MYCBP2 Gene

Name	MYC binding protein 2, E3 ubiquitin protein ligase
Description	This gene encodes an E3 ubiquitin-protein ligase and member of the PHR (Phr1/MYCBP2, highwire and RPM-1) family of proteins. The encoded protein plays a role in axon guidance and synapse formation in the developing nervous system. In mammalian cells, this protein regulates the cAMP and mTOR signaling pathways, and may additionally regulate autophagy. Reduced expression of this gene has been observed in acute lymphoblastic leukemia patients and a mutation in this gene has been identified in patients with a rare inherited vision defect. [provided by RefSeq, Mar 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMYCBP2, also known as PAM or PHR1, is an atypical E3 ubiquitin ligase endowed with a unique catalytic mechanism. In contrast to classical RING-type ligases that directly mediate ubiquitin transfer, MYCBP2 operates via a RING‐Cys‐relay mechanism that employs two essential catalytic cysteine residues to relay ubiquitin through thioester intermediates—with an unusual intrinsic selectivity for threonine residues. Distinct functional domains, such as an RCC1 homology region, further enable MYCBP2 to modulate critical signaling enzymes including adenylyl cyclase; indeed, studies have demonstrated that upon stimulation (e.g., by sphingosine-1-phosphate), MYCBP2 translocates in cells to inhibit adenylyl cyclase activity via specific domain interactions and key histidine residues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its core ubiquitin ligase activity, MYCBP2 engages in a variety of regulatory and developmental processes. In the nervous system, it associates with the tuberin–hamartin complex, hinting at roles in CNS development and synaptic growth. MYCBP2 also contributes to the precise regulation of circadian rhythms by participating in the ubiquitination and proteasomal degradation of key clock components such as Rev-erbα, and it exerts control over epithelial–mesenchymal transition by targeting core EMT-inducing transcription factors. In hematologic malignancies, diminished MYCBP2 expression has been linked to elevated c-MYC levels and adverse clinical features in acute lymphoblastic leukemia, while its activity is further essential for optimal activation of the mTOR pathway via facilitation of Rheb’s GDP/GTP exchange."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, MYCBP2 plays diverse roles in cell cycle regulation and neuronal signaling. During extended mitotic arrest, the FBXO45–MYCBP2 complex targets the tumor suppressor FBXW7 for ubiquitination and proteasomal degradation, promoting mitotic slippage and potentially contributing to chemoresistance. In the realm of neurodevelopment, de novo variants in MYCBP2 have been implicated in a spectrum of disorders characterized by corpus callosum dysgenesis and axon development defects, as evidenced by in vivo genetic models. MYCBP2 also forms part of a complex with the Eph receptor EPHB2—through an FBXO45-mediated interaction—that stabilizes the receptor and ensures robust downstream signaling in both neuronal and non-neuronal cell types. Finally, aberrant MYCBP2 expression correlates with increased immune cell infiltration and appears to impact the efficacy of immune checkpoint inhibitor therapies in thyroid cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sandra C Pierre, Julia Häusler, Kerstin Birod, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PAM mediates sustained inhibition of cAMP signaling by sphingosine-1-phosphate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7600321"}], "href": "https://doi.org/10.1038/sj.emboj.7600321"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15257286"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15257286"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xianlong Gao, Tarun B Patel "}, {"type": "b", "children": [{"type": "t", "text": "Histidine residues 912 and 913 in protein associated with Myc are necessary for the inhibition of adenylyl cyclase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharmacol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/mol.104.005355"}], "href": "https://doi.org/10.1124/mol.104.005355"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15470080"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15470080"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kuan-Chuan Pao, Nicola T Wood, Axel Knebel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-018-0026-1"}], "href": "https://doi.org/10.1038/s41586-018-0026-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29643511"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29643511"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Vanishree Murthy, Sangyeul Han, Roberta L Beauchamp, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pam and its ortholog highwire interact with and may negatively regulate the TSC1.TSC2 complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M310208200"}], "href": "https://doi.org/10.1074/jbc.M310208200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14559897"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14559897"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Christian Maeurer, Sabrina Holland, Sandra Pierre, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sphingosine-1-phosphate induced mTOR-activation is mediated by the E3-ubiquitin ligase PAM."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2008.10.016"}], "href": "https://doi.org/10.1016/j.cellsig.2008.10.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19000755"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19000755"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lei Yin, Shree Joshi, Nan Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "E3 ligases Arf-bp1 and Pam mediate lithium-stimulated degradation of the circadian heme receptor Rev-erb alpha."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1000438107"}], "href": "https://doi.org/10.1073/pnas.1000438107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20534529"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20534529"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ming Xu, Changhong Zhu, Xian Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 controls the core epithelial-to-mesenchymal transition-inducing transcription factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.2825"}], "href": "https://doi.org/10.18632/oncotarget.2825"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25460509"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25460509"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Zheng Ge, Xing Guo, Jianyong Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical significance of high c-MYC and low MYCBP2 expression and their association with Ikaros dysfunction in adult acute lymphoblastic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.5982"}], "href": "https://doi.org/10.18632/oncotarget.5982"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26517351"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26517351"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Kai T Richter, Yvonne T Kschonsak, Barbara Vodicska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FBXO45-MYCBP2 regulates mitotic cell fate by targeting FBXW7 for degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41418-019-0385-7"}], "href": "https://doi.org/10.1038/s41418-019-0385-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31285543"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31285543"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Lama AlAbdi, Muriel Desbois, Domniţa-Valeria Rusnac, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss-of-function variants in MYCBP2 cause neurobehavioural phenotypes and corpus callosum defects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/awac364"}], "href": "https://doi.org/10.1093/brain/awac364"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36200388"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36200388"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Guilin Wang, Chen Miao, Lijun Mo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MYCBP2 expression correlated with inflammatory cell infiltration and prognosis immunotherapy in thyroid cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2022.1048503"}], "href": "https://doi.org/10.3389/fimmu.2022.1048503"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36582246"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36582246"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Chao Chang, Sara L Banerjee, Sung Soon Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin ligase and signalling hub MYCBP2 is required for efficient EPHB2 tyrosine kinase receptor function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.89176"}], "href": "https://doi.org/10.7554/eLife.89176"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38289221"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38289221"}]}]}]}
Synonyms	PAM, Phr, Myc-bp2
Proteins	MYCB2_HUMAN
NCBI Gene ID	23077
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MYCBP2 has 11,289 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 132 datasets.

Click the + buttons to view associations for MYCBP2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MYCBP2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by MYCBP2 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of MYCBP2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of MYCBP2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of MYCBP2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of MYCBP2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of MYCBP2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of MYCBP2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of MYCBP2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of MYCBP2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of MYCBP2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MYCBP2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of MYCBP2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with MYCBP2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MYCBP2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of MYCBP2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MYCBP2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of MYCBP2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with MYCBP2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of MYCBP2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing MYCBP2 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of MYCBP2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MYCBP2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing MYCBP2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing MYCBP2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing MYCBP2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with MYCBP2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with MYCBP2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of MYCBP2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MYCBP2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with MYCBP2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with MYCBP2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of MYCBP2 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with MYCBP2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with MYCBP2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with MYCBP2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MYCBP2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at MYCBP2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of MYCBP2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of MYCBP2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing MYCBP2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.