Reviewed, UniProtKB/Swiss-Prot P08644 (RASK_RAT)

Names and origin

Protein names

Recommended name:
    GTPase KRas
Alternative name(s):
    K-Ras 2
    Ki-Ras
    c-K-ras
    c-Ki-ras
Cleaved into the following chain:
    1- Recommended name:
            GTPase KRas, N-terminally processed

Gene names

Name:	Kras
Synonyms:	Kras2

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › 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	Interacts with PHLPP. Ref.6
Subcellular location	Cell membrane; Lipid-anchor; Cytoplasmic side.
Sequence similarities	Belongs to the small GTPase superfamily. Ras family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Disease	Proto-oncogene
Ligand	GTP-binding Nucleotide-binding
PTM	Acetylation Lipoprotein Methylation Palmitate Prenylation
Gene Ontology (GO)
Biological process	cytokine-mediated signaling pathway Inferred from mutant phenotype. Source: RGD positive regulation of MAP kinase activity Inferred from mutant phenotype. Source: RGD positive regulation of NF-kappaB transcription factor activity Inferred from mutant phenotype. Source: RGD positive regulation of nitric-oxide synthase activity Inferred from mutant phenotype. Source: RGD response to glucocorticoid stimulus Inferred from expression pattern. Source: RGD response to mineralocorticoid stimulus Inferred from expression pattern. Source: RGD small GTPase mediated signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	internal side of plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell intracellular Inferred from electronic annotation. Source: InterPro membrane raft Ref.6 Inferred from direct assay. Source: RGD
Molecular function	GDP binding Ref.6 Inferred from direct assay. Source: RGD GMP binding Ref.6 Inferred from direct assay. Source: RGD GTP binding Inferred from electronic annotation. Source: UniProtKB-KW LRR domain binding Ref.6 Inferred from direct assay. Source: RGD
Complete GO annotation...

Alternative products

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

Note: Isoforms differ in the C-terminal region which is encoded by two alternative exons (IVA and IVB).

Isoform 2A (identifier: P08644-1)

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 2B (identifier: P08644-2)

The sequence of this isoform differs from the canonical sequence as follows:
     151-153: RVE → GVD
     165-189: QYRLKKISKEEKTPGCVKIKKCVIM → KHKEKMSKDGKKKKKKSRTRCIVM

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 186	186	GTPase KRas		PRO_0000082644
	Initiator methionine	1	1	Removed; alternate By similarity
	Chain	2 – 186	185	GTPase KRas, N-terminally processed		PRO_0000326483
	Propeptide	187 – 189	3	Removed in mature form By similarity		PRO_0000281294
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; in GTPase KRas; alternate By similarity
	Modified residue	2	1	N-acetylthreonine; in GTPase KRas, N-terminally processed By similarity
	Modified residue	186	1	Cysteine methyl ester; in isoform 2A By similarity
	Lipidation	180	1	S-palmitoyl cysteine By similarity
	Lipidation	186	1	S-farnesyl cysteine; in isoform 2A By similarity
Natural variations
	Alternative sequence	151 – 153	3	RVE → GVD in isoform 2B.		VSP_011144
	Alternative sequence	165 – 189	25	QYRLK…KCVIM → KHKEKMSKDGKKKKKKSRTR CIVM in isoform 2B.		VSP_011145
Experimental info
	Sequence conflict	12	1	G → C in AAA42011. Ref.3
	Sequence conflict	47	1	D → H in AAA42011. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2A [UniParc]. Last modified July 19, 2004. Version 3. Checksum: 97345422E01D2C81	FASTA	189	21,656
	10 20 30 40 50 60 MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET CLLDILDTAG 70 80 90 100 110 120 QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHHYREQI KRVKDSEDVP MVLVGNKCDL 130 140 150 160 170 180 PSRTVDTKQA QELARSYGIP FIETSAKTRQ RVEDAFYTLV REIRQYRLKK ISKEEKTPGC VKIKKCVIM
	Isoform 2B [UniParc] [UniParc]. Checksum: B0A55318AD158F51	FASTA	188	21,495
	10 20 30 40 50 60 MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET CLLDILDTAG 70 80 90 100 110 120 QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHHYREQI KRVKDSEDVP MVLVGNKCDL 130 140 150 160 170 180 PSRTVDTKQA QELARSYGIP FIETSAKTRQ GVDDAFYTLV REIRKHKEKM SKDGKKKKKK SRTRCIVM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Activation of the K-ras gene by insertion mutations in chemically induced rat renal mesenchymal tumors." Higinbotham K.G., Rice J.M., Buzard G.S., Perantoni A.O. Oncogene 9:2455-2459(1994) [PubMed: 8058308] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2B), MUTAGENESIS. Strain: Noble. Tissue: Kidney.
[2]	"Genome sequence of the Brown Norway rat yields insights into mammalian evolution." Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S. Nature 428:493-521(2004) [PubMed: 15057822] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Brown Norway.
[3]	"Structure of the c-Ki-ras gene in a rat fibrosarcoma induced by 1,8-dinitropyrene." Tahira T., Hayashi K., Ochiai M., Tsuchida N., Nagao M., Sugimura T. Mol. Cell. Biol. 6:1349-1351(1986) [PubMed: 3023884] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-96.
[4]	"Nucleotide sequence of exon I of the rat c-K-ras gene." Iritani A., Katayama N., Tahira T., Hayashi K., Tsuchida N. Bull. Tokyo Med. Dent. Univ. 33:35-40(1986) [PubMed: 3009041] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 1-37.
[5]	"Characterization of c-Ki-ras oncogene alleles by direct sequencing of enzymatically amplified DNA from carcinogen-induced tumors." McMahon G., Davis E., Wogan G.N. Proc. Natl. Acad. Sci. U.S.A. 84:4974-4978(1987) [PubMed: 3110778] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
[6]	"Suprachiasmatic nucleus circadian oscillatory protein, a novel binding partner of K-Ras in the membrane rafts, negatively regulates MAPK pathway." Shimizu K., Okada M., Nagai K., Fukada Y. J. Biol. Chem. 278:14920-14925(2003) [PubMed: 12594205] [Abstract] Cited for: INTERACTION WITH PHLPP.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U09793 mRNA. Translation: AAB60458.1. AABR03032592 Genomic DNA. No translation available. M12260, M12259 Genomic DNA. Translation: AAA42011.1. M54870 Genomic DNA. Translation: AAA40937.1. M16970 Genomic DNA. Translation: AAA41494.1.
IPI	IPI00203826. IPI00210097.
PIR	I58402.
RefSeq	NP_113703.1.
UniGene	Rn.24554
3D structure databases
HSSP	HSSP built from PDB template 1IAQ based on UniProtKB P01112.
SMR	P08644. Positions 1-166.
ModBase	Search...
Protein-protein interaction databases
STRING	P08644.
PTM databases
PhosphoSite	P08644.
Genome annotation databases
Ensembl	ENSRNOT00000012588; ENSRNOP00000012588; ENSRNOG00000009338; Rattus norvegicus. [Genome view] ENSRNOT00000012887; ENSRNOP00000012887; ENSRNOG00000009338; Rattus norvegicus. [Genome view]
GeneID	24525.
KEGG	rno:24525.
Organism-specific databases
CTD	24525.
RGD	2981. Kras.
Phylogenomic databases
HOVERGEN	P08644.
OMA	NEAKSFE.
Gene expression databases
ArrayExpress	P08644.
Genevestigator	P08644.
GermOnline	ENSRNOG00000009338. Rattus norvegicus.
Family and domain databases
InterPro	IPR003577. GTPase_Ras. IPR013753. Ras. IPR001806. Ras_GTPase. IPR015592. Ras_Ras_related. IPR005225. Small_GTP_bd. [Graphical view]
PANTHER	PTHR11708:SF125. Ras_Ras_related. 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 Resources
NextBio	603578.

Entry information

Entry name

RASK_RAT

Accession

Primary (citable) accession number: P08644
Secondary accession number(s): P46203, P97914

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	July 19, 2004
Last modified:	November 3, 2009
This is version 94 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)