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Protein

RAF proto-oncogene serine/threonine-protein kinase

Gene

RAF1

Organism
Gallus gallus (Chicken)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-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

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-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

GO - Cellular componenti

Complete GO annotation...

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

Protein-protein interaction databases

STRINGi9031.ENSGALP00000007991.

Structurei

3D structure databases

ProteinModelPortaliP05625.
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

Contains 1 phorbol-ester/DAG-type zinc finger.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 RBD (Ras-binding) domain.PROSITE-ProRule annotation

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.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000252972.
HOVERGENiHBG001886.
InParanoidiP05625.
KOiK04366.
OMAiDGPSCIS.
OrthoDBiEOG091G09SB.
PhylomeDBiP05625.
TreeFamiTF317006.

Family and domain databases

CDDicd00029. C1. 1 hit.
InterProiIPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
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-rel_dom.
[Graphical view]
PfamiPF00130. C1_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF02196. RBD. 1 hit.
[Graphical view]
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 1 hit.
SM00455. RBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. 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]

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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliP05625.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9031.ENSGALP00000007991.

PTM databases

iPTMnetiP05625.

Proteomic databases

PaxDbiP05625.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5894.

Phylogenomic databases

eggNOGiKOG0193. Eukaryota.
ENOG410Y4UP. LUCA.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000252972.
HOVERGENiHBG001886.
InParanoidiP05625.
KOiK04366.
OMAiDGPSCIS.
OrthoDBiEOG091G09SB.
PhylomeDBiP05625.
TreeFamiTF317006.

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.

Miscellaneous databases

PROiP05625.

Gene expression databases

BgeeiENSGALG00000004998.

Family and domain databases

CDDicd00029. C1. 1 hit.
InterProiIPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
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-rel_dom.
[Graphical view]
PfamiPF00130. C1_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF02196. RBD. 1 hit.
[Graphical view]
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 1 hit.
SM00455. RBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiRAF1_CHICK
AccessioniPrimary (citable) accession number: P05625
Secondary accession number(s): Q90893, Q90894
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: November 30, 2016
This is version 154 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.