DP00588_C010: Non-structural protein 5AFASTA viewXML view

General information
DisProt:DP00588_C010
Name:Non-structural protein 5A
Synonym(s):POLG_HCVH
NS5A
p56
cleavage product 10 of Genome polyprotein
First appeared in release:Release 5.4 (10/14/2010)
UniProt:P27958
UniGene: 
SwissProt: POLG_HCVH
TrEMBL:  
NCBI (GI):  
Source organism:Hepatitis C virus genotype 1a (isolate H) (HCV)
Sequence length:448
Percent disordered:3%
Homologues: 


Native sequence

        10         20         30         40         50         60
         |          |          |          |          |          |
SGSWLRDIWD WICEVLSDFK TWLKAKLMPQ LPGIPFVSCQ RGYRGVWRGD GIMHTRCHCG - 60
AEITGHVKNG TMRIVGPRTC KNMWSGTFFI NAYTTGPCTP LPAPNYKFAL WRVSAEEYVE - 120
IRRVGDFHYV SGMTTDNLKC PCQIPSPEFF TELDGVRLHR FAPPCKPLLR EEVSFRVGLH - 180
EYPVGSQLPC EPEPDVAVLT SMLTDPSHIT AEAAGRRLAR GSPPSMASSS ASQLSAPSLK - 240
ATCTANHDSP DAELIEANLL WRQEMGGNIT RVESENKVVI LDSFDPLVAE EDEREVSVPA - 300
EILRKSRRFA PALPVWARPD YNPLLVETWK KPDYEPPVVH GCPLPPPRSP PVPPPRKKRT - 360
VVLTESTLPT ALAELATKSF GSSSTSGITG DNTTTSSEPA PSGCPPDSDV ESYSSMPPLE - 420
GEPGDPDLSD GSWSTVSSGA DTEDVVCC



Functional narrative    

NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication. (UniProt). Non-structural protein 5A (NS5A) is cleavage product 10 of Genome polyprotein, comprising aa 1973-2420 of the parent protein.

Region 1: 1-4 Region 3: 15-17 Region 2: 5-25 Region 4: 26-31

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:N-terminal region of membrane anchor domain
Location:1 - 4
Length:4
Region sequence:

SGSW

Modification type: Engineered
Fragment
PDB: 1R7C:A, 1R7D:A, 1R7E:A, 1R7F:A, 1R7G:A
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. Nuclear magnetic resonance (NMR) (293 K; pH: 4.5; NS5A[1-31] peptide 1.2 mM; (TFE)-d2 50 %)

  2. Nuclear magnetic resonance (NMR) (313 K; pH: 6; (DTT)-d10 10 mM; NS5A[1-31] peptide (1-2 mM); (SDS)-d25 or (DPC)-d38 100 mM)

  3. Nuclear magnetic resonance (NMR) (313 K; pH: 6; MnCl2 (0.05 or 0.5 mM); NS5A[1-31] peptide 1 mM; (SDS)-d25 100 mM)
References:
  1. Penin F, Brass V, Appel N, Ramboarina S, Montserret R, Ficheux D, Blum HE, Bartenschlager R, Moradpour D. "Structure and function of the membrane anchor domain of hepatitis C virus nonstructural protein 5A." J. Biol. Chem.. 2004; 279(39): 40835-43. PubMed: 15247283
Comments:
 



Region 2
Type:Ordered
Name:amphipathic {alpha}helix
Location:5 - 25
Length:21
Region sequence:

LRDIWDWICEVLSDFKTWLKA

Modification type: Engineered
Fragment
PDB: 1R7C:A, 1R7D:A, 1R7E:A, 1R7F:A, 1R7G:A
Structural/functional type: Function arises from the ordered state
Functional classes: Molecular assembly
Functional subclasses: Protein-lipid interaction
Protein-protein binding
Detection methods:
  1. Nuclear magnetic resonance (NMR) (293 K; pH: 4.5; NS5A[1-31] peptide 1.2 mM; (TFE)-d2 50 %)

  2. Nuclear magnetic resonance (NMR) (313 K; pH: 6; (DTT)-d10 10 mM; NS5A[1-31] peptide (1-2 mM); (SDS)-d25 or (DPC)-d38 100 mM)

  3. Nuclear magnetic resonance (NMR) (313 K; pH: 6; MnCl2 (0.05 or 0.5 mM); NS5A[1-31] peptide 1 mM; (SDS)-d25 100 mM)
References:
  1. Penin F, Brass V, Appel N, Ramboarina S, Montserret R, Ficheux D, Blum HE, Bartenschlager R, Moradpour D. "Structure and function of the membrane anchor domain of hepatitis C virus nonstructural protein 5A." J. Biol. Chem.. 2004; 279(39): 40835-43. PubMed: 15247283
Comments:
According to Penin et al (2004), the well-ordered amphipathic {alpha}helix at aa 5-25 contains a "flexible helical element" at aa 15-17 that likely allows 'variable orientation of the of the ends of the {alpha}helix when...bound to phospholipids.'


Region 3
Type:Disordered
Name:flexible helical element
Location:15 - 17
Length:3
Region sequence:

VLS

Modification type: Engineered
Fragment
PDB: 1R7C:A, 1R7D:A, 1R7E:A, 1R7F:A, 1R7G:A
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular assembly
Entropic chain
Functional subclasses: Protein-lipid interaction
Protein-protein binding
Detection methods:
  1. Nuclear magnetic resonance (NMR) (293 K; pH: 4.5; NS5A[1-31] peptide 1.2 mM; (TFE)-d2 50 %)

  2. Nuclear magnetic resonance (NMR) (313 K; pH: 6; (DTT)-d10 10 mM; NS5A[1-31] peptide (1-2 mM); (SDS)-d25 or (DPC)-d38 100 mM)

  3. Nuclear magnetic resonance (NMR) (313 K; pH: 6; MnCl2 (0.05 or 0.5 mM); NS5A[1-31] peptide 1 mM; (SDS)-d25 100 mM)
References:
  1. Penin F, Brass V, Appel N, Ramboarina S, Montserret R, Ficheux D, Blum HE, Bartenschlager R, Moradpour D. "Structure and function of the membrane anchor domain of hepatitis C virus nonstructural protein 5A." J. Biol. Chem.. 2004; 279(39): 40835-43. PubMed: 15247283
Comments:
According to Penin et al (2004), the well-ordered amphipathic {alpha}helix at aa 5-25 contains a "flexible helical element" at aa 15-17 that likely allows 'variable orientation of the of the ends of the {alpha}helix when...bound to phospholipids.'


Region 4
Type:Disordered
Name:C-terminal region of membrane anchor domain
Location:26 - 31
Length:6
Region sequence:

KLMPQL

Modification type: Engineered
Fragment
PDB: 1R7C:A, 1R7D:A, 1R7E:A, 1R7F:A, 1R7G:A
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. Nuclear magnetic resonance (NMR) (293 K; pH: 4.5; NS5A[1-31] peptide 1.2 mM; (TFE)-d2 50 %)

  2. Nuclear magnetic resonance (NMR) (313 K; pH: 6; (DTT)-d10 10 mM; NS5A[1-31] peptide (1-2 mM); (SDS)-d25 or (DPC)-d38 100 mM)

  3. Nuclear magnetic resonance (NMR) (313 K; pH: 6; MnCl2 (0.05 or 0.5 mM); NS5A[1-31] peptide 1 mM; (SDS)-d25 100 mM)
References:
  1. Penin F, Brass V, Appel N, Ramboarina S, Montserret R, Ficheux D, Blum HE, Bartenschlager R, Moradpour D. "Structure and function of the membrane anchor domain of hepatitis C virus nonstructural protein 5A." J. Biol. Chem.. 2004; 279(39): 40835-43. PubMed: 15247283
Comments:
 



References

  1. Penin F, Brass V, Appel N, Ramboarina S, Montserret R, Ficheux D, Blum HE, Bartenschlager R, Moradpour D. "Structure and function of the membrane anchor domain of hepatitis C virus nonstructural protein 5A." J. Biol. Chem.. 2004; 279(39): 40835-43. PubMed: 15247283



Comments


Penin et al (2004) used synthesized NS5A[1-31] peptide in their experiments, representative of aa 1-31 of full-length native NS5A.


Previous entry DP00588 has been split into polyprotein (DP00588) and cleavage products (DP00588_C0XX).


NOTE on Organism: DP00588 is organism Hepatitis C virus genotype 1a (isolate H) (HCV), aka HCVH; DP00615 is Hepatitis C virus genotype 1b (isolate Con1) (HCV) aka HCV1b or HCVCO. These entries share 85% identity.


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