dbPTM

RASH_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	RASH_HUMAN
UniProt AC	P01112
Protein Name	GTPase HRas
Gene Name	HRAS
Organism	Homo sapiens (Human).
Sequence Length	189
Subcellular Localization	Cell membrane. Cell membrane Lipid-anchor Cytoplasmic side. Golgi apparatus. Golgi apparatus membrane Lipid-anchor. The active GTP-bound form is localized most strongly to membranes than the inactive GDP-bound form (By similarity). Shuttles betwee
Protein Description	Involved in the activation of Ras protein signal transduction. [PubMed: 22821884 Ras proteins bind GDP/GTP and possess intrinsic GTPase activity]
Protein Sequence	MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHQYREQIKRVKDSDDVPMVLVGNKCDLAARTVESRQAQDLARSYGIPYIETSAKTRQGVEDAFYTLVREIRQHKLRKLNPPDESGPGCMSCKCVLS

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Acetylation	-------MTEYKLVV -------CCCEEEEE	6.07	-
2	Acetylation	------MTEYKLVVV ------CCCEEEEEE	48.28	-
2	Phosphorylation	------MTEYKLVVV ------CCCEEEEEE	48.28	19690332
4	Phosphorylation	----MTEYKLVVVGA ----CCCEEEEEECC	10.64	19690332
32	Phosphorylation	QNHFVDEYDPTIEDS HHHCCCCCCCCCCHH	23.82	25884760
35	Phosphorylation	FVDEYDPTIEDSYRK CCCCCCCCCCHHHCC	33.82	28348404
35	O-linked_Glycosylation	FVDEYDPTIEDSYRK CCCCCCCCCCHHHCC	33.82	22665487
39	Phosphorylation	YDPTIEDSYRKQVVI CCCCCCHHHCCEEEE	17.66	23401153
40	Phosphorylation	DPTIEDSYRKQVVID CCCCCHHHCCEEEEC	33.86	23403867
41	ADP-ribosylation	PTIEDSYRKQVVIDG CCCCHHHCCEEEECC	27.21	-
64	Phosphorylation	DTAGQEEYSAMRDQY HHCCHHHHHHHHHHH	10.85	22322096
65	Phosphorylation	TAGQEEYSAMRDQYM HCCHHHHHHHHHHHH	20.90	28796482
80	S-nitrosylation	RTGEGFLCVFAINNT HHCCCEEEEEEECCC	1.90	24105792
96	Phosphorylation	SFEDIHQYREQIKRV CHHHHHHHHHHHHCC	11.27	-
117	Ubiquitination	PMVLVGNKCDLAART CEEEECCHHHHHHHH	24.17	-
118	S-nitrosylation	MVLVGNKCDLAARTV EEEECCHHHHHHHHH	6.34	9020151
118	Glutathionylation	MVLVGNKCDLAARTV EEEECCHHHHHHHHH	6.34	22833525
118	S-nitrosocysteine	MVLVGNKCDLAARTV EEEECCHHHHHHHHH	6.34	-
128	ADP-ribosylation	AARTVESRQAQDLAR HHHHHHHHHHHHHHH	23.50	-
135	ADP-ribosylation	RQAQDLARSYGIPYI HHHHHHHHHHCCCEE	37.39	-
136	Phosphorylation	QAQDLARSYGIPYIE HHHHHHHHHCCCEEE	23.31	20068231
137	Phosphorylation	AQDLARSYGIPYIET HHHHHHHHCCCEEEC	17.33	20068231
141	Phosphorylation	ARSYGIPYIETSAKT HHHHCCCEEECCCCH	14.96	20068231
144	Phosphorylation	YGIPYIETSAKTRQG HCCCEEECCCCHHHC	25.15	20068231
145	Phosphorylation	GIPYIETSAKTRQGV CCCEEECCCCHHHCH	18.25	20068231
145 (in isoform 2)	Phosphorylation	-	18.25	20068231
147	Ubiquitination	PYIETSAKTRQGVED CEEECCCCHHHCHHH	43.96	-
148	Phosphorylation	YIETSAKTRQGVEDA EEECCCCHHHCHHHH	28.13	22494971
157	Phosphorylation	QGVEDAFYTLVREIR HCHHHHHHHHHHHHH	10.82	25884760
158	Phosphorylation	GVEDAFYTLVREIRQ CHHHHHHHHHHHHHH	16.60	-
170	Ubiquitination	IRQHKLRKLNPPDES HHHHHHHHCCCCCCC	64.15	-
181	S-palmitoylation	PDESGPGCMSCKCVL CCCCCCCCCCCEEEE	1.72	27044110
181	S-nitrosylation	PDESGPGCMSCKCVL CCCCCCCCCCCEEEE	1.72	24105792
181	Glutathionylation	PDESGPGCMSCKCVL CCCCCCCCCCCEEEE	1.72	17320764
183	Phosphorylation	ESGPGCMSCKCVLS- CCCCCCCCCEEEEC-	17.94	22494971
184	Other	SGPGCMSCKCVLS-- CCCCCCCCEEEEC--	1.25	12684535
184	Glutathionylation	SGPGCMSCKCVLS-- CCCCCCCCEEEEC--	1.25	17320764
184	S-palmitoylation	SGPGCMSCKCVLS-- CCCCCCCCEEEEC--	1.25	27044110
186	Farnesylation	PGCMSCKCVLS---- CCCCCCEEEEC----	4.34	8626715
186	Glutathionylation	PGCMSCKCVLS---- CCCCCCEEEEC----	4.34	17320764
186	Methylation	PGCMSCKCVLS---- CCCCCCEEEEC----	4.34	8626715
186	Farnesylation	PGCMSCKCVLS---- CCCCCCEEEEC----	4.34	8626715

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
32	Y	Phosphorylation	Kinase	SRC	P12931	PSP
64	Y	Phosphorylation	Kinase	SRC	P12931	PSP
96	Y	Phosphorylation	Kinase	SRC	P12931	PSP
137	Y	Phosphorylation	Kinase	ABL1	P00519	GPS
137	Y	Phosphorylation	Kinase	ABL2	P42684	GPS
144	T	Phosphorylation	Kinase	GSK3B	P49841	PSP
148	T	Phosphorylation	Kinase	GSK3B	P49841	PSP
177	S	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
177	S	Phosphorylation	Kinase	PKC-FAMILY	-	GPS
183	S	Phosphorylation	Kinase	GSK3B	P49841	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	BTRC	Q9Y297	PMID:24658274
-	K	Ubiquitination	E3 ubiquitin ligase	NEDD4	P46934	PMID:24746824

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
104	K	Acetylation	-
Acetylation at Lys-104 prevents interaction with guanine nucleotide exchange factors (GEFs).
170	K	ubiquitylation	30442762
Ubiquitinated by the BCR(LZTR1) E3 ubiquitin ligase complex at Lys-170 in a non-degradative manner, leading to inhibit Ras signaling by decreasing Ras association with membranes.

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 RASH_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
BRAF_HUMAN	BRAF	physical	9154803
RGRF1_HUMAN	RASGRF1	physical	9154803
RAF1_HUMAN	RAF1	physical	9154803
RGDSR_HUMAN	RGL4	physical	9154803
RIN1_HUMAN	RIN1	physical	15031288
GNDS_HUMAN	RALGDS	physical	15031288
RAIN_HUMAN	RASIP1	physical	15031288
RGL2_HUMAN	RGL2	physical	15031288
RASF1_HUMAN	RASSF1	physical	10998413
RAF1_HUMAN	RAF1	physical	10783161
SHOC2_HUMAN	SHOC2	physical	10783161
PK3CA_HUMAN	PIK3CA	physical	10783161
GNDS_HUMAN	RALGDS	physical	10783161
SOS1_HUMAN	SOS1	physical	9690470
TIAM1_HUMAN	TIAM1	physical	12134164
BRAF_HUMAN	BRAF	physical	7706312
RASF5_HUMAN	RASSF5	physical	9488663
RAF1_HUMAN	RAF1	physical	9523700
AFAD_HUMAN	MLLT4	physical	10922060
GNDS_HUMAN	RALGDS	physical	10922060
PK3CD_HUMAN	PIK3CD	physical	10922060
RAF1_HUMAN	RAF1	physical	10922060
INSR_HUMAN	INSR	physical	3109943
RAF1_HUMAN	RAF1	physical	16803888
RAF1_HUMAN	RAF1	physical	7862125
RIN1_HUMAN	RIN1	physical	7862125
RAF1_HUMAN	RAF1	physical	7969158
MP2K1_HUMAN	MAP2K1	physical	7969158
GNDS_HUMAN	RALGDS	physical	7972015
IKZF3_HUMAN	IKZF3	physical	10369681
RAF1_HUMAN	RAF1	physical	10369681
GDS1_HUMAN	RAP1GDS1	physical	11948427
AFAD_HUMAN	MLLT4	physical	10334923
RAF1_HUMAN	RAF1	physical	8628317
NF1_HUMAN	NF1	physical	8628317
GNDS_HUMAN	RALGDS	physical	7809086
RAF1_HUMAN	RAF1	physical	12379659
PK3CG_HUMAN	PIK3CG	physical	11136978
LEG1_HUMAN	LGALS1	physical	11709720
RUXE_HUMAN	SNRPE	physical	9154803
GNDS_HUMAN	RALGDS	physical	9154803
ZHX2_HUMAN	ZHX2	physical	17533377
RGL2_HUMAN	RGL2	physical	20936779
GNDS_HUMAN	RALGDS	physical	20936779
RGL1_HUMAN	RGL1	physical	20936779
DEAF1_HUMAN	DEAF1	physical	21900206
FBW1A_HUMAN	BTRC	physical	19240121
SPY2_HUMAN	SPRY2	physical	18048363
CBL_HUMAN	CBL	physical	18048363
SH3K1_HUMAN	SH3KBP1	physical	18048363
BRAP_HUMAN	BRAP	physical	14724641
ASPP1_HUMAN	PPP1R13B	physical	21041410
LATS2_HUMAN	LATS2	physical	21041410
P53_HUMAN	TP53	physical	21041410
TPR_HUMAN	TPR	physical	22939629
RAF1_HUMAN	RAF1	physical	15664191
K1C18_HUMAN	KRT18	physical	21988832
RASF5_HUMAN	RASSF5	physical	24722188
DAB2P_HUMAN	DAB2IP	physical	24912918
ABL2_HUMAN	ABL2	physical	15886098
RIN1_HUMAN	RIN1	physical	15886098
LEG1_HUMAN	LGALS1	physical	22696230
BLID_HUMAN	BLID	physical	25640309
GROA_HUMAN	CXCL1	physical	25640309
GREB1_HUMAN	GREB1	physical	25640309
IL24_HUMAN	IL24	physical	25640309
TSP50_HUMAN	PRSS50	physical	25640309
MK08_HUMAN	MAPK8	genetic	8943324
NIBL1_HUMAN	FAM129B	physical	26721396
RASA1_HUMAN	RASA1	physical	26721396
SOS1_HUMAN	SOS1	physical	26721396
PA216_HUMAN	PLA2G16	physical	24884338
MPIP3_MOUSE	Cdc25c	physical	9266971

Drug and Disease Associations

Kegg Disease
H00022	Bladder cancer
H00025	Penile cancer
H00030	Cervical cancer
H00032	Thyroid cancer
H00040	Squamous cell carcinoma
H00048	Hepatocellular carcinoma
H00523	Noonan syndrome and related disorders, including: Noonan syndrome (NS); Leopard syndrome (LS); Noona
OMIM Disease
218040	Costello syndrome (CSTLO)
218040	Congenital myopathy with excess of muscle spindles (CMEMS)
607464	Hurthle cell thyroid carcinoma (HCTC)
	Note=Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors.
109800
163200	Schimmelpenning-Feuerstein-Mims syndrome (SFM)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of RASH_HUMAN

Related Literatures of Post-Translational Modification

Methylation
Reference	PubMed
"Palmitoylation of Ha-Ras facilitates membrane binding, activation ofdownstream effectors, and meiotic maturation in Xenopus oocytes."; Dudler T., Gelb M.H.; J. Biol. Chem. 271:11541-11547(1996). Cited for: PALMITOYLATION AT CYS-181 AND CYS-184, ISOPRENYLATION AT CYS-186,METHYLATION AT CYS-186, AND MUTAGENESIS OF CYS-181 AND CYS-184.	8626715 [Abstract]
Palmitoylation
Reference	PubMed
"An acylation cycle regulates localization and activity ofpalmitoylated Ras isoforms."; Rocks O., Peyker A., Kahms M., Verveer P.J., Koerner C.,Lumbierres M., Kuhlmann J., Waldmann H., Wittinghofer A.,Bastiaens P.I.H.; Science 307:1746-1752(2005). Cited for: PALMITOYLATION AT CYS-181 AND CYS-184, MUTAGENESIS OF CYS-181 ANDCYS-184, AND SUBCELLULAR LOCATION.	15705808 [Abstract]
"DHHC9 and GCP16 constitute a human protein fatty acyltransferase withspecificity for H- and N-Ras."; Swarthout J.T., Lobo S., Farh L., Croke M.R., Greentree W.K.,Deschenes R.J., Linder M.E.; J. Biol. Chem. 280:31141-31148(2005). Cited for: PALMITOYLATION AT CYS-181 AND CYS-184.	16000296 [Abstract]
"Palmitoylation of Ha-Ras facilitates membrane binding, activation ofdownstream effectors, and meiotic maturation in Xenopus oocytes."; Dudler T., Gelb M.H.; J. Biol. Chem. 271:11541-11547(1996). Cited for: PALMITOYLATION AT CYS-181 AND CYS-184, ISOPRENYLATION AT CYS-186,METHYLATION AT CYS-186, AND MUTAGENESIS OF CYS-181 AND CYS-184.	8626715 [Abstract]
"All ras proteins are polyisoprenylated but only some arepalmitoylated."; Hancock J.F., Magee A.I., Childs J.E., Marshall C.J.; Cell 57:1167-1177(1989). Cited for: PALMITOYLATION AT CYS-181 AND CYS-184.	2661017 [Abstract]
Prenylation
Reference	PubMed
"Palmitoylation of Ha-Ras facilitates membrane binding, activation ofdownstream effectors, and meiotic maturation in Xenopus oocytes."; Dudler T., Gelb M.H.; J. Biol. Chem. 271:11541-11547(1996). Cited for: PALMITOYLATION AT CYS-181 AND CYS-184, ISOPRENYLATION AT CYS-186,METHYLATION AT CYS-186, AND MUTAGENESIS OF CYS-181 AND CYS-184.	8626715 [Abstract]
S-nitrosylation
Reference	PubMed
"A molecular redox switch on p21(ras). Structural basis for the nitricoxide-p21(ras) interaction."; Lander H.M., Hajjar D.P., Hempstead B.L., Mirza U.A., Chait B.T.,Campbell S., Quilliam L.A.; J. Biol. Chem. 272:4323-4326(1997). Cited for: S-NITROSYLATION AT CYS-118, FUNCTION, MASS SPECTROMETRY, ANDMUTAGENESIS OF CYS-118.	9020151 [Abstract]

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