EKS-RAN-00050

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-RAN-00050

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TKL/RAF	413.9	3.9E-124	280	537	258

Status

Reviewed

Ensembl Protein

ENSRNOP00000013831

UniProt Accession

P11345;

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; Raf;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSRNOG00000010153	ENSRNOP00000013831	ENSRNOT00000013831

Organism

Rattus norvegicus

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. 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. Regulates Rho signaling and migration, and is required for normal wound healing. 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). Phosphorylates TNNT2/cardiac muscle troponin T.

Protein Length

579

Protein Sequence
(FASTA)

VNVRNGMSLH DCLMKALKVR GLQPECCAVF RLLQEHKGKK ARLDWNTDAA SLIGEELQVD 60

FLDHVPLTTH NFARKTFLKL AFCDICQKFL LNGFRCQTCG YKFHEHCSTK VPTMCVDWSN 120

IRQLLLFPNS TASDSGVPAP PSFTMRRMRE SVSRMPASSQ HRYSTPHAFT FNTSSPSSEG 180

SLSQRQRSTS TPNVHMVSTT LPVDSRMIED AIRSHSESAS PSALSSSPNN LSPTGWSQPK 240

TPVPAQRERA PGSGTQEKNK IRPRGQRDSS YYWEIEASEV MLSTRIGSGS FGTVYKGKWH 300

GDVAVKILKV VDPTPEQLQA FRNEVAVLRK TRHVNILLFM GYMTKDNLAI VTQWCEGSSL 360

YKHLHVQETK FQMFQLIDIA RQTAQGMDYL HAKNIIHRDM KSNNIFLHEG LTVKIGDFGL 420

ATVKSRWSGS QQVEQPTGSV LWMAPEVIRM QDNNPFSFQS DVYSYGIVLY ELMTGELPYS 480

HINNRDQIIF MVGRGYASPD LSRLYKNCPK AMKRLVADCV KKVKEERPLF PQILSSIELL 540

QHSLPKINRS ASEPSLHRAA HTEDINACTL TTSPRLPVF 579

Nucleotide Sequence
(FASTA)

GTCAATGTGC GGAATGGGAT GAGCTTGCAC GACTGCCTTA TGAAAGCTCT GAAGGTTAGA 60

GGCCTGCAGC CAGAGTGCTG TGCAGTGTTC AGACTTCTTC AGGAGCACAA AGGTAAGAAA 120

GCACGCTTAG ATTGGAACAC CGACGCCGCC TCTCTGATTG GAGAAGAACT GCAAGTGGAT 180

TTTTTGGATC ACGTTCCACT CACAACTCAC AACTTTGCTC GGAAAACGTT CCTGAAGCTT 240

GCATTCTGTG ACATCTGTCA AAAGTTCCTG CTAAATGGAT TTCGATGTCA GACTTGTGGC 300

TACAAGTTTC ATGAGCACTG TAGCACCAAA GTACCTACTA TGTGTGTGGA CTGGAGTAAT 360

ATCAGACAGC TCTTGCTGTT TCCAAATTCC ACTGCAAGTG ACAGTGGAGT CCCAGCACCA 420

CCCTCTTTCA CAATGCGTCG GATGCGAGAA TCTGTTTCCC GGATGCCTGC TAGTTCCCAG 480

CACAGATACT CCACACCCCA TGCCTTCACT TTCAACACCT CCAGCCCTTC CTCTGAAGGT 540

TCCCTGTCCC AGAGGCAGAG GTCAACGTCC ACTCCCAATG TCCACATGGT CAGCACCACC 600

CTGCCTGTGG ACAGCAGGAT GATTGAGGAT GCAATTCGAA GTCACAGTGA ATCAGCCTCA 660

CCTTCAGCCC TGTCCAGCAG CCCCAACAAC CTGAGCCCAA CAGGCTGGTC ACAGCCCAAA 720

ACCCCTGTGC CAGCACAAAG AGAGAGGGCG CCAGGATCTG GGACCCAGGA AAAAAACAAA 780

ATTAGGCCTC GTGGGCAGAG AGATTCAAGT TATTACTGGG AAATAGAAGC CAGTGAGGTG 840

ATGCTGTCTA CTCGGATTGG CTCGGGCTCC TTTGGCACTG TGTACAAGGG CAAGTGGCAT 900

GGAGATGTTG CAGTAAAGAT CCTAAAGGTG GTTGACCCAA CTCCAGAGCA ACTTCAGGCC 960

TTCAGGAACG AGGTGGCTGT TTTGCGCAAA ACACGGCATG TTAATATCCT GCTGTTCATG 1020

GGGTACATGA CAAAGGACAA CCTGGCGATT GTGACCCAGT GGTGTGAAGG CAGCAGTCTC 1080

TACAAACACC TGCATGTCCA GGAGACCAAA TTCCAGATGT TCCAGCTAAT TGACATTGCC 1140

CGGCAGACAG CTCAGGGAAT GGACTATTTA CATGCAAAGA ACATCATCCA CAGAGACATG 1200

AAATCCAACA ATATATTTCT CCATGAAGGC CTCACGGTGA AAATCGGAGA TTTTGGTTTG 1260

GCAACAGTGA AGTCGCGCTG GAGTGGTTCT CAGCAGGTTG AACAGCCCAC TGGCTCTGTG 1320

CTGTGGATGG CCCCAGAAGT AATCCGAATG CAGGATAACA ACCCGTTCAG CTTCCAGTCC 1380

GATGTCTACT CCTATGGCAT TGTGCTGTAT GAGCTGATGA CTGGGGAGCT TCCCTACTCC 1440

CACATCAACA ACCGAGACCA GATCATCTTC ATGGTGGGCC GTGGGTACGC CTCCCCAGAT 1500

CTTAGCAGGC TCTACAAGAA CTGCCCCAAG GCAATGAAGA GGTTGGTGGC TGACTGTGTG 1560

AAGAAAGTCA AAGAAGAAAG GCCTTTGTTT CCTCAGATCC TGTCTTCCAT TGAGCTGCTT 1620

CAGCACTCTC TGCCGAAAAT CAACAGGAGC GCCTCTGAGC CTTCCCTGCA TCGGGCAGCT 1680

CACACTGAGG ACATCAATGC TTGTACGCTG ACCACATCCC CAAGGCTACC AGTCTTCTAG 1740

Domain Profile

S: 1     velaekiGsGrfGtvyrgkwhGdvavkllnveelseeqleaFkkevaaykktRhenivLF  60

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

Q: 280   VMLSTRIGSGSFGTVYKGKWHGDVAVKILKVVDPTPEQLQAFRNEVAVLRKTRHVNILLF  339

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

S: 61    mGyvskpelaivtslckgssLykllheqetkldlaklidiarqiaqgmdYLhakkilhkD  120

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

Q: 340   MGYMTKDNLAIVTQWCEGSSLYKHLHVQETKFQMFQLIDIARQTAQGMDYLHAKNIIHRD  399

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

S: 121   lksknilleeglkvvitDFgllsvkrllsgrrekqleipkgwilylapeviralsidleq  180

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

Q: 400   MKSNNIFLHEGLTVKIGDFGLATVKSRWSG--SQQVEQPTGSVLWMAPEVIRM------Q  451

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

S: 181   delpfskesDvyafGivlyellarelpyke.esadqilfavgrG.lkpdlskvksklpke  238

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

Q: 452   DNNPFSFQSDVYSYGIVLYELMTGELPYSHiNNRDQIIFMVGRGyASPDLSRLYKNCPKA  511

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

S: 239   lkellleClkfekeeRPlftqilkkl  264

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

Q: 512   MKRLVADCVKKVKEERPLFPQILSSI  537

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

Domain Sequence
(FASTA)

VMLSTRIGSG SFGTVYKGKW HGDVAVKILK VVDPTPEQLQ AFRNEVAVLR KTRHVNILLF 60

MGYMTKDNLA IVTQWCEGSS LYKHLHVQET KFQMFQLIDI ARQTAQGMDY LHAKNIIHRD 120

MKSNNIFLHE GLTVKIGDFG LATVKSRWSG SQQVEQPTGS VLWMAPEVIR MQDNNPFSFQ 180

SDVYSYGIVL YELMTGELPY SHINNRDQII FMVGRGYASP DLSRLYKNCP KAMKRLVADC 240

VKKVKEERPL FPQILSSI 258

Keyword

3D-structure; 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"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gadus morhua"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Macropus eugenii"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>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"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Tursiops truncatus"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005829	; C:cytosol
GO:0005739	; C:mitochondrion
GO:0005634	; C:nucleus
GO:0005886	; C:plasma membrane
GO:0005524	; F:ATP binding
GO:0004709	; F:MAP kinase kinase kinase activity
GO:0046872	; F:metal ion binding
GO:0031434	; F:mitogen-activated protein kinase kinase binding
GO:0007507	; P:heart development
GO:0001666	; P:response to hypoxia

KEGG

rno:24703

;

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