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Protein

RAF proto-oncogene serine/threonine-protein kinase

Gene

RAF1

Organism
Gallus gallus (Chicken)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Serine/threonine-protein kinase that acts as a regulatory 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. 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) (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei375ATPPROSITE-ProRule annotation1
Active sitei468Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri138 – 184Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST47
Nucleotide bindingi355 – 363ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.11.1 1306
ReactomeiR-GGA-2672351 Stimuli-sensing channels
R-GGA-392517 Rap1 signalling
R-GGA-430116 GP1b-IX-V activation signalling
R-GGA-442742 CREB phosphorylation through the activation of Ras
R-GGA-5621575 CD209 (DC-SIGN) signaling
R-GGA-5673000 RAF activation
R-GGA-5674135 MAP2K and MAPK activation
R-GGA-5674499 Negative feedback regulation of MAPK pathway
R-GGA-5675221 Negative regulation of MAPK pathway

Names & Taxonomyi

Protein namesi
Recommended name:
RAF proto-oncogene serine/threonine-protein kinase (EC:2.7.11.1)
Alternative name(s):
C-MIL
C-RAF
MIL proto-oncogene serine/threonine-protein kinase
RAF-1
Gene namesi
Name:RAF1
Synonyms:MIL
OrganismiGallus gallus (Chicken)
Taxonomic identifieri9031 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiArchelosauriaArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalloanseraeGalliformesPhasianidaePhasianinaeGallus
Proteomesi
  • UP000000539 Componenti: Chromosome 12

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000865991 – 647RAF proto-oncogene serine/threonine-protein kinaseAdd BLAST647

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei43PhosphoserineBy similarity1
Modified residuei259PhosphoserineBy similarity1
Modified residuei268Phosphothreonine; by autocatalysisBy similarity1
Modified residuei338PhosphoserineBy similarity1
Modified residuei499PhosphoserineBy similarity1
Modified residuei621PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation at Ser-259 inactivates kinase activity. Dephosphorylation of Ser-259 by a complex containing protein phosphatase 1 relieves inactivation, leading to stimulate RAF1 activity (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP05625

PTM databases

iPTMnetiP05625

Expressioni

Tissue specificityi

Isoform 1 was present in all tissues tested: skeletal muscle, intestine, brain, gizzard, heart, lung, kidney, bone marrow, spleen and bursa of Fabricius. Isoform 2 was only detected in brain, heart and skeletal muscle. In brain and heart isoform 1 is more abundant than isoform 2. In skeletal muscle isoform 2 is more abundant than isoform 1.1 Publication

Gene expression databases

BgeeiENSGALG00000004998

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9031.ENSGALP00000007991

Structurei

3D structure databases

ProteinModelPortaliP05625
SMRiP05625
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini56 – 131RBDPROSITE-ProRule annotationAdd BLAST76
Domaini349 – 609Protein kinasePROSITE-ProRule annotationAdd BLAST261

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri138 – 184Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST47

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0193 Eukaryota
ENOG410Y4UP LUCA
GeneTreeiENSGT00900000140880
HOGENOMiHOG000252972
HOVERGENiHBG001886
InParanoidiP05625
KOiK04366
OMAiHQFIRKT
OrthoDBiEOG091G09SB
PhylomeDBiP05625
TreeFamiTF317006

Family and domain databases

CDDicd00029 C1, 1 hit
InterProiView protein in InterPro
IPR020454 DAG/PE-bd
IPR011009 Kinase-like_dom_sf
IPR002219 PE/DAG-bd
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR003116 RBD_dom
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008271 Ser/Thr_kinase_AS
IPR029071 Ubiquitin-like_domsf
PfamiView protein in Pfam
PF00130 C1_1, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF02196 RBD, 1 hit
PRINTSiPR00008 DAGPEDOMAIN
SMARTiView protein in SMART
SM00109 C1, 1 hit
SM00455 RBD, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF54236 SSF54236, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in 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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P05625-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MEHIQGAWKT ISNGFGLKDS VFDGPNCISP TIVQQFGYQR RASDDGKISD
60 70 80 90 100
TSKTSNTIRV FLPNKQRTVV NVRNGMTLHD CLMKALKVRG LQPECCAVFR
110 120 130 140 150
LVTEPKGKKV RLDWNTDAAS LIGEELQVDF LDHVPLTTHN FARKTFLKLA
160 170 180 190 200
FCDICQKFLL NGFRCQTCGY KFHEHCSTKV PTMCVDWSNI RQLLLFPNSN
210 220 230 240 250
ISDSGVPALP PLTMRRMRES VSRIPVSSQH RYSTPHVFTF NTSNPSSEGT
260 270 280 290 300
LSQRQRSTST PNVHMVSTTM PVDSRIIEDA IRNHSESASP SALSGSPNNM
310 320 330 340 350
SPTGWSQPKT PVPAQRERAP GTNTQEKNKI RPRGQRDSSY YWEIEASEVM
360 370 380 390 400
LSTRIGSGSF GTVYKGKWHG DVAVKILKVV DPTPEQFQAF RNEVAVLRKT
410 420 430 440 450
RHVNILLFMG YMTKDNLAIV TQWCEGSSLY KHLHVQETKF QMFQLIDIAR
460 470 480 490 500
QTAQGMDYLH AKNIIHRDMK SNNIFLHEGL TVKIGDFGLA TVKSRWSGSQ
510 520 530 540 550
QVEQPTGSIL WMAPEVIRMQ DSNPFSFQSD VYSYGIVLYE LMTGELPYSH
560 570 580 590 600
INNRDQIIFM VGRGYASPDL SKLYKNCPKA MKRLVADCLK KVREERPLFP
610 620 630 640
QILSSIELLQ HSLPKINRSA SEPSLHRASH TEDINSCTLT STRLPVF
Length:647
Mass (Da):73,125
Last modified:November 1, 1988 - v1
Checksum:i8E1443667312DFC0
GO
Isoform 2 (identifier: P05625-2) [UniParc]FASTAAdd to basket
Also known as: 1A

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

Show »
Length:667
Mass (Da):75,431
Checksum:iFB1437BCD25B18EB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti549S → F in AAA48952 (PubMed:2998016).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_034628278E → ENNSLNASPSSWCRRFCLRG R in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X07017 mRNA Translation: CAA30069.1
K03269
, K03259, K03260, K03261, K03262, K03263, K03264, K03265, K03266, K03267, K03268 Genomic DNA Translation: AAA48952.1
K03048, K03047 Genomic DNA Translation: AAA48951.1
M19461 mRNA Translation: AAA48953.1
X55430 Genomic DNA No translation available.
PIRiI50382
S00644
RefSeqiNP_990638.1, NM_205307.2 [P05625-1]
XP_015148495.1, XM_015293009.1 [P05625-2]
XP_015148496.1, XM_015293010.1 [P05625-2]
XP_015148497.1, XM_015293011.1 [P05625-2]
XP_015148498.1, XM_015293012.1 [P05625-2]
XP_015148499.1, XM_015293013.1 [P05625-1]
UniGeneiGga.42842

Genome annotation databases

EnsembliENSGALT00000033956; ENSGALP00000033314; ENSGALG00000004998 [P05625-1]
ENSGALT00000049372; ENSGALP00000046736; ENSGALG00000004998 [P05625-2]
GeneIDi396245
KEGGigga:396245

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiRAF1_CHICK
AccessioniPrimary (citable) accession number: P05625
Secondary accession number(s): Q90893, Q90894
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: April 25, 2018
This is version 161 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health