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UniProtKB - P01112 (RASH_HUMAN)

Protein

GTPase HRas

Gene

HRAS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Involved in the activation of Ras protein signal transduction (PubMed:22821884). Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:12740440, PubMed:14500341, PubMed:9020151).4 Publications

Activity regulationi

Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP).

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi10 – 17GTP8
Nucleotide bindingi57 – 61GTP5
Nucleotide bindingi116 – 119GTP4

GO - Molecular functioni

  • GDP binding Source: CAFA
  • GTPase activity Source: WormBase
  • GTP binding Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-112412 SOS-mediated signalling
R-HSA-1169092 Activation of RAS in B cells
R-HSA-1236382 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
R-HSA-1250196 SHC1 events in ERBB2 signaling
R-HSA-1250347 SHC1 events in ERBB4 signaling
R-HSA-1433557 Signaling by SCF-KIT
R-HSA-167044 Signalling to RAS
R-HSA-171007 p38MAPK events
R-HSA-179812 GRB2 events in EGFR signaling
R-HSA-180336 SHC1 events in EGFR signaling
R-HSA-186763 Downstream signal transduction
R-HSA-1963640 GRB2 events in ERBB2 signaling
R-HSA-210993 Tie2 Signaling
R-HSA-2179392 EGFR Transactivation by Gastrin
R-HSA-2424491 DAP12 signaling
R-HSA-2428933 SHC-related events triggered by IGF1R
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-375165 NCAM signaling for neurite out-growth
R-HSA-3928662 EPHB-mediated forward signaling
R-HSA-442982 Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-5218921 VEGFR2 mediated cell proliferation
R-HSA-5621575 CD209 (DC-SIGN) signaling
R-HSA-5637810 Constitutive Signaling by EGFRvIII
R-HSA-5654688 SHC-mediated cascade:FGFR1
R-HSA-5654693 FRS-mediated FGFR1 signaling
R-HSA-5654699 SHC-mediated cascade:FGFR2
R-HSA-5654700 FRS-mediated FGFR2 signaling
R-HSA-5654704 SHC-mediated cascade:FGFR3
R-HSA-5654706 FRS-mediated FGFR3 signaling
R-HSA-5654712 FRS-mediated FGFR4 signaling
R-HSA-5654719 SHC-mediated cascade:FGFR4
R-HSA-5655253 Signaling by FGFR2 in disease
R-HSA-5655291 Signaling by FGFR4 in disease
R-HSA-5655302 Signaling by FGFR1 in disease
R-HSA-5658442 Regulation of RAS by GAPs
R-HSA-5673000 RAF activation
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-5674135 MAP2K and MAPK activation
R-HSA-5675221 Negative regulation of MAPK pathway
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants
R-HSA-6802949 Signaling by RAS mutants
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-6802953 RAS signaling downstream of NF1 loss-of-function variants
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-74751 Insulin receptor signalling cascade
R-HSA-8849471 PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases
R-HSA-8851805 MET activates RAS signaling
R-HSA-8853334 Signaling by FGFR3 fusions in cancer
R-HSA-8853338 Signaling by FGFR3 point mutants in cancer
R-HSA-9026519 Activated NTRK2 signals through RAS
R-HSA-9028731 Activated NTRK2 signals through FRS2 and FRS3
R-HSA-9034864 Activated NTRK3 signals through RAS
SABIO-RKiP01112
SignaLinkiP01112
SIGNORiP01112

Names & Taxonomyi

Protein namesi
Recommended name:
GTPase HRas
Alternative name(s):
H-Ras-1
Ha-Ras
Transforming protein p21
c-H-ras
p21ras
Cleaved into the following chain:
GTPase HRas, N-terminally processed
Gene namesi
Name:HRAS
Synonyms:HRAS1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000174775.16
HGNCiHGNC:5173 HRAS
MIMi190020 gene
neXtProtiNX_P01112

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Golgi apparatus, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Costello syndrome (CSTLO)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare condition characterized by prenatally increased growth, postnatal growth deficiency, mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities.
See also OMIM:218040
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02610612G → A in CSTLO. 3 PublicationsCorresponds to variant dbSNP:rs104894230EnsemblClinVar.1
Natural variantiVAR_04597512G → C in CSTLO. 2 PublicationsCorresponds to variant dbSNP:rs104894229EnsemblClinVar.1
Natural variantiVAR_06881612G → D in CSTLO; severe mutation. 1 PublicationCorresponds to variant dbSNP:rs104894230EnsemblClinVar.1
Natural variantiVAR_04597612G → E in CSTLO. 1 Publication1
Natural variantiVAR_00683612G → V in CSTLO, bladder carcinoma and CMEMS; constitutively activated; interacts and recruits PLCE1 to plasma membrane. 4 PublicationsCorresponds to variant dbSNP:rs104894230EnsemblClinVar.1
Natural variantiVAR_02610713G → C in CSTLO. 1 PublicationCorresponds to variant dbSNP:rs104894228EnsemblClinVar.1
Natural variantiVAR_02610813G → D in CSTLO. 1 PublicationCorresponds to variant dbSNP:rs104894226EnsemblClinVar.1
Natural variantiVAR_06881837E → EE in CSTLO. 1 Publication1
Natural variantiVAR_04597858T → I in CSTLO. 1 PublicationCorresponds to variant dbSNP:rs121917758EnsemblClinVar.1
Natural variantiVAR_045981117K → R in CSTLO. 1 PublicationCorresponds to variant dbSNP:rs104894227EnsemblClinVar.1
Natural variantiVAR_045982146A → T in CSTLO. 1 PublicationCorresponds to variant dbSNP:rs104894231EnsemblClinVar.1
Natural variantiVAR_045983146A → V in CSTLO. 1 PublicationCorresponds to variant dbSNP:rs121917759EnsemblClinVar.1
Congenital myopathy with excess of muscle spindles (CMEMS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionVariant of Costello syndrome.
See also OMIM:218040
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04597722Q → K in CMEMS. 1 PublicationCorresponds to variant dbSNP:rs121917757EnsemblClinVar.1
Natural variantiVAR_04598063E → K in CMEMS. 1 PublicationCorresponds to variant dbSNP:rs121917756EnsemblClinVar.1
Thyroid cancer, non-medullary, 2 (NMTC2)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms.
See also OMIM:188470
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04597961Q → K in NMTC2; somatic mutation; increases transformation of cultured cell lines. 2 PublicationsCorresponds to variant dbSNP:rs28933406EnsemblClinVar.1
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.1 Publication
Bladder cancer (BLC)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas that begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences.
See also OMIM:109800
Schimmelpenning-Feuerstein-Mims syndrome (SFM)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects. Many oral manifestations have been reported, not only including hypoplastic and malformed teeth, and mucosal papillomatosis, but also ankyloglossia, hemihyperplastic tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous nevi follow the lines of Blaschko and these can continue as linear intraoral lesions, as in mucosal papillomatosis.
See also OMIM:163200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06881713G → R in SFM; somatic mutation; shows constitutive activation of the MAPK and PI3K-AKT signaling pathways. 1 PublicationCorresponds to variant dbSNP:rs104894228EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi17S → N: Dominant negative. Prevents PLCE1 EGF-induced recruitment to plasma membrane. No effect on subcellular location of isoform 2. 2 Publications1
Mutagenesisi26N → G: Loss of interaction with PLCE1; when associated with V-12. 1 Publication1
Mutagenesisi29V → A: No effect on interaction with PLCE1; when associated with V-12. 1 Publication1
Mutagenesisi32Y → F: Loss of interaction and recruitment to plasma membrane of PLCE1; when associated with V-12. 1 Publication1
Mutagenesisi34P → G: No effect on interaction with PLCE1; when associated with V-12. 1 Publication1
Mutagenesisi35T → S: Loss of interaction with PLCE1; when associated with V-12. 1 Publication1
Mutagenesisi37E → G: No effect on interaction with PLCE1; when associated with V-12. 1 Publication1
Mutagenesisi38D → N: No effect on interaction with PLCE1; when associated with V-12. 1 Publication1
Mutagenesisi39S → C: No effect on interaction with PLCE1; when associated with V-12. 1 Publication1
Mutagenesisi59A → T: Loss of GTPase activity and creation of an autophosphorylation site. 1
Mutagenesisi61Q → I: Moderately increased transformation of cultured cell lines. 1 Publication1
Mutagenesisi61Q → V: Strongly increased transformation of cultured cell lines. 1 Publication1
Mutagenesisi83A → T: GTP-binding activity reduced by factor of 30. 1 Publication1
Mutagenesisi118C → S: Abolishes S-nitrosylation. No stimulation of guanine nucleotide exchange. 2 Publications1
Mutagenesisi119D → N: Loss of GTP-binding activity. 1 Publication1
Mutagenesisi144T → I: GTP-binding activity reduced by factor of 25. 1 Publication1
Mutagenesisi164 – 165RQ → AV: Loss of GTP-binding activity. 1 Publication2
Mutagenesisi181C → S: Exclusively localized in Golgi. Non-specifically localized on all endomembranes; when associated with S-184. 2 Publications1
Mutagenesisi184C → S: Loss of S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine stimulation of Ras-GTPase activity. Mainly localized in Golgi. Non-specifically localized on all endomembranes; when associated with S-181. 3 Publications1

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi3265
GeneReviewsiHRAS
MalaCardsiHRAS
MIMi109800 phenotype
163200 phenotype
188470 phenotype
218040 phenotype
OpenTargetsiENSG00000174775
Orphaneti3071 Costello syndrome
2612 Linear nevus sebaceus syndrome
2874 Phakomatosis pigmentokeratotica
PharmGKBiPA29444

Chemistry databases

ChEMBLiCHEMBL2167
DrugBankiDB04315 Guanosine-5'-Diphosphate
DB04137 Guanosine-5'-Triphosphate
DB03226 Trifluoroethanol
GuidetoPHARMACOLOGYi2822

Polymorphism and mutation databases

BioMutaiHRAS
DMDMi131869

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000429961 – 186GTPase HRasAdd BLAST186
Initiator methionineiRemoved; alternate1 Publication
ChainiPRO_00003264762 – 186GTPase HRas, N-terminally processedAdd BLAST185
PropeptideiPRO_0000042997187 – 189Removed in mature form3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionine; in GTPase HRas; alternate1 Publication1
Modified residuei2N-acetylthreonine; in GTPase HRas, N-terminally processed1 Publication1
Modified residuei118S-nitrosocysteine1 Publication1
Lipidationi181S-palmitoyl cysteine4 Publications1
Lipidationi184S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine; alternate1 Publication1
Lipidationi184S-palmitoyl cysteine; alternate4 Publications1
Modified residuei186Cysteine methyl ester1 Publication1
Lipidationi186S-farnesyl cysteine1 Publication1

Post-translational modificationi

Palmitoylated by the ZDHHC9-GOLGA7 complex. A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi.
S-nitrosylated; critical for redox regulation. Important for stimulating guanine nucleotide exchange. No structural perturbation on nitrosylation.
The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S-nitrosylation and S-palmitoylation.
Acetylation at Lys-104 prevents interaction with guanine nucleotide exchange factors (GEFs).By similarity

Keywords - PTMi

Acetylation, Lipoprotein, Methylation, Palmitate, Prenylation, S-nitrosylation

Proteomic databases

EPDiP01112
PaxDbiP01112
PeptideAtlasiP01112
PRIDEiP01112
ProteomicsDBi12698 [P01112-2]
51321
51322 [P01112-2]

PTM databases

iPTMnetiP01112
PhosphoSitePlusiP01112
SwissPalmiP01112

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000174775 Expressed in 227 organ(s), highest expression level in skin of abdomen
CleanExiHS_HRAS
ExpressionAtlasiP01112 baseline and differential
GenevisibleiP01112 HS

Organism-specific databases

HPAiCAB002015
HPA049830

Interactioni

Subunit structurei

In its GTP-bound form interacts with PLCE1 (PubMed:11022048). Interacts with TBC1D10C (PubMed:17230191). Interacts with RGL3 (By similarity). Interacts with HSPD1 (By similarity). Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3 and RGS14 (By similarity). Interacts (active GTP-bound form) with RGS14 (via RBD 1 domain) (By similarity). Forms a signaling complex with RASGRP1 and DGKZ (PubMed:11257115). Interacts with RASSF5 (PubMed:18596699). Interacts with PDE6D (PubMed:11980706). Interacts with IKZF3 (PubMed:10369681). Interacts with RACK1 (PubMed:14500341). Interacts with PIK3CG; the interaction is required for membrane recruitment and beta-gamma G protein dimer-dependent activation of the PI3K gamma complex PIK3CG:PIK3R6 (By similarity). Interacts with RAPGEF2 (PubMed:10608844, PubMed:11598133).By similarity10 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi109501, 102 interactors
ComplexPortaliCPX-395 GTPase HRAS - Son of sevenless homolog 1 complex
CORUMiP01112
DIPiDIP-1050N
ELMiP01112
IntActiP01112, 62 interactors
MINTiP01112
STRINGi9606.ENSP00000309845

Chemistry databases

BindingDBiP01112

Structurei

Secondary structure

1189
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

DisProtiDP00153
ProteinModelPortaliP01112
SMRiP01112
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01112

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni166 – 185Hypervariable regionAdd BLAST20

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi32 – 40Effector region9

Sequence similaritiesi

Belongs to the small GTPase superfamily. Ras family.Curated

Phylogenomic databases

eggNOGiKOG0395 Eukaryota
COG1100 LUCA
GeneTreeiENSGT00860000133672
HOGENOMiHOG000233973
HOVERGENiHBG009351
InParanoidiP01112
KOiK02833
OMAiDCMNCKC
OrthoDBiEOG091G0UAU
PhylomeDBiP01112
TreeFamiTF312796

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR005225 Small_GTP-bd_dom
IPR001806 Small_GTPase
IPR020849 Small_GTPase_Ras-type
PANTHERiPTHR24070 PTHR24070, 1 hit
PfamiView protein in Pfam
PF00071 Ras, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00231 small_GTP, 1 hit
PROSITEiView protein in PROSITE
PS51421 RAS, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: P01112-1) [UniParc]FASTAAdd to basket
Also known as: H-Ras4A, p21

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET 
        60         70         80         90        100
CLLDILDTAG QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHQYREQI 
       110        120        130        140        150
KRVKDSDDVP MVLVGNKCDL AARTVESRQA QDLARSYGIP YIETSAKTRQ 
       160        170        180 
GVEDAFYTLV REIRQHKLRK LNPPDESGPG CMSCKCVLS
Length:189
Mass (Da):21,298
Last modified:July 21, 1986 - v1
Checksum:iEE6DC2D933E2856A
GO
Isoform 2 (identifier: P01112-2) [UniParc]FASTAAdd to basket
Also known as: H-RasIDX, p19

The sequence of this isoform differs from the canonical sequence as follows:
     152-189: VEDAFYTLVREIRQHKLRKLNPPDESGPGCMSCKCVLS → SRSGSSSSSGTLWDPPGPM

Show »
Length:170
Mass (Da):18,870
Checksum:iC3364C8DC783C191
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0J9YXG8A0A0J9YXG8_HUMAN
GTPase HRas
HRAS
14Annotation score:

Mass spectrometryi

Molecular mass is 6223±2 Da from positions 112 - 166. Determined by ESI. 1 Publication
Molecular mass is 6253±2 Da from positions 112 - 166. Determined by ESI. Includes one nitric oxide molecule.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02610612G → A in CSTLO. 3 PublicationsCorresponds to variant dbSNP:rs104894230EnsemblClinVar.1
Natural variantiVAR_04597512G → C in CSTLO. 2 PublicationsCorresponds to variant dbSNP:rs104894229EnsemblClinVar.1
Natural variantiVAR_06881612G → D in CSTLO; severe mutation. 1 PublicationCorresponds to variant dbSNP:rs104894230EnsemblClinVar.1
Natural variantiVAR_04597612G → E in CSTLO. 1 Publication1
Natural variantiVAR_00683712G → S in CSTLO and CMEMS; also found in patients with oral squamous cell carcinoma. 6 PublicationsCorresponds to variant dbSNP:rs104894229EnsemblClinVar.1
Natural variantiVAR_00683612G → V in CSTLO, bladder carcinoma and CMEMS; constitutively activated; interacts and recruits PLCE1 to plasma membrane. 4 PublicationsCorresponds to variant dbSNP:rs104894230EnsemblClinVar.1
Natural variantiVAR_02610713G → C in CSTLO. 1 PublicationCorresponds to variant dbSNP:rs104894228EnsemblClinVar.1
Natural variantiVAR_02610813G → D in CSTLO. 1 PublicationCorresponds to variant dbSNP:rs104894226EnsemblClinVar.1
Natural variantiVAR_06881713G → R in SFM; somatic mutation; shows constitutive activation of the MAPK and PI3K-AKT signaling pathways. 1 PublicationCorresponds to variant dbSNP:rs104894228EnsemblClinVar.1
Natural variantiVAR_04597722Q → K in CMEMS. 1 PublicationCorresponds to variant dbSNP:rs121917757EnsemblClinVar.1
Natural variantiVAR_06881837E → EE in CSTLO. 1 Publication1
Natural variantiVAR_04597858T → I in CSTLO. 1 PublicationCorresponds to variant dbSNP:rs121917758EnsemblClinVar.1
Natural variantiVAR_04597961Q → K in NMTC2; somatic mutation; increases transformation of cultured cell lines. 2 PublicationsCorresponds to variant dbSNP:rs28933406EnsemblClinVar.1
Natural variantiVAR_00683861Q → L in melanoma; strongly reduced GTP hydrolysis in the presence of RAF1; increases transformation of cultured cell lines. 1 PublicationCorresponds to variant dbSNP:rs121913233EnsemblClinVar.1
Natural variantiVAR_04598063E → K in CMEMS. 1 PublicationCorresponds to variant dbSNP:rs121917756EnsemblClinVar.1
Natural variantiVAR_07825989S → C Found in a patient with severe fetal hydrops and pleural effusion; unknown pathological significance; decreased activation of Ras protein signal transduction. 1 PublicationCorresponds to variant dbSNP:rs755322824EnsemblClinVar.1
Natural variantiVAR_045981117K → R in CSTLO. 1 PublicationCorresponds to variant dbSNP:rs104894227EnsemblClinVar.1
Natural variantiVAR_045982146A → T in CSTLO. 1 PublicationCorresponds to variant dbSNP:rs104894231EnsemblClinVar.1
Natural variantiVAR_045983146A → V in CSTLO. 1 PublicationCorresponds to variant dbSNP:rs121917759EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041597152 – 189VEDAF…KCVLS → SRSGSSSSSGTLWDPPGPM in isoform 2. 2 PublicationsAdd BLAST38

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J00277 Genomic DNA Translation: AAB02605.1
AJ437024 mRNA Translation: CAD24594.1
AF493916 mRNA Translation: AAM12630.1
CR536579 mRNA Translation: CAG38816.1
CR542271 mRNA Translation: CAG47067.1
BT019421 mRNA Translation: AAV38228.1
EF015887 Genomic DNA Translation: ABI97389.1
AB451336 mRNA Translation: BAG70150.1
AB451485 mRNA Translation: BAG70299.1
CH471158 Genomic DNA Translation: EAX02337.1
CH471158 Genomic DNA Translation: EAX02338.1
BC006499 mRNA Translation: AAH06499.1
BC095471 mRNA Translation: AAH95471.1
M17232 Genomic DNA Translation: AAA35685.1
CCDSiCCDS7698.1 [P01112-1]
CCDS7699.1 [P01112-2]
PIRiA93299 TVHUH
RefSeqiNP_001123914.1, NM_001130442.2 [P01112-1]
NP_001304983.1, NM_001318054.1
NP_005334.1, NM_005343.3 [P01112-1]
NP_789765.1, NM_176795.4 [P01112-2]
UniGeneiHs.37003

Genome annotation databases

EnsembliENST00000311189; ENSP00000309845; ENSG00000174775 [P01112-1]
ENST00000397594; ENSP00000380722; ENSG00000174775 [P01112-2]
ENST00000397596; ENSP00000380723; ENSG00000174775 [P01112-1]
ENST00000417302; ENSP00000388246; ENSG00000174775 [P01112-2]
ENST00000451590; ENSP00000407586; ENSG00000174775 [P01112-1]
ENST00000493230; ENSP00000434023; ENSG00000174775 [P01112-2]
ENST00000610977; ENSP00000480686; ENSG00000276536 [P01112-1]
ENST00000615062; ENSP00000482366; ENSG00000276536 [P01112-1]
ENST00000616241; ENSP00000480317; ENSG00000276536 [P01112-2]
ENST00000631404; ENSP00000488757; ENSG00000276536 [P01112-1]
ENST00000631967; ENSP00000488225; ENSG00000276536 [P01112-2]
ENST00000634098; ENSP00000488296; ENSG00000276536 [P01112-2]
GeneIDi3265
KEGGihsa:3265
UCSCiuc010qvw.3 human [P01112-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J00277 Genomic DNA Translation: AAB02605.1
AJ437024 mRNA Translation: CAD24594.1
AF493916 mRNA Translation: AAM12630.1
CR536579 mRNA Translation: CAG38816.1
CR542271 mRNA Translation: CAG47067.1
BT019421 mRNA Translation: AAV38228.1
EF015887 Genomic DNA Translation: ABI97389.1
AB451336 mRNA Translation: BAG70150.1
AB451485 mRNA Translation: BAG70299.1
CH471158 Genomic DNA Translation: EAX02337.1
CH471158 Genomic DNA Translation: EAX02338.1
BC006499 mRNA Translation: AAH06499.1
BC095471 mRNA Translation: AAH95471.1
M17232 Genomic DNA Translation: AAA35685.1
CCDSiCCDS7698.1 [P01112-1]
CCDS7699.1 [P01112-2]
PIRiA93299 TVHUH
RefSeqiNP_001123914.1, NM_001130442.2 [P01112-1]
NP_001304983.1, NM_001318054.1
NP_005334.1, NM_005343.3 [P01112-1]
NP_789765.1, NM_176795.4 [P01112-2]
UniGeneiHs.37003

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
121PX-ray1.54A1-166[»]
1AA9NMR-A1-171[»]
1AGPX-ray2.30A1-166[»]
1BKDX-ray2.80R1-166[»]
1CLUX-ray1.70A1-166[»]
1CRPNMR-A1-166[»]
1CRQNMR-A1-166[»]
1CRRNMR-A1-166[»]
1CTQX-ray1.26A1-166[»]
1GNPX-ray2.70A1-166[»]
1GNQX-ray2.50A1-166[»]
1GNRX-ray1.85A1-166[»]
1HE8X-ray3.00B1-166[»]
1IAQX-ray2.90A/B/C1-166[»]
1IOZX-ray2.00A1-171[»]
1JAHX-ray1.80A1-166[»]
1JAIX-ray1.80A1-166[»]
1K8RX-ray3.00A1-166[»]
1LF0X-ray1.70A1-166[»]
1LF5X-ray1.70A1-166[»]
1LFDX-ray2.10B/D1-167[»]
1NVUX-ray2.20Q/R1-166[»]
1NVVX-ray2.18Q/R1-166[»]
1NVWX-ray2.70Q/R1-166[»]
1NVXX-ray3.20Q/R1-166[»]
1P2SX-ray2.45A1-166[»]
1P2TX-ray2.00A1-166[»]
1P2UX-ray2.00A1-166[»]
1P2VX-ray2.30A1-166[»]
1PLJX-ray2.80A1-166[»]
1PLKX-ray2.80A1-166[»]
1PLLX-ray2.80A1-166[»]
1Q21X-ray2.20A1-171[»]
1QRAX-ray1.60A1-166[»]
1RVDX-ray1.90A1-166[»]
1WQ1X-ray2.50R1-166[»]
1XCMX-ray1.84A1-167[»]
1XD2X-ray2.70A/B1-166[»]
1XJ0X-ray1.70A1-166[»]
1ZVQX-ray2.00A1-166[»]
1ZW6X-ray1.50A1-166[»]
221PX-ray2.30A1-166[»]
2C5LX-ray1.90A/B1-166[»]
2CE2X-ray1.00X1-166[»]
2CL0X-ray1.80X1-166[»]
2CL6X-ray1.24X1-166[»]
2CL7X-ray1.25X1-166[»]
2CLCX-ray1.30X1-166[»]
2CLDX-ray1.22X1-166[»]
2EVWX-ray1.05X1-166[»]
2GDPmodel-A1-171[»]
2LCFNMR-A1-166[»]
2LWINMR-A1-166[»]
2N42NMR-A1-166[»]
2N46NMR-A1-166[»]
2Q21X-ray2.20A1-171[»]
2QUZX-ray1.49A1-166[»]
2RGAX-ray1.90A1-166[»]
2RGBX-ray1.35A1-166[»]
2RGCX-ray1.60A1-166[»]
2RGDX-ray2.00A1-166[»]
2RGEX-ray1.40A1-166[»]
2RGGX-ray1.45A1-166[»]
2UZIX-ray2.00R1-166[»]
2VH5X-ray2.70R1-166[»]
2X1VX-ray1.70A1-166[»]
3DDCX-ray1.80A1-166[»]
3I3SX-ray1.36R1-166[»]
3K8YX-ray1.30A1-166[»]
3K9LX-ray1.80A/B/C1-166[»]
3K9NX-ray2.00A1-166[»]
3KKMX-ray1.70A1-166[»]
3KKNX-ray2.09A1-166[»]
3KUDX-ray2.15A1-166[»]
3L8YX-ray2.02A1-166[»]
3L8ZX-ray1.44A1-166[»]
3LBHX-ray1.85A1-166[»]
3LBIX-ray2.09A1-166[»]
3LBNX-ray1.86A1-166[»]
3LO5X-ray2.57A/C/E1-166[»]
3OIUX-ray1.32A1-166[»]
3OIVX-ray1.84A1-166[»]
3OIWX-ray1.30A1-166[»]
3RRYX-ray1.60A1-166[»]
3RRZX-ray1.60A1-166[»]
3RS0X-ray1.40A1-166[»]
3RS2X-ray1.84A1-166[»]
3RS3X-ray1.52A1-166[»]
3RS4X-ray1.70A1-166[»]
3RS5X-ray1.68A1-166[»]
3RS7X-ray1.70A1-166[»]
3RSLX-ray1.70A1-166[»]
3RSOX-ray1.60A1-166[»]
3TGPX-ray1.31A1-166[»]
421PX-ray2.20A1-166[»]
4DLRX-ray1.32A1-166[»]
4DLSX-ray1.82A1-166[»]
4DLTX-ray1.70A1-166[»]
4DLUX-ray1.60A1-166[»]
4DLVX-ray1.57A1-166[»]
4DLWX-ray1.72A1-166[»]
4DLXX-ray1.73A1-166[»]
4DLYX-ray1.57A1-166[»]
4DLZX-ray1.66A1-166[»]
4DSTX-ray2.30A2-167[»]
4DSUX-ray1.70A2-167[»]
4EFLX-ray1.90A1-166[»]
4EFMX-ray1.90A1-166[»]
4EFNX-ray2.30A1-166[»]
4G0NX-ray2.45A1-166[»]
4G3XX-ray3.25A1-166[»]
4K81X-ray2.40B/D/F/H1-166[»]
4L9SX-ray1.61A1-166[»]
4L9WX-ray1.95A1-166[»]
4NYIX-ray2.96Q/R1-166[»]
4NYJX-ray2.85Q/R1-166[»]
4NYMX-ray3.55Q/R1-166[»]
4Q21X-ray2.00A1-189[»]
4RSGneutron diffraction1.91A1-166[»]
4URUX-ray2.83R1-166[»]
4URVX-ray2.58R1-166[»]
4URWX-ray2.76R1-166[»]
4URXX-ray2.49R1-166[»]
4URYX-ray2.47R1-166[»]
4URZX-ray2.24R1-166[»]
4US0X-ray2.17R1-166[»]
4US1X-ray2.65R1-166[»]
4US2X-ray2.48R1-166[»]
4XVQX-ray1.89A1-166[»]
4XVRX-ray2.03A1-166[»]
521PX-ray2.60A1-166[»]
5B2ZX-ray1.56A1-166[»]
5B30X-ray1.60A1-166[»]
5E95X-ray1.40A1-166[»]
5P21X-ray1.35A1-166[»]
5VBEX-ray1.57A1-166[»]
5VBZX-ray2.20A/B/C1-166[»]
5WDOX-ray1.65A1-166[»]
5WDPX-ray1.35A1-166[»]
5WDQX-ray1.25A1-166[»]
5WFOX-ray1.99Q/R1-166[»]
5WFPX-ray2.08Q/R1-166[»]
5WFQX-ray2.26Q/R1-166[»]
5WFRX-ray2.46Q/R1-166[»]
5WPLX-ray2.15A/D/G/J1-166[»]
5X9SX-ray2.50A1-166[»]
621PX-ray2.40A1-166[»]
6AMBX-ray2.50A1-168[»]
6AXGX-ray3.30B/D/F/H/J/L1-166[»]
6Q21X-ray1.95A/B/C/D1-171[»]
721PX-ray2.00A1-166[»]
821PX-ray1.50A1-166[»]
DisProtiDP00153
ProteinModelPortaliP01112
SMRiP01112
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109501, 102 interactors
ComplexPortaliCPX-395 GTPase HRAS - Son of sevenless homolog 1 complex
CORUMiP01112
DIPiDIP-1050N
ELMiP01112
IntActiP01112, 62 interactors
MINTiP01112
STRINGi9606.ENSP00000309845

Chemistry databases

BindingDBiP01112
ChEMBLiCHEMBL2167
DrugBankiDB04315 Guanosine-5'-Diphosphate
DB04137 Guanosine-5'-Triphosphate
DB03226 Trifluoroethanol
GuidetoPHARMACOLOGYi2822

PTM databases

iPTMnetiP01112
PhosphoSitePlusiP01112
SwissPalmiP01112

Polymorphism and mutation databases

BioMutaiHRAS
DMDMi131869

Proteomic databases

EPDiP01112
PaxDbiP01112
PeptideAtlasiP01112
PRIDEiP01112
ProteomicsDBi12698 [P01112-2]
51321
51322 [P01112-2]

Protocols and materials databases

DNASUi3265
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000311189; ENSP00000309845; ENSG00000174775 [P01112-1]
ENST00000397594; ENSP00000380722; ENSG00000174775 [P01112-2]
ENST00000397596; ENSP00000380723; ENSG00000174775 [P01112-1]
ENST00000417302; ENSP00000388246; ENSG00000174775 [P01112-2]
ENST00000451590; ENSP00000407586; ENSG00000174775 [P01112-1]
ENST00000493230; ENSP00000434023; ENSG00000174775 [P01112-2]
ENST00000610977; ENSP00000480686; ENSG00000276536 [P01112-1]
ENST00000615062; ENSP00000482366; ENSG00000276536 [P01112-1]
ENST00000616241; ENSP00000480317; ENSG00000276536 [P01112-2]
ENST00000631404; ENSP00000488757; ENSG00000276536 [P01112-1]
ENST00000631967; ENSP00000488225; ENSG00000276536 [P01112-2]
ENST00000634098; ENSP00000488296; ENSG00000276536 [P01112-2]
GeneIDi3265
KEGGihsa:3265
UCSCiuc010qvw.3 human [P01112-1]

Organism-specific databases

CTDi3265
DisGeNETi3265
EuPathDBiHostDB:ENSG00000174775.16
GeneCardsiHRAS
GeneReviewsiHRAS
HGNCiHGNC:5173 HRAS
HPAiCAB002015
HPA049830
MalaCardsiHRAS
MIMi109800 phenotype
163200 phenotype
188470 phenotype
190020 gene
218040 phenotype
neXtProtiNX_P01112
OpenTargetsiENSG00000174775
Orphaneti3071 Costello syndrome
2612 Linear nevus sebaceus syndrome
2874 Phakomatosis pigmentokeratotica
PharmGKBiPA29444
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0395 Eukaryota
COG1100 LUCA
GeneTreeiENSGT00860000133672
HOGENOMiHOG000233973
HOVERGENiHBG009351
InParanoidiP01112
KOiK02833
OMAiDCMNCKC
OrthoDBiEOG091G0UAU
PhylomeDBiP01112
TreeFamiTF312796

Enzyme and pathway databases

ReactomeiR-HSA-112412 SOS-mediated signalling
R-HSA-1169092 Activation of RAS in B cells
R-HSA-1236382 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
R-HSA-1250196 SHC1 events in ERBB2 signaling
R-HSA-1250347 SHC1 events in ERBB4 signaling
R-HSA-1433557 Signaling by SCF-KIT
R-HSA-167044 Signalling to RAS
R-HSA-171007 p38MAPK events
R-HSA-179812 GRB2 events in EGFR signaling
R-HSA-180336 SHC1 events in EGFR signaling
R-HSA-186763 Downstream signal transduction
R-HSA-1963640 GRB2 events in ERBB2 signaling
R-HSA-210993 Tie2 Signaling
R-HSA-2179392 EGFR Transactivation by Gastrin
R-HSA-2424491 DAP12 signaling
R-HSA-2428933 SHC-related events triggered by IGF1R
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-375165 NCAM signaling for neurite out-growth
R-HSA-3928662 EPHB-mediated forward signaling
R-HSA-442982 Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-5218921 VEGFR2 mediated cell proliferation
R-HSA-5621575 CD209 (DC-SIGN) signaling
R-HSA-5637810 Constitutive Signaling by EGFRvIII
R-HSA-5654688 SHC-mediated cascade:FGFR1
R-HSA-5654693 FRS-mediated FGFR1 signaling
R-HSA-5654699 SHC-mediated cascade:FGFR2
R-HSA-5654700 FRS-mediated FGFR2 signaling
R-HSA-5654704 SHC-mediated cascade:FGFR3
R-HSA-5654706 FRS-mediated FGFR3 signaling
R-HSA-5654712 FRS-mediated FGFR4 signaling
R-HSA-5654719 SHC-mediated cascade:FGFR4
R-HSA-5655253 Signaling by FGFR2 in disease
R-HSA-5655291 Signaling by FGFR4 in disease
R-HSA-5655302 Signaling by FGFR1 in disease
R-HSA-5658442 Regulation of RAS by GAPs
R-HSA-5673000 RAF activation
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-5674135 MAP2K and MAPK activation
R-HSA-5675221 Negative regulation of MAPK pathway
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants
R-HSA-6802949 Signaling by RAS mutants
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-6802953 RAS signaling downstream of NF1 loss-of-function variants
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-74751 Insulin receptor signalling cascade
R-HSA-8849471 PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases
R-HSA-8851805 MET activates RAS signaling
R-HSA-8853334 Signaling by FGFR3 fusions in cancer
R-HSA-8853338 Signaling by FGFR3 point mutants in cancer
R-HSA-9026519 Activated NTRK2 signals through RAS
R-HSA-9028731 Activated NTRK2 signals through FRS2 and FRS3
R-HSA-9034864 Activated NTRK3 signals through RAS
SABIO-RKiP01112
SignaLinkiP01112
SIGNORiP01112

Miscellaneous databases

EvolutionaryTraceiP01112
GeneWikiiHRAS
GenomeRNAii3265
PROiPR:P01112
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000174775 Expressed in 227 organ(s), highest expression level in skin of abdomen
CleanExiHS_HRAS
ExpressionAtlasiP01112 baseline and differential
GenevisibleiP01112 HS

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR005225 Small_GTP-bd_dom
IPR001806 Small_GTPase
IPR020849 Small_GTPase_Ras-type
PANTHERiPTHR24070 PTHR24070, 1 hit
PfamiView protein in Pfam
PF00071 Ras, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00231 small_GTP, 1 hit
PROSITEiView protein in PROSITE
PS51421 RAS, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRASH_HUMAN
AccessioniPrimary (citable) accession number: P01112
Secondary accession number(s): B5BUA0
, Q14080, Q6FHV9, Q9BR65, Q9UCE2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: October 10, 2018
This is version 236 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. SIMILARITY comments
    Index of protein domains and families
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
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