P20171 (RASH_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
GTPase HRas

Alternative name(s):
H-Ras-1
Transforming protein p21
c-H-ras
p21ras

Cleaved into the following chain:

1. GTPase HRas, N-terminally processed

Gene names

Name:	Hras1
Synonyms:	Hras

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	189 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
Enzyme regulation	Alternate 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).
Subunit structure	Forms a signaling complex with RASGRP1 and DGKZ. In its GTP-bound form interacts with PLCE1. Interacts with TBC1D10C. Interacts with RGL3 and RASSF5. Interacts with HSPD1. Interacts with PDE6D. Interacts with IKZF3. Interacts with GNB2L1 By similarity. Found in a complex with at least BRAF, HRAS1, MAP2K1, MAPK3 and RGS14. Interacts (active GTP-bound form) with RGS14 (via RBD 1 domain). 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. Ref.5 Ref.6 Ref.7
Subcellular location	Cell membrane. Cell membrane; Lipid-anchor; Cytoplasmic side By similarity. Golgi apparatus By similarity. Golgi apparatus membrane; Lipid-anchor By similarity. Note: Shuttles between the plasma membrane and the Golgi apparatus By similarity. The active GTP-bound form is localized most strongly to membranes than the inactive GDP-bound form. Ref.7
Post-translational modification	Palmitoylated by the ZDHHC9-GOLGA7 complex. A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi By similarity. 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 By similarity. Acetylation at Lys-104 prevents interaction with guanine nucleotide exchange factors (GEFs) By similarity.
Sequence similarities	Belongs to the small GTPase superfamily. Ras family.
Sequence caution	The sequence AAH86608.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAH99130.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cell membrane Golgi apparatus Membrane
Disease	Proto-oncogene
Ligand	GTP-binding Nucleotide-binding
PTM	Acetylation Lipoprotein Methylation Palmitate Prenylation S-nitrosylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Ras protein signal transduction Inferred from mutant phenotype PubMed 12077341. Source: RGD actin cytoskeleton organization Inferred from electronic annotation. Source: Compara apoptotic process Inferred from mutant phenotype PubMed 14988264. Source: RGD cell cycle arrest Inferred from electronic annotation. Source: Compara cell proliferation Inferred from electronic annotation. Source: Compara cellular senescence Inferred from electronic annotation. Source: Compara endocytosis Inferred from electronic annotation. Source: Compara induction of apoptosis Inferred from electronic annotation. Source: Compara intrinsic apoptotic signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of DNA replication Inferred from mutant phenotype PubMed 9487126. Source: RGD positive regulation of ERK1 and ERK2 cascade Inferred from mutant phenotype PubMed 18163378. Source: RGD positive regulation of JNK cascade Inferred from electronic annotation. Source: Compara positive regulation of Rac protein signal transduction Inferred from electronic annotation. Source: Compara positive regulation of Ras protein signal transduction Inferred from mutant phenotype PubMed 19029245. Source: MGI positive regulation of epithelial cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of protein phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara protein heterooligomerization Inferred from physical interaction PubMed 15917294. Source: RGD regulation of long-term neuronal synaptic plasticity Inferred from electronic annotation. Source: Compara regulation of synaptic transmission, GABAergic Inferred from electronic annotation. Source: Compara social behavior Inferred from expression pattern PubMed 19616040. Source: RGD striated muscle cell differentiation Inferred from electronic annotation. Source: Compara visual learning Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi apparatus Inferred from sequence or structural similarity. Source: UniProtKB Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	GTP binding Inferred from sequence or structural similarity. Source: UniProtKB GTPase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 186

186

GTPase HRas

PRO_0000043000

Initiator methionine

1

1

Removed; alternate By similarity

Chain

2 – 186

185

GTPase HRas, N-terminally processed

PRO_0000326479

Propeptide

187 – 189

3

Removed in mature form By similarity

PRO_0000043001

Regions

Nucleotide binding

10 – 17

8

GTP

Nucleotide binding

57 – 61

5

GTP

Nucleotide binding

116 – 119

4

GTP

Region

166 – 185

20

Hypervariable region

Motif

32 – 40

9

Effector region

Amino acid modifications

Modified residue

1

1

N-acetylmethionine; alternate By similarity

Modified residue

2

1

N-acetylthreonine; in GTPase HRas, N-terminally processed By similarity

Modified residue

118

1

S-nitrosocysteine By similarity

Modified residue

186

1

Cysteine methyl ester Ref.4

Lipidation

181

1

S-palmitoyl cysteine By similarity

Lipidation

184

1

S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine; alternate By similarity

Lipidation

184

1

S-palmitoyl cysteine; alternate

Lipidation

186

1

S-farnesyl cysteine Ref.4

Experimental info

Mutagenesis

26

1

N → G: Interacts and partially stimulates PLCE1; when associated with L-61. Ref.5

Mutagenesis

35

1

T → S: No interaction and stimulation of PLCE1; when associated with L-61. Ref.5

Mutagenesis

37

1

E → G: Reduced interaction and stimulation of PLCE1; when associated with L-61. Ref.5

Mutagenesis

38

1

D → N: Reduced interaction and stimulation of PLCE1; when associated with L-61. Ref.5

Mutagenesis

40

1

Y → C: No interaction and stimulation of PLCE1; when associated with L-61. Ref.5

Mutagenesis

61

1

Q → L: Constitutively active. Constitutively interacts and stimulates PLCE1 phospholipase activity. Reduced interaction and stimulation of PLCE1; when associated with G-37 and N-38. No interaction and stimulation of PLCE1; when associated with S-35 and C-40. Interacts and partially stimulates PLCE1; when associated with G-26. Interacts but does not stimulate PLCE1; when associated with S-186. Ref.5

Mutagenesis

186

1

C → S: Interacts but does not stimulate PLCE1; when associated with L-61. Ref.5

Sequence conflict

179

1

P → L in AAA42009. Ref.1

Secondary structure

1

.

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189

Helix Strand Turn

Details...

Beta strand

2 – 11

10

Helix

16 – 25

10

Beta strand

36 – 46

11

Beta strand

49 – 58

10

Helix

62 – 64

3

Helix

68 – 72

5

Beta strand

76 – 83

8

Helix

87 – 91

5

Helix

93 – 104

12

Beta strand

111 – 116

6

Helix

127 – 137

11

Beta strand

141 – 143

3

Turn

146 – 148

3

Helix

152 – 163

12

Sequences

	Sequence		Length	Mass (Da)
	P20171 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: EE6DC2D933E2856A	FASTA	189	21,298
	10 20 30 40 50 60 MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET CLLDILDTAG 70 80 90 100 110 120 QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHQYREQI KRVKDSDDVP MVLVGNKCDL 130 140 150 160 170 180 AARTVESRQA QDLARSYGIP YIETSAKTRQ GVEDAFYTLV REIRQHKLRK LNPPDESGPG CMSCKCVLS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of the two rat cellular rasH genes." Ruta M., Wolford R., Dhar R., Defeo-Jones D., Ellis R.W., Scolnick E.M. Mol. Cell. Biol. 6:1706-1710(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Thymus.
[3]	"Nucleotide sequence and characterization of the 5' flanking region of the rat Ha-ras protooncogene." Damante G., Filetti S., Rapoport B. Proc. Natl. Acad. Sci. U.S.A. 84:774-778(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-37.
[4]	"Posttranslational modification of the Ha-ras oncogene protein: evidence for a third class of protein carboxyl methyltransferases." Clarke S., Vogel J.P., Deschenes R.J., Stock J. Proc. Natl. Acad. Sci. U.S.A. 85:4643-4647(1988) [PubMed] [Europe PMC] [Abstract] Cited for: ISOPRENYLATION AT CYS-186, CLEAVAGE, METHYLATION AT CYS-186.
[5]	"Phospholipase C(epsilon): a novel Ras effector." Kelley G.G., Reks S.E., Ondrako J.M., Smrcka A.V. EMBO J. 20:743-754(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PLCE1, MUTAGENESIS OF ASN-26; THR-35; GLU-37; ASP-38; TYR-40; GLN-61 AND CYS-186.
[6]	"Regulator of G-protein signaling 14 (RGS14) is a selective H-Ras effector." Willard F.S., Willard M.D., Kimple A.J., Soundararajan M., Oestreich E.A., Li X., Sowa N.A., Kimple R.J., Doyle D.A., Der C.J., Zylka M.J., Snider W.D., Siderovski D.P. PLoS ONE 4:E4884-E4884(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH BRAF; MAP2K1; MAPK3 AND RGS14, INTERACTION WITH RGS14.
[7]	"RGS14 is a multifunctional scaffold that integrates G protein and Ras/Raf MAPkinase signalling pathways." Shu F.J., Ramineni S., Hepler J.R. Cell. Signal. 22:366-376(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RGS14, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M13011 Genomic DNA. Translation: AAA42009.1.
BC086608 mRNA. Translation: AAH86608.1. Different initiation.
BC099130 mRNA. Translation: AAH99130.1. Different initiation.
M15188 Genomic DNA. Translation: AAA42008.1.

IPI

IPI00196529.

PIR

A25229.

RefSeq

NP_001091711.1. NM_001098241.1.
NP_001123913.1. NM_001130441.1.

UniGene

Rn.102180.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3V4F	X-ray	1.39	A	1-166	[»]

ProteinModelPortal

P20171.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-4996514.

STRING

10116.ENSRNOP00000022363.

Proteomic databases

PaxDb

P20171.

PRIDE

P20171.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000022363; ENSRNOP00000022363; ENSRNOG00000016611.

GeneID

293621.

KEGG

rno:293621.

UCSC

RGD:2827. rat.

Organism-specific databases

CTD

3265.

RGD

2827. Hras.

Phylogenomic databases

eggNOG

COG1100.

GeneTree

ENSGT00690000101785.

HOGENOM

HOG000233973.

HOVERGEN

HBG009351.

InParanoid

P20171.

KO

K02833.

OMA

IDDETCL.

Enzyme and pathway databases

Reactome

REACT_111984. Signal Transduction.

Gene expression databases

ArrayExpress

P20171.

Genevestigator

P20171.

GermOnline

ENSRNOG00000016611. Rattus norvegicus.

Family and domain databases

InterPro

IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]

PANTHER

PTHR24070. PTHR24070. 1 hit.

Pfam

PF00071. Ras. 1 hit.
[Graphical view]

PRINTS

PR00449. RASTRNSFRMNG.

SMART

SM00173. RAS. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00231. small_GTP. 1 hit.

PROSITE

PS51421. RAS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P20171.

NextBio

636547.

Entry information

Entry name

RASH_RAT

Accession

Primary (citable) accession number: P20171
Secondary accession number(s): Q4KLL6, Q5RJJ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program