UniProt functional annotation for P01106



	UniProt functional annotation for P01106

UniProt code: P01106.

Organism: Homo sapiens (Human).

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

Function: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes. Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis (PubMed:24940000). Regulator of somatic reprogramming, controls self-renewal of embryonic stem cells. Functions with TAF6L to activate target gene expression through RNA polymerase II pause release (By similarity). {ECO:0000250|UniProtKB:P01108, ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:25956029}.

Subunit: Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX (PubMed:9680483). Interacts with TAF1C and SPAG9. Interacts with PARP10. Interacts with KDM5A and KDM5B. Interacts (when phosphorylated at Thr-58 and Ser-62) with FBXW7(PubMed:25775507, PubMed:17558397). Interacts with PIM2. Interacts with RIOX1. The heterodimer MYC:MAX interacts with ABI1; the interaction may enhance MYC:MAX transcriptional activity. Interacts with TRIM6 (By similarity). Interacts with NPM1; the binary complex is recruited to the promoter of MYC target genes and enhances their transcription (PubMed:25956029). Interacts with CIP2A; leading to the stabilization of MYC (PubMed:17632056). {ECO:0000250|UniProtKB:P01108, ECO:0000269|PubMed:15103331, ECO:0000269|PubMed:15674325, ECO:0000269|PubMed:15723054, ECO:0000269|PubMed:17308053, ECO:0000269|PubMed:17311883, ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:17632056, ECO:0000269|PubMed:17873522, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:25956029, ECO:0000269|PubMed:9680483}.

Subcellular location: Nucleus, nucleoplasm {ECO:0000269|PubMed:17558397}. Nucleus, nucleolus {ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:25775507}.

Ptm: Phosphorylated by PRKDC. Phosphorylation at Ser-329 by PIM2 leads to the stabilization of MYC (By similarity). Phosphorylation at Ser-62 by CDK2 prevents Ras-induced senescence. Phosphorylated at Ser-62 by DYRK2; this primes the protein for subsequent phosphorylation by GSK3B at Thr-58. Phosphorylation at Thr-58 and Ser-62 by GSK3 is required for ubiquitination and degradation by the proteasome. {ECO:0000250, ECO:0000269|PubMed:15103331, ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:19966300, ECO:0000269|PubMed:20713526, ECO:0000269|PubMed:22307329, ECO:0000269|PubMed:8386367}.

Ptm: Ubiquitinated by the SCF(FBXW7) complex when phosphorylated at Thr-58 and Ser-62, leading to its degradation by the proteasome. In the nucleoplasm, ubiquitination is counteracted by USP28, which interacts with isoform 1 of FBXW7 (FBW7alpha), leading to its deubiquitination and preventing degradation. In the nucleolus, however, ubiquitination is not counteracted by USP28 but by USP36, due to the lack of interaction between isoform 3 of FBXW7 (FBW7gamma) and USP28, explaining the selective MYC degradation in the nucleolus (PubMed:25775507,PubMed:17558397). Also polyubiquitinated by the DCX(TRUSS) complex. Ubiquitinated by TRIM6 in a phosphorylation- independent manner (By similarity). {ECO:0000250|UniProtKB:P01108, ECO:0000269|PubMed:15103331, ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:19966300, ECO:0000269|PubMed:20713526, ECO:0000269|PubMed:22307329, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:8386367}.

Disease: Note=A chromosomal aberration involving MYC may be a cause of a form of B-cell chronic lymphocytic leukemia. Translocation t(8;12)(q24;q22) with BTG1. {ECO:0000269|PubMed:2069907}.

Disease: Burkitt lymphoma (BL) [MIM:113970]: A form of undifferentiated malignant lymphoma commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. {ECO:0000269|PubMed:2166998, ECO:0000269|PubMed:8220424}. Note=The gene represented in this entry is involved in disease pathogenesis. Chromosomal aberrations involving MYC are usually found in Burkitt lymphoma. Translocations t(8;14), t(8;22) or t(2;8) which juxtapose MYC to one of the heavy or light chain immunoglobulin gene loci.

Biotechnology: POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four Yamanaka factors. When combined, these factors are sufficient to reprogram differentiated cells to an embryonic-like state designated iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology and growth properties of ES cells and express ES cell marker genes. {ECO:0000269|PubMed:18035408}.

Miscellaneous: [Isoform 2]: Initiates from CTG codon. {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:		Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes. Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis (PubMed:24940000). Regulator of somatic reprogramming, controls self-renewal of embryonic stem cells. Functions with TAF6L to activate target gene expression through RNA polymerase II pause release (By similarity). {ECO:0000250\|UniProtKB:P01108, ECO:0000269\|PubMed:24940000, ECO:0000269\|PubMed:25956029}.


Subunit:		Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX (PubMed:9680483). Interacts with TAF1C and SPAG9. Interacts with PARP10. Interacts with KDM5A and KDM5B. Interacts (when phosphorylated at Thr-58 and Ser-62) with FBXW7(PubMed:25775507, PubMed:17558397). Interacts with PIM2. Interacts with RIOX1. The heterodimer MYC:MAX interacts with ABI1; the interaction may enhance MYC:MAX transcriptional activity. Interacts with TRIM6 (By similarity). Interacts with NPM1; the binary complex is recruited to the promoter of MYC target genes and enhances their transcription (PubMed:25956029). Interacts with CIP2A; leading to the stabilization of MYC (PubMed:17632056). {ECO:0000250\|UniProtKB:P01108, ECO:0000269\|PubMed:15103331, ECO:0000269\|PubMed:15674325, ECO:0000269\|PubMed:15723054, ECO:0000269\|PubMed:17308053, ECO:0000269\|PubMed:17311883, ECO:0000269\|PubMed:17558397, ECO:0000269\|PubMed:17632056, ECO:0000269\|PubMed:17873522, ECO:0000269\|PubMed:25775507, ECO:0000269\|PubMed:25956029, ECO:0000269\|PubMed:9680483}.
Subcellular location:		Nucleus, nucleoplasm {ECO:0000269\|PubMed:17558397}. Nucleus, nucleolus {ECO:0000269\|PubMed:17558397, ECO:0000269\|PubMed:25775507}.
Ptm:		Phosphorylated by PRKDC. Phosphorylation at Ser-329 by PIM2 leads to the stabilization of MYC (By similarity). Phosphorylation at Ser-62 by CDK2 prevents Ras-induced senescence. Phosphorylated at Ser-62 by DYRK2; this primes the protein for subsequent phosphorylation by GSK3B at Thr-58. Phosphorylation at Thr-58 and Ser-62 by GSK3 is required for ubiquitination and degradation by the proteasome. {ECO:0000250, ECO:0000269\|PubMed:15103331, ECO:0000269\|PubMed:17558397, ECO:0000269\|PubMed:19966300, ECO:0000269\|PubMed:20713526, ECO:0000269\|PubMed:22307329, ECO:0000269\|PubMed:8386367}.
Ptm:		Ubiquitinated by the SCF(FBXW7) complex when phosphorylated at Thr-58 and Ser-62, leading to its degradation by the proteasome. In the nucleoplasm, ubiquitination is counteracted by USP28, which interacts with isoform 1 of FBXW7 (FBW7alpha), leading to its deubiquitination and preventing degradation. In the nucleolus, however, ubiquitination is not counteracted by USP28 but by USP36, due to the lack of interaction between isoform 3 of FBXW7 (FBW7gamma) and USP28, explaining the selective MYC degradation in the nucleolus (PubMed:25775507,PubMed:17558397). Also polyubiquitinated by the DCX(TRUSS) complex. Ubiquitinated by TRIM6 in a phosphorylation- independent manner (By similarity). {ECO:0000250\|UniProtKB:P01108, ECO:0000269\|PubMed:15103331, ECO:0000269\|PubMed:17558397, ECO:0000269\|PubMed:19966300, ECO:0000269\|PubMed:20713526, ECO:0000269\|PubMed:22307329, ECO:0000269\|PubMed:25775507, ECO:0000269\|PubMed:8386367}.
Disease:		Note=A chromosomal aberration involving MYC may be a cause of a form of B-cell chronic lymphocytic leukemia. Translocation t(8;12)(q24;q22) with BTG1. {ECO:0000269\|PubMed:2069907}.
Disease:		Burkitt lymphoma (BL) [MIM:113970]: A form of undifferentiated malignant lymphoma commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. {ECO:0000269\|PubMed:2166998, ECO:0000269\|PubMed:8220424}. Note=The gene represented in this entry is involved in disease pathogenesis. Chromosomal aberrations involving MYC are usually found in Burkitt lymphoma. Translocations t(8;14), t(8;22) or t(2;8) which juxtapose MYC to one of the heavy or light chain immunoglobulin gene loci.
Biotechnology:		POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four Yamanaka factors. When combined, these factors are sufficient to reprogram differentiated cells to an embryonic-like state designated iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology and growth properties of ES cells and express ES cell marker genes. {ECO:0000269\|PubMed:18035408}.
Miscellaneous:		[Isoform 2]: Initiates from CTG codon. {ECO:0000305}.