dbPTM

NOS3_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	NOS3_HUMAN
UniProt AC	P29474
Protein Name	Nitric oxide synthase, endothelial
Gene Name	NOS3
Organism	Homo sapiens (Human).
Sequence Length	1203
Subcellular Localization	Cell membrane. Membrane, caveola. Cytoplasm, cytoskeleton. Golgi apparatus. Specifically associates with actin cytoskeleton in the G2 phase of the cell cycle which is favored by interaction with NOSIP and results in a reduced enzymatic activity.
Protein Description	Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.; Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1..
Protein Sequence	MGNLKSVAQEPGPPCGLGLGLGLGLCGKQGPATPAPEPSRAPASLLPPAPEHSPPSSPLTQPPEGPKFPRVKNWEVGSITYDTLSAQAQQDGPCTPRRCLGSLVFPRKLQGRPSPGPPAPEQLLSQARDFINQYYSSIKRSGSQAHEQRLQEVEAEVAATGTYQLRESELVFGAKQAWRNAPRCVGRIQWGKLQVFDARDCRSAQEMFTYICNHIKYATNRGNLRSAITVFPQRCPGRGDFRIWNSQLVRYAGYRQQDGSVRGDPANVEITELCIQHGWTPGNGRFDVLPLLLQAPDDPPELFLLPPELVLEVPLEHPTLEWFAALGLRWYALPAVSNMLLEIGGLEFPAAPFSGWYMSTEIGTRNLCDPHRYNILEDVAVCMDLDTRTTSSLWKDKAAVEINVAVLHSYQLAKVTIVDHHAATASFMKHLENEQKARGGCPADWAWIVPPISGSLTPVFHQEMVNYFLSPAFRYQPDPWKGSAAKGTGITRKKTFKEVANAVKISASLMGTVMAKRVKATILYGSETGRAQSYAQQLGRLFRKAFDPRVLCMDEYDVVSLEHETLVLVVTSTFGNGDPPENGESFAAALMEMSGPYNSSPRPEQHKSYKIRFNSISCSDPLVSSWRRKRKESSNTDSAGALGTLRFCVFGLGSRAYPHFCAFARAVDTRLEELGGERLLQLGQGDELCGQEEAFRGWAQAAFQAACETFCVGEDAKAAARDIFSPKRSWKRQRYRLSAQAEGLQLLPGLIHVHRRKMFQATIRSVENLQSSKSTRATILVRLDTGGQEGLQYQPGDHIGVCPPNRPGLVEALLSRVEDPPAPTEPVAVEQLEKGSPGGPPPGWVRDPRLPPCTLRQALTFFLDITSPPSPQLLRLLSTLAEEPREQQELEALSQDPRRYEEWKWFRCPTLLEVLEQFPSVALPAPLLLTQLPLLQPRYYSVSSAPSTHPGEIHLTVAVLAYRTQDGLGPLHYGVCSTWLSQLKPGDPVPCFIRGAPSFRLPPDPSLPCILVGPGTGIAPFRGFWQERLHDIESKGLQPTPMTLVFGCRCSQLDHLYRDEVQNAQQRGVFGRVLTAFSREPDNPKTYVQDILRTELAAEVHRVLCLERGHMFVCGDVTMATNVLQTVQRILATEGDMELDEAGDVIGVLRDQQRYHEDIFGLTLRTQEVTSRIRTQSFSLQERQLRGAVPWAFDPPGSDTNSP

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	N-myristoyl glycine	------MGNLKSVAQ ------CCCHHHHCC	60.53	-
2	Myristoylation	------MGNLKSVAQ ------CCCHHHHCC	60.53	-
5	Methylation	---MGNLKSVAQEPG ---CCCHHHHCCCCC	47.05	-
15	S-palmitoylation	AQEPGPPCGLGLGLG CCCCCCCCCCCCCCC	8.71	16864653
26	S-palmitoylation	LGLGLGLCGKQGPAT CCCCCCCCCCCCCCC	6.41	16864653
33	Phosphorylation	CGKQGPATPAPEPSR CCCCCCCCCCCCCCC	24.10	23403867
39	Phosphorylation	ATPAPEPSRAPASLL CCCCCCCCCCCHHHC	39.14	23403867
44	Phosphorylation	EPSRAPASLLPPAPE CCCCCCHHHCCCCCC	29.40	25072903
53	Phosphorylation	LPPAPEHSPPSSPLT CCCCCCCCCCCCCCC	36.52	23403867
56	Phosphorylation	APEHSPPSSPLTQPP CCCCCCCCCCCCCCC	48.23	23403867
57	Phosphorylation	PEHSPPSSPLTQPPE CCCCCCCCCCCCCCC	29.69	23403867
60	Phosphorylation	SPPSSPLTQPPEGPK CCCCCCCCCCCCCCC	42.27	26657352
78	O-linked_Glycosylation	VKNWEVGSITYDTLS CCCCEEEEEEHHHHC	19.55	OGP
81	Nitration	WEVGSITYDTLSAQA CEEEEEEHHHHCHHH	12.78	-
81	Phosphorylation	WEVGSITYDTLSAQA CEEEEEEHHHHCHHH	12.78	22817900
83	Phosphorylation	VGSITYDTLSAQAQQ EEEEEHHHHCHHHHC	16.52	21082442
94	S-nitrosocysteine	QAQQDGPCTPRRCLG HHHCCCCCCHHHCCE	11.35	-
94	S-nitrosylation	QAQQDGPCTPRRCLG HHHCCCCCCHHHCCE	11.35	22178444
99	S-nitrosocysteine	GPCTPRRCLGSLVFP CCCCHHHCCEEEECC	5.50	-
99	S-nitrosylation	GPCTPRRCLGSLVFP CCCCHHHCCEEEECC	5.50	22178444
102	Phosphorylation	TPRRCLGSLVFPRKL CHHHCCEEEECCHHH	14.38	23403867
114	Phosphorylation	RKLQGRPSPGPPAPE HHHCCCCCCCCCCHH	40.92	23403867
163	Nitration	EVAATGTYQLRESEL HHHCCCEEEEEHHHE	13.59	-
184	S-nitrosocysteine	AWRNAPRCVGRIQWG HHHCCCCEEEEEEEC	3.56	-
184	S-nitrosylation	AWRNAPRCVGRIQWG HHHCCCCEEEEEEEC	3.56	22178444
201	S-nitrosocysteine	QVFDARDCRSAQEMF EEEEHHHCCCHHHHH	2.85	-
201	S-nitrosylation	QVFDARDCRSAQEMF EEEEHHHCCCHHHHH	2.85	22178444
210	Nitration	SAQEMFTYICNHIKY CHHHHHHHHHHHHHH	7.69	-
210	Phosphorylation	SAQEMFTYICNHIKY CHHHHHHHHHHHHHH	7.69	-
212	S-nitrosocysteine	QEMFTYICNHIKYAT HHHHHHHHHHHHHHH	1.82	-
212	S-nitrosylation	QEMFTYICNHIKYAT HHHHHHHHHHHHHHH	1.82	22178444
260	Phosphorylation	GYRQQDGSVRGDPAN CEECCCCCCCCCCCC	19.55	24719451
331	Nitration	AALGLRWYALPAVSN HHCCCHHHHHHHHHH	7.57	-
357	Nitration	AAPFSGWYMSTEIGT CCCCCCCEEECCCCC	5.68	-
373	Nitration	NLCDPHRYNILEDVA CCCCHHHCCCHHHEE	11.97	-
410	Nitration	NVAVLHSYQLAKVTI EEEEEEHHEEEEEEE	9.22	-
470	Phosphorylation	EMVNYFLSPAFRYQP HHHHHHHCHHHHCCC	12.32	24719451
483	Phosphorylation	QPDPWKGSAAKGTGI CCCCCCCCCCCCCCC	22.71	23879269
494	Acetylation	GTGITRKKTFKEVAN CCCCCCCHHHHHHHH	56.77	23806688
495	Dephosphorylation	TGITRKKTFKEVANA CCCCCCHHHHHHHHH	42.87	11397791
495	Phosphorylation	TGITRKKTFKEVANA CCCCCCHHHHHHHHH	42.87	11292821
504	Acetylation	KEVANAVKISASLMG HHHHHHHHHHHHHHH	28.65	23806688
508	Phosphorylation	NAVKISASLMGTVMA HHHHHHHHHHHHHHH	16.46	-
512	Phosphorylation	ISASLMGTVMAKRVK HHHHHHHHHHHHHCE	7.98	-
524	Nitration	RVKATILYGSETGRA HCEEEEEECCCCCCH	18.11	-
534	Nitration	ETGRAQSYAQQLGRL CCCCHHHHHHHHHHH	9.06	-
556	Nitration	RVLCMDEYDVVSLEH CEEECCCCCEEEECC	15.13	-
600	Phosphorylation	MSGPYNSSPRPEQHK HCCCCCCCCCHHHCC	22.69	24275569
609	Nitration	RPEQHKSYKIRFNSI CHHHCCCCEEEECCC	18.42	-
615	Phosphorylation	SYKIRFNSISCSDPL CCEEEECCCCCCCCH	17.11	12171920
617	Phosphorylation	KIRFNSISCSDPLVS EEEECCCCCCCCHHH	13.85	23403867
619	Phosphorylation	RFNSISCSDPLVSSW EECCCCCCCCHHHHH	35.16	23312004
624	Phosphorylation	SCSDPLVSSWRRKRK CCCCCHHHHHHHHHC	31.69	23403867
625	Phosphorylation	CSDPLVSSWRRKRKE CCCCHHHHHHHHHCC	19.68	23403867
633	Phosphorylation	WRRKRKESSNTDSAG HHHHHCCCCCCCCHH	31.74	26846344
634	Phosphorylation	RRKRKESSNTDSAGA HHHHCCCCCCCCHHH	44.86	23403867
636	Phosphorylation	KRKESSNTDSAGALG HHCCCCCCCCHHHHH	33.02	23403867
638	Phosphorylation	KESSNTDSAGALGTL CCCCCCCCHHHHHHH	26.94	23403867
657	Nitration	FGLGSRAYPHFCAFA HCCCCCCCHHHHHHH	8.98	-
657	Phosphorylation	FGLGSRAYPHFCAFA HCCCCCCCHHHHHHH	8.98	18483407
661	S-nitrosocysteine	SRAYPHFCAFARAVD CCCCHHHHHHHHHHH	2.50	-
661	S-nitrosylation	SRAYPHFCAFARAVD CCCCHHHHHHHHHHH	2.50	22178444
689	Glutathionylation	LGQGDELCGQEEAFR CCCCCCCCCCHHHHH	5.07	22833525
725	Phosphorylation	AAARDIFSPKRSWKR HHHHHHCCCCHHHHH	29.82	24719451
738	Phosphorylation	KRQRYRLSAQAEGLQ HHHHHHHHHHHHHHH	14.88	27251275
773	Ubiquitination	VENLQSSKSTRATIL HHHHHCCCCCCEEEE	62.18	21906983
785	Phosphorylation	TILVRLDTGGQEGLQ EEEEEECCCCCCCCE	48.05	24043423
793	Nitration	GGQEGLQYQPGDHIG CCCCCCEECCCCCCE	23.01	-
793	Phosphorylation	GGQEGLQYQPGDHIG CCCCCCEECCCCCCE	23.01	24043423
802	S-nitrosocysteine	PGDHIGVCPPNRPGL CCCCCEECCCCCCCH	3.80	-
802	S-nitrosylation	PGDHIGVCPPNRPGL CCCCCEECCCCCCCH	3.80	22178444
834	Ubiquitination	VAVEQLEKGSPGGPP CCHHHHCCCCCCCCC	73.59	21906983
836	Phosphorylation	VEQLEKGSPGGPPPG HHHHCCCCCCCCCCC	31.29	24275569
853	S-nitrosocysteine	RDPRLPPCTLRQALT CCCCCCCCHHHHHHH	5.45	-
853	S-nitrosylation	RDPRLPPCTLRQALT CCCCCCCCHHHHHHH	5.45	22178444
854	Phosphorylation	DPRLPPCTLRQALTF CCCCCCCHHHHHHHH	30.65	20393185
866	O-linked_Glycosylation	LTFFLDITSPPSPQL HHHHHHCCCCCCHHH	34.54	32863226
870	Phosphorylation	LDITSPPSPQLLRLL HHCCCCCCHHHHHHH	28.76	21815630
904	Ubiquitination	PRRYEEWKWFRCPTL CHHHHHHHHHCCHHH	39.47	-
908	Glutathionylation	EEWKWFRCPTLLEVL HHHHHHCCHHHHHHH	1.88	22833525
939	Nitration	LPLLQPRYYSVSSAP CCCCCCCEEECCCCC	13.53	-
940	Nitration	PLLQPRYYSVSSAPS CCCCCCEEECCCCCC	12.13	-
962	Nitration	LTVAVLAYRTQDGLG EEEEEEEECCCCCCC	15.27	-
973	Nitration	DGLGPLHYGVCSTWL CCCCCCCCCHHHHHH	20.95	-
976	S-nitrosocysteine	GPLHYGVCSTWLSQL CCCCCCHHHHHHHHC	2.32	-
976	S-nitrosylation	GPLHYGVCSTWLSQL CCCCCCHHHHHHHHC	2.32	22178444
981	Phosphorylation	GVCSTWLSQLKPGDP CHHHHHHHHCCCCCC	25.65	24719451
991	S-nitrosocysteine	KPGDPVPCFIRGAPS CCCCCCCCEECCCCC	4.51	-
991	S-nitrosylation	KPGDPVPCFIRGAPS CCCCCCCCEECCCCC	4.51	22178444
1035	Ubiquitination	RLHDIESKGLQPTPM HHHHHHHCCCCCCCE	51.34	-
1048	S-nitrosocysteine	PMTLVFGCRCSQLDH CEEEEEEEEHHHCCH	2.42	-
1048	S-nitrosylation	PMTLVFGCRCSQLDH CEEEEEEEEHHHCCH	2.42	22178444
1050	S-nitrosocysteine	TLVFGCRCSQLDHLY EEEEEEEHHHCCHHH	3.37	-
1050	S-nitrosylation	TLVFGCRCSQLDHLY EEEEEEEHHHCCHHH	3.37	22178444
1085	Ubiquitination	SREPDNPKTYVQDIL CCCCCCCCHHHHHHH	59.76	21906983
1087	Nitration	EPDNPKTYVQDILRT CCCCCCHHHHHHHHH	11.40	-
1094	Phosphorylation	YVQDILRTELAAEVH HHHHHHHHHHHHHHH	31.72	-
1114	S-nitrosocysteine	ERGHMFVCGDVTMAT CCCCEEEECCHHHHH	2.35	-
1114	S-nitrosylation	ERGHMFVCGDVTMAT CCCCEEEECCHHHHH	2.35	22178444
1118	Phosphorylation	MFVCGDVTMATNVLQ EEEECCHHHHHHHHH	13.06	25332170
1155	Nitration	VLRDQQRYHEDIFGL EECCCCHHHHHCCCE	12.77	-
1175	Phosphorylation	EVTSRIRTQSFSLQE HHHHHHHHCCCCHHH	26.62	26846344
1177	Dephosphorylation	TSRIRTQSFSLQERQ HHHHHHCCCCHHHHH	19.05	12501214
1177	O-linked_Glycosylation	TSRIRTQSFSLQERQ HHHHHHCCCCHHHHH	19.05	20166139
1177	Phosphorylation	TSRIRTQSFSLQERQ HHHHHHCCCCHHHHH	19.05	26846344
1179	Phosphorylation	RIRTQSFSLQERQLR HHHHCCCCHHHHHHC	34.10	26846344
1198	Phosphorylation	WAFDPPGSDTNSP-- CCCCCCCCCCCCC--	47.22	28857561
1200	Phosphorylation	FDPPGSDTNSP---- CCCCCCCCCCC----	39.01	28857561
1202	Phosphorylation	PPGSDTNSP------ CCCCCCCCC------	33.79	23403867

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
114	S	Phosphorylation	Kinase	CDK5	Q00535	Uniprot
495	T	Phosphorylation	Kinase	AMPK	Q9Y478	Uniprot
495	T	Phosphorylation	Kinase	PRKCA	P17252	GPS
495	T	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
495	T	Phosphorylation	Kinase	PRKG2	Q13237	GPS
495	T	Phosphorylation	Kinase	PRKACA	P17612	GPS
615	S	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
615	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
615	S	Phosphorylation	Kinase	PKB_GROUP	-	PhosphoELM
615	S	Phosphorylation	Kinase	AKT1	P31749	PSP
633	S	Phosphorylation	Kinase	PKA_GROUP	-	PhosphoELM
633	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
633	S	Phosphorylation	Kinase	CDK7	P50613	GPS
633	S	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
633	S	Phosphorylation	Kinase	PRKG2	Q13237	GPS
633	S	Phosphorylation	Kinase	PRKAA1	Q13131	GPS
633	S	Phosphorylation	Kinase	PIM1	P11309	PSP
657	Y	Phosphorylation	Kinase	PTK2B	Q14289	GPS
1177	S	Phosphorylation	Kinase	PKB_GROUP	-	PhosphoELM
1177	S	Phosphorylation	Kinase	AMPK	Q9Y478	Uniprot
1177	S	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
1177	S	Phosphorylation	Kinase	PRKG2	Q13237	GPS
1177	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
1177	S	Phosphorylation	Kinase	CDK7	P50613	GPS
1177	S	Phosphorylation	Kinase	AKT1	P31749	PSP
1177	S	Phosphorylation	Kinase	PRKAA1	Q13131	GPS
1179	S	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
1179	S	Phosphorylation	Kinase	PKB_GROUP	-	PhosphoELM
-	K	Ubiquitination	E3 ubiquitin ligase	STUB1	Q9UNE7	PMID:14507928

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
114	S	Phosphorylation	20213743
Phosphorylation of Ser-114 by CDK5 reduces activity.
495	T	Phosphorylation	16126727
In absence of Ca(2+)-calmodulin, AMPK also phosphorylates Thr-495, resulting in inhibition of activity (By similarity).
1177	S	Phosphorylation	16126727
Phosphorylation by AMPK at Ser-1177 in the presence of Ca(2+)-calmodulin (CaM) activates activity.

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 NOS3_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
HS90A_HUMAN	HSP90AA1	physical	12676772
GCYB1_HUMAN	GUCY1B3	physical	12676772
CAV1_HUMAN	CAV1	physical	8910295
NOSTN_HUMAN	NOSTRIN	physical	12446846
KCC2A_HUMAN	CAMK2A	physical	11397791
HS90A_HUMAN	HSP90AA1	physical	11988487
NOSIP_HUMAN	NOSIP	physical	11149895
NOS3_HUMAN	NOS3	physical	11149895
HS90A_HUMAN	HSP90AA1	physical	11425855
AKT1_HUMAN	AKT1	physical	11425855
A4_HUMAN	APP	physical	21163940
CDC37_HUMAN	CDC37	physical	21163940
F10A1_HUMAN	ST13	physical	21163940
GCDH_HUMAN	GCDH	physical	21163940
ELAV3_HUMAN	ELAVL3	physical	21163940
P4K2A_HUMAN	PI4K2A	physical	21163940
ELAV1_HUMAN	ELAVL1	physical	21163940
KANK2_HUMAN	KANK2	physical	21163940
RNF32_HUMAN	RNF32	physical	21163940
CEP55_HUMAN	CEP55	physical	21163940
EXOS1_HUMAN	EXOSC1	physical	21163940
PAXI1_HUMAN	PAXIP1	physical	21163940
PSN2_HUMAN	PSEN2	physical	21163940
FBLN3_HUMAN	EFEMP1	physical	21163940
FIS1_HUMAN	FIS1	physical	21163940
FBLN4_HUMAN	EFEMP2	physical	21163940
RNF31_HUMAN	RNF31	physical	21163940
UMPS_HUMAN	UMPS	physical	21163940
MIC60_HUMAN	IMMT	physical	21163940
MPRIP_HUMAN	MPRIP	physical	21163940
HTRA1_HUMAN	HTRA1	physical	21163940
TXD11_HUMAN	TXNDC11	physical	21163940
ACTN2_HUMAN	ACTN2	physical	21163940
ACTN4_HUMAN	ACTN4	physical	21163940
H33_HUMAN	H3F3A	physical	21163940
TECR_HUMAN	TECR	physical	21163940
APOE_HUMAN	APOE	physical	21163940
ACTB_HUMAN	ACTB	physical	17502619
CAV1_HUMAN	CAV1	physical	17502619
CAV1_HUMAN	CAV1	physical	12852865
NOS3_HUMAN	NOS3	physical	15721862
NOS3_HUMAN	NOS3	physical	12176133
NOS3_HUMAN	NOS3	physical	10074942
NOS3_HUMAN	NOS3	physical	12437348
NOS3_HUMAN	NOS3	physical	18849972

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
D09018	Tilarginine acetate (USAN)
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of NOS3_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"CDK5 phosphorylates eNOS at Ser-113 and regulates NO production."; Lee C.-H., Wei Y.-W., Huang Y.-T., Lin Y.-T., Lee Y.-C., Lee K.-H.,Lu P.-J.; J. Cell. Biochem. 110:112-117(2010). Cited for: PHOSPHORYLATION AT SER-114, AND MUTAGENESIS OF SER-114.	20213743 [Abstract]
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer."; Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; Cell 131:1190-1203(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-81, AND MASSSPECTROMETRY.	18083107 [Abstract]

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