Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  GTPase HRas  

UniProtKB / Swiss-Prot ID :  RASH_HUMAN

Gene Name (Synonyms) : 
HRAS, HRAS1  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Cell membrane. Cell membrane; Lipid-anchor; Cytoplasmic side. Golgi apparatus. Golgi apparatus membrane; Lipid-anchor. Note=The active GTP-bound form is localized most strongly to membranes than the inactive GDP-bound form (By similarity). Shuttles betwe 

Protein Function :  Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. 

Protein Sequence MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQ...
Predicted Secondary Structure CCEEEEEEEECCCCCHHHHHHHHHCCCCCCCCCCCEEEEEEEEEEECCEEEEEEEEECCCCHHHHHHHHH...
Protein Variant
LocationDescription
12G -> A (in FCSS). VAR_026106
12G -> C (in FCSS). VAR_045975
12G -> E (in FCSS). VAR_045976
12G -> S (in FCSS, OSCC and CMEMS). VAR_006837
12G -> V (in FCSS, bladder carcinoma andCMEMS; constitutively activated;
13G -> C (in FCSS). VAR_026107
13G -> D (in FCSS). VAR_026108
22Q -> K (in CMEMS). VAR_045977
58T -> I (in FCSS). VAR_045978
61Q -> K (in follicular thyroid carcinomasamples; somatic mutation; increases
61Q -> L (in melanoma; strongly reduced GTPhydrolysis in the presence of RAF1;
63E -> K (in CMEMS). VAR_045980
117K -> R (in FCSS). VAR_045981
146A -> T (in FCSS). VAR_045982
146A -> V (in FCSS). VAR_045983
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
1N-acetylmethionine; in GTPase HRas;alternate.----MTEYK
----CCEEE
6.07UniProtKB
Link
2N-acetylthreonine; in GTPase HRas, N-terminally processed.---MTEYKL
---CCEEEE
48.28UniProtKB
Link
35PhosphothreonineEYDPTIEDS
CCCCCEEEE
33.82PhosphoELM
Link
35PhosphothreonineEYDPTIEDS
CCCCCEEEE
33.82Phosphositeplus
Link
41ADP-ribosylarginineEDSYRKQVV
EEEEEEEEE
27.21HPRD
Link
64PhosphotyrosineGQEEYSAMR
CCHHHHHHH
10.85Phosphositeplus
Link
118S-nitrosocysteineVGNKCDLAA
EEECCCCCC
6.34dbSNO
Link
118S-nitrosocysteineVGNKCDLAA
EEECCCCCC
6.34HPRD
Link
118S-nitrosocysteine.VGNKCDLAA
EEECCCCCC
6.34UniProtKB
Link
128ADP-ribosylarginineTVESRQAQD
CCCHHHHHH
23.50HPRD
Link
135ADP-ribosylarginineQDLARSYGI
HHHHHHCCC
37.39HPRD
Link
136PhosphoserineDLARSYGIP
HHHHHCCCC
23.31HPRD
Link
144PhosphothreoninePYIETSAKT
CEEEEEECC
25.15Phosphositeplus
Link
145PhosphoserineYIETSAKTR
EEEEEECCC
18.25HPRD
Link
145PhosphoserineYIETSAKTR
EEEEEECCC
18.25Phosphositeplus
Link
148PhosphothreonineTSAKTRQGV
EEECCCCCH
28.13Phosphositeplus
Link
157PhosphotyrosineEDAFYTLVR
HHHHHHHHH
10.82Phosphositeplus
Link
181N-palmitoyl cysteineSGPGCMSCK
CCCCCCCCC
1.72HPRD
Link-
181S-palmitoyl cysteine.SGPGCMSCK
CCCCCCCCC
1.72UniProtKB
Link-
183PhosphoserinePGCMSCKCV
CCCCCCCCE
17.94Phosphositeplus
Link-
184N-palmitoyl cysteineGCMSCKCVL
CCCCCCCEE
1.25HPRD
Link-
184S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine; alternate.GCMSCKCVL
CCCCCCCEE
1.25UniProtKB
Link-
184S-palmitoyl cysteine; alternate.GCMSCKCVL
CCCCCCCEE
1.25UniProtKB
Link-
186Cysteine methyl ester.MSCKCVLS
CCCCCEEC
4.34UniProtKB
Link-
186S-farnesyl cysteineMSCKCVLS
CCCCCEEC
4.34HPRD
Link-
186S-farnesyl cysteineMSCKCVLS
CCCCCEEC
4.34HPRD
Link-
186S-farnesyl cysteineMSCKCVLS
CCCCCEEC
4.34HPRD
Link-
186S-farnesyl cysteine.MSCKCVLS
CCCCCEEC
4.34UniProtKB
Link-
186S-methylcysteineMSCKCVLS
CCCCCEEC
4.34HPRD
Link-
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
RAF1_HUMANphysical interactionMINT-14959MINT8530446
RAF1_HUMANphysical interactionMINT-16616MINT8035810
RAF1_HUMANphysical interactionMINT-60984MINT15688026
RAF1_HUMANphysical interactionMINT-18357MINT8332195
RAF1_HUMANphysical interactionMINT-16870MINT7730360
FYN_HUMANphysical interactionMINT-50377MINT12695509
SRC_HUMANphysical interactionMINT-50376MINT12695509
RASA1_HUMANphysical interactionMINT-18377MINT2833817
CAV1_HUMANphysical interactionMINT-14114MINT8621645
SOS1_HUMANdirect interactionMINT-3389635MINT17084389
RPGF1_HUMANphysical interactionMINT-16413MINT10514505
Q15278_HUMANphysical interactionMINT-15039MINT9099670
SHOC2_HUMANphysical interactionMINT-16522MINT10783161
BRAF1_HUMANphysical interactionDIP:468EDIP8668348
RAF1_HUMANphysical interaction
direct interaction
DIP:470EDIP9261098
18073111
RASA1_HUMANphysical interactionDIP:84EDIP9219684
RIN1_HUMANphysical interaction
physical interaction
physical interaction
physical interaction
DIP:286EDIP9144171
9144171
9144171
9144171
MPIP1_HUMANphysical interaction
physical interaction
DIP:1107EDIP7744247
7744247
SOS1_HUMANdirect interaction
direct interaction
direct interaction
direct interaction
direct interaction
direct interaction
EBI-1035828
EBI-1035839
EBI-1
intact12628188
12628188
12628188
12628188
15507210
9690470
ABL2_HUMANphysical interaction
physical interaction
EBI-1102856
EBI-1102844
intact15886098
15886098
RIN1_HUMANphysical interaction
physical interaction
physical interaction
physical interaction
physical interaction
physical interaction
EBI-1102856
EBI-1102914
EBI-1
intact15886098
9144171
9144171
9144171
9144171
10545207
RASA1_HUMANdirect interactionEBI-1026524
intact9219684
BRAF1_HUMANphysical interactionEBI-365960
intact10545207
GNDS_HUMANphysical interactionEBI-365960
intact10545207
RGL1_HUMANphysical interaction
physical interaction
EBI-365960
EBI-366060
intact10545207
10545207
AFAD_HUMANphysical interactionEBI-365960
intact10545207
BRAP_HUMANphysical interaction
physical interaction
physical interaction
EBI-350169
EBI-350178
EBI-350
intact14724641
14724641
14724641
GRB2_HUMANin vivoHPRD:01813HPRD11352655
MPIP1_HUMANin vitroHPRD:01813HPRD7744247
RASA1_HUMANin vitro
in vivo
HPRD:01813HPRD7628625
9219684
2833817
8663024
INSR_HUMANin vitroHPRD:01813HPRD3109943
BRAF1_HUMANin vitroHPRD:01813HPRD7706312
RAF1_HUMANin vitro
in vivo
yeast 2-hybrid
HPRD:01813HPRD8530446
8911690
8035810
9099670
7730360
8332187
AFAD_HUMANyeast 2-hybridHPRD:01813HPRD10922060
LEG1_HUMANin vitro
in vivo
HPRD:01813HPRD11709720
NF1_HUMANin vitroHPRD:01813HPRD8628317
VAV_HUMANin vivoHPRD:01813HPRD8554611
BCL2_HUMANin vivoHPRD:01813HPRD10490827
MP2K1_HUMANin vivoHPRD:01813HPRD7969158
P85A_HUMANin vivoHPRD:01813HPRD10212255
PK3CA_HUMANin vivoHPRD:01813HPRD9150145
SOS1_HUMANin vivoHPRD:01813HPRD11560935
9690470
AGTR1_HUMANin vitro
in vivo
HPRD:01813HPRD8753867
PLCE1_HUMANin vitro
yeast 2-hybrid
HPRD:01813HPRD11022048
KPCI_HUMANin vivoHPRD:01813HPRD10848576
TLR2_HUMANin vivoHPRD:01813HPRD15496409
TLR9_HUMANin vitro
in vivo
HPRD:01813HPRD12867418
RHOD_HUMANin vitroHPRD:01813HPRD15187129
ST2B1_HUMANENSP00000309845STRING
MK01_HUMANENSP00000309845STRING
CCND1_HUMANENSP00000309845STRING
INS_HUMANENSP00000309845STRING
INS_HUMANENSP00000309845STRING
RAF1_HUMANENSP00000309845STRING
MK03_HUMANENSP00000309845STRING
PK3CA_HUMANENSP00000309845STRING
P3C2G_HUMANENSP00000309845STRING
P53_HUMANENSP00000309845STRING
P85A_HUMANENSP00000309845STRING
RASA1_HUMANENSP00000309845STRING
BRAF1_HUMANENSP00000309845STRING
S10A1_HUMANENSP00000309845STRING
ADCY1_HUMANENSP00000309845STRING
SPRE1_HUMANENSP00000309845STRING
SPRE1_HUMANENSP00000309845STRING
VAV_HUMANENSP00000309845STRING
MP2K1_HUMANENSP00000309845STRING
INSR_HUMANENSP00000309845STRING
IRS1_HUMANENSP00000309845STRING
GRP1_HUMANENSP00000309845STRING
GRP1_HUMANENSP00000309845STRING
GRP1_HUMANENSP00000309845STRING
GRP1_HUMANENSP00000309845STRING
GRP1_HUMANENSP00000309845STRING
RIN1_HUMANENSP00000309845STRING
PAK2_HUMANENSP00000309845STRING
PDGFB_HUMANENSP00000309845STRING
FAK1_HUMANENSP00000309845STRING
SPRE2_HUMANENSP00000309845STRING
NF1_HUMANENSP00000309845STRING
MK08_HUMANENSP00000309845STRING
PK3CD_HUMANENSP00000309845STRING
PK3CD_HUMANENSP00000309845STRING
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Disease Reference
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
218040Costello syndrome (CSTLO)
218040Congenital myopathy with excess of muscle spindles (CMEMS)
607464Hurthle 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
163200Schimmelpenning-Feuerstein-Mims syndrome (SFM)
Drug Reference
There are no disease associations of PTM sites.
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Related Literatures of Post-Translational Modification
Methylation
ReferencePubMed
"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.
Palmitoylation
ReferencePubMed
"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.
"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.
"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.
"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.
Prenylation
ReferencePubMed
"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.
S-nitrosylation
ReferencePubMed
"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.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures