dbPTM

HNF4A_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	HNF4A_HUMAN
UniProt AC	P41235
Protein Name	Hepatocyte nuclear factor 4-alpha
Gene Name	HNF4A
Organism	Homo sapiens (Human).
Sequence Length	474
Subcellular Localization	Nucleus.
Protein Description	Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine..
Protein Sequence	MRLSKTLVDMDMADYSAALDPAYTTLEFENVQVLTMGNDTSPSEGTNLNAPNSLGVSALCAICGDRATGKHYGASSCDGCKGFFRRSVRKNHMYSCRFSRQCVVDKDKRNQCRYCRLKKCFRAGMKKEAVQNERDRISTRRSSYEDSSLPSINALLQAEVLSRQITSPVSGINGDIRAKKIASIADVCESMKEQLLVLVEWAKYIPAFCELPLDDQVALLRAHAGEHLLLGATKRSMVFKDVLLLGNDYIVPRHCPELAEMSRVSIRILDELVLPFQELQIDDNEYAYLKAIIFFDPDAKGLSDPGKIKRLRSQVQVSLEDYINDRQYDSRGRFGELLLLLPTLQSITWQMIEQIQFIKLFGMAKIDNLLQEMLLGGSPSDAPHAHHPLHPHLMQEHMGTNVIVANTMPTHLSNGQMCEWPRPRGQAATPETPQPSPPGGSGSEPYKLLPGAVATIVKPLSAIPQPTITKQEVI

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
23	Phosphorylation	SAALDPAYTTLEFEN HHHHCCCCCEEEEEC	12.97	22308320
72	Phosphorylation	DRATGKHYGASSCDG CCCCCCCCCCCCCCC	20.20	-
75	Phosphorylation	TGKHYGASSCDGCKG CCCCCCCCCCCCCCH	27.43	-
76	Phosphorylation	GKHYGASSCDGCKGF CCCCCCCCCCCCCHH	18.72	-
95	Phosphorylation	VRKNHMYSCRFSRQC HHCCCCEECCEECCE	7.40	-
99	Phosphorylation	HMYSCRFSRQCVVDK CCEECCEECCEEECH	11.33	-
106	Acetylation	SRQCVVDKDKRNQCR ECCEEECHHHCCCHH	54.24	10882110
108	Acetylation	QCVVDKDKRNQCRYC CEEECHHHCCCHHHH	60.01	10882110
126	Acetylation	KCFRAGMKKEAVQNE HHHHHCCCHHHHHCH	46.69	10882110
127	Acetylation	CFRAGMKKEAVQNER HHHHCCCHHHHHCHH	41.85	10882110
138	Phosphorylation	QNERDRISTRRSSYE HCHHHHHHHCHHHCC	19.43	21598922
139	Phosphorylation	NERDRISTRRSSYED CHHHHHHHCHHHCCC	27.94	-
142	Phosphorylation	DRISTRRSSYEDSSL HHHHHCHHHCCCCCC	33.70	21708125
143	Phosphorylation	RISTRRSSYEDSSLP HHHHCHHHCCCCCCH	30.63	26657352
144	Phosphorylation	ISTRRSSYEDSSLPS HHHCHHHCCCCCCHH	25.63	26657352
147	Phosphorylation	RRSSYEDSSLPSINA CHHHCCCCCCHHHHH	23.10	21598922
148	Phosphorylation	RSSYEDSSLPSINAL HHHCCCCCCHHHHHH	57.53	29116813
151	Phosphorylation	YEDSSLPSINALLQA CCCCCCHHHHHHHHH	33.49	21598922
166	Phosphorylation	EVLSRQITSPVSGIN HHHHHCCCCCCCCCC	20.74	26657352
167	Phosphorylation	VLSRQITSPVSGING HHHHCCCCCCCCCCC	25.57	22617229
170	Phosphorylation	RQITSPVSGINGDIR HCCCCCCCCCCCCHH	37.02	27987026
190	Phosphorylation	SIADVCESMKEQLLV HHHHHHHHHHHHHHH	29.99	16351573
204	Phosphorylation	VLVEWAKYIPAFCEL HHHHHHHHCHHHHCC	12.37	29083192
234	Ubiquitination	HLLLGATKRSMVFKD HHHHCCHHHHHHHHC	41.77	21708125
262	Phosphorylation	CPELAEMSRVSIRIL CHHHHHHCCHHHHHH	22.49	-
265	Phosphorylation	LAEMSRVSIRILDEL HHHHCCHHHHHHHHH	12.68	-
286	Phosphorylation	LQIDDNEYAYLKAII EECCCCHHEEEEEEE	13.55	22308320
288	Phosphorylation	IDDNEYAYLKAIIFF CCCCHHEEEEEEEEE	14.08	22308320
303	Phosphorylation	DPDAKGLSDPGKIKR CCCCCCCCCCHHHHH	50.88	21598922
307	Ubiquitination	KGLSDPGKIKRLRSQ CCCCCCHHHHHHHHH	50.90	21708125
309	Ubiquitination	LSDPGKIKRLRSQVQ CCCCHHHHHHHHHEE	49.19	-
313	Phosphorylation	GKIKRLRSQVQVSLE HHHHHHHHHEEEEHH	39.02	16351573
318	Phosphorylation	LRSQVQVSLEDYIND HHHHEEEEHHHHHHC	14.67	21598922
378	Phosphorylation	QEMLLGGSPSDAPHA HHHHHCCCCCCCCCC	21.31	21598922
429	Phosphorylation	RPRGQAATPETPQPS CCCCCCCCCCCCCCC	25.36	26657352
432	Phosphorylation	GQAATPETPQPSPPG CCCCCCCCCCCCCCC	28.55	21082442
436	Phosphorylation	TPETPQPSPPGGSGS CCCCCCCCCCCCCCC	38.18	21598922
441	Phosphorylation	QPSPPGGSGSEPYKL CCCCCCCCCCCCCCC	45.09	28857561
443	Phosphorylation	SPPGGSGSEPYKLLP CCCCCCCCCCCCCCC	36.78	21598922
446	Phosphorylation	GGSGSEPYKLLPGAV CCCCCCCCCCCCCCE	15.37	25072903
455	Phosphorylation	LLPGAVATIVKPLSA CCCCCEEEEEECHHH	21.50	21598922
458	Ubiquitination	GAVATIVKPLSAIPQ CCEEEEEECHHHCCC	36.07	-
458	Acetylation	GAVATIVKPLSAIPQ CCEEEEEECHHHCCC	36.07	21708125
461	Phosphorylation	ATIVKPLSAIPQPTI EEEEECHHHCCCCCC	32.45	-
467	Phosphorylation	LSAIPQPTITKQEVI HHHCCCCCCCCCCCC	35.71	-
469	Phosphorylation	AIPQPTITKQEVI-- HCCCCCCCCCCCC--	29.20	16351573

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
23	Y	Phosphorylation	Kinase	SRC	P12931	PSP
95	S	Phosphorylation	Kinase	ERK1	P27361	PSP
138	S	Phosphorylation	Kinase	ERK1	P27361	PSP
139	T	Phosphorylation	Kinase	ERK1	P27361	PSP
142	S	Phosphorylation	Kinase	ERK1	P27361	PSP
143	S	Phosphorylation	Kinase	ERK1	P27361	PSP
147	S	Phosphorylation	Kinase	ERK1	P27361	PSP
148	S	Phosphorylation	Kinase	ERK1	P27361	PSP
151	S	Phosphorylation	Kinase	ERK1	P27361	PSP
166	T	Phosphorylation	Kinase	ERK1	P27361	PSP
167	S	Phosphorylation	Kinase	MAPK11	Q15759	GPS
167	S	Phosphorylation	Kinase	MAPK14	Q16539	GPS
167	S	Phosphorylation	Kinase	ERK1	P27361	PSP
262	S	Phosphorylation	Kinase	ERK1	P27361	PSP
265	S	Phosphorylation	Kinase	ERK1	P27361	PSP
286	Y	Phosphorylation	Kinase	SRC	P12931	PSP
288	Y	Phosphorylation	Kinase	SRC	P12931	PSP
313	S	Phosphorylation	Kinase	AMPK-FAMILY	-	GPS
313	S	Phosphorylation	Kinase	AMPK	Q9Y478	Uniprot
313	S	Phosphorylation	Kinase	AMPK_GROUP	-	PhosphoELM
313	S	Phosphorylation	Kinase	ERK1	P27361	PSP
313	S	Phosphorylation	Kinase	PRKAA1	P54645	GPS
313	S	Phosphorylation	Kinase	AMPKA1	Q13131	PSP
461	S	Phosphorylation	Kinase	ERK1	P27361	PSP
467	T	Phosphorylation	Kinase	ERK1	P27361	PSP
469	T	Phosphorylation	Kinase	ERK1	P27361	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
313	S	Phosphorylation	12740371
Phosphorylation at Ser-313 by AMPK reduces the ability to form homodimers and bind DNA.
458	K	Acetylation	21708125
Acetylation at Lys-458 lowers transcriptional activation by about two-fold.

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
106	Acetylation	114 (8)	T ⇒ I	rs1800961	Fibrinogen levels HDL cholesterol Cholesterol, total C-reactive protein	28107422 20686565 22939635 19060906 21300955 24097068 26561523 25961943 27286809 27863252
108	Acetylation	114 (6)	T ⇒ I	rs1800961	Fibrinogen levels HDL cholesterol Cholesterol, total C-reactive protein	28107422 20686565 22939635 19060906 21300955 24097068 26561523 25961943 27286809 27863252
126	Acetylation	132 (6)	T ⇒ I	rs1800961	Fibrinogen levels HDL cholesterol Cholesterol, total C-reactive protein C-reactive protein levels C-reactive protein levels or total cholesterol levels (pleiotropy) C-reactive protein levels or LDL-cholesterol levels (pleiotropy) C-reactive protein levels or HDL-cholesterol levels (pleiotropy) Sum neutrophil eosinophil counts Sum basophil neutrophil counts	28107422 20686565 22939635 19060906 21300955 24097068 26561523 25961943 27286809 27863252
127	Acetylation	132 (5)	T ⇒ I	rs1800961	Fibrinogen levels HDL cholesterol Cholesterol, total C-reactive protein C-reactive protein levels C-reactive protein levels or total cholesterol levels (pleiotropy) C-reactive protein levels or LDL-cholesterol levels (pleiotropy) C-reactive protein levels or HDL-cholesterol levels (pleiotropy) Sum neutrophil eosinophil counts Sum basophil neutrophil counts	28107422 20686565 22939635 19060906 21300955 24097068 26561523 25961943 27286809 27863252
138	Phosphorylation	132 (6)	T ⇒ I	rs1800961	Fibrinogen levels HDL cholesterol Cholesterol, total C-reactive protein C-reactive protein levels C-reactive protein levels or total cholesterol levels (pleiotropy) C-reactive protein levels or LDL-cholesterol levels (pleiotropy) C-reactive protein levels or HDL-cholesterol levels (pleiotropy) Sum neutrophil eosinophil counts Sum basophil neutrophil counts	28107422 20686565 22939635 19060906 21300955 24097068 26561523 25961943 27286809 27863252
142	Phosphorylation	132 (10)	T ⇒ I	rs1800961	Fibrinogen levels HDL cholesterol Cholesterol, total C-reactive protein C-reactive protein levels C-reactive protein levels or total cholesterol levels (pleiotropy) C-reactive protein levels or LDL-cholesterol levels (pleiotropy) C-reactive protein levels or HDL-cholesterol levels (pleiotropy) Sum neutrophil eosinophil counts Sum basophil neutrophil counts	28107422 20686565 22939635 19060906 21300955 24097068 26561523 25961943 27286809 27863252

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SYUG_HUMAN	SNCG	physical	17353931
STK16_HUMAN	STK16	physical	17353931
RAD50_HUMAN	RAD50	physical	17353931
PABP4_HUMAN	PABPC4	physical	17353931
EXT2_HUMAN	EXT2	physical	17353931
CBP_HUMAN	CREBBP	physical	9434765
NCOA1_HUMAN	NCOA1	physical	9812974
NCOA2_HUMAN	NCOA2	physical	9812974
P53_HUMAN	TP53	physical	11818510
TCP4_HUMAN	SUB1	physical	11741883
MED23_HUMAN	MED23	physical	12089346
MED14_HUMAN	MED14	physical	12089346
MED1_HUMAN	MED1	physical	12089346
ZNHI3_HUMAN	ZNHIT3	physical	11916906
MED1_HUMAN	MED1	physical	12101254
MED14_HUMAN	MED14	physical	12101254
MED24_HUMAN	MED24	physical	12101254
MED17_HUMAN	MED17	physical	12101254
MED16_HUMAN	MED16	physical	12101254
MED7_HUMAN	MED7	physical	12101254
MED21_HUMAN	MED21	physical	12101254
MED10_HUMAN	MED10	physical	12101254
SP1_HUMAN	SP1	physical	19115260
FOXO1_HUMAN	FOXO1	physical	19740748
ANM1_HUMAN	PRMT1	physical	17052457
PHS_HUMAN	PCBD1	physical	20211142
NCOA6_HUMAN	NCOA6	physical	18552123
CBP_HUMAN	CREBBP	physical	18552123
PRGC1_HUMAN	PPARGC1A	physical	18552123
TGS1_HUMAN	TGS1	physical	18552123
NR1I3_HUMAN	NR1I3	physical	18552123
CTNB1_HUMAN	CTNNB1	physical	12944908
PRGC1_HUMAN	PPARGC1A	physical	15322103
CBP_HUMAN	CREBBP	physical	10882110
PRGC1_HUMAN	PPARGC1A	physical	17636037
SIR1_HUMAN	SIRT1	physical	20375098
VDR_HUMAN	VDR	physical	20371703
SRBP2_HUMAN	SREBF2	physical	20926756
PRGC1_HUMAN	PPARGC1A	physical	20926756
NR0B2_HUMAN	NR0B2	physical	20516075
HNF4A_HUMAN	HNF4A	physical	15604093
PROX1_HUMAN	PROX1	physical	15604093
UBC9_HUMAN	UBE2I	physical	15604093
NRIP1_HUMAN	NRIP1	physical	15604093
ANF_HUMAN	NPPA	physical	15604093
PNRC1_HUMAN	PNRC1	physical	15604093
CSN5_HUMAN	COPS5	physical	15604093
PNRC2_HUMAN	PNRC2	physical	15604093
NCOA6_HUMAN	NCOA6	physical	15604093
NR0B2_HUMAN	NR0B2	physical	15604093
SMAD3_HUMAN	SMAD3	physical	10995777
HNF4A_HUMAN	HNF4A	genetic	17464991
MDM2_HUMAN	MDM2	physical	22197810
TBP_HUMAN	TBP	physical	9792714
TAF9_HUMAN	TAF9	physical	9792714
TAF6_HUMAN	TAF6	physical	9792714
TF2B_HUMAN	GTF2B	physical	9792714
TF2H1_HUMAN	GTF2H1	physical	9792714
TAD2A_HUMAN	TADA2A	physical	9792714
TCP4_HUMAN	SUB1	physical	9792714
SRBP1_HUMAN	SREBF1	physical	20817729
CTNB1_HUMAN	CTNNB1	physical	25241761
NR1I2_HUMAN	NR1I2	physical	16455805
NR0B2_HUMAN	NR0B2	physical	16455805
NR1I2_HUMAN	NR1I2	physical	15331348
PRGC1_HUMAN	PPARGC1A	physical	15331348
NR0B2_HUMAN	NR0B2	physical	11535594
EZH2_HUMAN	EZH2	physical	25391650
SUZ12_HUMAN	SUZ12	physical	25391650
EED_HUMAN	EED	physical	25391650
BMI1_HUMAN	BMI1	physical	25391650
P53_HUMAN	TP53	physical	28514442
HIF1A_HUMAN	HIF1A	physical	12097158
ARNT_HUMAN	ARNT	physical	12097158

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
125850	Maturity-onset diabetes of the young 1 (MODY1)
125853	Diabetes mellitus, non-insulin-dependent (NIDDM)
616026	Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young (FRTS4)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of HNF4A_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Multiple post-translational modifications in hepatocyte nuclearfactor 4alpha."; Yokoyama A., Katsura S., Ito R., Hashiba W., Sekine H., Fujiki R.,Kato S.; Biochem. Biophys. Res. Commun. 410:749-753(2011). Cited for: PHOSPHORYLATION AT SER-142; THR-166; SER-167; THR-432 AND SER-436,UBIQUITINATION AT LYS-234 AND LYS-307, AND ACETYLATION AT LYS-458.	21708125 [Abstract]
Phosphorylation
Reference	PubMed
"Multiple post-translational modifications in hepatocyte nuclearfactor 4alpha."; Yokoyama A., Katsura S., Ito R., Hashiba W., Sekine H., Fujiki R.,Kato S.; Biochem. Biophys. Res. Commun. 410:749-753(2011). Cited for: PHOSPHORYLATION AT SER-142; THR-166; SER-167; THR-432 AND SER-436,UBIQUITINATION AT LYS-234 AND LYS-307, AND ACETYLATION AT LYS-458.	21708125 [Abstract]
"AMP-activated protein kinase regulates HNF4alpha transcriptionalactivity by inhibiting dimer formation and decreasing proteinstability."; Hong Y.H., Varanasi U.S., Yang W., Leff T.; J. Biol. Chem. 278:27495-27501(2003). Cited for: PHOSPHORYLATION AT SER-313, AND MUTAGENESIS OF SER-313.	12740371 [Abstract]
Ubiquitylation
Reference	PubMed
"Multiple post-translational modifications in hepatocyte nuclearfactor 4alpha."; Yokoyama A., Katsura S., Ito R., Hashiba W., Sekine H., Fujiki R.,Kato S.; Biochem. Biophys. Res. Commun. 410:749-753(2011). Cited for: PHOSPHORYLATION AT SER-142; THR-166; SER-167; THR-432 AND SER-436,UBIQUITINATION AT LYS-234 AND LYS-307, AND ACETYLATION AT LYS-458.	21708125 [Abstract]

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