4I80

Crystal structure of human menin in complex with a high-affinity macrocyclic peptidomimetics

External Resource: Annotation

Domain Annotation: ECOD Classification
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Protein Modification Annotation

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	Menin_2nd	e4i80A2	A: alpha superhelices	X: Repetitive alpha hairpins	H: ARM repeat (From Topology)	T: ARM repeat	F: Menin_2nd	ECOD (1.6)
A	Menin_1st	e4i80A3	A: a+b complex topology	X: Cysteine proteinases-like	H: Cysteine proteinases (From Topology)	T: Cysteine proteinases	F: Menin_1st	ECOD (1.6)

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Menin	SMAD binding protein binding binding R-SMAD binding DNA binding sequence-specific DNA binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding double-stranded DNA binding organic cyclic compound binding nucleic acid binding transcription regulatory region nucleic acid binding phosphoprotein binding DNA secondary structure binding SMAD binding protein binding binding R-SMAD binding DNA binding sequence-specific DNA binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding double-stranded DNA binding organic cyclic compound binding nucleic acid binding transcription regulatory region nucleic acid binding phosphoprotein binding DNA secondary structure binding Y-form DNA binding protein-containing complex binding chromatin binding protein-macromolecule adaptor activity molecular adaptor activity four-way junction DNA binding	cellular response to stimulus cellular response to stress response to stimulus DNA damage response response to stress cellular process regulation of cellular process negative regulation of biological process negative regulation of cellular metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription regulation of RNA metabolic process cellular response to stimulus cellular response to stress response to stimulus DNA damage response response to stress cellular process regulation of cellular process negative regulation of biological process negative regulation of cellular metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription regulation of RNA metabolic process organic substance biosynthetic process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process negative regulation of DNA-templated transcription regulation of biological process cellular metabolic process negative regulation of metabolic process primary metabolic process regulation of cellular metabolic process negative regulation of cellular biosynthetic process organic cyclic compound metabolic process regulation of gene expression biosynthetic process negative regulation of macromolecule biosynthetic process organic cyclic compound biosynthetic process metabolic process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of DNA-templated transcription regulation of metabolic process negative regulation of RNA metabolic process cellular biosynthetic process RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process organic substance metabolic process negative regulation of cellular process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of biosynthetic process biological regulation regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of cellular biosynthetic process negative regulation of biosynthetic process positive regulation of macromolecule biosynthetic process positive regulation of gene expression, epigenetic positive regulation of metabolic process transcription by RNA polymerase II chromatin organization positive regulation of macromolecule metabolic process transcription initiation at RNA polymerase II promoter transcription initiation-coupled chromatin remodeling positive regulation of biological process positive regulation of cellular metabolic process protein-DNA complex organization cellular component organization positive regulation of biosynthetic process chromatin remodeling cellular component organization or biogenesis positive regulation of cellular process protein-containing complex organization epigenetic regulation of gene expression DNA-templated transcription initiation positive regulation of gene expression positive regulation of cellular biosynthetic process negative regulation of DNA-binding transcription factor activity negative regulation of molecular function regulation of molecular function regulation of DNA-binding transcription factor activity positive regulation of cell communication cell surface receptor protein serine/threonine kinase signaling pathway positive regulation of signal transduction cellular response to growth factor stimulus signaling cellular response to transforming growth factor beta stimulus regulation of transmembrane receptor protein serine/threonine kinase signaling pathway regulation of signal transduction cell communication regulation of transforming growth factor beta receptor signaling pathway positive regulation of response to stimulus cellular response to endogenous stimulus signal transduction enzyme-linked receptor protein signaling pathway regulation of signaling cell surface receptor signaling pathway regulation of cellular response to transforming growth factor beta stimulus response to endogenous stimulus positive regulation of transforming growth factor beta receptor signaling pathway regulation of cellular response to growth factor stimulus positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway positive regulation of cellular response to transforming growth factor beta stimulus response to transforming growth factor beta regulation of response to stimulus transforming growth factor beta receptor signaling pathway regulation of cell communication response to growth factor transforming growth factor beta receptor superfamily signaling pathway positive regulation of signaling developmental process regulation of osteoblast differentiation multicellular organismal process regulation of developmental process cellular developmental process negative regulation of osteoblast differentiation negative regulation of developmental process regulation of cell differentiation osteoblast differentiation ossification cell differentiation negative regulation of cell differentiation negative regulation of cell cycle cell cycle regulation of cell cycle regulation of protein modification process regulation of protein phosphorylation negative regulation of phosphate metabolic process regulation of phosphate metabolic process phosphate-containing compound metabolic process negative regulation of protein modification process protein metabolic process protein modification process phosphorus metabolic process negative regulation of protein metabolic process organonitrogen compound metabolic process protein phosphorylation phosphorylation regulation of protein metabolic process negative regulation of protein phosphorylation macromolecule modification negative regulation of phosphorus metabolic process regulation of phosphorylation regulation of phosphorus metabolic process negative regulation of phosphorylation regulation of catalytic activity negative regulation of catalytic activity regulation of cyclin-dependent protein kinase activity regulation of transferase activity negative regulation of kinase activity negative regulation of transferase activity regulation of cyclin-dependent protein serine/threonine kinase activity regulation of kinase activity regulation of protein serine/threonine kinase activity negative regulation of cyclin-dependent protein serine/threonine kinase activity negative regulation of protein serine/threonine kinase activity negative regulation of cyclin-dependent protein kinase activity negative regulation of protein kinase activity regulation of protein kinase activity osteoblast development anatomical structure development cell development negative regulation of signaling negative regulation of intracellular signal transduction intracellular signal transduction negative regulation of cell communication negative regulation of JNK cascade regulation of intracellular signal transduction JNK cascade intracellular signaling cassette negative regulation of response to stimulus regulation of JNK cascade regulation of MAPK cascade negative regulation of signal transduction MAPK cascade negative regulation of MAPK cascade regulation of DNA biosynthetic process DNA metabolic process DNA biosynthetic process negative regulation of DNA biosynthetic process regulation of DNA metabolic process regulation of telomerase activity negative regulation of telomerase activity negative regulation of DNA metabolic process response to light stimulus response to radiation response to abiotic stimulus response to UV DNA repair negative regulation of cell population proliferation cell population proliferation regulation of cell population proliferation mononuclear cell differentiation lymphocyte activation lymphocyte differentiation cell activation involved in immune response CD4-positive, alpha-beta T cell differentiation CD4-positive, alpha-beta T cell differentiation involved in immune response alpha-beta T cell differentiation involved in immune response leukocyte activation alpha-beta T cell differentiation type 2 immune response T cell activation involved in immune response alpha-beta T cell activation involved in immune response T cell activation CD4-positive, alpha-beta T cell activation leukocyte activation involved in immune response alpha-beta T cell activation T-helper 2 cell differentiation T cell differentiation lymphocyte activation involved in immune response immune response T-helper cell differentiation hemopoiesis cell activation T cell differentiation involved in immune response immune effector process immune system process leukocyte differentiation response to ionizing radiation response to gamma radiation regulation of transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II positive regulation of nucleobase-containing compound metabolic process positive regulation of transcription by RNA polymerase II positive regulation of RNA metabolic process positive regulation of DNA-templated transcription positive regulation of RNA biosynthetic process	membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle cellular anatomical entity intracellular organelle lumen intracellular organelle organelle lumen organelle nuclear periphery nuclear lumen nuclear matrix protein-containing complex membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle cellular anatomical entity intracellular organelle lumen intracellular organelle organelle lumen organelle nuclear periphery nuclear lumen nuclear matrix protein-containing complex histone methyltransferase complex catalytic complex nuclear protein-containing complex transferase complex nucleoplasm methyltransferase complex cytoplasm cytosol MLL1/2 complex cell division site cell periphery cleavage furrow membrane plasma membrane plasma membrane region protein-DNA complex intracellular non-membrane-bounded organelle chromatin chromosome non-membrane-bounded organelle endomembrane system endoplasmic reticulum lumen endoplasmic reticulum transcription regulator complex transcription repressor complex chromosome, telomeric region chromosomal region MLL1 complex
B	macrocyclic peptidomimetic	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR007747	Menin	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: O00255	multiple endocrine neoplasia type 1 adrenal cortex carcinoma pancreatic insulinoma glucagonoma neuroendocrine neoplasm VIPoma prolactin-producing pituitary gland adenoma Zollinger-Ellison syndrome pancreatic cholera hyperparathyroidism 1 multiple endocrine neoplasia cancer gastrin-producing neuroendocrine tumor malignant pancreatic neoplasm non-functioning pituitary gland neoplasm multiple endocrine neoplasia type 1 adrenal cortex carcinoma pancreatic insulinoma glucagonoma neuroendocrine neoplasm VIPoma prolactin-producing pituitary gland adenoma Zollinger-Ellison syndrome pancreatic cholera hyperparathyroidism 1 multiple endocrine neoplasia cancer gastrin-producing neuroendocrine tumor malignant pancreatic neoplasm non-functioning pituitary gland neoplasm parathyroid gland adenoma ACTH-independent macronodular adrenal hyperplasia Carney complex hyperparathyroidism malignant mesothelioma neuroendocrine carcinoma pancreatic neoplasm adenoma attention deficit hyperactivity disorder, inattentive type familial isolated hyperparathyroidism lung cancer pancreatic endocrine carcinoma pituitary gland adenoma adrenal carcinoma gout malignant colon neoplasm

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
B	1E3
B	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

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), 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 R01GM133198.