Q61411 (RASH_MOUSE) 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

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [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 › Mus › Mus

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 and RASSF5. Interacts with PDE6D. Interacts with IKZF3. 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 GNB2L1 By similarity. Interacts with RGL3. Interacts with HSPD1. 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. Ref.7 Ref.8 Ref.9
Subcellular location	Cell membrane By similarity. 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. The active GTP-bound form is localized most strongly to membranes than the inactive GDP-bound form By similarity.
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 AAH61885.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cell membrane Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing
Disease	Proto-oncogene
Ligand	GTP-binding Nucleotide-binding
PTM	Acetylation Lipoprotein Methylation Palmitate Prenylation S-nitrosylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	Ras protein signal transduction Traceable author statement PubMed 10871846. Source: MGI cell aging Inferred from direct assay PubMed 12878730PubMed 15572682. Source: MGI cell cycle arrest Inferred from electronic annotation. Source: Compara cell proliferation Inferred from physical interaction PubMed 14712229. Source: MGI cellular senescence Inferred from electronic annotation. Source: Compara endocytosis Inferred from direct assay PubMed 12446704. Source: MGI induction of apoptosis Inferred from genetic interaction PubMed 16954213. Source: MGI intrinsic apoptotic signaling pathway Inferred from mutant phenotype PubMed 16954213. Source: MGI negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of neuron apoptotic process Inferred from direct assay PubMed 10845775. Source: MGI positive regulation of DNA replication Inferred from electronic annotation. Source: Compara positive regulation of ERK1 and ERK2 cascade Inferred from electronic annotation. Source: Compara positive regulation of JNK cascade Inferred from electronic annotation. Source: Compara positive regulation of Ras protein signal transduction Inferred from sequence orthology PubMed 19029245. Source: MGI positive regulation of cell proliferation Inferred from direct assay PubMed 16478791. Source: MGI positive regulation of epithelial cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of gene expression Inferred from direct assay PubMed 21357543. Source: MGI 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 electronic annotation. Source: Compara regulation of long-term neuronal synaptic plasticity Inferred from mutant phenotype PubMed 12427827. Source: MGI social behavior 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 sequence or structural similarity. Source: UniProtKB
Molecular_function	GTP binding Inferred from direct assay PubMed 18604197. Source: MGI GTPase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Rassf5	Q5EBH1	2	EBI-400273,EBI-960530

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q61411-1)

Also known as: p21; H-Ras4A;

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.

Isoform 2 (identifier: Q61411-2)

Also known as: p19; H-RasIDX;

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 186	186	GTPase HRas		PRO_0000042998
	Initiator methionine	1	1	Removed; alternate By similarity
	Chain	2 – 186	185	GTPase HRas, N-terminally processed		PRO_0000326478
	Propeptide	187 – 189	3	Removed in mature form By similarity		PRO_0000042999
Regions
	Nucleotide binding	10 – 17	8	GTP By similarity
	Nucleotide binding	57 – 61	5	GTP By similarity
	Nucleotide binding	116 – 119	4	GTP By similarity
	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 By similarity
	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 By similarity
	Lipidation	186	1	S-farnesyl cysteine By similarity
Natural variations
	Alternative sequence	152 – 189	38	VEDAF…KCVLS → SRSGSSSGTLWDPPSPGTHV TQRPSSWRGGCLLYTSP in isoform 2.		VSP_041598
Experimental info
	Mutagenesis	61	1	Q → R: Found in chemically induced liver tumors. Ref.4
	Sequence conflict	55	1	I → Y in CAA90306. Ref.1
Isoform 2:
	Sequence conflict	163	1	D → G in CAD24593. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (p21) (H-Ras4A) [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
	Isoform 2 (p19) (H-RasIDX) [UniParc]. Checksum: BD42AE50A77341FF	FASTA	188	20,880
	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 GSRSGSSSGT LWDPPSPGTH VTQRPSSWRG GCLLYTSP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of c-H-ras-1 gene from B6C3F1 mice." Przybojewska B., Plucienniczak G. Acta Biochim. Pol. 43:575-578(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: C57BL/6 X C3H. Tissue: Liver.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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] (ISOFORM 1). Tissue: Olfactory epithelium.
[4]	"Spontaneous mutation at codon 61 of the Ha-ras gene in the nascent liver of B6C3F1, C3H/He and C57BL/6 mice." Moulds B.A., Goodman J.I. Mutat. Res. 311:1-7(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 59-75, MUTAGENESIS OF GLN-61.
[5]	Lubec G., Kang S.U. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 136-147, MASS SPECTROMETRY. Strain: C57BL/6. Tissue: Brain.
[6]	"Alternative splicing of the human proto-oncogene c-H-ras renders a new Ras family protein that trafficks to cytoplasm and nucleus." Guil S., de La Iglesia N., Fernandez-Larrea J., Cifuentes D., Ferrer J.C., Guinovart J.J., Bach-Elias M. Cancer Res. 63:5178-5187(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 151-189 (ISOFORM 2), ALTERNATIVE SPLICING. Strain: NIH/3T3.
[7]	"An interaction between p21ras and heat shock protein hsp60, a chaperonin." Ikawa S., Weinberg R.A. Proc. Natl. Acad. Sci. U.S.A. 89:2012-2016(1992) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HSPD1.
[8]	"A novel RalGEF-like protein, RGL3, as a candidate effector for rit and Ras." Shao H., Andres D.A. J. Biol. Chem. 275:26914-26924(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RGL3.
[9]	"Ras is an indispensable coregulator of the class IB phosphoinositide 3-kinase p87/p110gamma." Kurig B., Shymanets A., Bohnacker T., Prajwal X., Brock C., Ahmadian M.R., Schaefer M., Gohla A., Harteneck C., Wymann M.P., Jeanclos E., Nurnberg B. Proc. Natl. Acad. Sci. U.S.A. 106:20312-20317(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PIK3CG.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z50013 Genomic DNA. Translation: CAA90306.1. AC108908 Genomic DNA. No translation available. BC061885 mRNA. Translation: AAH61885.1. Different initiation. S74119 Genomic DNA. Translation: AAP21090.1. AJ437023 mRNA. Translation: CAD24593.1.
IPI	IPI00605942. IPI01023179.
PIR	S57718.
RefSeq	NP_001123915.1. NM_001130443.1. NP_001123916.1. NM_001130444.1. NP_032310.2. NM_008284.2.
UniGene	Mm.334313.
3D structure databases
ProteinModelPortal	Q61411.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29361N.
IntAct	Q61411. 7 interactions.
MINT	MINT-1215825.
PTM databases
PhosphoSite	Q61411.
Proteomic databases
PaxDb	Q61411.
PRIDE	Q61411.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000026572; ENSMUSP00000026572; ENSMUSG00000025499. ENSMUST00000097957; ENSMUSP00000095570; ENSMUSG00000025499. ENSMUST00000168550; ENSMUSP00000132110; ENSMUSG00000025499.
GeneID	15461.
KEGG	mmu:15461.
Organism-specific databases
CTD	15461.
MGI	MGI:96224. Hras1.
Phylogenomic databases
eggNOG	COG1100.
GeneTree	ENSGT00690000101785.
HOGENOM	HOG000233973.
HOVERGEN	HBG009351.
KO	K02833.
OMA	IDDETCL.
OrthoDB	EOG4BRWMX.
Gene expression databases
ArrayExpress	Q61411.
Bgee	Q61411.
CleanEx	MM_HRAS1.
Genevestigator	Q61411.
GermOnline	ENSMUSG00000025499. Mus musculus.
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	Q61411.
ChiTaRS	HRAS. mouse.
NextBio	288278.
SOURCE	Search...

Entry information

Entry name

RASH_MOUSE

Accession

Primary (citable) accession number: Q61411
Secondary accession number(s): Q6P716, Q80WD2, Q811B9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 117 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program