3EWF

Crystal Structure Analysis of human HDAC8 H143A variant complexed with substrate.

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Protein Modification Annotation

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d3ewfb_	Alpha and beta proteins (a/b)	Arginase/deacetylase	Arginase/deacetylase	Histone deacetylase, HDAC	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d3ewfc_	Alpha and beta proteins (a/b)	Arginase/deacetylase	Arginase/deacetylase	Histone deacetylase, HDAC	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d3ewfa_	Alpha and beta proteins (a/b)	Arginase/deacetylase	Arginase/deacetylase	Histone deacetylase, HDAC	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d3ewfd_	Alpha and beta proteins (a/b)	Arginase/deacetylase	Arginase/deacetylase	Histone deacetylase, HDAC	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
B	SCOP2B Superfamily	Arginase/deacetylase-like	8040016	3000260	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Arginase/deacetylase-like	8040016	3000260	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Arginase/deacetylase-like	8040016	3000260	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Arginase/deacetylase-like	8040016	3000260	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
B	Hist_deacetyl	e3ewfB1	A: a/b three-layered sandwiches	X: HAD domain-like	H: HAD domain-related	T: Arginase/deacetylase	F: Hist_deacetyl	ECOD (1.6)
C	Hist_deacetyl	e3ewfC1	A: a/b three-layered sandwiches	X: HAD domain-like	H: HAD domain-related	T: Arginase/deacetylase	F: Hist_deacetyl	ECOD (1.6)
A	Hist_deacetyl	e3ewfA1	A: a/b three-layered sandwiches	X: HAD domain-like	H: HAD domain-related	T: Arginase/deacetylase	F: Hist_deacetyl	ECOD (1.6)
D	Hist_deacetyl	e3ewfD1	A: a/b three-layered sandwiches	X: HAD domain-like	H: HAD domain-related	T: Arginase/deacetylase	F: Hist_deacetyl	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	3.40.800.20	Alpha Beta	3-Layer(aba) Sandwich	Arginase	Chain A	CATH (4.3.0)
C	3.40.800.20	Alpha Beta	3-Layer(aba) Sandwich	Arginase	Chain A	CATH (4.3.0)
A	3.40.800.20	Alpha Beta	3-Layer(aba) Sandwich	Arginase	Chain A	CATH (4.3.0)
D	3.40.800.20	Alpha Beta	3-Layer(aba) Sandwich	Arginase	Chain A	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF00850	Histone deacetylase domain (Hist_deacetyl)	Histone deacetylase domain	Histones can be reversibly acetylated on several lysine residues. Regulation of transcription is caused in part by this mechanism. Histone deacetylases catalyse the removal of the acetyl group. Histone deacetylases are related to other proteins [1]. ...	Histones can be reversibly acetylated on several lysine residues. Regulation of transcription is caused in part by this mechanism. Histone deacetylases catalyse the removal of the acetyl group. Histone deacetylases are related to other proteins [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	Histone deacetylase 8	Hsp90 protein binding protein binding binding heat shock protein binding Hsp70 protein binding protein-folding chaperone binding deacetylase activity protein lysine deacetylase activity catalytic activity, acting on a protein deacylase activity catalytic activity hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides hydrolase activity histone modifying activity Hsp90 protein binding protein binding binding heat shock protein binding Hsp70 protein binding protein-folding chaperone binding deacetylase activity protein lysine deacetylase activity catalytic activity, acting on a protein deacylase activity catalytic activity hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides hydrolase activity histone modifying activity protein decrotonylase activity histone decrotonylase activity hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds transcription factor binding DNA-binding transcription factor binding cation binding ion binding metal ion binding small molecule binding histone deacetylase activity	negative regulation of post-translational protein modification regulation of cellular process regulation of protein modification process negative regulation of biological process regulation of protein ubiquitination regulation of primary metabolic process protein ubiquitination negative regulation of protein modification process negative regulation of cellular process protein metabolic process negative regulation of protein ubiquitination regulation of protein modification by small protein conjugation or removal protein modification process negative regulation of protein metabolic process negative regulation of post-translational protein modification regulation of cellular process regulation of protein modification process negative regulation of biological process regulation of protein ubiquitination regulation of primary metabolic process protein ubiquitination negative regulation of protein modification process negative regulation of cellular process protein metabolic process negative regulation of protein ubiquitination regulation of protein modification by small protein conjugation or removal protein modification process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process regulation of biological process negative regulation of protein modification by small protein conjugation or removal regulation of post-translational protein modification regulation of protein metabolic process negative regulation of metabolic process biological regulation primary metabolic process regulation of macromolecule metabolic process macromolecule modification metabolic process cellular process macromolecule metabolic process post-translational protein modification regulation of metabolic process protein modification by small protein conjugation protein modification by small protein conjugation or removal regulation of biosynthetic process epigenetic regulation of gene expression gene expression macromolecule biosynthetic process cellular component organization regulation of gene expression biosynthetic process chromatin organization chromatin remodeling regulation of macromolecule biosynthetic process cellular component organization or biogenesis regulation of telomere maintenance regulation of cellular component organization telomere organization nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process chromosome organization regulation of chromosome organization DNA metabolic process regulation of organelle organization nucleic acid metabolic process telomere maintenance organelle organization regulation of DNA metabolic process regulation of protein stability regulation of biological quality mitotic sister chromatid cohesion sister chromatid cohesion cell cycle cell cycle process RNA metabolic process negative regulation of RNA biosynthetic process RNA biosynthetic process DNA-templated transcription nucleic acid biosynthetic process regulation of RNA metabolic process transcription by RNA polymerase II negative regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II nucleobase-containing compound biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of DNA-templated transcription negative regulation of RNA metabolic process	cellular anatomical structure intracellular anatomical structure cytoplasm membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen nuclear chromosome cellular anatomical structure intracellular anatomical structure cytoplasm membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen nuclear chromosome intracellular membraneless organelle chromosome membraneless organelle protein-containing complex catalytic complex nuclear protein-containing complex histone deacetylase complex
E [auth I], F [auth J], G [auth K], H [auth L]	PEPTIDIC SUBSTRATE	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR000286	Histone deacetylase family	Family
A, B, C, D	IPR023801	Histone deacetylase domain	Domain
A, B, C, D	IPR003084	Histone deacetylase	Family
A, B, C, D	IPR037138	Histone deacetylase domain superfamily	Homologous Superfamily
A, B, C, D	IPR023696	Ureohydrolase domain superfamily	Homologous Superfamily
A, B, C, D	IPR050284	Histone deacetylase and polyamine deacetylase	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: Q9BY41	Cornelia de Lange syndrome Cornelia de Lange syndrome 5 intellectual disability Wilson-Turner syndrome acquired metabolic disease osteosarcoma plasma cell myeloma Radial club hand mature T-cell and NK-cell non-Hodgkin lymphoma pancreatic intraductal papillary-mucinous neoplasm primary cutaneous T-cell lymphoma obesity disorder pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
E [auth I], F [auth J], G [auth K], H [auth L]	ACE	RESID: AA0041 , AA0042 , AA0043 , AA0044 , AA0045 , AA0046 , AA0049 , AA0050 , AA0051 , AA0052 , AA0053 , AA0054 , AA0354 PSI-MOD : N-acetyl-L-alanine MOD:00050 , N-acetyl-L-aspartic acid MOD:00051 , N-acetyl-L-cysteine MOD:00052 , N-acetyl-S-archeol-cysteine MOD:00897 , N-acetyl-L-glutamic acid MOD:00053 , N-acetyl-L-glutamine MOD:00054 , N-acetylglycine MOD:00055 , N-acetyl-L-methionine MOD:00058 , N-acetyl-L-proline MOD:00059 , N-acetyl-L-serine MOD:00060 , N,O-diacetylated L-serine MOD:00648 , N-acetyl-L-threonine MOD:00061 , N-acetyl-L-tyrosine MOD:00062 , N-acetyl-L-valine MOD:00063 , N2-acetyl-L-arginine MOD:00359
E [auth I], F [auth J], G [auth K], H [auth L]	ALY	Parent Component: LYS RESID: AA0041 , AA0042 , AA0043 , AA0044 , AA0045 , AA0046 , AA0049 , AA0050 , AA0051 , AA0052 , AA0053 , AA0054 , AA0354 , AA0055 PSI-MOD : N-acetyl-L-alanine MOD:00050 , N-acetyl-L-aspartic acid MOD:00051 , N-acetyl-L-cysteine MOD:00052 , N-acetyl-S-archeol-cysteine MOD:00897 , N-acetyl-L-glutamic acid MOD:00053 , N-acetyl-L-glutamine MOD:00054 , N-acetylglycine MOD:00055 , N-acetyl-L-methionine MOD:00058 , N-acetyl-L-proline MOD:00059 , N-acetyl-L-serine MOD:00060 , N,O-diacetylated L-serine MOD:00648 , N-acetyl-L-threonine MOD:00061 , N-acetyl-L-tyrosine MOD:00062 , N-acetyl-L-valine MOD:00063 , N2-acetyl-L-arginine MOD:00359 , N6-acetyl-L-lysine MOD:00064

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.