonal
特異性:
Acetyl-Histone H3 (Lys9/14/18/23/27) Antibody detects endogenous levels of Acetyl-Histone H3 only when acetylated at Lys9/14/18/23/27.
RRID:
AB_2844627
引用形式: Affinity Biosciences Cat# AF4365, RRID:AB_2844627.
コンジュゲート:
Unconjugated.
精製:
The antiserum was purified by peptide affinity chromatography using SulfoLink™ Coupling Resin (Thermo Fisher Scientific).
保存:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
別名:

折りたたみ/展開

H3 histone family, member A; H3/A; H31_HUMAN; H3FA; Hist1h3a; HIST1H3B; HIST1H3C; HIST1H3D; HIST1H3E; HIST1H3F; HIST1H3G; HIST1H3H; HIST1H3I; HIST1H3J; histone 1, H3a; Histone cluster 1, H3a; Histone H3.1; Histone H3/a; Histone H3/b; Histone H3/c; Histone H3/d; Histone H3/f; Histone H3/h; Histone H3/i; Histone H3/j; Histone H3/k; Histone H3/l; ;H3.3A; HIST1 cluster, H3E; H3 histone family, member A; H3.1; H3/l; H3F3; H3FF; H3FJ; H3FL; Histone gene cluster 1, H3 histone family, member E; histone H3.1t; Histone H3/o; FLJ92264; H 3; H3; H3 histone family, member B; H3 histone family, member C; H3 histone family, member D; H3 histone family, member F; H3 histone family, member H; H3 histone family, member I; H3 histone family, member J; H3 histone family, member K; H3 histone family, member L; H3 histone family, member T; H3 histone, family 3A; H3/A; H3/b; H3/c; H3/d; h3/f; H3/h; H3/i; H3/j; H3/k; H3/t; H31_HUMAN; H3F1K; H3F3A; H3FA; H3FB; H3FC; H3FD; H3FH; H3FI; H3FK; HIST1 cluster, H3A; HIST1 cluster, H3B; HIST1 cluster, H3C; HIST1 cluster, H3D; HIST1 cluster, H3F; HIST1 cluster, H3G; HIST1 cluster, H3H; HIST1 cluster, H3I; HIST1 cluster, H3J; HIST1H3A; HIST1H3B; HIST1H3C; HIST1H3D; HIST1H3E; HIST1H3F; HIST1H3G; HIST1H3H; HIST1H3I; HIST1H3J; HIST3H3; Histone 1, H3a; Histone 1, H3b; Histone 1, H3c; Histone 1, H3d; Histone 1, H3e; Histone 1, H3f; Histone 1, H3g; Histone 1, H3h; Histone 1, H3i; Histone 3, H3; histone cluster 1 H3 family member a; histone cluster 1 H3 family member b; histone cluster 1 H3 family member c; histone cluster 1 H3 family member d; histone cluster 1 H3 family member e; histone cluster 1 H3 family member f; histone cluster 1 H3 family member g; histone cluster 1 H3 family member h; histone cluster 1 H3 family member i; histone cluster 1 H3 family member j; Histone cluster 1, H3a; Histone cluster 1, H3b; Histone cluster 1, H3c; Histone cluster 1, H3d; Histone cluster 1, H3e; Histone cluster 1, H3f; Histone cluster 1, H3g; Histone cluster 1, H3i; Histone cluster 1, H3j; Histone gene cluster 1, H3 histone family, member A; Histone gene cluster 1, H3 histone family, member B; Histone gene cluster 1, H3 histone family, member C; Histone gene cluster 1, H3 histone family, member D; Histone gene cluster 1, H3 histone family, member F; Histone gene cluster 1, H3 histone family, member G; Histone gene cluster 1, H3 histone family, member H; Histone gene cluster 1, H3 histone family, member I; Histone gene cluster 1, H3 histone family, member J; Histone gene cluster 1, H3A; Histone gene cluster 1, H3B; Histone gene cluster 1, H3C; Histone gene cluster 1, H3D; Histone gene cluster 1, H3E; Histone gene cluster 1, H3F; Histone gene cluster 1, H3G; Histone gene cluster 1, H3H; Histone gene cluster 1, H3I; Histone gene cluster 1, H3J; Histone H 3; Histone H3.1; Histone H3.2; Histone H3.3; Histone H3/a; Histone H3/b; Histone H3/c; Histone H3/d; Histone H3/f; Histone H3/h; Histone H3/i; Histone H3/j; Histone H3/k; Histone H3/l; Histone H3/m; H3 histone family 3A; H3 histone family 3B; H3 histone, family 3B (H3.3B); H3.3; H3.3A; H3.3B; H33_HUMAN; H3F3; H3F3A; H3f3b; Histone H3.3; Histone H3.3Q; Histone H3.A; Histone H3.B; MGC87782; MGC87783;

免疫原

免疫原:
Uniprot:
遺伝子(ID):
タンパク質配列:
MARTKQTARKSTGGKAPRKQLATKAARKSAPATGGVKKPHRYRPGTVALREIRRYQKSTELLIRKLPFQRLVREIAQDFKTDLRFQSSAVMALQEACEAYLVGLFEDTNLCAIHAKRVTIMPKDIQLARRIRGERA

MARTKQTARKSTGGKAPRKQLATKAARKSAPATGGVKKPHRYRPGTVALREIRRYQKSTELLIRKLPFQRLVREIAQDFKTDLRFQSSAVMALQEASEAYLVGLFEDTNLCAIHAKRVTIMPKDIQLARRIRGERA

MARTKQTARKSTGGKAPRKQLATKAARKSAPSTGGVKKPHRYRPGTVALREIRRYQKSTELLIRKLPFQRLVREIAQDFKTDLRFQSAAIGALQEASEAYLVGLFEDTNLCAIHAKRVTIMPKDIQLARRIRGERA

種類予測

種類予測:

Score>80(red) has high confidence and is suggested to be used for WB detection. *The prediction model is mainly based on the alignment of immunogen sequences, the results are for reference only, not as the basis of quality assurance.

Species
Results
Score
Bovine
100
Pig
0
Horse
0
Sheep
0
Dog
0
Xenopus
0
Zebrafish
0
Chicken
0
Rabbit
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - P68431/Q71DI3/P84243 基板として

Site PTM Type Enzyme
M1 Acetylation
R3 Methylation
T4 Phosphorylation Q99986 (VRK1)
K5 Acetylation
K5 Methylation
T7 Phosphorylation
K10 Acetylation
K10 Methylation
S11 Phosphorylation P31751 (AKT2) , Q99986 (VRK1) , Q96KB5 (PBK) , Q13153 (PAK1) , Q96GD4 (AURKB) , O14965 (AURKA) , Q16539 (MAPK14) , P51812 (RPS6KA3) , P11309 (PIM1) , P21980 (TGM2) , Q9UQB9 (AURKC) , O75582 (RPS6KA5)
T12 Phosphorylation O14757 (CHEK1) , O43293 (DAPK3)
K15 Acetylation
R18 Methylation
K19 Acetylation
K19 Methylation
K24 Acetylation
K24 Methylation
K28 Acetylation
K28 Methylation
S29 Phosphorylation P27361 (MAPK3) , P31751 (AKT2) , Q96GD4 (AURKB) , P45984 (MAPK9) , O75582 (RPS6KA5) , P28482 (MAPK1) , Q16539 (MAPK14) , P45983 (MAPK8)
K37 Acetylation
K37 Methylation
K37 Ubiquitination
K38 Methylation
Y42 Phosphorylation
T46 Phosphorylation Q05655 (PRKCD) , P31751 (AKT2)
K57 Acetylation
K57 Methylation
S58 Phosphorylation
K65 Methylation
K80 Acetylation
K80 Methylation
T81 Phosphorylation
S87 Phosphorylation
C97 S-Nitrosylation
K116 Acetylation
K123 Acetylation
K123 Methylation
Site PTM Type Enzyme
M1 Acetylation
R3 Methylation
T4 Phosphorylation
K5 Acetylation
K5 Methylation
T7 Phosphorylation
R9 Methylation
K10 Acetylation
K10 Methylation
S11 Phosphorylation
T12 Phosphorylation
K15 Acetylation
K15 Sumoylation
K15 Ubiquitination
R18 Methylation
K19 Acetylation
K19 Methylation
K19 Sumoylation
K19 Ubiquitination
K24 Acetylation
K24 Methylation
K24 Sumoylation
K24 Ubiquitination
K28 Acetylation
K28 Methylation
K28 Ubiquitination
S29 Phosphorylation
K37 Acetylation
K37 Methylation
K37 Ubiquitination
K38 Methylation
R41 Methylation
Y42 Phosphorylation
R43 Methylation
T46 Phosphorylation
R50 Methylation
K57 Acetylation
K57 Methylation
K57 Sumoylation
K57 Ubiquitination
S58 Phosphorylation
T59 Phosphorylation
R64 Methylation
K65 Methylation
K80 Acetylation
K80 Methylation
K80 Sumoylation
K80 Ubiquitination
T81 Phosphorylation
R84 Methylation
S97 Phosphorylation
Y100 Phosphorylation
T108 Phosphorylation
K116 Acetylation
K116 Ubiquitination
T119 Phosphorylation
K123 Acetylation
K123 Methylation
K123 Sumoylation
K123 Ubiquitination
R129 Methylation
Site PTM Type Enzyme
M1 Acetylation
R3 Methylation
T4 Phosphorylation
K5 Acetylation
K5 Methylation
T7 Phosphorylation
K10 Acetylation
K10 Methylation
S11 Phosphorylation P51812 (RPS6KA3) , O75582 (RPS6KA5) , O15111 (CHUK) , P06241 (FYN) , P31749 (AKT1) , Q15418 (RPS6KA1) , Q96GD4 (AURKB) , P17612 (PRKACA)
T12 Phosphorylation O14757 (CHEK1)
K15 Acetylation
R18 Methylation
K19 Acetylation
K19 Methylation
K24 Acetylation
K24 Methylation
K28 Acetylation
K28 Methylation
S29 Phosphorylation P17612 (PRKACA) , P28482 (MAPK1) , P27361 (MAPK3) , O75582 (RPS6KA5) , P45983 (MAPK8) , P45984 (MAPK9)
S32 Phosphorylation
K37 Acetylation
K37 Methylation
K37 Ubiquitination
Y42 Phosphorylation O60674 (JAK2)
T46 Phosphorylation
K57 Acetylation
K57 Methylation
S58 Phosphorylation
K65 Methylation
K80 Acetylation
K80 Methylation
T81 Phosphorylation
S87 Phosphorylation
C111 S-Nitrosylation
K116 Acetylation
K123 Acetylation
K123 Methylation

研究背景

機能:

Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.

PTMs:

Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.

Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.

Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters.

Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.

Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Thr-12 (H3T11ph) by chromatin-associated CHEK1 regulates the transcription of cell cycle regulatory genes by modulating acetylation of Lys-10 (H3K9ac). Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.

Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination (By similarity). Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins.

Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression.

Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.

Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.

Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.

Serine ADP-ribosylation constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).

細胞の位置付け:

Nucleus. Chromosome.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
サブユニット構造:

The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.

タンパク質ファミリー:

Belongs to the histone H3 family.

機能:

Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.

PTMs:

Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.

Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.

Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters.

Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.

Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.

Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination. Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins.

Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression.

Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.

Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.

Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.

Serine ADP-ribosylation constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).

細胞の位置付け:

Nucleus. Chromosome.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
サブユニット構造:

The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. During nucleosome assembly the chaperone ASF1A interacts with the histone H3-H4 heterodimer.

タンパク質ファミリー:

Belongs to the histone H3 family.

機能:

Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes. Constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. Deposited at sites of nucleosomal displacement throughout transcribed genes, suggesting that it represents an epigenetic imprint of transcriptionally active chromatin. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.

PTMs:

Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.

Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.

Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters.

Specifically enriched in modifications associated with active chromatin such as methylation at Lys-5 (H3K4me), Lys-37 and Lys-80. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me), which are linked to gene repression, are underrepresented. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.

Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin. Phosphorylation on Ser-32 (H3S31ph) is specific to regions bordering centromeres in metaphase chromosomes.

Ubiquitinated. Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination (By similarity).

Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression.

Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.

Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.

Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.

Serine ADP-ribosylation constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).

細胞の位置付け:

Nucleus. Chromosome.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
サブユニット構造:

The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Interacts with HIRA, a chaperone required for its incorporation into nucleosomes. Interacts with ZMYND11; when trimethylated at 'Lys-36' (H3.3K36me3).

タンパク質ファミリー:

Specific interaction of trimethylated form at 'Lys-36' (H3.3K36me3) with ZMYND11 is mediated by the encapsulation of Ser-32 residue with a composite pocket formed by the tandem bromo-PWWP domains.

Belongs to the histone H3 family.

研究領域

· Human Diseases > Substance dependence > Alcoholism.

· Human Diseases > Cancers: Overview > Transcriptional misregulation in cancer.

· Human Diseases > Immune diseases > Systemic lupus erythematosus.

参考文献

1). Lactate drives epithelial-mesenchymal transition in diabetic kidney disease via the H3K14la/KLF5 pathway. Redox biology, 2024 (PubMed: 38925041) [IF=11.4]

2). Antidepressant effect and mechanism of TMP269 on stress-induced depressive-like behavior in mice. Biochemical pharmacology, 2024 (PubMed: 38801927) [IF=5.8]

3). Sodium valproate attenuates the iE-DAP induced inflammatory response by inhibiting the NOD1-NF-κB pathway and histone modifications in bovine mammary epithelial cells. International Immunopharmacology, 2020 (PubMed: 32182568) [IF=5.6]

Application: WB    Species: bovine    Sample: BMECs

Fig. 5. |Protein expression and location of STAT1, HDACs and acetylated histone H3 in iE-DAP-stimulated BMECs after pretreatment with VPA. Western blot analysis showing the expression levels of STAT1 and HDAC1-3 (B), histone H3 and acetylated histone H3 (C) and the ratio of acetylated histone H3 to histone H3 (D).

4). Synthesis and Biological Evaluation of HDAC Inhibitors With a Novel Zinc Binding Group. Frontiers in Chemistry, 2020 (PubMed: 32351936) [IF=5.5]

5). Synthesis and biological evaluation of novel 2,4-dianilinopyrimidine derivatives as potent dual janus kinase 2 and histone deacetylases inhibitors. Journal of Molecular Structure, 2022 [IF=3.8]

6). Sodium butyrate promotes lipopolysaccharide-induced innate immune responses by enhancing mitogen-activated protein kinase activation and histone acetylation in bovine mammary epithelial cells. JOURNAL OF DAIRY SCIENCE, 2020 (PubMed: 33010913) [IF=3.5]

Application: WB    Species:    Sample: macrophages

Figure 7.| Relationship between histone acetylation and the upregulation of proinflammatory cytokines, chemokines, and β-defensin transcription by sodium butyrate (NaB) during LPS stimulation. (A) Bands of the protein related to histone H3 and acetylated histone H3. Quantification of the bands from Western blots.

7). Deletion of ACLY Disrupts Histone Acetylation and IL-10 Secretion in Trophoblasts, Which Inhibits M2 Polarization of Macrophages: A Possible Role in Recurrent Spontaneous Abortion. Oxidative Medicine and Cellular Longevity, 2022 (PubMed: 35602106)

Application: WB    Species: Human    Sample:

Figure 6 Downregulation of ACLY leads to change in IL-10 expression through histone acetylation. (a) The protein levels of acetylated histone H3 in villi of patients with the RSA and the HC groups, as measured using immunohistochemistry (n = 5). (b) The levels of total acetylated histone H3 and histone H3, as detected using Western blotting. (c) The expression of IL10, as detected using qRT-PCR. (d) The protein level of IL-10, as detected using ELISA. ∗∗p < 0.01, compared with the HC group; ∗∗p < 0.01, compared with shCtrl; #p < 0.05, ##p < 0.01, compared with shACLY. IOD: Integrated Optical Density. Scale bar: 200x = 50 μm, 400x = 20 μm.

Application: IHC    Species: Human    Sample:

Figure 6 Downregulation of ACLY leads to change in IL-10 expression through histone acetylation. (a) The protein levels of acetylated histone H3 in villi of patients with the RSA and the HC groups, as measured using immunohistochemistry (n = 5). (b) The levels of total acetylated histone H3 and histone H3, as detected using Western blotting. (c) The expression of IL10, as detected using qRT-PCR. (d) The protein level of IL-10, as detected using ELISA. ∗∗p < 0.01, compared with the HC group; ∗∗p < 0.01, compared with shCtrl; #p < 0.05, ##p < 0.01, compared with shACLY. IOD: Integrated Optical Density. Scale bar: 200x = 50 μm, 400x = 20 μm.

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