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P05625

- RAF1_CHICK

UniProt

P05625 - RAF1_CHICK

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Protein
RAF proto-oncogene serine/threonine-protein kinase
Gene
RAF1, MIL
Organism
Gallus gallus (Chicken)
Status
Reviewed - Annotation score: 5 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.

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei375 – 3751ATP By similarity
Active sitei468 – 4681Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri138 – 18447Phorbol-ester/DAG-type
Add
BLAST
Nucleotide bindingi355 – 3639ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. metal ion binding Source: UniProtKB-KW
  3. protein serine/threonine kinase activity Source: UniProtKB-KW
  4. receptor signaling protein activity Source: InterPro

GO - Biological processi

  1. death-inducing signaling complex assembly Source: Ensembl
  2. intermediate filament cytoskeleton organization Source: Ensembl
  3. negative regulation of apoptotic process Source: Ensembl
  4. negative regulation of cell proliferation Source: Ensembl
  5. negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: Ensembl
  6. negative regulation of protein complex assembly Source: Ensembl
  7. neurotrophin TRK receptor signaling pathway Source: Ensembl
  8. positive regulation of peptidyl-serine phosphorylation Source: Ensembl
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.
ReactomeiREACT_197481. CREB phosphorylation through the activation of Ras.
REACT_197905. Stimuli-sensing channels.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiTestudines + Archosauria groupArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalliformesPhasianidaePhasianinaeGallus
ProteomesiUP000000539: Chromosome 12

Subcellular locationi

Cytoplasm By similarity. Cell membrane By similarity

GO - Cellular componenti

  1. Golgi apparatus Source: Ensembl
  2. cytoplasm Source: UniProtKB
  3. plasma membrane Source: UniProtKB
  4. pseudopodium Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 647647RAF proto-oncogene serine/threonine-protein kinase
PRO_0000086599Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei43 – 431Phosphoserine By similarity
Modified residuei259 – 2591Phosphoserine By similarity
Modified residuei268 – 2681Phosphothreonine; by autocatalysis By similarity
Modified residuei338 – 3381Phosphoserine By similarity
Modified residuei499 – 4991Phosphoserine By similarity
Modified residuei621 – 6211Phosphoserine By similarity

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.

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP05625.
PRIDEiP05625.

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

Structurei

3D structure databases

ProteinModelPortaliP05625.
SMRiP05625. Positions 55-132, 136-187, 342-615.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini56 – 13176RBD
Add
BLAST
Domaini349 – 609261Protein kinase
Add
BLAST

Sequence similaritiesi

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00750000117324.
HOGENOMiHOG000252972.
HOVERGENiHBG001886.
InParanoidiP05625.
KOiK04366.
OMAiDGPSCIS.
OrthoDBiEOG7F5128.
PhylomeDBiP05625.
TreeFamiTF317006.

Family and domain databases

InterProiIPR020454. 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]
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.
[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. Align

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

MEHIQGAWKT ISNGFGLKDS VFDGPNCISP TIVQQFGYQR RASDDGKISD    50
TSKTSNTIRV FLPNKQRTVV NVRNGMTLHD CLMKALKVRG LQPECCAVFR 100
LVTEPKGKKV RLDWNTDAAS LIGEELQVDF LDHVPLTTHN FARKTFLKLA 150
FCDICQKFLL NGFRCQTCGY KFHEHCSTKV PTMCVDWSNI RQLLLFPNSN 200
ISDSGVPALP PLTMRRMRES VSRIPVSSQH RYSTPHVFTF NTSNPSSEGT 250
LSQRQRSTST PNVHMVSTTM PVDSRIIEDA IRNHSESASP SALSGSPNNM 300
SPTGWSQPKT PVPAQRERAP GTNTQEKNKI RPRGQRDSSY YWEIEASEVM 350
LSTRIGSGSF GTVYKGKWHG DVAVKILKVV DPTPEQFQAF RNEVAVLRKT 400
RHVNILLFMG YMTKDNLAIV TQWCEGSSLY KHLHVQETKF QMFQLIDIAR 450
QTAQGMDYLH AKNIIHRDMK SNNIFLHEGL TVKIGDFGLA TVKSRWSGSQ 500
QVEQPTGSIL WMAPEVIRMQ DSNPFSFQSD VYSYGIVLYE LMTGELPYSH 550
INNRDQIIFM VGRGYASPDL SKLYKNCPKA MKRLVADCLK KVREERPLFP 600
QILSSIELLQ HSLPKINRSA SEPSLHRASH TEDINSCTLT STRLPVF 647
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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei278 – 2781E → ENNSLNASPSSWCRRFCLRG R in isoform 2.
VSP_034628

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti549 – 5491S → F in AAA48952. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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]
UniGeneiGga.42842.

Genome annotation databases

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

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
PIRi I50382.
S00644.
RefSeqi NP_990638.1. NM_205307.2. [P05625-1 ]
UniGenei Gga.42842.

3D structure databases

ProteinModelPortali P05625.
SMRi P05625. Positions 55-132, 136-187, 342-615.
ModBasei Search...
MobiDBi Search...

Proteomic databases

PaxDbi P05625.
PRIDEi P05625.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSGALT00000033956 ; ENSGALP00000033314 ; ENSGALG00000004998 . [P05625-1 ]
GeneIDi 396245.
KEGGi gga:396245.

Organism-specific databases

CTDi 5894.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00750000117324.
HOGENOMi HOG000252972.
HOVERGENi HBG001886.
InParanoidi P05625.
KOi K04366.
OMAi DGPSCIS.
OrthoDBi EOG7F5128.
PhylomeDBi P05625.
TreeFami TF317006.

Enzyme and pathway databases

BRENDAi 2.7.11.1. 1306.
Reactomei REACT_197481. CREB phosphorylation through the activation of Ras.
REACT_197905. Stimuli-sensing channels.

Miscellaneous databases

NextBioi 20816297.
PROi P05625.

Family and domain databases

InterProi IPR020454. 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 ]
Pfami PF00130. C1_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF02196. RBD. 1 hit.
[Graphical view ]
PRINTSi PR00008. DAGPEDOMAIN.
SMARTi SM00109. C1. 1 hit.
SM00455. RBD. 1 hit.
[Graphical view ]
SUPFAMi SSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi 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.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

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: September 3, 2014
This is version 131 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

External Data

Dasty 3

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