製品: Phospho-Histone H3 (Ser11) Antibody
カタログ: AF3358
タンパク質の説明: Rabbit polyclonal antibody to Phospho-Histone H3 (Ser11)
アプリケーション: WB IHC IF/ICC
反応性: Human, Mouse, Rat, Spodoptera frugiperda
予測: Bovine
分子量: 17kDa; 15kD(Calculated).
ユニプロット: P68431 | Q71DI3 | P84243
RRID: AB_2834773

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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, IHC 1:50-1:200, IF/ICC 1:100-1:500
*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,Spodoptera frugiperda
予測:
Bovine(100%)
クローナリティ:
Polyclonal
特異性:
Phospho-Histone H3 (Ser11) Antibody detects endogenous levels of Histone H3 only when phosphorylated at Serine 11.
RRID:
AB_2834773
引用形式: Affinity Biosciences Cat# AF3358, RRID:AB_2834773.
コンジュゲート:
Unconjugated.
精製:
The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.
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):
タンパク質の説明:
H3F3A 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.
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). Prpf31 is essential for the survival and differentiation of retinal progenitor cells by modulating alternative splicing. NUCLEIC ACIDS RESEARCH, 2021 (PubMed: 33476374) [IF=14.9]

Application: IF/ICC    Species: zebrafish    Sample: EDU (S-phase cells) and pH3 (M-phase cells)

Figure 4. Prpf31 deficiency causes abnormal spindle structure and mitotic arrest. (A) Double staining of EDU (S-phase cells) and pH3 (M-phase cells) in the retinal sections of WT siblings and prpf31−/− mutants at 36 and 48 hpf. The number of M-phase cells were significantly increased in the prpf31−/− mutants compared with siblings, suggesting that RPCs may be arrested in M phase. White arrows, overlapping signals of EDU and pH3. Scale bars: left, 100 μm; right, 10 μm. (B) Quantification of EDU+, pH3+ and EDU+ / pH3+ cells shown in (A). n = 6 for each panel. (C) In vivo imaging of the H2A-mCherry labeled chromosomes showed the mitotic progression of RPCs at 36 and 48 hpf. The time point of nuclear envelope breakdown (NEBD) was set as the start of mitosis. Scale bar, 10 μm. (D, E) Quantification of the time from NEBD to anaphase in RPCs at 36 and 48 hpf. 15 cells from more than five embryos were observed for each group. For abnormally divided cells, the longest observation time was 150 min. Scale bar, 10 μm. (F) The spindle and nuclei of RPCs from mutants and WT siblings were stained with anti-α-tubulin (green) antibody and PI (red), respectively. The different types of spindle anomalies are displayed in the panels (Abnormal 1–4). Scale bar, 10 μm. (G) Quantitative analysis of the RPCs numbers in each of the phases of mitosis in sibling and prpf31 mutant embryos at 36 and 48 hpf.

2). PpV, acting via the JNK pathway, represses apoptosis during normal development of Drosophila wing. APOPTOSIS, 2018 (PubMed: 30159848) [IF=7.2]

3). Securinine inhibits the tumor growth of human bladder cancer cells by suppressing Wnt/β-catenin signaling pathway and activating p38 and JNK signaling pathways. Biochemical pharmacology, 2024 (PubMed: 38484850) [IF=5.8]

Application: WB    Species: Human    Sample: BC cells

Fig. 1. SEC inhibits the proliferation and induces cell cycle arrest of BC cells. (A) The chemical structure of SEC. (B) The effect of SEC on the viability of BC cells (Crystal violet staining). (C) The effect of SEC on the viability of BC cells (MTT). (D) The effect of SEC on the colony-forming ability of BC cells (Colony formation assay). (E) The effect of SEC on the protein level of PCNA and c-Myc of BC cells (Western blot). (F) The effect of SEC on the cell cycle of BC cells (Flow cytometry). (G) The effect of SEC on the protein levels of CDK2, Cyclin A, Cyclin B1 and P-Histone H3 of BC cells (Western blot). Data are shown as mean ± SD from three independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001, vs. control group. #P < 0.05, ##P < 0.01, ###P < 0.001. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

4). Rictor regulates the vasculogenic mimicry of melanoma via the AKT-MMP-2/9 pathway. Journal of Cellular and Molecular Medicine, 2017 (PubMed: 28699701) [IF=5.3]

Application: WB    Species: human    Sample:

Fig. 3 Knockdown of Rictor inhibits melanoma cells proliferation and blocked the cell cycle in G2/M phase. (A) Cell viability of A375 and MUM-2B cells after Rictor knockdown evaluated by MTT assay (*P < 0.05, **P < 0.01). (B) Cell cycle of A375 and MUM-2B cells after Rictor knockdown examined by FCM. (C) The expression of p-CDK2 and p-Histone H3 induced by knockdown of Rictor.

5). MAD2-p31comet axis deficiency reduces cell proliferation, migration and sensitivity of microtubule-interfering agents in glioma. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2018 (PubMed: 29408509) [IF=3.1]

Application: WB    Species: human    Sample: shMAD2-U87 and shMAD2-U251 cells

Figure.4| MAD2 depletion or p31comet overexpression reduces sensitivity of glioma cells to microtubule-interfering agents. (E) The expression levels of cell cycle regulators (Cyclin B1, p-Aurora A/B, p-H3S10 and Histone H3 protein) were analyzed by western blot expression in control or p31comet OE-U87 and p31comet OE-U251 cells in the presence of paclitaxel (100 nM) or vinblastine (100 nM). GPADH was used as internal control in (D) and (E).

6). Schisandrin A and B enhance the dentate gyrus neurogenesis in mouse hippocampus. JOURNAL OF CHEMICAL NEUROANATOMY, 2020 (PubMed: 32027950) [IF=2.8]

Application: IF/ICC    Species: Mouse    Sample: hippocampus

Fig. 2. Sch A and B promote DG proliferation. (ADe) PHH3 immunostaining in the DG of the Blank, Olive oil, Sch A and Sch B groups respectively. (A'–D') Merged images of PHH3 and DAPI staining. (E) Statistical analysis of the numbers of PHH3+ cells among 4 groups. Data were the mean ± S.D.; * P < 0.05; ** P < 0.01; Scale bar = 50 μm in (A-D').

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