E3 ubiquitin-protein ligase MYCBP2 (MYCBP2)
The protein contains 4678 amino acids for an estimated molecular weight of 513636 Da.
Atypical E3 ubiquitin-protein ligase which specifically mediates ubiquitination of threonine and serine residues on target proteins, instead of ubiquitinating lysine residues (PubMed:29643511). Shows esterification activity towards both threonine and serine, with a preference for threonine, and acts via two essential catalytic cysteine residues that relay ubiquitin to its substrate via thioester intermediates (PubMed:29643511). Interacts with the E2 enzymes UBE2D1, UBE2D3, UBE2E1 and UBE2L3 (PubMed:18308511, PubMed:29643511). Plays a key role in neural development, probably by mediating ubiquitination of threonine residues on target proteins (Probable). Involved in different processes such as regulation of neurite outgrowth, synaptic growth, synaptogenesis and axon degeneration (By similarity). Required for the formation of major central nervous system axon tracts (By similarity). Required for proper axon growth by regulating axon navigation and axon branching: acts by regulating the subcellular location and stability of MAP3K12/DLK (By similarity). Required for proper localization of retinogeniculate projections but not for eye-specific segregation (By similarity). Regulates axon guidance in the olfactory system (By similarity). Involved in Wallerian axon degeneration, an evolutionarily conserved process that drives the loss of damaged axons: acts by promoting destabilization of NMNAT2, probably via ubiquitination of NMNAT2 (By similarity). Catalyzes ubiquitination of threo (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs35887505 | |
| dbSNP:rs9574002 |
No binding partner found
Biological Process
Branchiomotor neuron axon guidance
Central nervous system projection neuron axonogenesis
Circadian regulation of gene expression
Negative regulation of protein catabolic process
Neuromuscular process
Positive regulation of protein ubiquitination
Protein ubiquitination
Regulation of axon guidance
Regulation of cytoskeleton organization
Regulation of protein localization
The reference OMIM entry for this protein is 610392
Myc-binding protein 2; mycbp2
Protein associated with myc; pam
Kiaa0916
CLONING
Using the transcription-activating domain of MYC (190080) as bait in a yeast 2-hybrid screen of a Burkitt lymphoma cell line cDNA library, followed by screening several cDNA libraries, Guo et al. (1998) obtained a full-length cDNA encoding MYCBP2, which they called PAM. The deduced 4,641-amino acid protein has a calculated molecular mass of 510 kD. PAM contains an N-terminal leucine zipper; 2 RCC1 (179710) homology domains (RHD1 and RHD2) separated by a basic region; a cell division sequence motif; 2 direct repeats of 91 amino acids (PAM repeats); a second leucine zipper; a serine-rich region that contains a domain homologous to histone-binding proteins, such as Xenopus N1/N2 (NASP; 603185); a putative nuclear localization signal; a potential ring zinc finger domain; and 2 putative C2H2-type zinc finger motifs. Northern blot analysis detected highest expression of a 15-kb PAM transcript in brain and thymus. Expression was moderate in skeletal muscle, pancreas, and ovary and weak in all other tissues examined. By sequencing clones obtained from a size-fractionated brain cDNA library, Nagase et al. (1998) cloned MYCBP2, which they designated KIAA0916. RT-PCR ELISA detected high expression in brain, low expression in spleen, skeletal muscle, and fetal liver, and moderate expression in all other peripheral tissues and specific brain regions examined. Using tuberin (TSC; 191092) as bait in a yeast 2-hybrid screen of a human fetal frontal cortex library, Murthy et al. (2004) cloned PAM. Immunofluorescence analysis of cultured primary rat cortical neurons detected strong nuclear Pam staining and punctate staining along axons and dendrites.GENE FUNCTION
Guo et al. (1998) determined that a central region of PAM, between the second leucine zipper and the histone-binding protein homology domain, contains the MYC-binding domain. By coimmunoprecipitation analysis of a rat adrenal pheochromocytoma cell line and rat embryonic brain, Murthy et al. (2004) found that Pam interacted with tuberin in vitro and in vivo. Pierre et al. (2004) found that PAM localized to the endoplasmic reticulum in HeLa cells. Upon serum stimulation, PAM was recruited by sphingosine-1-phosphate (S1P) to the plasma membrane, where it inhibited adenylyl cyclase (see ADCY1; 103072) activity. S1P inhibited adenylyl cyclase in 2 phases: an initial phase (1 to 10 min), which was PAM independent, and a late phase (20 to 240 min), which was PAM dependent. PAM activation by S1P required protein kinase C (see PRKCA; 176960) and phospholipase C (see PLCB1; 607120) activity. Gao and Patel (2005) showed that RHD2 of PAM was sufficient for inhibition of Gs-alpha (GNAS; 139320)-stimulated adenyly cyclase-5 (ADCY5; 600293) activity and that binding of RHD2 to the C2 domain of ADCY5 was necessary, but not sufficient, for this inhibition. Moreover, they identified his912 and his913 of PAM as critical for inhibition of ADCY5.MAPPING
By screening a genomic YAC library and sequence analysis, Guo et al. (1998) mapped the MYCBP2 gene to chromosome 13q22. ... More on the omim web site
Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 610392 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).