HIF1A_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: HIF1A_HUMAN
• UniProt AC: Q16665
• Protein Name: Hypoxia-inducible factor 1-alpha {ECO:0000303|PubMed:7539918}
• Gene Name: HIF1A {ECO:0000303|PubMed:7539918}
• Organism: Homo sapiens (Human).
• Sequence Length: 826
• Subcellular Localization: Cytoplasm . Nucleus . Nucleus speckle . Colocalizes with HIF3A in the nucleus and speckles (By similarity). Cytoplasmic in normoxia, nuclear translocation in response to hypoxia (PubMed:9822602).
• Protein Description: Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia..
• Protein Sequence: MEGAGGANDKKKISSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLLDAGDLDIEDDMKAQMNCFYLKALDGFVMVLTDDGDMIYISDNVNKYMGLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGLVKKGKEQNTQRSFFLRMKCTLTSRGRTMNIKSATWKVLHCTGHIHVYDTNSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSKTFLSRHSLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQVTTGQYRMLAKRGGYVWVETQATVIYNTKNSQPQCIVCVNYVVSGIIQHDLIFSLQQTECVLKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPAAGDTIISLDFGSNDTETDDQQLEEVPLYNDVMLPSPNEKLQNINLAMSPLPTAETPKPLRSSADPALNQEVALKLEPNPESLELSFTMPQIQDQTPSPSDGSTRQSSPEPNSPSEYCFYVDSDMVNEFKLELVEKLFAEDTEAKNPFSTQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESSSASPESASPQSTVTVFQQTQIQEPTANATTTTATTDELKTVTKDRMEDIKILIASPSPTHIHKETTSATSSPYRDTQSRTASPNRAGKGVIEQTEKSHPRSPNVLSVALSQRTTVPEEELNPKILALQNAQRKRKMEHDGSLFQAVGIGTLLQQPDDHAATTSLSWKRVKGCKSSEQNGMEQKTIILIPSDLACRLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
10	Sumoylation	GAGGANDKKKISSER CCCCCCCHHHCCHHH	56.63	-
10	Acetylation	GAGGANDKKKISSER CCCCCCCHHHCCHHH	56.63	21917920
10	Sumoylation	GAGGANDKKKISSER CCCCCCCHHHCCHHH	56.63	-
10	Ubiquitination	GAGGANDKKKISSER CCCCCCCHHHCCHHH	56.63	-
11	Acetylation	AGGANDKKKISSERR CCCCCCHHHCCHHHH	59.19	21917920
11	Ubiquitination	AGGANDKKKISSERR CCCCCCHHHCCHHHH	59.19	-
12	Acetylation	GGANDKKKISSERRK CCCCCHHHCCHHHHH	54.27	21917920
12	Ubiquitination	GGANDKKKISSERRK CCCCCHHHCCHHHHH	54.27	-
14	Phosphorylation	ANDKKKISSERRKEK CCCHHHCCHHHHHHH	34.72	24702127
15	Phosphorylation	NDKKKISSERRKEKS CCHHHCCHHHHHHHH	38.30	24702127
19	Acetylation	KISSERRKEKSRDAA HCCHHHHHHHHHHHH	75.59	21917920
21	Acetylation	SSERRKEKSRDAARS CHHHHHHHHHHHHHH	54.55	21917920
28	Phosphorylation	KSRDAARSRRSKESE HHHHHHHHHHHHHHH	27.58	22210691
31	Phosphorylation	DAARSRRSKESEVFY HHHHHHHHHHHHHHH	39.40	-
32	Ubiquitination	AARSRRSKESEVFYE HHHHHHHHHHHHHHH	64.55	21906983
32 (in isoform 1)	Ubiquitination	-	64.55	21890473
32 (in isoform 2)	Ubiquitination	-	64.55	21890473
38 (in isoform 3)	Phosphorylation	-	18.40	26552605
39 (in isoform 3)	Phosphorylation	-	28.19	26552605
56 (in isoform 2)	Ubiquitination	-	49.25	-
58	Phosphorylation	SSHLDKASVMRLTIS HHHCCHHHHHHHHHH	23.37	24719451
63	Phosphorylation	KASVMRLTISYLRVR HHHHHHHHHHHHHHH	9.49	24719451
65	Phosphorylation	SVMRLTISYLRVRKL HHHHHHHHHHHHHHH	16.93	24719451
66	Phosphorylation	VMRLTISYLRVRKLL HHHHHHHHHHHHHHH	8.48	24719451
71	Ubiquitination	ISYLRVRKLLDAGDL HHHHHHHHHHHCCCC	51.01	21906983
71 (in isoform 1)	Ubiquitination	-	51.01	21890473
71 (in isoform 2)	Ubiquitination	-	51.01	21890473
85	Ubiquitination	LDIEDDMKAQMNCFY CCCCCHHHHHHHHHH	42.32	-
113	Phosphorylation	DGDMIYISDNVNKYM CCCEEEEECCCHHHC	13.22	-
123	Phosphorylation	VNKYMGLTQFELTGH CHHHCCCEEEEEECC	26.03	22210691
136	Phosphorylation	GHSVFDFTHPCDHEE CCCEECCCCCCCHHH	27.10	22210691
149	Phosphorylation	EEMREMLTHRNGLVK HHHHHHHHHCCCCCC	19.92	22210691
172	Ubiquitination	RSFFLRMKCTLTSRG CEEEEHHEEEEEECC	20.03	-
185	Sumoylation	RGRTMNIKSATWKVL CCCEEEEEECEEEEE	29.09	-
185	Sumoylation	RGRTMNIKSATWKVL CCCEEEEEECEEEEE	29.09	-
185	Ubiquitination	RGRTMNIKSATWKVL CCCEEEEEECEEEEE	29.09	21906983
185 (in isoform 1)	Ubiquitination	-	29.09	21890473
185 (in isoform 2)	Ubiquitination	-	29.09	21890473
247	Phosphorylation	KTFLSRHSLDMKFSY CCCHHHHCCCCCEEE	25.59	24719451
251	Ubiquitination	SRHSLDMKFSYCDER HHHCCCCCEEECCHH	30.72	-
251 (in isoform 2)	Ubiquitination	-	30.72	-
289	Ubiquitination	LDSDHLTKTHHDMFT HCCCCCCCCCHHCCC	52.82	21906983
289 (in isoform 1)	Ubiquitination	-	52.82	21890473
289 (in isoform 2)	Ubiquitination	-	52.82	21890473
290	Phosphorylation	DSDHLTKTHHDMFTK CCCCCCCCCHHCCCC	21.14	29083192
296	Phosphorylation	KTHHDMFTKGQVTTG CCCHHCCCCCCCCHH	27.85	29083192
297	Ubiquitination	THHDMFTKGQVTTGQ CCHHCCCCCCCCHHH	35.76	21906983
297 (in isoform 1)	Ubiquitination	-	35.76	21890473
297 (in isoform 2)	Ubiquitination	-	35.76	21890473
301	Phosphorylation	MFTKGQVTTGQYRML CCCCCCCCHHHHEEH	19.81	29083192
302	Phosphorylation	FTKGQVTTGQYRMLA CCCCCCCHHHHEEHH	24.35	29083192
305	Phosphorylation	GQVTTGQYRMLAKRG CCCCHHHHEEHHHCC	10.19	29083192
377	Sumoylation	KMTQLFTKVESEDTS CEEEEEEECCCCCCH	36.35	-
377	Ubiquitination	KMTQLFTKVESEDTS CEEEEEEECCCCCCH	36.35	21906983
377 (in isoform 1)	Ubiquitination	-	36.35	21890473
377 (in isoform 2)	Ubiquitination	-	36.35	21890473
380	Phosphorylation	QLFTKVESEDTSSLF EEEEECCCCCCHHHH	43.70	19053533
389	Acetylation	DTSSLFDKLKKEPDA CCHHHHHHHHCCCCH	55.67	6161603
389	Ubiquitination	DTSSLFDKLKKEPDA CCHHHHHHHHCCCCH	55.67	21906983
389 (in isoform 1)	Ubiquitination	-	55.67	21890473
389 (in isoform 2)	Ubiquitination	-	55.67	21890473
391	Sumoylation	SSLFDKLKKEPDALT HHHHHHHHCCCCHHH	61.91	-
391	Methylation	SSLFDKLKKEPDALT HHHHHHHHCCCCHHH	61.91	190310425
391	Sumoylation	SSLFDKLKKEPDALT HHHHHHHHCCCCHHH	61.91	17610843
391	Ubiquitination	SSLFDKLKKEPDALT HHHHHHHHCCCCHHH	61.91	21906983
391 (in isoform 1)	Ubiquitination	-	61.91	21890473
391 (in isoform 2)	Ubiquitination	-	61.91	21890473
392	Ubiquitination	SLFDKLKKEPDALTL HHHHHHHCCCCHHHE	82.18	-
402	Hydroxylation	DALTLLAPAAGDTII CHHHEEECCCCCEEE	23.70	11566883
451	Phosphorylation	QNINLAMSPLPTAET CCCCCCCCCCCCCCC	20.06	25159151
455	Phosphorylation	LAMSPLPTAETPKPL CCCCCCCCCCCCCCC	44.82	22777824
458	Phosphorylation	SPLPTAETPKPLRSS CCCCCCCCCCCCCCC	33.86	22777824
460	Ubiquitination	LPTAETPKPLRSSAD CCCCCCCCCCCCCCC	65.19	-
465	Phosphorylation	TPKPLRSSADPALNQ CCCCCCCCCCHHHCH	30.20	-
475 (in isoform 3)	Phosphorylation	-	9.76	27251275
477	Sumoylation	LNQEVALKLEPNPES HCHHHHHHCCCCHHH	40.86	-
477	Sumoylation	LNQEVALKLEPNPES HCHHHHHHCCCCHHH	40.86	17610843
477	Ubiquitination	LNQEVALKLEPNPES HCHHHHHHCCCCHHH	40.86	21906983
477 (in isoform 1)	Ubiquitination	-	40.86	21890473
477 (in isoform 2)	Ubiquitination	-	40.86	21890473
482 (in isoform 3)	Phosphorylation	-	43.18	27251275
488	Phosphorylation	NPESLELSFTMPQIQ CHHHEEEEEECCCCC	14.86	28348404
500	Phosphorylation	QIQDQTPSPSDGSTR CCCCCCCCCCCCCCC	40.18	28348404
509	Phosphorylation	SDGSTRQSSPEPNSP CCCCCCCCCCCCCCC	44.57	24043423
510	Phosphorylation	DGSTRQSSPEPNSPS CCCCCCCCCCCCCCC	25.58	24043423
515	Phosphorylation	QSSPEPNSPSEYCFY CCCCCCCCCCCCEEE	40.28	24043423
517	Phosphorylation	SPEPNSPSEYCFYVD CCCCCCCCCCEEEEC	40.81	24043423
519	Phosphorylation	EPNSPSEYCFYVDSD CCCCCCCCEEEECHH	7.69	24043423
520	S-nitrosocysteine	PNSPSEYCFYVDSDM CCCCCCCEEEECHHH	1.42	-
520	S-nitrosylation	PNSPSEYCFYVDSDM CCCCCCCEEEECHHH	1.42	22178444
522	Phosphorylation	SPSEYCFYVDSDMVN CCCCCEEEECHHHHC	10.37	24043423
525	Phosphorylation	EYCFYVDSDMVNEFK CCEEEECHHHHCHHH	19.98	24043423
532	Acetylation	SDMVNEFKLELVEKL HHHHCHHHHHHHHHH	34.57	12464182
532	Ubiquitination	SDMVNEFKLELVEKL HHHHCHHHHHHHHHH	34.57	12464182
538	Ubiquitination	FKLELVEKLFAEDTE HHHHHHHHHHCCCCC	41.23	18781797
538 (in isoform 1)	Ubiquitination	-	41.23	21890473
538 (in isoform 2)	Ubiquitination	-	41.23	21890473
547	Ubiquitination	FAEDTEAKNPFSTQD HCCCCCCCCCCCCCC	59.94	16862177
551	Phosphorylation	TEAKNPFSTQDTDLD CCCCCCCCCCCCCCC	26.81	20889502
555	Phosphorylation	NPFSTQDTDLDLEML CCCCCCCCCCCHHHH	28.75	20889502
556	Acetylation	PFSTQDTDLDLEMLA CCCCCCCCCCHHHHC	46.61	10944113
556	Ubiquitination	PFSTQDTDLDLEMLA CCCCCCCCCCHHHHC	46.61	10944113
562	Ubiquitination	TDLDLEMLAPYIPMD CCCCHHHHCCCCCCC	2.95	21890473
564	Hydroxylation	LDLEMLAPYIPMDDD CCHHHHCCCCCCCCC	24.51	11566883
565	Phosphorylation	DLEMLAPYIPMDDDF CHHHHCCCCCCCCCC	16.43	-
576	Phosphorylation	DDDFQLRSFDQLSPL CCCCCCCCHHHCCCC	41.59	20889502
589	Phosphorylation	PLESSSASPESASPQ CCCCCCCCCCCCCCC	31.02	20889502
636	Ubiquitination	KDRMEDIKILIASPS HHHHHHCEEEEECCC	43.72	-
641	Phosphorylation	DIKILIASPSPTHIH HCEEEEECCCCCCCC	20.93	25159151
643	Phosphorylation	KILIASPSPTHIHKE EEEEECCCCCCCCCC	39.68	25159151
645	Phosphorylation	LIASPSPTHIHKETT EEECCCCCCCCCCCC	37.49	30108239
649	Ubiquitination	PSPTHIHKETTSATS CCCCCCCCCCCCCCC	57.03	-
651	Phosphorylation	PTHIHKETTSATSSP CCCCCCCCCCCCCCC	30.74	-
652	Phosphorylation	THIHKETTSATSSPY CCCCCCCCCCCCCCC	19.91	27134283
653	Phosphorylation	HIHKETTSATSSPYR CCCCCCCCCCCCCCC	36.65	21712546
656	Phosphorylation	KETTSATSSPYRDTQ CCCCCCCCCCCCCCC	29.09	21712546
657	Phosphorylation	ETTSATSSPYRDTQS CCCCCCCCCCCCCCC	22.92	20889502
667 (in isoform 3)	Phosphorylation	-	23.14	27251275
668	Phosphorylation	DTQSRTASPNRAGKG CCCCCCCCCCCCCCC	23.30	26329039
674	Acetylation	ASPNRAGKGVIEQTE CCCCCCCCCHHHCCC	49.36	20620956
674	Ubiquitination	ASPNRAGKGVIEQTE CCCCCCCCCHHHCCC	49.36	21906983
674 (in isoform 1)	Ubiquitination	-	49.36	21890473
674 (in isoform 2)	Ubiquitination	-	49.36	21890473
682	Ubiquitination	GVIEQTEKSHPRSPN CHHHCCCCCCCCCCC	58.41	-
683	Phosphorylation	VIEQTEKSHPRSPNV HHHCCCCCCCCCCCH	32.27	28348404
687	Phosphorylation	TEKSHPRSPNVLSVA CCCCCCCCCCHHHHH	25.85	20873877
692	Phosphorylation	PRSPNVLSVALSQRT CCCCCHHHHHHCCCC	10.89	23898821
696	Phosphorylation	NVLSVALSQRTTVPE CHHHHHHCCCCCCCH	14.10	21095582
700	Phosphorylation	VALSQRTTVPEEELN HHHCCCCCCCHHHHC	35.93	-
707 (in isoform 3)	Phosphorylation	-	38.81	27251275
709	Acetylation	PEEELNPKILALQNA CHHHHCHHHHHHHHH	49.64	24681946
709	Ubiquitination	PEEELNPKILALQNA CHHHHCHHHHHHHHH	49.64	2190698
709 (in isoform 1)	Ubiquitination	-	49.64	21890473
709 (in isoform 2)	Ubiquitination	-	49.64	21890473
721	Ubiquitination	QNAQRKRKMEHDGSL HHHHHHHHCCCCCCH	52.23	-
727	Phosphorylation	RKMEHDGSLFQAVGI HHCCCCCCHHHHHCH	31.87	-
760	Phosphorylation	KRVKGCKSSEQNGME EECCCCCCHHHCCCC	43.09	-
761	Phosphorylation	RVKGCKSSEQNGMEQ ECCCCCCHHHCCCCC	28.79	-
769	Ubiquitination	EQNGMEQKTIILIPS HHCCCCCCEEEEECH	28.52	-
796	Phosphorylation	ESGLPQLTSYDCEVN CCCCCCCCCCEEEEC	21.72	11983697
800	S-nitrosocysteine	PQLTSYDCEVNAPIQ CCCCCCEEEECCCCC	4.83	-
800	S-nitrosylation	PQLTSYDCEVNAPIQ CCCCCCEEEECCCCC	4.83	12914934
803	Hydroxylation	TSYDCEVNAPIQGSR CCCEEEECCCCCCCC	20.08	12080085
809	Phosphorylation	VNAPIQGSRNLLQGE ECCCCCCCCHHHCHH	11.13	-

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
63	T	Phosphorylation	Kinase	PRKACA	P17612	GPS
247	S	Phosphorylation	Kinase	CK1	-	Uniprot
247	S	Phosphorylation	Kinase	CK1-FAMILY	-	GPS
247	S	Phosphorylation	Kinase	CSNK1D	P48730	GPS
455	T	Phosphorylation	Kinase	PRKACA	P17612	GPS
465	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
551	S	Phosphorylation	Kinase	GSK3B	P49841	GPS
555	T	Phosphorylation	Kinase	GSK3B	P49841	GPS
576	S	Phosphorylation	Kinase	PLK3	Q9H4B4	Uniprot
589	S	Phosphorylation	Kinase	GSK3B	P49841	GPS
641	S	Phosphorylation	Kinase	ERK2	P63085	PSP
641	S	Phosphorylation	Kinase	MAPK1	P28482	GPS
643	S	Phosphorylation	Kinase	ERK2	P63085	PSP
643	S	Phosphorylation	Kinase	MAPK1	P28482	GPS
657	S	Phosphorylation	Kinase	PLK3	Q9H4B4	Uniprot
668	S	Phosphorylation	Kinase	CDK1	P06493	PSP
687	S	Phosphorylation	Kinase	CDK5	Q00535	PSP
692	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
696	S	Phosphorylation	Kinase	ATM	Q13315	PSP
700	T	Phosphorylation	Kinase	PRKACA	P17612	GPS
727	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
760	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
761	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
809	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	MDM2	Q00987	PMID:10640274
-	K	Ubiquitination	E3 ubiquitin ligase	F12	P00748	PMID:18838541
-	K	Ubiquitination	E3 ubiquitin ligase	FBXW7	Q969H0	PMID:24658274
-	K	Ubiquitination	E3 ubiquitin ligase	VHL	P40337	PMID:10353251
-	K	Ubiquitination	E3 ubiquitin ligase	SIAH1	Q8IUQ4	PMID:17047048
-	K	Ubiquitination	E3 ubiquitin ligase	RACK1	P63244	PMID:17244529
-	K	Ubiquitination	E3 ubiquitin ligase	STUB1	Q9UNE7	PMID:19940151
-	K	Ubiquitination	E3 ubiquitin ligase	SIAH2	O43255	PMID:22055192
-	K	Ubiquitination	E3 ubiquitin ligase	SAG	P10523	PMID:23136067

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
247	S	Phosphorylation	Phosphorylation at Ser-247 by CSNK1D/CK1 represses kinase activity and impairs ARNT binding.	20699359
402	P	Hydroxylation	In normoxia, is hydroxylated on Pro-402 and Pro-564 in the oxygen-dependent degradation domain (ODD) by EGLN1/PHD2 and EGLN2/PHD1.	11566883
532	K	Acetylation	Acetylation of Lys-532 by ARD1 increases interaction with VHL and stimulates subsequent proteasomal degradation.	10944113
532	K	ubiquitylation	Lys-532 appears to be the principal site of ubiquitination.	10944113
564	P	Hydroxylation	EGLN3/PHD3 has also been shown to hydroxylate Pro-564.	11566883
564	P	Hydroxylation	In normoxia, is hydroxylated on Pro-402 and Pro-564 in the oxygen-dependent degradation domain (ODD) by EGLN1/PHD2 and EGLN2/PHD1.	11566883
709	K	Acetylation	Deacetylation of Lys-709 by SIRT2 increases its interaction with and hydroxylation by EGLN1 thereby inactivating HIF1A activity by inducing its proteasomal degradation.	24681946
709	K	Hydroxylation	Deacetylation of Lys-709 by SIRT2 increases its interaction with and hydroxylation by EGLN1 thereby inactivating HIF1A activity by inducing its proteasomal degradation.	24681946
800	C	S-nitrosylation	S-nitrosylation of Cys-800 may be responsible for increased recruitment of p300 coactivator necessary for transcriptional activity of HIF-1 complex.	10202154
803	N	Hydroxylation	Clioquinol, the Cu/Zn-chelator, inhibits ubiquitination through preventing hydroxylation at Asn-803.	12080085
803	N	Hydroxylation	In normoxia, is hydroxylated on Asn-803 by HIF1AN, thus abrogating interaction with CREBBP and EP300 and preventing transcriptional activation.	12080085
803	N	ubiquitylation	Clioquinol, the Cu/Zn-chelator, inhibits ubiquitination through preventing hydroxylation at Asn-803.	12080085

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of HIF1A_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SSX4_HUMAN	SSX4	physical	16189514
ZN197_HUMAN	ZNF197	physical	12682018
VHL_HUMAN	VHL	physical	12682018
MDM2_HUMAN	MDM2	physical	12606552
P53_HUMAN	TP53	physical	12606552
HIF1N_HUMAN	HIF1AN	physical	11641274
VHL_HUMAN	VHL	physical	11641274
CBP_HUMAN	CREBBP	physical	10202154
PSA7_HUMAN	PSMA7	physical	11389899
NCOA1_HUMAN	NCOA1	physical	10594042
P53_HUMAN	TP53	physical	12124396
P53_HUMAN	TP53	physical	9537326
VHL_HUMAN	VHL	physical	11504942
STAT3_HUMAN	STAT3	physical	18985005
VHL_HUMAN	VHL	physical	18985005
VHL_HUMAN	VHL	physical	18694926
VHL_HUMAN	VHL	physical	18426857
NR4A1_HUMAN	NR4A1	physical	18305400
VHL_HUMAN	VHL	physical	17973296
VHL_RAT	Vhl	physical	17942596
SAT1_HUMAN	SAT1	physical	17875644
RACK1_HUMAN	GNB2L1	physical	17875644
MTA1_HUMAN	MTA1	physical	16511565
HDAC1_HUMAN	HDAC1	physical	16511565
NAA10_HUMAN	NAA10	physical	16511565
SAT2_HUMAN	SAT2	physical	17558023
VHL_HUMAN	VHL	physical	17558023
ELOC_HUMAN	TCEB1	physical	17558023
CUL2_HUMAN	CUL2	physical	17439941
VHL_HUMAN	VHL	physical	16611863
HSP74_HUMAN	HSPA4	physical	16507982
SEPT9_HUMAN	SEPT9	physical	16424018
EGLN1_HUMAN	EGLN1	physical	16407130
ARNT_HUMAN	ARNT	physical	20562859
BANP_HUMAN	BANP	physical	20562859
NAA10_HUMAN	NAA10	physical	16288748
HDAC4_HUMAN	HDAC4	physical	19071119
HDAC5_HUMAN	HDAC5	physical	19071119
UBP20_HUMAN	USP20	physical	15776016
OS9_HUMAN	OS9	physical	15721254
EGLN1_HUMAN	EGLN1	physical	15721254
EGLN3_HUMAN	EGLN3	physical	15721254
VHL_HUMAN	VHL	physical	15721254
HS90A_HUMAN	HSP90AA1	physical	16951198
HSP74_HUMAN	HSPA4	physical	16951198
HS90A_HUMAN	HSP90AA1	physical	16507982
HS90A_HUMAN	HSP90AA1	physical	15147973
VHLL_HUMAN	VHLL	physical	14757845
HSP74_HUMAN	HSPA4	physical	14726529
HS90A_HUMAN	HSP90AA1	physical	14726529
EP300_HUMAN	EP300	physical	14691445
VHL_HUMAN	VHL	physical	14600153
VHL_HUMAN	VHL	physical	12925778
EGLN2_HUMAN	EGLN2	physical	18264140
EGLN1_HUMAN	EGLN1	physical	18264140
EGLN3_HUMAN	EGLN3	physical	18264140
VHL_HUMAN	VHL	physical	18264140
ARNT_HUMAN	ARNT	physical	15347669
SMCA2_HUMAN	SMARCA2	physical	15347669
SMCA4_HUMAN	SMARCA4	physical	15347669
CBP_HUMAN	CREBBP	physical	15154850
MYC_HUMAN	MYC	physical	15071503
EP300_HUMAN	EP300	physical	11940656
VHL_HUMAN	VHL	physical	11865071
VHL_HUMAN	VHL	physical	10973499
VHL_HUMAN	VHL	physical	10878807
RUVB2_HUMAN	RUVBL2	physical	20603076
MCM7_HUMAN	MCM7	physical	21658608
MCM3_HUMAN	MCM3	physical	21658608
ELOC_HUMAN	TCEB1	physical	21658608
ELOC_HUMAN	TCEB1	physical	17965024
HS90B_HUMAN	HSP90AB1	physical	19802386
COMD1_HUMAN	COMMD1	physical	19802386
HSP74_HUMAN	HSPA4	physical	19802386
CUL2_HUMAN	CUL2	physical	17132228
VHL_HUMAN	VHL	physical	17132228
ARNT_HUMAN	ARNT	physical	21435239
VHL_HUMAN	VHL	physical	21332579
ARNT_HUMAN	ARNT	physical	20049704
HS90A_HUMAN	HSP90AA1	physical	20724477
JUN_HUMAN	JUN	physical	19738058
HSP74_HUMAN	HSPA4	physical	19940151
CHIP_HUMAN	STUB1	physical	19940151
VHL_HUMAN	VHL	physical	19940151
ELOC_HUMAN	TCEB1	physical	19940151
ELOB_HUMAN	TCEB2	physical	19940151
CUL2_HUMAN	CUL2	physical	19940151
HIF1N_HUMAN	HIF1AN	physical	19940151
EP300_HUMAN	EP300	physical	19940151
FBXW7_HUMAN	FBXW7	physical	21964756
VHL_HUMAN	VHL	physical	21335603
EP300_HUMAN	EP300	physical	12778114
HIF1N_HUMAN	HIF1AN	physical	17244529
RACK1_HUMAN	GNB2L1	physical	17244529
HS90A_HUMAN	HSP90AA1	physical	17244529
ELOC_HUMAN	TCEB1	physical	17244529
KDM3A_HUMAN	KDM3A	physical	22645302
BCR_HUMAN	BCR	physical	21124777
HSP74_HUMAN	HSPA4	physical	21124777
DNJB1_HUMAN	DNAJB1	physical	21124777
UBP19_HUMAN	USP19	physical	22128162
VHL_HUMAN	VHL	physical	12205091
VHL_HUMAN	VHL	physical	16140212
VHL_HUMAN	VHL	physical	12586829
VHL_HUMAN	VHL	physical	18222538
HS90A_HUMAN	HSP90AA1	physical	15319539
ARNT_HUMAN	ARNT	physical	15319539
HSP74_HUMAN	HSPA4	physical	15319539
TEBP_HUMAN	PTGES3	physical	15319539
VHL_HUMAN	VHL	physical	15082527
CSN5_HUMAN	COPS5	physical	15082527
VHL_HUMAN	VHL	physical	11226425
FA12_HUMAN	F12	physical	18838541
VHL_HUMAN	VHL	physical	22932900
CSN5_MOUSE	Cops5	physical	11707426
VHL_HUMAN	VHL	physical	10353251
RUNX2_HUMAN	RUNX2	physical	22351759
VHL_HUMAN	VHL	physical	22351759
BRCA1_HUMAN	BRCA1	physical	16543242
LAMP2_HUMAN	LAMP2	physical	19458911
EP300_HUMAN	EP300	physical	19696166
MDM2_HUMAN	MDM2	physical	19696166
HIF1N_HUMAN	HIF1AN	physical	19696166
VHL_HUMAN	VHL	physical	19147576
BCL2_HUMAN	BCL2	physical	20668552
HS90A_HUMAN	HSP90AA1	physical	20668552
HS90B_HUMAN	HSP90AB1	physical	20668552
NECD_HUMAN	NDN	physical	15978586
VHL_HUMAN	VHL	physical	19123984
EP300_HUMAN	EP300	physical	15261140
CDN2A_HUMAN	CDKN2A	physical	11382768
ARF_HUMAN	CDKN2A	physical	11382768
RPTOR_HUMAN	RPTOR	physical	17502379
EP300_HUMAN	EP300	physical	17502379
TF65_HUMAN	RELA	physical	23123196
KPYM_HUMAN	PKM	physical	21620138
SMAD3_HUMAN	SMAD3	physical	11486006
BMAL1_MOUSE	Arntl	physical	9704006
SRC_HUMAN	SRC	physical	15735682
STAT3_HUMAN	STAT3	physical	15735682
MAFG_HUMAN	MAFG	physical	18538669
HS90A_HUMAN	HSP90AA1	physical	18538669
HS90B_HUMAN	HSP90AB1	physical	18538669
MAFK_HUMAN	MAFK	physical	18538669
CUL2_HUMAN	CUL2	physical	23401859
ELOB_HUMAN	TCEB2	physical	23401859
RBX1_HUMAN	RBX1	physical	23401859
VHL_HUMAN	VHL	physical	23401859
ELOB_HUMAN	TCEB2	physical	18323857
ELOC_HUMAN	TCEB1	physical	18323857
CUL2_HUMAN	CUL2	physical	18323857
VHL_HUMAN	VHL	physical	18323857
PCGF2_HUMAN	PCGF2	physical	21602890
VHL_HUMAN	VHL	physical	21602890
SP1_HUMAN	SP1	physical	12228247
SMAD3_HUMAN	SMAD3	physical	12228247
RB_HUMAN	RB1	physical	15674338
HSP7C_HUMAN	HSPA8	physical	23880665
HEXI1_HUMAN	HEXIM1	physical	24015760
VHL_HUMAN	VHL	physical	24015760
EGLN3_HUMAN	EGLN3	physical	24015760
HDAC1_HUMAN	HDAC1	physical	24015760
VHL_HUMAN	VHL	physical	20724477
EGLN1_HUMAN	EGLN1	physical	20724477
VHL_HUMAN	VHL	physical	24316222
HS90A_HUMAN	HSP90AA1	physical	23722539
RACK1_HUMAN	GNB2L1	physical	23722539
TRAF6_HUMAN	TRAF6	physical	23722539
VHL_HUMAN	VHL	physical	23318261
TIF1B_HUMAN	TRIM28	physical	24278015
SIN3A_HUMAN	SIN3A	physical	24278015
HS90A_HUMAN	HSP90AA1	physical	19491109
VHL_HUMAN	VHL	physical	23387829
EP300_HUMAN	EP300	physical	25192544
EP300_HUMAN	EP300	physical	16847340
EP300_HUMAN	EP300	physical	17906695
EP300_HUMAN	EP300	physical	22684029
EP300_HUMAN	EP300	physical	19680224
SENP3_HUMAN	SENP3	physical	19680224
EP300_HUMAN	EP300	physical	12042299
EGLN3_HUMAN	EGLN3	physical	25416956
EP300_HUMAN	EP300	physical	19589782
FHL2_HUMAN	FHL2	physical	22219185
EP300_HUMAN	EP300	physical	22219185
CBP_HUMAN	CREBBP	physical	22219185
CBP_HUMAN	CREBBP	physical	19880525
ARNT_HUMAN	ARNT	physical	11829741
EP300_HUMAN	EP300	physical	12588875
EP300_HUMAN	EP300	physical	8917528
CBP_HUMAN	CREBBP	physical	8917528
EP300_HUMAN	EP300	physical	22807441
HIF1N_HUMAN	HIF1AN	physical	19074848
CTNB1_HUMAN	CTNNB1	physical	24650032
WWOX_HUMAN	WWOX	physical	25447306
WWTR1_HUMAN	WWTR1	physical	25447306
EP300_HUMAN	EP300	physical	23746844
CDK8_HUMAN	CDK8	physical	23746844
MED12_HUMAN	MED12	physical	23746844
MED13_HUMAN	MED13	physical	23746844
MD13L_HUMAN	MED13L	physical	23746844
MED14_HUMAN	MED14	physical	23746844
MED15_HUMAN	MED15	physical	23746844
MED23_HUMAN	MED23	physical	23746844
EAF2_HUMAN	EAF2	physical	24421387
SSX4_HUMAN	SSX4	physical	21516116
ARNT_HUMAN	ARNT	physical	26496610
ADX_HUMAN	FDX1	physical	26496610
FINC_HUMAN	FN1	physical	26496610
TTC1_HUMAN	TTC1	physical	26496610
VHL_HUMAN	VHL	physical	26496610
PIAS1_HUMAN	PIAS1	physical	26496610
Z518A_HUMAN	ZNF518A	physical	26496610
CE350_HUMAN	CEP350	physical	26496610
NEST_HUMAN	NES	physical	26496610
TRIM1_HUMAN	MID2	physical	26496610
PKHA5_HUMAN	PLEKHA5	physical	26496610
UACA_HUMAN	UACA	physical	26496610
NEUL_HUMAN	NLN	physical	26496610
NBEL1_HUMAN	NBEAL1	physical	26496610
GKAP1_HUMAN	GKAP1	physical	26496610
UTP23_HUMAN	UTP23	physical	26496610
MIC13_HUMAN	C19orf70	physical	26496610
TEAN2_HUMAN	TCEANC2	physical	26496610
LYSM2_HUMAN	LYSMD2	physical	26496610
EP300_HUMAN	EP300	physical	22735262
OTU7B_HUMAN	OTUD7B	physical	25355043
PLD2_HUMAN	PLD2	physical	26611735
EGLN1_HUMAN	EGLN1	physical	26611735
ING1_HUMAN	ING1	physical	25611387
VHL_HUMAN	VHL	physical	26735336
VHL_HUMAN	VHL	physical	26037477
EGLN2_HUMAN	EGLN2	physical	17353276
EGLN1_HUMAN	EGLN1	physical	17353276
EGLN3_HUMAN	EGLN3	physical	17353276
EGLN1_HUMAN	EGLN1	physical	23413029
SPY2_HUMAN	SPRY2	physical	27281823
P53_HUMAN	TP53	physical	27345397
MYH6_HUMAN	MYH6	physical	28514442
MYH2_HUMAN	MYH2	physical	28514442
MYH1_HUMAN	MYH1	physical	28514442
MYH3_HUMAN	MYH3	physical	28514442
ACTS_HUMAN	ACTA1	physical	28514442
MYH4_HUMAN	MYH4	physical	28514442
ARNT_HUMAN	ARNT	physical	28514442
VHL_HUMAN	VHL	physical	28514442
MYL1_HUMAN	MYL1	physical	28514442
H2AX_HUMAN	H2AFX	physical	27918549
TRAF6_HUMAN	TRAF6	physical	27918549
VHL_HUMAN	VHL	physical	27563096
NEMO_HUMAN	IKBKG	physical	26500060
HS71L_HUMAN	HSPA1L	physical	28759037
EP300_HUMAN	EP300	physical	22908229
KAT2B_HUMAN	KAT2B	physical	22908229
HDAC7_HUMAN	HDAC7	physical	15280364
HDAC4_HUMAN	HDAC4	physical	15280364
EP300_HUMAN	EP300	physical	15280364

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• There are no disease associations of PTM sites.
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• DB01136: Carvedilol

Related Literatures of Post-Translational Modification

Hydroxylation

"FIH-1 is an asparaginyl hydroxylase enzyme that regulates thetranscriptional activity of hypoxia-inducible factor.";
Lando D., Peet D.J., Gorman J.J., Whelan D.A., Whitelaw M.L.,Bruick R.K.;
Genes Dev. 16:1466-1471(2002).
Cited for: HYDROXYLATION AT ASN-803, AND MASS SPECTROMETRY.
PubMed: 12080085

"Biochemical purification and pharmacological inhibition of amammalian prolyl hydroxylase acting on hypoxia-inducible factor.";
Ivan M., Haberberger T., Gervasi D.C., Michelson K.S., Guenzler V.,Kondo K., Yang H., Sorokina I., Conaway R.C., Conaway J.W.,Kaelin W.G. Jr.;
Proc. Natl. Acad. Sci. U.S.A. 99:13459-13464(2002).
Cited for: HYDROXYLATION AT PRO-564, AND MASS SPECTROMETRY.
PubMed: 12351678

"Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylationcomplex by O2-regulated prolyl hydroxylation.";
Jaakkola P., Mole D.R., Tian Y.-M., Wilson M.I., Gielbert J.,Gaskell S.J., von Kriegsheim A., Hebestreit H.F., Mukherji M.,Schofield C.J., Maxwell P.H., Pugh C.W., Ratcliffe P.J.;
Science 292:468-472(2001).
Cited for: UBIQUITINATION, FUNCTION, AND HYDROXYLATION AT PRO-564.
PubMed: 11292861

"Independent function of two destruction domains in hypoxia-induciblefactor-alpha chains activated by prolyl hydroxylation.";
Masson N., Willam C., Maxwell P.H., Pugh C.W., Ratcliffe P.J.;
EMBO J. 20:5197-5206(2001).
Cited for: HYDROXYLATION AT PRO-402 AND PRO-564, UBIQUITINATION, INTERACTION WITHTHE VHLE COMPLEX, FUNCTION, AND MUTAGENESIS OF PRO-394; LEU-397;LEU-400; PRO-402 AND PRO-564.
PubMed: 11566883

Phosphorylation

"Casein kinase 1 regulates human hypoxia-inducible factor HIF-1.";
Kalousi A., Mylonis I., Politou A.S., Chachami G., Paraskeva E.,Simos G.;
J. Cell Sci. 123:2976-2986(2010).
Cited for: PHOSPHORYLATION AT SER-247 BY CSNK1D/CK1, MUTAGENESIS OF SER-247, ANDINTERACTION WITH ARNT.
PubMed: 20699359

"Plk3 functions as an essential component of the hypoxia regulatorypathway by direct phosphorylation of HIF-1alpha.";
Xu D., Yao Y., Lu L., Costa M., Dai W.;
J. Biol. Chem. 285:38944-38950(2010).
Cited for: PHOSPHORYLATION AT SER-551; THR-555; SER-576; SER-589 AND SER-657, ANDMUTAGENESIS OF SER-576 AND SER-657.
PubMed: 20889502

Sumoylation

"SUMOylation of hypoxia-inducible factor-1alpha reduces itstranscriptional activity.";
Berta M.A., Mazure N., Hattab M., Pouyssegur J., Brahimi-Horn M.C.;
Biochem. Biophys. Res. Commun. 360:646-652(2007).
Cited for: SUMOYLATION AT LYS-391 AND LYS-477, FUNCTION, AND MUTAGENESIS OFLYS-377; LYS-391; LYS-477 AND LYS-532.
PubMed: 17610843

"Sumoylation increases HIF-1alpha stability and its transcriptionalactivity.";
Bae S.-H., Jeong J.-W., Park J.A., Kim S.-H., Bae M.-K., Choi S.-J.,Kim K.-W.;
Biochem. Biophys. Res. Commun. 324:394-400(2004).
Cited for: SUMOYLATION AT LYS-391 AND LYS-477, FUNCTION, AND MUTAGENESIS OFLYS-389; LYS-391; LYS-392; LYS-442; LYS-460; LYS-477; LYS-532; LYS-538AND LYS-547.
PubMed: 15465032