Reviewed, UniProtKB/Swiss-Prot Q99N57 (RAF1_MOUSE)

Names and origin

Protein names

Recommended name:
    RAF proto-oncogene serine/threonine-protein kinase
    EC=2.7.11.1
Alternative name(s):
    C-RAF
      Short name=cRaf
    Raf-1

Gene names

Name:	Raf1
Synonyms:	Craf

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	648 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. Part of the Ras-dependent signaling pathway from receptors to the nucleus. Protects cells from apoptosis mediated by STK3 By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Binds 2 zinc ions per subunit By similarity.
Subunit structure	Forms a multiprotein complex with Ras (M-Ras/MRAS), SHOC2 and protein phosphatase 1 (PPP1CA, PPP1CB and PPP1CC). Interacts with Ras proteins; the interaction is antagonized by RIN1. Weakly interacts with RIT1 By similarity. Interacts with STK3; the interaction inhibits its pro-apoptotic activity. Interacts (when phosphorylated at Ser-259) with YWHAZ (unphosphorylated at 'Thr-232').
Tissue specificity	Present in all tissues tested: testis, ovary, small intestine, colon, peripheral blood leukocytes, fetal liver, bone marrow, thymus, lymph node and spleen, and the cell lines melanoma G361, lung carcinoma A549, colorectal adenocarcinoma SW480, Burkitt's lymphoma Raji and lymphoblastic leukemia MOLT-4. In skeletal muscle, isoform 1 is more abundant than isoform 2. Ref.1 Ref.4
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylation at Thr-269 increases its kinase activity. Phosphorylation at Ser-259 induces the interaction with YWHAZ and inactivates kinase activity. Dephosphorylation of Ser-259 by the complex containing protein phosphatase 1, SHOC2 and M-Ras/MRAS relieves inactivation, leading to stimulate RAF1 activity. Ref.5
Sequence similarities	Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily. Contains 1 phorbol-ester/DAG-type zinc finger. Contains 1 protein kinase domain. Contains 1 RBD (Ras-binding) domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Disease	Proto-oncogene
Domain	Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	apoptosis Inferred from genetic interaction. Source: MGI cytoskeleton organization Inferred from mutant phenotype. Source: MGI nerve growth factor receptor signaling pathway Inferred from mutant phenotype. Source: MGI protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro protein kinase cascade Traceable author statement. Source: MGI
Cellular component	cytosol Traceable author statement. Source: MGI plasma membrane Traceable author statement. Source: MGI
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW receptor signaling protein activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CNKSR1	Q969H4	1	EBI-397757,EBI-741671	From a different organism.
Kras	P32883-2	2	EBI-397757,EBI-644285

Alternative products

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

Isoform 1 (identifier: Q99N57-1)

Also known as: 6C;

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: Q99N57-2)

Also known as: 1A;

The sequence of this isoform differs from the canonical sequence as follows:
     278-278: E → ESNSLNASPRACSRRFCLRGR

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 648	648	RAF proto-oncogene serine/threonine-protein kinase		PRO_0000086597
Regions
	Domain	56 – 131	76	RBD
	Domain	349 – 609	261	Protein kinase
	Zinc finger	138 – 184	47	Phorbol-ester/DAG-type
	Nucleotide binding	355 – 363	9	ATP By similarity
Sites
	Active site	468	1	Proton acceptor By similarity
	Metal binding	139	1	Zinc 1 By similarity
	Metal binding	152	1	Zinc 2 By similarity
	Metal binding	155	1	Zinc 2 By similarity
	Metal binding	165	1	Zinc 1 By similarity
	Metal binding	168	1	Zinc 1 By similarity
	Metal binding	173	1	Zinc 2 By similarity
	Metal binding	176	1	Zinc 2 By similarity
	Metal binding	184	1	Zinc 1 By similarity
	Binding site	375	1	ATP By similarity
Amino acid modifications
	Modified residue	43	1	Phosphoserine By similarity
	Modified residue	244	1	Phosphoserine By similarity
	Modified residue	252	1	Phosphoserine By similarity
	Modified residue	257	1	Phosphoserine By similarity
	Modified residue	258	1	Phosphothreonine By similarity
	Modified residue	259	1	Phosphoserine By similarity
	Modified residue	268	1	Phosphothreonine; by autocatalysis By similarity
	Modified residue	269	1	Phosphothreonine By similarity
	Modified residue	289	1	Phosphoserine By similarity
	Modified residue	294	1	Phosphoserine By similarity
	Modified residue	301	1	Phosphoserine By similarity
	Modified residue	338	1	Phosphoserine By similarity
	Modified residue	499	1	Phosphoserine By similarity
	Modified residue	612	1	Phosphoserine By similarity
	Modified residue	621	1	Phosphoserine Ref.5
	Modified residue	642	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	278	1	E → ESNSLNASPRACSRRFCLRG R in isoform 2.		VSP_034629
Experimental info
	Sequence conflict	522	1	D → N in AAH92040. Ref.3
	Sequence conflict	543	1	A → T in AAH92040. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (6C) [UniParc]. Last modified March 1, 2002. Version 2. Checksum: B70104AEF51C44A5	FASTA	648	72,917
	10 20 30 40 50 60 MEHIQGAWKT ISNGFGLKDA VFDGSSCISP TIVQQFGYQR RASDDGKLTD SSKTSNTIRV 70 80 90 100 110 120 FLPNKQRTVV NVRNGMSLHD CLMKALKVRG LQPECCAVFR LLQEHKGKKA RLDWNTDAAS 130 140 150 160 170 180 LIGEELQVDF LDHVPLTTHN FARKTFLKLA FCDICQKFLL NGFRCQTCGY KFHEHCSTKV 190 200 210 220 230 240 PTMCVDWSNI RQLLLFPNST VGDSGVPAPP SFPMRRMRES VSRMPASSQH RYSTPHAFTF 250 260 270 280 290 300 NTSSPSSEGS LSQRQRSTST PNVHMVSTTL HVDSRMIEDA IRSHSESASP SALSSSPNNL 310 320 330 340 350 360 SPTGWSQPKT PVPAQRERAP GSGTQEKNKI RPRGQRDSSY YWEIEASEVM LSTRIGSGSF 370 380 390 400 410 420 GTVYKGKWHG DVAVKILKVV DPTPEQLQAF RNEVAVLRKT RHVNILLFMG YMTKDNLAIV 430 440 450 460 470 480 TQWCEGSSLY KHLHVQETKF QMFQLIDIAR QTAQGMDYLH AKNIIHRDMK SNNIFLHEGL 490 500 510 520 530 540 TVKIGDFGLA TVKSRWSGSQ QVEQPTGSVL WMAPEVIRMQ DDNPFSFQSD VYSYGIVLYE 550 560 570 580 590 600 LMAGELPYAH INNRDQIIFM VGRGYASPDL SRLYKNCPKA MKRLVADCVK KVKEERPLFP 610 620 630 640 QILSSIELLQ HSLPKINRSA SEPSLHRAAH TEDINACTLT TSPRLPVF
	Isoform 2 (1A). Checksum: D70FF05B80BCF8ED	FASTA	668	75,151
	10 20 30 40 50 60 MEHIQGAWKT ISNGFGLKDA VFDGSSCISP TIVQQFGYQR RASDDGKLTD SSKTSNTIRV 70 80 90 100 110 120 FLPNKQRTVV NVRNGMSLHD CLMKALKVRG LQPECCAVFR LLQEHKGKKA RLDWNTDAAS 130 140 150 160 170 180 LIGEELQVDF LDHVPLTTHN FARKTFLKLA FCDICQKFLL NGFRCQTCGY KFHEHCSTKV 190 200 210 220 230 240 PTMCVDWSNI RQLLLFPNST VGDSGVPAPP SFPMRRMRES VSRMPASSQH RYSTPHAFTF 250 260 270 280 290 300 NTSSPSSEGS LSQRQRSTST PNVHMVSTTL HVDSRMIESN SLNASPRACS RRFCLRGRDA 310 320 330 340 350 360 IRSHSESASP SALSSSPNNL SPTGWSQPKT PVPAQRERAP GSGTQEKNKI RPRGQRDSSY 370 380 390 400 410 420 YWEIEASEVM LSTRIGSGSF GTVYKGKWHG DVAVKILKVV DPTPEQLQAF RNEVAVLRKT 430 440 450 460 470 480 RHVNILLFMG YMTKDNLAIV TQWCEGSSLY KHLHVQETKF QMFQLIDIAR QTAQGMDYLH 490 500 510 520 530 540 AKNIIHRDMK SNNIFLHEGL TVKIGDFGLA TVKSRWSGSQ QVEQPTGSVL WMAPEVIRMQ 550 560 570 580 590 600 DDNPFSFQSD VYSYGIVLYE LMAGELPYAH INNRDQIIFM VGRGYASPDL SRLYKNCPKA 610 620 630 640 650 660 MKRLVADCVK KVKEERPLFP QILSSIELLQ HSLPKINRSA SEPSLHRAAH TEDINACTLT TSPRLPVF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Phylogenetic conservation of the makorin-2 gene, encoding a multiple zinc-finger protein, antisense to the raf1 proto-oncogene." Gray T.A., Azama K., Whitmore K., Min A., Abe S., Nicholls R.D. Genomics 77:119-126(2001) [PubMed: 11597136] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Liver.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J. Tissue: Embryo.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: Czech II and FVB/N. Tissue: Kidney and Mammary tumor.
[4]	"An alternatively spliced c-mil/raf mRNA is predominantly expressed in chicken muscular tissues and conserved among vertebrate species." Dozier C., Ansieau S., Ferreira E., Coll J., Stehelin D. Oncogene 6:1307-1311(1991) [PubMed: 1886707] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[5]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed: 18973353] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-621, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB057655 mRNA. Translation: BAB39748.1. AB057663 mRNA. Translation: BAB39743.2. AK141745 mRNA. Translation: BAE24820.1. BC015273 mRNA. Translation: AAH15273.1. BC092040 mRNA. Translation: AAH92040.1. X55432 Genomic DNA. No translation available.
IPI	IPI00118101. IPI00830899.
RefSeq	NP_084056.1.
UniGene	Mm.184163
3D structure databases
SMR	Q99N57. Positions 55-131, 136-187.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99N57. 5 interactions.
STRING	Q99N57.
PTM databases
PhosphoSite	Q99N57.
Proteomic databases
PRIDE	Q99N57.
Genome annotation databases
Ensembl	ENSMUST00000000451; ENSMUSP00000000451; ENSMUSG00000000441; Mus musculus. [Genome view] ENSMUST00000112949; ENSMUSP00000108571; ENSMUSG00000000441; Mus musculus. [Genome view]
GeneID	110157.
KEGG	mmu:110157.
UCSC	uc009dix.1. mouse.
Organism-specific databases
CTD	110157.
MGI	MGI:97847. Raf1.
Phylogenomic databases
HOGENOM	Q99N57.
HOVERGEN	Q99N57.
OMA	DGPSCIS
OrthoDB	EOG9QC3QR
Enzyme and pathway databases
BRENDA	2.7.11.1. 244.
Gene expression databases
ArrayExpress	Q99N57.
Bgee	Q99N57.
CleanEx	MM_RAF1.
Genevestigator	Q99N57.
GermOnline	ENSMUSG00000000441. Mus musculus.
Family and domain databases
InterPro	IPR020454. DAG/PE_bd. IPR011009. Kinase-like_dom. IPR002219. Prot_Kinase_C-like_PE/DAG_bd. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR003116. Raf-like_ras_bd. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. [Graphical view]
Pfam	PF00130. C1_1. 1 hit. PF00069. Pkinase. 1 hit. PF02196. RBD. 1 hit. [Graphical view]
PRINTS	PR00008. DAGPEDOMAIN.
SMART	SM00109. C1. 1 hit. SM00455. RBD. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS50898. RBD. 1 hit. PS00479. ZF_DAG_PE_1. 1 hit. PS50081. ZF_DAG_PE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	363431.
SOURCE	Search...

Entry information

Entry name

RAF1_MOUSE

Accession

Primary (citable) accession number: Q99N57
Secondary accession number(s): Q3UR68 , Q58E75, Q91WH1, Q99N58, Q9QUU8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 15, 2003
Last sequence update:	March 1, 2002
Last modified:	November 24, 2009
This is version 83 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)