dbPTM

MITF_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MITF_HUMAN
UniProt AC	O75030
Protein Name	Microphthalmia-associated transcription factor
Gene Name	MITF
Organism	Homo sapiens (Human).
Sequence Length	526
Subcellular Localization	Nucleus .
Protein Description	Transcription factor that regulates the expression of genes with essential roles in cell differentiation, proliferation and survival. Binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoters of target genes, such as BCL2 and tyrosinase (TYR). Plays an important role in melanocyte development by regulating the expression of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1). Plays a critical role in the differentiation of various cell types, such as neural crest-derived melanocytes, mast cells, osteoclasts and optic cup-derived retinal pigment epithelium..
Protein Sequence	MQSESGIVPDFEVGEEFHEEPKTYYELKSQPLKSSSSAEHPGASKPPISSSSMTSRILLRQQLMREQMQEQERREQQQKLQAAQFMQQRVPVSQTPAINVSVPTTLPSATQVPMEVLKVQTHLENPTKYHIQQAQRQQVKQYLSTTLANKHANQVLSLPCPNQPGDHVMPPVPGSSAPNSPMAMLTLNSNCEKEGFYKFEEQNRAESECPGMNTHSRASCMQMDDVIDDIISLESSYNEEILGLMDPALQMANTLPVSGNLIDLYGNQGLPPPGLTISNSCPANLPNIKRELTACIFPTESEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDYIRKLQREQQRAKELENRQKKLEHANRHLLLRIQELEMQARAHGLSLIPSTGLCSPDLVNRIIKQEPVLENCSQDLLQHHADLTCTTTLDLTDGTITFNNNLGTGTEANQAYSVPTKMGSKLEDILMDDTLSPVGVTDPLLSSVSPGASKTSSRRSSMSMEETEHTC

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
23	Phosphorylation	EFHEEPKTYYELKSQ HHHCCCCCCEEECCC	41.89	27642862
24	Phosphorylation	FHEEPKTYYELKSQP HHCCCCCCEEECCCC	10.89	27642862
25	Phosphorylation	HEEPKTYYELKSQPL HCCCCCCEEECCCCC	21.73	27642862
27 (in isoform 6)	Phosphorylation	-	3.60	20068231
27 (in isoform 5)	Phosphorylation	-	3.60	20068231
32 (in isoform 6)	Phosphorylation	-	6.96	20068231
32 (in isoform 5)	Phosphorylation	-	6.96	20068231
37	Phosphorylation	QPLKSSSSAEHPGAS CCCCCCCCCCCCCCC	39.36	28555341
39 (in isoform 8)	Phosphorylation	-	53.19	26267517
39 (in isoform 7)	Phosphorylation	-	53.19	26267517
45	Acetylation	AEHPGASKPPISSSS CCCCCCCCCCCCCCH	55.04	26051181
50	Phosphorylation	ASKPPISSSSMTSRI CCCCCCCCCHHHHHH	27.44	20068231
54	Phosphorylation	PISSSSMTSRILLRQ CCCCCHHHHHHHHHH	19.46	19060867
55	Phosphorylation	ISSSSMTSRILLRQQ CCCCHHHHHHHHHHH	14.53	24719451
79	Sumoylation	ERREQQQKLQAAQFM HHHHHHHHHHHHHHH	37.92	-
101	O-linked_Glycosylation	QTPAINVSVPTTLPS CCCCCEEECCCCCCC	20.21	30620550
105	O-linked_Glycosylation	INVSVPTTLPSATQV CEEECCCCCCCCCCC	30.51	30620550
128	Acetylation	THLENPTKYHIQQAQ HHCCCCCHHHHHHHH	35.77	26051181
140	Sumoylation	QAQRQQVKQYLSTTL HHHHHHHHHHHHHHH	28.96	-
144	Ubiquitination	QQVKQYLSTTLANKH HHHHHHHHHHHHHHC	17.89	10694430
157	Phosphorylation	KHANQVLSLPCPNQP HCCCCEECCCCCCCC	31.26	20068231
175	Phosphorylation	VMPPVPGSSAPNSPM CCCCCCCCCCCCCCC	19.77	20068231
176	Phosphorylation	MPPVPGSSAPNSPMA CCCCCCCCCCCCCCE	54.37	20068231
180	Phosphorylation	PGSSAPNSPMAMLTL CCCCCCCCCCEEEEC	18.26	20068231
186	Phosphorylation	NSPMAMLTLNSNCEK CCCCEEEECCCCCHH	15.71	24144214
189	Phosphorylation	MAMLTLNSNCEKEGF CEEEECCCCCHHCCC	46.07	24144214
200	Ubiquitination	KEGFYKFEEQNRAES HCCCCHHHHHCCCCC	55.30	10694430
206	Ubiquitination	FEEQNRAESECPGMN HHHHCCCCCCCCCCC	43.78	10694430
214	Phosphorylation	SECPGMNTHSRASCM CCCCCCCHHCHHHHH	16.61	29255136
216	Phosphorylation	CPGMNTHSRASCMQM CCCCCHHCHHHHHCH	27.74	29255136
255	Ubiquitination	ALQMANTLPVSGNLI HHHHHHCCCCCCCEE	3.85	10694430
289	Sumoylation	PANLPNIKRELTACI CCCCCCHHCCEEEEE	46.60	-
289	Sumoylation	PANLPNIKRELTACI CCCCCCHHCCEEEEE	46.60	15507434
299 (in isoform 12)	Phosphorylation	-	41.20	24719451
301	Phosphorylation	ACIFPTESEARALAK EEECCCHHHHHHHHH	38.75	20068231
302 (in isoform 12)	Phosphorylation	-	35.62	24719451
307	Ubiquitination	ESEARALAKERQKKD HHHHHHHHHHHHHHH	15.64	10694430
308	Ubiquitination	SEARALAKERQKKDN HHHHHHHHHHHHHHC	55.04	-
330	Methylation	RRFNINDRIKELGTL HHCCHHHHHHHHHHC	37.07	-
356 (in isoform 12)	Phosphorylation	-	16.02	24719451
357	Phosphorylation	KGTILKASVDYIRKL HHHHHHHHHHHHHHH	17.59	24719451
360	Phosphorylation	ILKASVDYIRKLQRE HHHHHHHHHHHHHHH	10.64	24719451
399 (in isoform 2)	Phosphorylation	-	14.87	10587587
399	Phosphorylation	IQELEMQARAHGLSL HHHHHHHHHHCCCCC	14.87	10587587
405	Phosphorylation	QARAHGLSLIPSTGL HHHHCCCCCCCCCCC	28.92	24732914
408	Phosphorylation	AHGLSLIPSTGLCSP HCCCCCCCCCCCCCH	31.00	20068231
409	Phosphorylation	HGLSLIPSTGLCSPD CCCCCCCCCCCCCHH	28.28	24732914
410	Phosphorylation	GLSLIPSTGLCSPDL CCCCCCCCCCCCHHH	28.90	24732914
414	Phosphorylation	IPSTGLCSPDLVNRI CCCCCCCCHHHHHHH	26.87	29255136
423	Sumoylation	DLVNRIIKQEPVLEN HHHHHHHHCCHHHHH	46.36	-
423	Sumoylation	DLVNRIIKQEPVLEN HHHHHHHHCCHHHHH	46.36	15507434
446 (in isoform 12)	Phosphorylation	-	27.75	24719451
485	Phosphorylation	GSKLEDILMDDTLSP CCCHHHHHCCCCCCC	4.81	20068231
489	Phosphorylation	EDILMDDTLSPVGVT HHHHCCCCCCCCCCC	25.52	28387310
491	Phosphorylation	ILMDDTLSPVGVTDP HHCCCCCCCCCCCCH	21.45	25159151
496	Phosphorylation	TLSPVGVTDPLLSSV CCCCCCCCCHHHHCC	26.43	28387310
498	Phosphorylation	SPVGVTDPLLSSVSP CCCCCCCHHHHCCCC	26.32	20068231
501	Phosphorylation	GVTDPLLSSVSPGAS CCCCHHHHCCCCCCC	36.05	29255136
502	Phosphorylation	VTDPLLSSVSPGASK CCCHHHHCCCCCCCC	26.95	29255136
504	Phosphorylation	DPLLSSVSPGASKTS CHHHHCCCCCCCCCC	21.40	29255136
508	Phosphorylation	SSVSPGASKTSSRRS HCCCCCCCCCCCCCC	42.24	29255136
510	Phosphorylation	VSPGASKTSSRRSSM CCCCCCCCCCCCCCC	29.46	25159151
511	Phosphorylation	SPGASKTSSRRSSMS CCCCCCCCCCCCCCC	26.11	25159151
512	Phosphorylation	PGASKTSSRRSSMSM CCCCCCCCCCCCCCH	36.62	21712546
515	Phosphorylation	SKTSSRRSSMSMEET CCCCCCCCCCCHHHC	29.32	23663014
516	Phosphorylation	KTSSRRSSMSMEETE CCCCCCCCCCHHHCC	17.05	29255136
518	Phosphorylation	SSRRSSMSMEETEHT CCCCCCCCHHHCCCC	25.62	23663014
525	Phosphorylation	SMEETEHTC------ CHHHCCCCC------	17.43	28985074

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
180	S	Phosphorylation	Kinase	MAPK	-	Uniprot
399	S	Phosphorylation	Kinase	GSK3B	P49841	PhosphoELM
405	S	Phosphorylation	Kinase	GSK3B	P49841	GPS
405	S	Phosphorylation	Kinase	GSK-FAMILY	-	GPS
405	S	Phosphorylation	Kinase	GSK3	-	Uniprot
516	S	Phosphorylation	Kinase	AKT1	P31749	PSP
516	S	Phosphorylation	Kinase	RPS6KA1	Q15418	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
180	S	Phosphorylation	10673502
Phosphorylated at Ser-180 and Ser-516 following KIT signaling, triggering a short live activation: Phosphorylation at Ser-180 and Ser-516 by MAPK and RPS6KA1, respectively, activate the transcription factor activity but also promote ubiquitination and subsequent degradation by the proteasome.
180	S	Phosphorylation	10673502
Ubiquitinated following phosphorylation at Ser-180, leading to subsequent degradation by the proteasome.
180	S	ubiquitylation	10673502
Phosphorylated at Ser-180 and Ser-516 following KIT signaling, triggering a short live activation: Phosphorylation at Ser-180 and Ser-516 by MAPK and RPS6KA1, respectively, activate the transcription factor activity but also promote ubiquitination and subsequent degradation by the proteasome.
180	S	ubiquitylation	10673502
Ubiquitinated following phosphorylation at Ser-180, leading to subsequent degradation by the proteasome.
405	S	Phosphorylation	10587587
Phosphorylation at Ser-405 significantly enhances the ability to bind the tyrosinase promoter.
516	S	Phosphorylation	10673502
Phosphorylated at Ser-180 and Ser-516 following KIT signaling, triggering a short live activation: Phosphorylation at Ser-180 and Ser-516 by MAPK and RPS6KA1, respectively, activate the transcription factor activity but also promote ubiquitination and subsequent degradation by the proteasome.
516	S	ubiquitylation	10673502
Phosphorylated at Ser-180 and Ser-516 following KIT signaling, triggering a short live activation: Phosphorylation at Ser-180 and Ser-516 by MAPK and RPS6KA1, respectively, activate the transcription factor activity but also promote ubiquitination and subsequent degradation by the proteasome.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of MITF_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
LEF1_HUMAN	LEF1	physical	12032083
PIAS3_HUMAN	PIAS3	physical	11709556
PATZ1_HUMAN	PATZ1	physical	11751862
UBC9_HUMAN	UBE2I	physical	10694430
FOS_HUMAN	FOS	physical	9918847
TFE3_HUMAN	TFE3	physical	11818452
TFEC_HUMAN	TFEC	physical	11818452
PIAS1_HUMAN	PIAS1	physical	16029420
PIAS3_HUMAN	PIAS3	physical	16029420
PIAS2_HUMAN	PIAS2	physical	16029420
PSDE_HUMAN	PSMD14	physical	20058232
MARK3_HUMAN	MARK3	physical	20058232
HINT1_HUMAN	HINT1	physical	22647378
A4_HUMAN	APP	physical	21832049
LEF1_HUMAN	LEF1	physical	12048204
CHIP_HUMAN	STUB1	physical	21988832
TFEB_HUMAN	TFEB	physical	28514442
TFE3_HUMAN	TFE3	physical	28514442
RBM6_HUMAN	RBM6	physical	28514442
KLH20_HUMAN	KLHL20	physical	28514442

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
193510	Waardenburg syndrome 2A (WS2A)
103470	Waardenburg syndrome 2, with ocular albinism, autosomal recessive (WS2-OA)
103500	Tietz syndrome (TIETZS)
614456	Melanoma, cutaneous malignant 8 (CMM8)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of MITF_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-414, AND MASSSPECTROMETRY.	18669648 [Abstract]
"Combining protein-based IMAC, peptide-based IMAC, and MudPIT forefficient phosphoproteomic analysis."; Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,Yates J.R. III; J. Proteome Res. 7:1346-1351(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-414, AND MASSSPECTROMETRY.	18220336 [Abstract]
"Ser298 of MITF, a mutation site in Waardenburg syndrome type 2, is aphosphorylation site with functional significance."; Takeda K., Takemoto C., Kobayashi I., Watanabe A., Nobukuni Y.,Fisher D.E., Tachibana M.; Hum. Mol. Genet. 9:125-132(2000). Cited for: MUTAGENESIS OF SER-405, AND PHOSPHORYLATION AT SER-405.	10587587 [Abstract]
"c-Kit triggers dual phosphorylations, which couple activation anddegradation of the essential melanocyte factor Mi."; Wu M., Hemesath T.J., Takemoto C.M., Horstmann M.A., Wells A.G.,Price E.R., Fisher D.Z., Fisher D.E.; Genes Dev. 14:301-312(2000). Cited for: PHOSPHORYLATION AT SER-180 AND SER-516, UBIQUITINATION, ANDMUTAGENESIS OF SER-180 AND SER-516.	10673502 [Abstract]
"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column."; Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.; Anal. Sci. 24:161-166(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-54, AND MASSSPECTROMETRY.	18187866 [Abstract]
Sumoylation
Reference	PubMed
"Sumoylation of MITF and its related family members TFE3 and TFEB."; Miller A.J., Levy C., Davis I.J., Razin E., Fisher D.E.; J. Biol. Chem. 280:146-155(2005). Cited for: SUMOYLATION AT LYS-289 AND LYS-423, AND MUTAGENESIS OF LYS-289 ANDLYS-423.	15507434 [Abstract]

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