DP00171: RAF proto-oncogene serine/threonine-protein kinaseFASTA viewXML view

General information
DisProt:DP00171
Name:RAF proto-oncogene serine/threonine-protein kinase
Synonym(s):RAF1_HUMAN
EC=2.7.11.1
C-RAF
cRaf
Raf-1
First appeared in release:Release 2.0 (02/14/2005)
UniProt:P04049
UniGene:Hs.159130
SwissProt: RAF1_HUMAN
TrEMBL:  
NCBI (GI): 125651
Source organism:Homo sapiens (Human)
Sequence length:648
Percent disordered:5%
Homologues: 


Native sequence

        10         20         30         40         50         60
         |          |          |          |          |          |
MEHIQGAWKT ISNGFGFKDA VFDGSSCISP TIVQQFGYQR RASDDGKLTD PSKTSNTIRV - 60
FLPNKQRTVV NVRNGMSLHD CLMKALKVRG LQPECCAVFR LLHEHKGKKA RLDWNTDAAS - 120
LIGEELQVDF LDHVPLTTHN FARKTFLKLA FCDICQKFLL NGFRCQTCGY KFHEHCSTKV - 180
PTMCVDWSNI RQLLLFPNST IGDSGVPALP SLTMRRMRES VSRMPVSSQH RYSTPHAFTF - 240
NTSSPSSEGS LSQRQRSTST PNVHMVSTTL PVDSRMIEDA IRSHSESASP SALSSSPNNL - 300
SPTGWSQPKT PVPAQRERAP VSGTQEKNKI RPRGQRDSSY YWEIEASEVM LSTRIGSGSF - 360
GTVYKGKWHG DVAVKILKVV DPTPEQFQAF RNEVAVLRKT RHVNILLFMG YMTKDNLAIV - 420
TQWCEGSSLY KHLHVQETKF QMFQLIDIAR QTAQGMDYLH AKNIIHRDMK SNNIFLHEGL - 480
TVKIGDFGLA TVKSRWSGSQ QVEQPTGSVL WMAPEVIRMQ DNNPFSFQSD VYSYGIVLYE - 540
LMTGELPYSH INNRDQIIFM VGRGYASPDL SKLYKNCPKA MKRLVADCVK KVKEERPLFP - 600
QILSSIELLQ HSLPKINRSA SEPSLHRAAH TEDINACTLT TSPRLPVF



Functional narrative    

Raf-1, a member of the serine/threonine protein kinase family, is an intermediate in the Ras signal transduction pathway, which controls cell growth and differention. This protein interacts directly with Ras and Rap-1A, and indirectly with GTP and GDP. Because mutated forms of Ras still retain the ability to bind with Raf-1, the reaction between these two proteins may be key in developing a treatment for various forms of cancer. The function of the disordered regions of this protein have not been determined at the time of this annotation.

Region 1: 51-54 Region 2: 55-55 Region 3: 64-64 Region 4: 73-76 Region 6: 104-107 Region 5: 102-108 Region 7: 113-117 Region 8: 132-132 Region 9: 136-138 Region 10: 146-150 Region 11: 185-187

Map of ordered and disordered regions







Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.


Region 1
Type:Disordered
Name: 
Location:51 - 54
Length:4
Region sequence:

PSKT

Modification type: Engineered
Fragment
PDB:  
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. X-ray crystallography (298 K; pH: 7.6; monomethylether PEG 5000 (Fluka) 10 %; ammonium sulphate 50 mM; CaCl2 5 mM; MgCl2 2.5 mM; Dithioerythritol (DTE) 0.5 mM; Tris-HCl 32.2 mM)
References:
  1. Nassar N, Horn G, Herrmann C, Scherer A, McCormick F, Wittinghofer A. "The 2.2 A crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with Rap1A and a GTP analogue." Nature. 1995; 375(6532): 554-560. PubMed: 7791872
Comments:
Disordered region may be present due to the fragmentation of the sequence.


Region 2
Type:Disordered
Name: 
Location:55 - 55
Length:1
Region sequence:

S

Modification type: Engineered
Fragment
PDB:  
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. Nuclear magnetic resonance (NMR) (298 K; pH: 5.3; 15N labeled protein 1.4 mM; dithiothreitol 0.1 mM; sodium acetate-d3 10 mM; sodium azide (in 100%D2O or 94% H2O/6% D2O) 0.05 %)

  2. Nuclear magnetic resonance (NMR) (298 K; pH: 5.3; 13C/15N labeled protein 1.4 mM; dithiolthreitol 0.1 mM; sodium acetate-d3 10 mM; sodium azide (in 100%D2O or 94% H2O/6% D2O) 0.05 %)
References:
  1. Emerson SD, Madison VS, Palermo RE, Waugh DS, Scheffler JE, Tsao KL, Kiefer SE, Liu SP, Fry DC. "Solution structure of the Ras-binding domain of c-Raf-1 and identification of its Ras interaction surface." Biochemistry. 1995; 34(21): 6911-8. PubMed: 7766599
Comments:
Disordered region may be present due to the fragmentation of the sequence.


Region 3
Type:Disordered
Name: 
Location:64 - 64
Length:1
Region sequence:

N

Modification type: Engineered
Fragment
PDB:  
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. Nuclear magnetic resonance (NMR) (298 K; pH: 5.3; 15N labeled protein 1.4 mM; dithiothreitol 1 mM; sodium acetate-d3 10 mM; sodium azide (in 100%D2O or 94% H2O/6% D2O) 0.05 %)

  2. Nuclear magnetic resonance (NMR) (298 K; pH: 5.3; 13C/15N labeled protein 1.4 mM; dithiolthreitol 0.1 mM; sodium acetate-d3 10 mM; sodium azide (in 100%D2O or 94% H2O/6% D2O) 0.05 %)
References:
  1. Emerson SD, Madison VS, Palermo RE, Waugh DS, Scheffler JE, Tsao KL, Kiefer SE, Liu SP, Fry DC. "Solution structure of the Ras-binding domain of c-Raf-1 and identification of its Ras interaction surface." Biochemistry. 1995; 34(21): 6911-8. PubMed: 7766599
Comments:
Disordered region may be present due to the fragmentation of the sequence.


Region 4
Type:Disordered
Name: 
Location:73 - 76
Length:4
Region sequence:

RNGM

Modification type: Engineered
Fragment
PDB:  
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. Nuclear magnetic resonance (NMR) (298 K; pH: 5.3; 15N labeled protein 1.4 mM; dithiothreitol 0.1 mM; sodium acetate-d3 10 mM; sodium azide (in 100%D2O or 94% H2O/6% D2O) 0.05 %)

  2. Nuclear magnetic resonance (NMR) (298 K; pH: 5.3; 13C/15N labeled protein 1.4 mM; dithiolthreitol 0.1 mM; sodium acetate-d3 10 mM; sodium azide (in 100%D2O or 94% H2O/6% D2O) 0.05 %)
References:
  1. Emerson SD, Madison VS, Palermo RE, Waugh DS, Scheffler JE, Tsao KL, Kiefer SE, Liu SP, Fry DC. "Solution structure of the Ras-binding domain of c-Raf-1 and identification of its Ras interaction surface." Biochemistry. 1995; 34(21): 6911-8. PubMed: 7766599
Comments:
Disordered region may be present due to the fragmentation of the sequence.


Region 5
Type:Disordered
Name: 
Location:102 - 108
Length:7
Region sequence:

LHEHKGK

Modification type: Engineered
Fragment
PDB:  
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. X-ray crystallography (298 K; pH: 7.6; ammonium sulphate 50 mM; CaCl2 5 mM; Dithioerythritol (DTE) 0.5 mM; MgCl2 2.5 mM; monomethylether PEG 5000 (Fluka) 10 %; Tris-HCl 32.2 mM)
References:
  1. Nassar N, Horn G, Herrmann C, Scherer A, McCormick F, Wittinghofer A. "The 2.2 A crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with Rap1A and a GTP analogue." Nature. 1995; 375(6532): 554-560. PubMed: 7791872
Comments:
Disordered region may be present due to the fragmentation of the sequence.


Region 6
Type:Disordered - Extended
Name: 
Location:104 - 107
Length:4
Region sequence:

EHKG

Modification type: Engineered
Fragment
PDB: 1GUA:B
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. X-ray crystallography (292 K; calcium acetate (20-50 mM); dithiothreitol 2 mM; MgCl2 5 mM; PEG 4000 11 %; Tris-HCl (pH 7.6) 80 mM)
References:
  1. Nassar N, Horn G, Herrmann C, Block C, Janknecht R, Wittinghofer A. "Ras/Rap effector specificity determined by charge reversal." Nat Struct Biol. 1996; 3(8): 723-729. PubMed: 8756332
Comments:
 



Region 7
Type:Disordered
Name: 
Location:113 - 117
Length:5
Region sequence:

DWNTD

Modification type: Engineered
Fragment
PDB:  
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. Nuclear magnetic resonance (NMR) (298 K; pH: 5.3; 15N labeled protein 1.4 mM; dithiothreitol 0.1 mM; sodium acetate-d3 10 mM; sodium azide (in 100%D2O or 94% H2O/6% D2O) 0.05 %)

  2. Nuclear magnetic resonance (NMR) (298 K; pH: 5.3; 13C/15N labeled protein 1.4 mM; dithiolthreitol 0.1 mM; sodium acetate-d3 10 mM; sodium azide (in 100%D2O or 94% H2O/6% D2O) 0.05 %)
References:
  1. Emerson SD, Madison VS, Palermo RE, Waugh DS, Scheffler JE, Tsao KL, Kiefer SE, Liu SP, Fry DC. "Solution structure of the Ras-binding domain of c-Raf-1 and identification of its Ras interaction surface." Biochemistry. 1995; 34(21): 6911-8. PubMed: 7766599
Comments:
Disordered region may be present due to the fragmentation of the sequence.


Region 8
Type:Disordered
Name: 
Location:132 - 132
Length:1
Region sequence:

D

Modification type: Engineered
Fragment
PDB:  
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. Nuclear magnetic resonance (NMR) (298 K; pH: 5.3; 15N labeled protein 1.4 mM; dithiothreitol 0.1 mM; sodium acetate-d3 10 mM; sodium azide (in 100%D2O or 94% H2O/6% D2O) 0.05 %)

  2. Nuclear magnetic resonance (NMR) (298 K; pH: 5.3; 13C/15N labeled protein 1.4 mM; dithiolthreitol 0.1 mM; sodium acetate-d3 10 mM; sodium azide (in 100%D2O or 94% H2O/6% D2O) 0.05 %)
References:
  1. Emerson SD, Madison VS, Palermo RE, Waugh DS, Scheffler JE, Tsao KL, Kiefer SE, Liu SP, Fry DC. "Solution structure of the Ras-binding domain of c-Raf-1 and identification of its Ras interaction surface." Biochemistry. 1995; 34(21): 6911-8. PubMed: 7766599
Comments:
Disordered region may be present due to the fragmentation of the sequence.


Region 9
Type:Disordered
Name: 
Location:136 - 138
Length:3
Region sequence:

LTT

Modification type: Engineered
Fragment
PDB: 1FAQ:A, 1FAR:A
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. Nuclear magnetic resonance (NMR) (298 K; pH: 6.2; d10-DTT 1 mM; d11-Tris d3-acetate 30 mM; D2O 10 %; Na2SO4 75 mM; NaN3 0.01 %; ZnCl2 10 µM)
References:
  1. Mott HR, Carpenter JW, Zhong S, Ghosh S, Bell RM, Campbell SL. "The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site." Proc Natl Acad Sci U S A. 1996; 93(16): 8312-8317. PubMed: 8710867
Comments:
Disordered region may be present due to the fragmentation of the sequence.


Region 10
Type:Disordered
Name: 
Location:146 - 150
Length:5
Region sequence:

FLKLA

Modification type: Engineered
Fragment
PDB:  
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. Nuclear magnetic resonance (NMR) (298 K; pH: 6.2; d10-DTT 1 mM; d11-Tris d3-acetate 30 mM; D2O 10 %; Na2SO4 75 mM; NaN3 0.01 %; ZnCl2 10 µM)
References:
  1. Mott HR, Carpenter JW, Zhong S, Ghosh S, Bell RM, Campbell SL. "The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site." Proc Natl Acad Sci U S A. 1996; 93(16): 8312-8317. PubMed: 8710867
Comments:
Disordered region may be present due to the fragmentation of the sequence.


Region 11
Type:Disordered
Name: 
Location:185 - 187
Length:3
Region sequence:

VDW

Modification type: Engineered
Fragment
PDB: 1FAQ:A, 1FAR:A
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. Nuclear magnetic resonance (NMR) (298 K; pH: 6.2; d10-DTT 1 mM; d11-Tris d3-acetate 30 mM; D2O 10 %; Na2SO4 75 mM; NaN3 0.01 %; ZnCl2 10 µM)
References:
  1. Mott HR, Carpenter JW, Zhong S, Ghosh S, Bell RM, Campbell SL. "The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site." Proc Natl Acad Sci U S A. 1996; 93(16): 8312-8317. PubMed: 8710867
Comments:
Disordered region may be present due to the fragmentation of the sequence.

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