KGP1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: KGP1_HUMAN
• UniProt AC: Q13976
• Protein Name: cGMP-dependent protein kinase 1
• Gene Name: PRKG1
• Organism: Homo sapiens (Human).
• Sequence Length: 671
• Subcellular Localization: Cytoplasm. Colocalized with TRPC7 in the plasma membrane..
• Protein Description: Serine/threonine protein kinase that acts as key mediator of the nitric oxide (NO)/cGMP signaling pathway. GMP binding activates PRKG1, which phosphorylates serines and threonines on many cellular proteins. Numerous protein targets for PRKG1 phosphorylation are implicated in modulating cellular calcium, but the contribution of each of these targets may vary substantially among cell types. Proteins that are phosphorylated by PRKG1 regulate platelet activation and adhesion, smooth muscle contraction, cardiac function, gene expression, feedback of the NO-signaling pathway, and other processes involved in several aspects of the CNS like axon guidance, hippocampal and cerebellar learning, circadian rhythm and nociception. Smooth muscle relaxation is mediated through lowering of intracellular free calcium, by desensitization of contractile proteins to calcium, and by decrease in the contractile state of smooth muscle or in platelet activation. Regulates intracellular calcium levels via several pathways: phosphorylates MRVI1/IRAG and inhibits IP3-induced Ca(2+) release from intracellular stores, phosphorylation of KCNMA1 (BKCa) channels decreases intracellular Ca(2+) levels, which leads to increased opening of this channel. PRKG1 phosphorylates the canonical transient receptor potential channel (TRPC) family which inactivates the associated inward calcium current. Another mode of action of NO/cGMP/PKGI signaling involves PKGI-mediated inactivation of the Ras homolog gene family member A (RhoA). Phosphorylation of RHOA by PRKG1 blocks the action of this protein in myriad processes: regulation of RHOA translocation; decreasing contraction; controlling vesicle trafficking, reduction of myosin light chain phosphorylation resulting in vasorelaxation. Activation of PRKG1 by NO signaling alters also gene expression in a number of tissues. In smooth muscle cells, increased cGMP and PRKG1 activity influence expression of smooth muscle-specific contractile proteins, levels of proteins in the NO/cGMP signaling pathway, down-regulation of the matrix proteins osteopontin and thrombospondin-1 to limit smooth muscle cell migration and phenotype. Regulates vasodilator-stimulated phosphoprotein (VASP) functions in platelets and smooth muscle..
• Protein Sequence: MSELEEDFAKILMLKEERIKELEKRLSEKEEEIQELKRKLHKCQSVLPVPSTHIGPRTTRAQGISAEPQTYRSFHDLRQAFRKFTKSERSKDLIKEAILDNDFMKNLELSQIQEIVDCMYPVEYGKDSCIIKEGDVGSLVYVMEDGKVEVTKEGVKLCTMGPGKVFGELAILYNCTRTATVKTLVNVKLWAIDRQCFQTIMMRTGLIKHTEYMEFLKSVPTFQSLPEEILSKLADVLEETHYENGEYIIRQGARGDTFFIISKGTVNVTREDSPSEDPVFLRTLGKGDWFGEKALQGEDVRTANVIAAEAVTCLVIDRDSFKHLIGGLDDVSNKAYEDAEAKAKYEAEAAFFANLKLSDFNIIDTLGVGGFGRVELVQLKSEESKTFAMKILKKRHIVDTRQQEHIRSEKQIMQGAHSDFIVRLYRTFKDSKYLYMLMEACLGGELWTILRDRGSFEDSTTRFYTACVVEAFAYLHSKGIIYRDLKPENLILDHRGYAKLVDFGFAKKIGFGKKTWTFCGTPEYVAPEIILNKGHDISADYWSLGILMYELLTGSPPFSGPDPMKTYNIILRGIDMIEFPKKIAKNAANLIKKLCRDNPSERLGNLKNGVKDIQKHKWFEGFNWEGLRKGTLTPPIIPSVASPTDTSNFDSFPEDNDEPPPDDNSGWDIDF

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
2	Phosphorylation	------MSELEEDFA ------CCHHHHHHH	51.38	29396449
2	Acetylation	------MSELEEDFA ------CCHHHHHHH	51.38	22223895
9 (in isoform 2)	Phosphorylation	-	15.42	-
11 (in isoform 3)	Phosphorylation	-	2.16	22617229
27	Phosphorylation	KELEKRLSEKEEEIQ HHHHHHHHHHHHHHH	51.13	24961811
42	Malonylation	ELKRKLHKCQSVLPV HHHHHHHHCCCCCCC	44.39	26320211
51 (in isoform 2)	Phosphorylation	-	32.62	26657352
51	Phosphorylation	QSVLPVPSTHIGPRT CCCCCCCCCCCCCCC	32.62	19168131
52	Phosphorylation	SVLPVPSTHIGPRTT CCCCCCCCCCCCCCC	16.08	27251275
57 (in isoform 2)	Phosphorylation	-	43.44	12609995
58	Phosphorylation	STHIGPRTTRAQGIS CCCCCCCCCCCCCCC	24.62	26437602
59	Phosphorylation	THIGPRTTRAQGISA CCCCCCCCCCCCCCC	25.86	12609995
64 (in isoform 2)	Phosphorylation	-	2.04	26657352
65	Phosphorylation	TTRAQGISAEPQTYR CCCCCCCCCCCCHHH	33.14	19168131
66 (in isoform 2)	Phosphorylation	-	30.48	24275569
70	Phosphorylation	GISAEPQTYRSFHDL CCCCCCCHHHHHHHH	31.45	26699800
71	Phosphorylation	ISAEPQTYRSFHDLR CCCCCCHHHHHHHHH	10.06	26699800
71	Nitration	ISAEPQTYRSFHDLR CCCCCCHHHHHHHHH	10.06	-
73	Phosphorylation	AEPQTYRSFHDLRQA CCCCHHHHHHHHHHH	19.27	26699800
74 (in isoform 2)	Phosphorylation	-	3.72	-
80 (in isoform 2)	Phosphorylation	-	10.36	-
85	Phosphorylation	RQAFRKFTKSERSKD HHHHHHHCHHHHHHH	36.37	19168131
104	Sulfoxidation	AILDNDFMKNLELSQ HHHCCHHHHCCCHHH	2.91	30846556
141	Nitration	GDVGSLVYVMEDGKV CCCCEEEEEEECCEE	10.20	-
151	O-linked_Glycosylation	EDGKVEVTKEGVKLC ECCEEEEEECCEEEE	15.18	29351928
212	Nitration	GLIKHTEYMEFLKSV CCCCHHHHHHHHHCC	11.78	-
212	Phosphorylation	GLIKHTEYMEFLKSV CCCCHHHHHHHHHCC	11.78	-
218	Phosphorylation	EYMEFLKSVPTFQSL HHHHHHHCCCCHHHC	35.16	-
231	Phosphorylation	SLPEEILSKLADVLE HCCHHHHHHHHHHHH	31.14	-
247	Nitration	THYENGEYIIRQGAR HHHHCCCEEEEECCC	11.75	-
247	Phosphorylation	THYENGEYIIRQGAR HHHHCCCEEEEECCC	11.75	-
269	Phosphorylation	SKGTVNVTREDSPSE ECCEEEEECCCCCCC	24.12	28270605
273	Phosphorylation	VNVTREDSPSEDPVF EEEECCCCCCCCCCE	26.10	25554490
275	Phosphorylation	VTREDSPSEDPVFLR EECCCCCCCCCCEEE	59.59	22496350
322	Malonylation	VIDRDSFKHLIGGLD EECHHHHHHHHCCHH	41.26	26320211
336	Nitration	DDVSNKAYEDAEAKA HHHCCHHHHHHHHHH	18.89	-
345	Nitration	DAEAKAKYEAEAAFF HHHHHHHHHHHHHHH	25.82	-
431	Phosphorylation	LYRTFKDSKYLYMLM HHHHHCCCHHHHHHH	24.64	29759185
433	Phosphorylation	RTFKDSKYLYMLMEA HHHCCCHHHHHHHHH	13.66	-
435	Phosphorylation	FKDSKYLYMLMEACL HCCCHHHHHHHHHHH	5.77	-
497	Phosphorylation	LILDHRGYAKLVDFG EEECCCCCEEEEECC	10.66	-
515	Phosphorylation	KIGFGKKTWTFCGTP HCCCCCCEEEECCCC	32.97	19369195
517	Phosphorylation	GFGKKTWTFCGTPEY CCCCCEEEECCCCHH	17.80	27499020
521	Phosphorylation	KTWTFCGTPEYVAPE CEEEECCCCHHCCCH	17.71	26657352
524	Phosphorylation	TFCGTPEYVAPEIIL EECCCCHHCCCHHHH	11.78	24076635
532	Phosphorylation	VAPEIILNKGHDISA CCCHHHHCCCCCCCH	37.54	32142685
549	Nitration	WSLGILMYELLTGSP HHHHHHHHHHHHCCC	10.44	-
566	Phosphorylation	SGPDPMKTYNIILRG CCCCCHHHHHHHHHC	18.62	20049867
567	Nitration	GPDPMKTYNIILRGI CCCCHHHHHHHHHCC	9.99	-
567	Phosphorylation	GPDPMKTYNIILRGI CCCCHHHHHHHHHCC	9.99	20049867
607	Acetylation	SERLGNLKNGVKDIQ HHHHHCCCCHHHHHH	56.51	25953088
615	Acetylation	NGVKDIQKHKWFEGF CHHHHHHHCCCCCCC	47.70	18584351
617	Acetylation	VKDIQKHKWFEGFNW HHHHHHCCCCCCCCC	61.69	18584365

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
58	T	Phosphorylation	Kinase	PKC-FAMILY	-	GPS
59	T	Phosphorylation	Kinase	PRKCA	P17252	GPS
65	S	Phosphorylation	Kinase	PRKG1	Q13976	GPS
65	S	Phosphorylation	Kinase	PRKG1	Q13976-2	GPS
81	S	Phosphorylation	Kinase	PRKG1	Q13976-2	GPS

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of KGP1_HUMAN !!

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of KGP1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
ANPRA_HUMAN	NPR1	physical	12855709
MRVI1_HUMAN	MRVI1	physical	10724174
ITPR1_HUMAN	ITPR1	physical	10724174
MYPT2_HUMAN	PPP1R12B	physical	10567269
MYPT1_HUMAN	PPP1R12A	physical	10567269
GTF2I_HUMAN	GTF2I	physical	12082086
TNNT1_HUMAN	TNNT1	physical	10601315
HDAC1_HUMAN	HDAC1	physical	12082111
LYAM1_HUMAN	SELL	physical	15192100
CREB1_HUMAN	CREB1	physical	11175347
ANXA7_HUMAN	ANXA7	physical	11278415
TA2R_HUMAN	TBXA2R	physical	14530262
ZN646_HUMAN	ZNF646	physical	25416956
F124A_HUMAN	FAM124A	physical	25416956
MEP50_HUMAN	WDR77	physical	23755100
ANDR_HUMAN	AR	physical	23755100
FAK1_HUMAN	PTK2	physical	28514442
ZKSC1_HUMAN	ZKSCAN1	physical	28514442

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• 615436: Aortic aneurysm, familial thoracic 8 (AAT8)
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"Large-scale proteomics analysis of the human kinome.";
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.;
Mol. Cell. Proteomics 8:1751-1764(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-515, AND MASSSPECTROMETRY.
PubMed: 19369195