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P05625 (RAF1_CHICK) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:RAF1
Synonyms:MIL
OrganismGallus gallus (Chicken) [Reference proteome]
Taxonomic identifier9031 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiTestudines + Archosauria groupArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalliformesPhasianidaePhasianinaeGallus

Protein attributes

Sequence length647 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subcellular location

Cytoplasm By similarity. Cell membrane By similarity.

Tissue specificity

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. Ref.5

Post-translational modification

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.

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
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityAlternative splicing
   DiseaseProto-oncogene
   DomainZinc-finger
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdeath-inducing signaling complex assembly

Inferred from electronic annotation. Source: Ensembl

intermediate filament cytoskeleton organization

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of extrinsic apoptotic signaling pathway via death domain receptors

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein complex assembly

Inferred from electronic annotation. Source: Ensembl

neurotrophin TRK receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

pseudopodium

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-KW

receptor signaling protein activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P05625-1)

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: P05625-2)

Also known as: 1A;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 647647RAF proto-oncogene serine/threonine-protein kinase
PRO_0000086599

Regions

Domain56 – 13176RBD
Domain349 – 609261Protein kinase
Zinc finger138 – 18447Phorbol-ester/DAG-type
Nucleotide binding355 – 3639ATP By similarity

Sites

Active site4681Proton acceptor By similarity
Binding site3751ATP By similarity

Amino acid modifications

Modified residue431Phosphoserine By similarity
Modified residue2591Phosphoserine By similarity
Modified residue2681Phosphothreonine; by autocatalysis By similarity
Modified residue3381Phosphoserine By similarity
Modified residue4991Phosphoserine By similarity
Modified residue6211Phosphoserine By similarity

Natural variations

Alternative sequence2781E → ENNSLNASPSSWCRRFCLRG R in isoform 2.
VSP_034628

Experimental info

Sequence conflict5491S → F in AAA48952. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (6C) [UniParc].

Last modified November 1, 1988. Version 1.
Checksum: 8E1443667312DFC0

FASTA64773,125
        10         20         30         40         50         60 
MEHIQGAWKT ISNGFGLKDS VFDGPNCISP TIVQQFGYQR RASDDGKISD TSKTSNTIRV 

        70         80         90        100        110        120 
FLPNKQRTVV NVRNGMTLHD CLMKALKVRG LQPECCAVFR LVTEPKGKKV RLDWNTDAAS 

       130        140        150        160        170        180 
LIGEELQVDF LDHVPLTTHN FARKTFLKLA FCDICQKFLL NGFRCQTCGY KFHEHCSTKV 

       190        200        210        220        230        240 
PTMCVDWSNI RQLLLFPNSN ISDSGVPALP PLTMRRMRES VSRIPVSSQH RYSTPHVFTF 

       250        260        270        280        290        300 
NTSNPSSEGT LSQRQRSTST PNVHMVSTTM PVDSRIIEDA IRNHSESASP SALSGSPNNM 

       310        320        330        340        350        360 
SPTGWSQPKT PVPAQRERAP GTNTQEKNKI RPRGQRDSSY YWEIEASEVM LSTRIGSGSF 

       370        380        390        400        410        420 
GTVYKGKWHG DVAVKILKVV DPTPEQFQAF RNEVAVLRKT RHVNILLFMG YMTKDNLAIV 

       430        440        450        460        470        480 
TQWCEGSSLY KHLHVQETKF QMFQLIDIAR QTAQGMDYLH AKNIIHRDMK SNNIFLHEGL 

       490        500        510        520        530        540 
TVKIGDFGLA TVKSRWSGSQ QVEQPTGSIL WMAPEVIRMQ DSNPFSFQSD VYSYGIVLYE 

       550        560        570        580        590        600 
LMTGELPYSH INNRDQIIFM VGRGYASPDL SKLYKNCPKA MKRLVADCLK KVREERPLFP 

       610        620        630        640 
QILSSIELLQ HSLPKINRSA SEPSLHRASH TEDINSCTLT STRLPVF 

« Hide

Isoform 2 (1A) [UniParc].

Checksum: FB1437BCD25B18EB
Show »

FASTA66775,431

References

[1]"Primary structure of the chicken c-mil protein: identification of domains shared with or absent from the retroviral v-mil protein."
Koenen M., Sippel A.E., Trachmann C., Bister K.
Oncogene 2:179-185(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Erythroblast.
[2]"Nucleotide sequence analysis of the chicken gene c-mil, the progenitor of the retroviral oncogene v-mil."
Jansen H.W., Bister K.
Virology 143:359-367(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 228-647.
[3]"Analysis of the cellular proto-oncogene mht/raf: relationship to the 5' sequences of v-mht in avian carcinoma virus MH2 and v-raf in murine sarcoma virus 3611."
Flordellis C.S., Kan N.C., Lautenberger J.A., Samuel K.P., Garon C.F., Papas T.S.
Virology 141:267-274(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 230-330.
[4]"Alternative splicing of RNAs transcribed from the chicken c-mil gene."
Dozier C., Denhez F., Henry C., Coll J., Begue A., Quatannens B., Saule S., Stehelin D.
Mol. Cell. Biol. 8:1835-1838(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 275-283 (ISOFORM 2), ALTERNATIVE SPLICING.
Tissue: Embryo.
[5]"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] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, TISSUE SPECIFICITY.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X07017 mRNA. Translation: CAA30069.1.
K03269 expand/collapse EMBL AC list , 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.
PIRI50382.
S00644.
RefSeqNP_990638.1. NM_205307.2. [P05625-1]
UniGeneGga.42842.

3D structure databases

ProteinModelPortalP05625.
SMRP05625. Positions 55-132, 136-187, 342-615.
ModBaseSearch...
MobiDBSearch...

Proteomic databases

PaxDbP05625.
PRIDEP05625.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSGALT00000033956; ENSGALP00000033314; ENSGALG00000004998. [P05625-1]
GeneID396245.
KEGGgga:396245.

Organism-specific databases

CTD5894.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117324.
HOGENOMHOG000252972.
HOVERGENHBG001886.
InParanoidP05625.
KOK04366.
OMADGPSCIS.
OrthoDBEOG7F5128.
PhylomeDBP05625.
TreeFamTF317006.

Enzyme and pathway databases

BRENDA2.7.11.1. 1306.

Family and domain databases

InterProIPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR003116. Raf-like_ras-bd.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamPF00130. C1_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF02196. RBD. 1 hit.
[Graphical view]
PRINTSPR00008. DAGPEDOMAIN.
SMARTSM00109. C1. 1 hit.
SM00455. RBD. 1 hit.
[Graphical view]
SUPFAMSSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. 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]
ProtoNetSearch...

Other

NextBio20816297.
PROP05625.

Entry information

Entry nameRAF1_CHICK
AccessionPrimary (citable) accession number: P05625
Secondary accession number(s): Q90893, Q90894
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: June 11, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families