EKS-MUM-00051

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00051

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TKL/RAF	413.1	1.4E-123	349	606	258

Status

Reviewed

Ensembl Protein

ENSMUSP00000000451

UniProt Accession

Q99N57; Q3UR68; Q58E75; Q91WH1; Q99N58; Q9QUU8;

Protein Name

RAF proto-oncogene serine/threonine-protein kinase

Protein Synonyms/Alias

Proto-oncogene c-RAF; cRaf; Raf-1;

Gene Name

Raf1

Gene Synonyms/Alias

Raf1; Craf;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSMUSG00000000441	ENSMUSP00000000451	ENSMUST00000000451
ENSMUSG00000000441	ENSMUSP00000115424	ENSMUST00000147979
ENSMUSG00000000441	ENSMUSP00000108571	ENSMUST00000112949

Organism

Mus musculus

Functional Description

Serine/threonine-protein kinase that acts as aregulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2- antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down- regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation (By similarity). Regulates Rho signaling and migration, and is required for normal wound healing.

Protein Length

648

Protein Sequence
(FASTA)

MEHIQGAWKT ISNGFGLKDA VFDGSSCISP TIVQQFGYQR RASDDGKLTD SSKTSNTIRV 60

FLPNKQRTVV NVRNGMSLHD CLMKALKVRG LQPECCAVFR LLQEHKGKKA RLDWNTDAAS 120

LIGEELQVDF LDHVPLTTHN FARKTFLKLA FCDICQKFLL NGFRCQTCGY KFHEHCSTKV 180

PTMCVDWSNI RQLLLFPNST VGDSGVPAPP SFPMRRMRES VSRMPASSQH RYSTPHAFTF 240

NTSSPSSEGS LSQRQRSTST PNVHMVSTTL HVDSRMIEDA IRSHSESASP SALSSSPNNL 300

SPTGWSQPKT PVPAQRERAP GSGTQEKNKI RPRGQRDSSY YWEIEASEVM LSTRIGSGSF 360

GTVYKGKWHG DVAVKILKVV DPTPEQLQAF RNEVAVLRKT RHVNILLFMG YMTKDNLAIV 420

TQWCEGSSLY KHLHVQETKF QMFQLIDIAR QTAQGMDYLH AKNIIHRDMK SNNIFLHEGL 480

TVKIGDFGLA TVKSRWSGSQ QVEQPTGSVL WMAPEVIRMQ DDNPFSFQSD VYSYGIVLYE 540

LMAGELPYAH INNRDQIIFM VGRGYASPDL SRLYKNCPKA MKRLVADCVK KVKEERPLFP 600

QILSSIELLQ HSLPKINRSA SEPSLHRAAH TEDINACTLT TSPRLPVF 648

Nucleotide Sequence
(FASTA)

ATGGAGCACA TACAGGGAGC TTGGAAGACG ATCAGCAATG GCTTTGGACT CAAAGATGCG 60

GTGTTTGATG GCTCCAGCTG CATCTCCCCT ACCATTGTTC AGCAGTTTGG CTATCAGCGC 120

CGGGCCTCAG ATGATGGCAA GCTCACGGAT TCTTCTAAGA CAAGCAATAC TATCCGGGTT 180

TTCTTGCCGA ATAAGCAAAG GACTGTGGTC AATGTGCGGA ATGGAATGAG CTTACATGAC 240

TGCCTTATGA AAGCTCTGAA GGTGAGAGGC CTGCAGCCAG AGTGCTGTGC AGTGTTCAGA 300

CTTCTCCAGG AACACAAAGG TAAGAAAGCA CGCTTAGATT GGAACACCGA TGCCGCCTCT 360

CTGATTGGAG AAGAACTGCA AGTGGATTTT TTGGATCATG TTCCACTCAC AACTCACAAC 420

TTTGCTCGGA AAACGTTCCT GAAGCTTGCA TTCTGTGACA TCTGTCAGAA GTTCCTGCTA 480

AATGGATTTC GATGTCAGAC TTGTGGCTAC AAGTTTCATG AGCACTGTAG CACCAAAGTA 540

CCTACTATGT GTGTGGACTG GAGTAATATC AGACAGCTCT TGCTGTTTCC AAATTCCACT 600

GTTGGTGACA GTGGAGTCCC AGCACCACCT TCTTTCCCAA TGCGTCGGAT GCGAGAATCT 660

GTTTCCCGGA TGCCTGCTAG TTCCCAGCAC AGATACTCTA CACCCCATGC CTTCACTTTC 720

AACACCTCCA GCCCTTCCTC AGAAGGTTCC CTGTCCCAGA GGCAGAGGTC AACGTCCACT 780

CCCAATGTCC ACATGGTCAG CACCACCCTG CATGTGGACA GCAGGATGAT TGAGGATGCA 840

ATTCGAAGTC ACAGTGAATC AGCCTCACCT TCAGCCCTGT CCAGCAGCCC AAACAACCTG 900

AGTCCAACAG GCTGGTCACA GCCCAAAACC CCTGTGCCAG CACAAAGAGA GCGGGCACCA 960

GGATCTGGGA CCCAGGAAAA AAACAAAATT AGGCCTCGTG GGCAGAGAGA CTCGAGTTAT 1020

TACTGGGAAA TAGAAGCCAG TGAGGTGATG CTGTCTACTC GGATCGGGTC AGGTTCCTTT 1080

GGCACTGTGT ACAAGGGCAA GTGGCATGGA GATGTTGCAG TAAAGATCCT AAAGGTGGTT 1140

GACCCAACTC CAGAGCAACT TCAGGCCTTC AGGAACGAGG TGGCTGTTTT GCGCAAAACA 1200

CGGCATGTTA ACATCCTGCT GTTCATGGGG TACATGACAA AGGACAACCT GGCGATTGTG 1260

ACTCAGTGGT GTGAAGGCAG CAGTCTCTAC AAACACCTGC ATGTCCAGGA GACCAAATTC 1320

CAGATGTTCC AGCTAATTGA CATTGCCCGA CAGACAGCTC AGGGAATGGA CTATTTGCAT 1380

GCAAAGAACA TCATCCACAG AGACATGAAA TCCAACAATA TATTTCTCCA TGAAGGCCTC 1440

ACGGTGAAAA TTGGAGATTT TGGTTTGGCA ACAGTGAAGT CACGCTGGAG TGGTTCTCAG 1500

CAGGTTGAAC AGCCCACTGG CTCTGTGCTG TGGATGGCCC CAGAAGTAAT CCGGATGCAG 1560

GATGACAACC CGTTCAGCTT CCAGTCCGAC GTGTACTCGT ACGGCATCGT GCTGTACGAG 1620

CTGATGGCTG GGGAGCTTCC CTACGCCCAC ATCAACAACC GAGACCAGAT CATCTTCATG 1680

GTAGGCCGTG GGTATGCATC CCCTGATCTC AGCAGGCTCT ACAAGAACTG CCCCAAGGCA 1740

ATGAAGAGGT TGGTGGCTGA CTGTGTGAAG AAAGTCAAAG AAGAGAGACC TTTGTTTCCC 1800

CAGATCCTGT CTTCCATCGA GCTGCTTCAG CACTCTCTGC CGAAAATCAA CAGGAGCGCC 1860

TCTGAGCCTT CCCTGCATCG GGCAGCTCAC ACTGAGGACA TCAATGCTTG CACGCTGACT 1920

ACATCCCCAA GGCTACCAGT CTTCTAG 1947

Domain Profile

S: 1     velaekiGsGrfGtvyrgkwhGdvavkllnveelseeqleaFkkevaaykktRhenivLF  60

         v+l+++iGsG+fGtvy+gkwhGdvavk+l+v ++++eql+aF++eva+++ktRh+ni+LF

Q: 349   VMLSTRIGSGSFGTVYKGKWHGDVAVKILKVVDPTPEQLQAFRNEVAVLRKTRHVNILLF  408

         57899*******************************************************

S: 61    mGyvskpelaivtslckgssLykllheqetkldlaklidiarqiaqgmdYLhakkilhkD  120

         mGy++k++laivt++c+gssLyk+lh+qetk+++ +lidiarq+aqgmdYLhak+i+h+D

Q: 409   MGYMTKDNLAIVTQWCEGSSLYKHLHVQETKFQMFQLIDIARQTAQGMDYLHAKNIIHRD  468

         ************************************************************

S: 121   lksknilleeglkvvitDFgllsvkrllsgrrekqleipkgwilylapeviralsidleq  180

         +ks+ni+l+egl+v+i+DFgl++vk+++sg  ++q+e+p+g++l++apevir+      q

Q: 469   MKSNNIFLHEGLTVKIGDFGLATVKSRWSG--SQQVEQPTGSVLWMAPEVIRM------Q  520

         ******************************..*********************......*

S: 181   delpfskesDvyafGivlyellarelpyke.esadqilfavgrG.lkpdlskvksklpke  238

         d++pfs++sDvy++Givlyel+a+elpy++ +++dqi+f+vgrG ++pdls++++++pk+

Q: 521   DDNPFSFQSDVYSYGIVLYELMAGELPYAHiNNRDQIIFMVGRGyASPDLSRLYKNCPKA  580

         ************************************************************

S: 239   lkellleClkfekeeRPlftqilkkl  264

         +k+l+++C+k+ keeRPlf+qil+++

Q: 581   MKRLVADCVKKVKEERPLFPQILSSI  606

         **********************9875

Domain Sequence
(FASTA)

VMLSTRIGSG SFGTVYKGKW HGDVAVKILK VVDPTPEQLQ AFRNEVAVLR KTRHVNILLF 60

MGYMTKDNLA IVTQWCEGSS LYKHLHVQET KFQMFQLIDI ARQTAQGMDY LHAKNIIHRD 120

MKSNNIFLHE GLTVKIGDFG LATVKSRWSG SQQVEQPTGS VLWMAPEVIR MQDDNPFSFQ 180

SDVYSYGIVL YELMAGELPY AHINNRDQII FMVGRGYASP DLSRLYKNCP KAMKRLVADC 240

VKKVKEERPL FPQILSSI 258

Keyword

Alternative splicing; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Kinase; Membrane; Metal-binding; Methylation; Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein; Proto-oncogene; Reference proteome; Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Caenorhabditis elegans"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Danio rerio"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Ochotona princeps"; ?>Oreochromis niloticus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Procavia capensis"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005829	; C:cytosol
GO:0005739	; C:mitochondrion
GO:0005634	; C:nucleus
GO:0005886	; C:plasma membrane
GO:0031143	; C:pseudopodium
GO:0005524	; F:ATP binding
GO:0004709	; F:MAP kinase kinase kinase activity
GO:0046872	; F:metal ion binding
GO:0004672	; F:protein kinase activity
GO:0000186	; P:activation of MAPKK activity
GO:0006915	; P:apoptotic process
GO:0007010	; P:cytoskeleton organization
GO:0007507	; P:heart development
GO:0007243	; P:intracellular protein kinase cascade
GO:0043066	; P:negative regulation of apoptotic process
GO:0008285	; P:negative regulation of cell proliferation
GO:0031333	; P:negative regulation of protein complex assembly
GO:0048011	; P:nerve growth factor receptor signaling pathway
GO:0033138	; P:positive regulation of peptidyl-serine phosphorylation
GO:0001666	; P:response to hypoxia

KEGG

mmu:110157

;

InterPros

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.
IPR001245	; Ser-Thr/Tyr_kinase_cat_dom.
IPR008271	; Ser/Thr_kinase_AS.

Pfam

PF00130	; C1_1; 1.
PF07714	; Pkinase_Tyr; 1.
PF02196	; RBD; 1.

SMARTs

SM00109	; C1; 1.
SM00455	; RBD; 1.

Prosites

PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00108	; PROTEIN_KINASE_ST; 1.
PS50898	; RBD; 1.
PS00479	; ZF_DAG_PE_1; 1.
PS50081	; ZF_DAG_PE_2; 1.

Prints

PR00008

; DAGPEDOMAIN.

Created Date

20-Feb-2013