| + |
UBE2I | down-regulates 
ubiquitination
|
MITF |
0.554 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-75117 |
Lys308 |
SEARALAkERQKKDN |
Homo sapiens |
|
| pmid |
sentence |
| 10673502 |
Furthermore, we identified lysine 201 as a potential ubiquitination site. A lysine to arginine mutation abolished mitf (k201r) degradation by hubc9 in vivo. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK3 | down-regulates quantity by destabilization
phosphorylation
|
MITF |
0.531 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249620 |
Ser180 |
PGSSAPNsPMAMLTL |
|
|
| pmid |
sentence |
| 10841026 |
More interestingly, ERK-dependent phosphorylation of MITF at Ser 73 is essential for MITF ubiquitinilation and degradation (87). Putting together all these findings, it can be proposed that MAPK activation inhibits melanogenesis due to an increased MITF degradation which is dependent on the MAPK-induced MITF phosphorylation and ubiquitinilation. In summary, although the phosphorylation of MITF at Ser73 increases its intrinsic transcriptional activity, this phosphorylation also targets MITF to the proteasome for its degradation. Consequently, the decrease in MITF levels leads to a down-regulation of melanogenic enzymes expression and to an inhibition of melanogenesis. |
|
| Publications: |
1 |
| + |
ERK1/2 | down-regulates
phosphorylation
|
MITF |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249575 |
Ser180 |
PGSSAPNsPMAMLTL |
Homo sapiens |
|
| pmid |
sentence |
| 10673502 |
The current study reveals that c-kit signaling triggers two phosphorylation events on mi, which up-regulate transactivation potential yet simultaneously target mi for ubiquitin-dependent proteolysis. The specific activation/degradation signals derive from mapk/erk targeting of serine 73the results suggested that s1p reduced melanin synthesis via s1p(3) receptor-mediated erk and rsk-1 activation, and subsequent mitf dual phosphorylation and degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Malignant Melanoma |
| + |
MAPK1 | down-regulates
phosphorylation
|
MITF |
0.698 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-75030 |
Ser180 |
PGSSAPNsPMAMLTL |
Homo sapiens |
|
| pmid |
sentence |
| 10673502 |
The current study reveals that c-kit signaling triggers two phosphorylation events on mi, which up-regulate transactivation potential yet simultaneously target mi for ubiquitin-dependent proteolysis. The specific activation/degradation signals derive from mapk/erk targeting of serine 73the results suggested that s1p reduced melanin synthesis via s1p(3) receptor-mediated erk and rsk-1 activation, and subsequent mitf dual phosphorylation and degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
GSK3B | up-regulates quantity by stabilization 
phosphorylation
|
MITF |
0.442 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276475 |
Ser405 |
QARAHGLsLIPSTGL |
Homo sapiens |
|
| pmid |
sentence |
| 25605940 |
We also show that the MITF protein was stabilized by Wnt signaling, through the novel C-terminal GSK3 phosphorylations identified here. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276477 |
Ser405 |
QARAHGLsLIPSTGL |
Homo sapiens |
C32-TG Cell |
| pmid |
sentence |
| 25605940 |
We also show that the MITF protein was stabilized by Wnt signaling, through the novel C-terminal GSK3 phosphorylations identified here. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276476 |
Ser419 |
S-->N |
Homo sapiens |
|
| pmid |
sentence |
| 25605940 |
We also show that the MITF protein was stabilized by Wnt signaling, through the novel C-terminal GSK3 phosphorylations identified here. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
GSK3B | up-regulates activity
phosphorylation
|
MITF |
0.442 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275967 |
Ser405 |
QARAHGLsLIPSTGL |
in vitro |
|
| pmid |
sentence |
| 10587587 |
Here, we show that Ser298, which locates downstream of the bHLHZip and was previously found to be mutated in individuals with WS2, plays an important role in MITF function. Glycogen synthase kinase 3 (GSK3) was found to phosphorylate Ser298 in vitro, thereby enhancing the binding of MITF to the tyrosinase promoter. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276356 |
|
|
Homo sapiens |
T-98G Cell |
| pmid |
sentence |
| 21873430 |
Both MITF and USF1 were activated by glycogen synthase kinase (GSK) 3, with GSK3 phosphorylation sites on USF1 identified as the previously described activating site threonine 153 as well as serine 186. |
|
| Publications: |
2 |
Organism: |
In Vitro, Homo Sapiens |
| + |
GSK3A | up-regulates
phosphorylation
|
MITF |
0.297 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-72878 |
Ser405 |
QARAHGLsLIPSTGL |
Homo sapiens |
|
| pmid |
sentence |
| 10587587 |
Glycogen synthase kinase 3 (gsk3) was found to phosphorylate ser298 in vitro, thereby enhancing the binding of mitf to the tyrosinase promoter |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RPS6KA1 | down-regulates
phosphorylation
|
MITF |
0.416 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-174760 |
Ser409 |
HGLSLIPsTGLCSPD |
Homo sapiens |
|
| pmid |
sentence |
| 21749389 |
The current study reveals that c-kit signaling triggers two phosphorylation events on mi, which up-regulate transactivation potential yet simultaneously target mi for ubiquitin-dependent proteolysis. The specific activation/degradation signals derive from mapk/erk targeting of serine 73, whereas serine 409 serves as a substrate for p90 rsk-1. An unphosphorylatable double mutant at these two residues is at once profoundly stable and transcriptionally inert. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-75034 |
Ser409 |
HGLSLIPsTGLCSPD |
Homo sapiens |
|
| pmid |
sentence |
| 10673502 |
The current study reveals that c-kit signaling triggers two phosphorylation events on mi, which up-regulate transactivation potential yet simultaneously target mi for ubiquitin-dependent proteolysis. The specific activation/degradation signals derive from mapk/erk targeting of serine 73, whereas serine 409 serves as a substrate for p90 rsk-1. An unphosphorylatable double mutant at these two residues is at once profoundly stable and transcriptionally inert. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
RPS6K | down-regulates
phosphorylation
|
MITF |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252791 |
Ser409 |
HGLSLIPsTGLCSPD |
Homo sapiens |
|
| pmid |
sentence |
| 10673502 |
The current study reveals that c-kit signaling triggers two phosphorylation events on mi, which up-regulate transactivation potential yet simultaneously target mi for ubiquitin-dependent proteolysis. The specific activation/degradation signals derive from mapk/erk targeting of serine 73, whereas serine 409 serves as a substrate for p90 rsk-1. An unphosphorylatable double mutant at these two residues is at once profoundly stable and transcriptionally inert. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252795 |
Ser409 |
HGLSLIPsTGLCSPD |
Homo sapiens |
|
| pmid |
sentence |
| 21749389 |
The current study reveals that c-kit signaling triggers two phosphorylation events on mi, which up-regulate transactivation potential yet simultaneously target mi for ubiquitin-dependent proteolysis. The specific activation/degradation signals derive from mapk/erk targeting of serine 73, whereas serine 409 serves as a substrate for p90 rsk-1. An unphosphorylatable double mutant at these two residues is at once profoundly stable and transcriptionally inert. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
PRKDC | up-regulates activity
phosphorylation
|
MITF |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277899 |
Ser431 |
S-->C |
Homo sapiens |
Melanoma Cell |
| pmid |
sentence |
| 38316520 |
These results suggest that DNA-PK can target MITF-S325 for phosphorylation. In melanocytes and melanoma cells, MITF is rapidly phosphorylated by DNA-PK and interacts with NBS1–RAD50 but not MRE11, destabilizing the MRN complex. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AKT1 | down-regulates quantity by destabilization
phosphorylation
|
MITF |
0.448 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277281 |
Ser516 |
KTSSRRSsMSMEETE |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 27702651 |
We found that AKT phosphorylates MITF at S510. Phosphorylated MITF S510 enhances its affinity to TP53 and promotes CDKN1A expression. Phosphorylation of MITF by AKT induces its degradation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CLK4 | down-regulates quantity by destabilization
phosphorylation
|
MITF |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-274116 |
Tyr360 |
ILKASVDyIRKLQRE |
Homo sapiens |
KYSE-150 Cell |
| pmid |
sentence |
| 35092699 |
Mechanistically, wild type CLK4 (WT-CLK4) but not kinase-dead CLK4-K189R mutant phosphorylated MITF at Y360. This modification promoted its interaction with E3 ligase COP1 and its K63-linked ubiquitination at K308/K372, leading to sequestosome 1 recognition and autophagic degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MITF | up-regulates quantity by expression 
transcriptional regulation
|
OCA2 |
0.359 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254556 |
|
|
Homo sapiens |
Melanocyte |
| pmid |
sentence |
| 22234890 |
the SNP rs12913832 has strong statistical association with human pigmentation. It is located within an intron of the nonpigment gene HERC2, 21 kb upstream of the pigment gene OCA2, and the region surrounding rs12913832 is highly conserved among animal species.In darkly pigmented human melanocytes carrying the rs12913832 T-allele, we detected binding of the transcription factors HLTF, LEF1, and MITF to the HERC2 rs12913832 enhancer, and a long-range chromatin loop between this enhancer and the OCA2 promoter that leads to elevated OCA2 expression. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MITF | up-regulates quantity by expression
transcriptional regulation
|
TYRP1 |
0.497 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254591 |
|
|
Homo sapiens |
Melanocyte |
| pmid |
sentence |
| 22371403 |
MITF transcription factor regulates melanogenesis by activation of tyrosinase, TRP1 and TRP2 transcription. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MITF | up-regulates quantity by expression
transcriptional regulation
|
PMEL |
0.442 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254589 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12819038 |
The results of the present work demonstrate that the essential melanocyte-specific transcription factor MITF regulates expression of the genes encoding the melanoma tumor markers MLANA and SILV. MITF up- or down-regulation is seen to correspondingly modulate expression of MLANA and SILV in parallel directions, at both mRNA and protein levels. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MITF | up-regulates quantity by expression
transcriptional regulation
|
BCL2 |
0.462 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249618 |
|
|
|
|
| pmid |
sentence |
| 12086670 |
MITF directly occupies the BCL2 promoter in vivo and this suggest that BCL2 may be a direct transcriptional target of MITF |
|
| Publications: |
1 |
| Pathways: | Malignant Melanoma |
| + |
SOX9 | up-regulates activity
binding
|
MITF |
0.39 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255183 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 20530484 |
BEST1 promoter activity was increased by SOX9 overexpression and decreased by siRNA-mediated SOX9 knockdown. SOX9 physically interacted with MITF and OTX2 and orchestrated synergistic activation of the BEST1 promoter with the paired SOX site playing essential roles. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
MITF | up-regulates quantity by expression
transcriptional regulation
|
BEST1 |
0.382 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254586 |
|
|
Homo sapiens |
D-407 Cell |
| pmid |
sentence |
| 14982938 |
These studies define the VMD2 promoter region sufficient to drive RPE-specific expression in the eye, identify positive regulatory regions in vitro, and suggest that MITF as well as other E-box binding factors may act as positive regulators of VMD2 expression. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255185 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 20530484 |
BEST1 promoter activity was increased by SOX9 overexpression and decreased by siRNA-mediated SOX9 knockdown. SOX9 physically interacted with MITF and OTX2 and orchestrated synergistic activation of the BEST1 promoter with the paired SOX site playing essential roles. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens, Mus Musculus |
| + |
MITF | up-regulates quantity by expression
transcriptional regulation
|
MLANA |
0.478 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254590 |
|
|
Homo sapiens |
Melanoma Cell |
| pmid |
sentence |
| 12819038 |
The results of the present work demonstrate that the essential melanocyte-specific transcription factor MITF regulates expression of the genes encoding the melanoma tumor markers MLANA and SILV. MITF up- or down-regulation is seen to correspondingly modulate expression of MLANA and SILV in parallel directions, at both mRNA and protein levels. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MITF | up-regulates quantity by expression
transcriptional regulation
|
SERPINF1 |
0.31 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254587 |
|
|
Homo sapiens |
Retinal Pigment Epithelium |
| pmid |
sentence |
| 22115973 |
Here we show that the basic-helix-loop-helix-leucine zipper microphthalmia-associated transcription factor (MITF), which plays central roles in the development and function of a variety of cell types including RPE cells, upregulates the expression of a multifunctional factor PEDF in RPE cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MITF | up-regulates quantity by expression
transcriptional regulation
|
TRPM1 |
0.432 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254588 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 14744763 |
Mice homozygously mutated in MITF showed a dramatic decrease in TRPM1 expression. Finally, the slope of TRPM1 induction by MITF was particularly steep compared with other MITF target genes, suggesting it is a sensitive indicator of MITF expression and correspondingly of melanocytic differentiation. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
MITF | up-regulates quantity by expression
transcriptional regulation
|
DCT |
0.47 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254592 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22371403 |
MITF transcription factor regulates melanogenesis by activation of tyrosinase, TRP1 and TRP2 transcription. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CREB1 | up-regulates quantity by expression
transcriptional regulation
|
MITF |
0.626 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249619 |
|
|
|
|
| pmid |
sentence |
| 10841026 |
Therefore, the molecular steps linking cAMPto melanogenesis up-regulation appear currently better elucidated. cAMP activates PKA, and PKA phosphorylates and activates CREB which, when activated, binds to the CRE domain present in the microphthalmia promoter,thereby up-regulating its transcription. |
|
| Publications: |
1 |
| Pathways: | Malignant Melanoma |
| + |
Gbeta | down-regulates quantity by destabilization
phosphorylation
|
MITF |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270029 |
|
|
|
|
| pmid |
sentence |
| 10841026 |
More interestingly, ERK-dependent phosphorylation of MITF at Ser 73 is essential for MITF ubiquitinilation and degradation (87). Putting together all these findings, it can be proposed that MAPK activation inhibits melanogenesis due to an increased MITF degradation which is dependent on the MAPK-induced MITF phosphorylation and ubiquitinilation. In summary, although the phosphorylation of MITF at Ser73 increases its intrinsic transcriptional activity, this phosphorylation also targets MITF to the proteasome for its degradation. Consequently, the decrease in MITF levels leads to a down-regulation of melanogenic enzymes expression and to an inhibition of melanogenesis. |
|
| Publications: |
1 |
| + |
POU3F2 | up-regulates quantity by expression
transcriptional regulation
|
MITF |
0.446 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249616 |
|
|
|
|
| pmid |
sentence |
| 18628967 |
We further demonstrate that BRN2 induces MITF transcription through a binding site located at 50/36 of the MITF promoter |
|
| Publications: |
1 |
| + |
MITF | up-regulates quantity by expression
transcriptional regulation
|
ACP5 |
0.351 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254584 |
|
|
Mus musculus |
RAW-264.7 Cell |
| pmid |
sentence |
| 11481336 |
The combination of MITF and PU.1 synergistically activated the TRAP promoter in transient assays. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
MITF | up-regulates quantity by expression
transcriptional regulation
|
TPSAB1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251725 |
|
|
Homo sapiens |
Mast Cell |
| pmid |
sentence |
| 20513998 |
The transcription of tryptase gene in human mast cells is regulated by mi transcription factor |Using mutant constructs of tryptase promoter, we observed that two E-box (CANNTG) motifs including between -817 to -715 and -421 to -202 are able to involve in the transactivation of tryptase gene by MITF-A. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MITF | up-regulates quantity by expression
transcriptional regulation
|
TYR |
0.589 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254593 |
|
|
Homo sapiens |
Melanocyte |
| pmid |
sentence |
| 10080955 |
Microphthalmia transcription factor MITF, a melanocyte-specific basic helix-loop-helix protein, has been shown to transactivate tyrosinase and TRP-1 genes in vitro by binding to a shared regulatory sequence known as M box. both activation of positive factors such as MITF and inactivation of negative regulatory factors may be required for TRP-1 gene expression during melanocytic differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
MITF
- 
- 