UniProt functional annotation for P62805



	UniProt functional annotation for P62805

UniProt code: P62805.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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.

Subunit: 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.

Subcellular location: Nucleus. Chromosome.

Ptm: Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin. {ECO:0000269|PubMed:17967882, ECO:0000269|PubMed:2474456, ECO:0000269|PubMed:7664735}.

Ptm: Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation. {ECO:0000269|PubMed:11387442, ECO:0000269|PubMed:11448779, ECO:0000269|PubMed:15345777, ECO:0000269|PubMed:16567635}.

Ptm: Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage. {ECO:0000269|PubMed:11387442, ECO:0000269|PubMed:11448779, ECO:0000269|PubMed:15345777}.

Ptm: Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:12086618, PubMed:15964846, PubMed:17967882). Monomethylation is performed by KMT5A/SET8 (PubMed:15964846). Dimethylation and trimethylation is performed by KMT5B and KMT5C and induces gene silencing (By similarity). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (PubMed:31061526). {ECO:0000250|UniProtKB:P62806, ECO:0000269|PubMed:12086618, ECO:0000269|PubMed:15964846, ECO:0000269|PubMed:17967882, ECO:0000269|PubMed:31061526}.

Ptm: Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4. {ECO:0000269|PubMed:17967882, ECO:0000269|PubMed:21724829}.

Ptm: 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. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me). {ECO:0000269|PubMed:12086618, ECO:0000269|PubMed:15964846, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:17967882, ECO:0000269|PubMed:19818714}.

Ptm: Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage. {ECO:0000269|PubMed:30886146}.

Ptm: Sumoylated, which is associated with transcriptional repression. {ECO:0000269|PubMed:14578449}.

Ptm: 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. {ECO:0000269|PubMed:21925322}.

Ptm: Butyrylation of histones marks active promoters and competes with histone acetylation. {ECO:0000250|UniProtKB:P62806}.

Ptm: Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes. {ECO:0000269|PubMed:31542297}.

Ptm: Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription. {ECO:0000269|PubMed:31645732}.

Disease: Note=Chromosomal aberrations involving HISTONE H4 is a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;6)(q27;p21), with BCL6. {ECO:0000269|PubMed:12414651}.

Similarity: Belongs to the histone H4 family. {ECO:0000305}.

Sequence caution: Sequence=AAI28106.1; Type=Frameshift; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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.


Subunit:		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.
Subcellular location:		Nucleus. Chromosome.
Ptm:		Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin. {ECO:0000269\|PubMed:17967882, ECO:0000269\|PubMed:2474456, ECO:0000269\|PubMed:7664735}.
Ptm:		Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation. {ECO:0000269\|PubMed:11387442, ECO:0000269\|PubMed:11448779, ECO:0000269\|PubMed:15345777, ECO:0000269\|PubMed:16567635}.
Ptm:		Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage. {ECO:0000269\|PubMed:11387442, ECO:0000269\|PubMed:11448779, ECO:0000269\|PubMed:15345777}.
Ptm:		Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:12086618, PubMed:15964846, PubMed:17967882). Monomethylation is performed by KMT5A/SET8 (PubMed:15964846). Dimethylation and trimethylation is performed by KMT5B and KMT5C and induces gene silencing (By similarity). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (PubMed:31061526). {ECO:0000250\|UniProtKB:P62806, ECO:0000269\|PubMed:12086618, ECO:0000269\|PubMed:15964846, ECO:0000269\|PubMed:17967882, ECO:0000269\|PubMed:31061526}.
Ptm:		Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4. {ECO:0000269\|PubMed:17967882, ECO:0000269\|PubMed:21724829}.
Ptm:		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. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me). {ECO:0000269\|PubMed:12086618, ECO:0000269\|PubMed:15964846, ECO:0000269\|PubMed:16678110, ECO:0000269\|PubMed:17967882, ECO:0000269\|PubMed:19818714}.
Ptm:		Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage. {ECO:0000269\|PubMed:30886146}.
Ptm:		Sumoylated, which is associated with transcriptional repression. {ECO:0000269\|PubMed:14578449}.
Ptm:		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. {ECO:0000269\|PubMed:21925322}.
Ptm:		Butyrylation of histones marks active promoters and competes with histone acetylation. {ECO:0000250\|UniProtKB:P62806}.
Ptm:		Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes. {ECO:0000269\|PubMed:31542297}.
Ptm:		Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription. {ECO:0000269\|PubMed:31645732}.
Disease:		Note=Chromosomal aberrations involving HISTONE H4 is a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;6)(q27;p21), with BCL6. {ECO:0000269\|PubMed:12414651}.
Similarity:		Belongs to the histone H4 family. {ECO:0000305}.
Sequence caution:		Sequence=AAI28106.1; Type=Frameshift; Evidence={ECO:0000305};