DP00644: C-C motif chemokine 1FASTA viewXML view

General information
DisProt:DP00644
Name:C-C motif chemokine 1
Synonym(s):CCL1_HUMAN
Small-inducible cytokine A1
T lymphocyte-secreted protein I-309
First appeared in release:Release 6.01 (10/15/2012)
UniProt:P22362
UniGene:Hs.72918
SwissProt: CCL1_HUMAN
TrEMBL:  
NCBI (GI): 123950
Source organism:Homo sapiens (Human)
Sequence length:96
Percent disordered:38%
Homologues: 


Native sequence

        10         20         30         40         50         60
         |          |          |          |          |          |
MQIITTALVC LLLAGMWPED VDSKSMQVPF SRCCFSFAEQ EIPLRAILCY RNTSSICSNE - 60
GLIFKLKRGK EACALDTVGW VQRHRKMLRH CPSKRK



Functional narrative    

Cytokine that is chemotactic for monocytes but not for neutrophils. Binds to CCR8. Belongs to the intercrine beta (chemokine CC) family.

The C-C motif chemokine 1 protein contains a signal peptide at aa M1-D22; the mature protein comprises aa S23-K96.
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Region 1: 23-32 Region 2: 35-43 Region 3: 44-52 Region 4: 53-60 Region 5: 61-87 Region 6: 88-91 Region 7: 92-96

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
Location:23 - 32
Length:10
Region sequence:

SKSMQVPFSR

Modification type: Monomeric
Native
PDB: 1EL0:A
Structural/functional type: Function arises from the disordered state
Functional classes:  
Functional subclasses:  
Detection methods:
  1. Nuclear magnetic resonance (NMR) (303 K; pH: 5; I-309 protein 2 mM; sodium acetate (buffer) 20 mM; DSS; 90% H2O, 10% D2O (or 99% D2O))
References:
  1. Keizer DW, Crump MP, Lee TW, Slupsky CM, Clark-Lewis I, Sykes BD. "Human CC chemokine I-309, structural consequences of the additional disulfide bond." Biochemistry. 2000; 39(20): 6053-9. PubMed: 10821677
Comments:
See overall Comments at the end of this DisProt record.


Region 2
Type:Disordered
Name:loop
Location:35 - 43
Length:9
Region sequence:

FSFAEQEIP

Modification type: Monomeric
Native
PDB: 1EL0:A
Structural/functional type: Function arises from the disordered state
Functional classes:  
Functional subclasses:  
Detection methods:
  1. Nuclear magnetic resonance (NMR) (303 K; pH: 5; 90% H2O, 10% D2O (or 99% D2O); DSS; I-309 protein 2 mM; sodium acetate (buffer) 20 mM)
References:
  1. Keizer DW, Crump MP, Lee TW, Slupsky CM, Clark-Lewis I, Sykes BD. "Human CC chemokine I-309, structural consequences of the additional disulfide bond." Biochemistry. 2000; 39(20): 6053-9. PubMed: 10821677
Comments:
See overall Comments at the end of this DisProt record.


Region 3
Type:Ordered
Name:ordered region
Location:44 - 52
Length:9
Region sequence:

LRAILCYRN

Modification type: Monomeric
Native
PDB: 1EL0:A
Structural/functional type: Function arises from the ordered state
Functional classes:  
Functional subclasses:  
Detection methods:
  1. Nuclear magnetic resonance (NMR) (303 K; pH: 5; 90% H2O, 10% D2O (or 99% D2O); DSS; I-309 protein 2 mM; sodium acetate (buffer) 20 mM)
References:
  1. Keizer DW, Crump MP, Lee TW, Slupsky CM, Clark-Lewis I, Sykes BD. "Human CC chemokine I-309, structural consequences of the additional disulfide bond." Biochemistry. 2000; 39(20): 6053-9. PubMed: 10821677
Comments:
See overall Comments at the end of this DisProt record.


Region 4
Type:Disordered
Name:disordered loop
Location:53 - 60
Length:8
Region sequence:

TSSICSNE

Modification type: Monomeric
Native
PDB: 1EL0:A
Structural/functional type: Function arises from the disordered state
Functional classes:  
Functional subclasses:  
Detection methods:
  1. Nuclear magnetic resonance (NMR) (303 K; pH: 5; 90% H2O/ 10% D2O (or 99% D2O); DSS; I-309 protein 2 mM; sodium acetate (buffer) 20 mM)
References:
  1. Keizer DW, Crump MP, Lee TW, Slupsky CM, Clark-Lewis I, Sykes BD. "Human CC chemokine I-309, structural consequences of the additional disulfide bond." Biochemistry. 2000; 39(20): 6053-9. PubMed: 10821677
Comments:
See overall Comments at the end of this DisProt record.


Region 5
Type:Ordered
Name:ordered region
Location:61 - 87
Length:27
Region sequence:

GLIFKLKRGKEACALDTVGWVQRHRKM

Modification type: Monomeric
Native
PDB: 1EL0:A
Structural/functional type: Function arises from the ordered state
Functional classes:  
Functional subclasses:  
Detection methods:
  1. Nuclear magnetic resonance (NMR) (303 K; pH: 5; 90% H2O/ 10% D2O (or 99% D2O); DSS; I-309 protein 2 mM; sodium acetate (buffer) 20 mM)
References:
  1. Keizer DW, Crump MP, Lee TW, Slupsky CM, Clark-Lewis I, Sykes BD. "Human CC chemokine I-309, structural consequences of the additional disulfide bond." Biochemistry. 2000; 39(20): 6053-9. PubMed: 10821677
Comments:
See overall Comments at the end of this DisProt record.


Region 6
Type:Disordered - Extended
Name:extended strand
Location:88 - 91
Length:4
Region sequence:

LRHC

Modification type: Monomeric
Native
PDB: 1EL0:A
Structural/functional type: Function arises from the disordered state
Functional classes:  
Functional subclasses:  
Detection methods:
  1. Nuclear magnetic resonance (NMR) (303 K; pH: 5; 90% H2O/ 10% D2O (or 99% D2O); DSS; I-309 protein 2 mM; sodium acetate (buffer) 20 mM)
References:
  1. Keizer DW, Crump MP, Lee TW, Slupsky CM, Clark-Lewis I, Sykes BD. "Human CC chemokine I-309, structural consequences of the additional disulfide bond." Biochemistry. 2000; 39(20): 6053-9. PubMed: 10821677
Comments:
See overall Comments at the end of this DisProt record.


Region 7
Type:Disordered
Name:C-terminal
Location:92 - 96
Length:5
Region sequence:

PSKRK

Modification type: Monomeric
Native
PDB: 1EL0:A
Structural/functional type: Function arises from the disordered state
Functional classes:  
Functional subclasses:  
Detection methods:
  1. Nuclear magnetic resonance (NMR) (303 K; pH: 5; 90% H2O/ 10% D2O (or 99% D2O); DSS; I-309 protein 2 mM; sodium acetate (buffer) 20 mM)
References:
  1. Keizer DW, Crump MP, Lee TW, Slupsky CM, Clark-Lewis I, Sykes BD. "Human CC chemokine I-309, structural consequences of the additional disulfide bond." Biochemistry. 2000; 39(20): 6053-9. PubMed: 10821677
Comments:
See overall Comments at the end of this DisProt record.


Comments


According to Keizer et al (2000), C-C motif chemokine 1 (also called protein I-309) remains a monomer when biologically active, unlike many other C-C chemokines that function when dimerized.

Protein I-309 contains disulfide bonds at C34 to C57 and C35 to C73, plus an uncommon third CC bond at C49 to C91. This third bond truncates the C-terminal alpha-helix found at G79-M87, producing an extended strand at L88-C91. Keizer et al (2000) surmise that this structural arrangement likely "blocks the dimerization interface along the first beta-strand, preventing the formation of the 'CXC' type dimer."

Additionally, Keizer et al state that "[protein] I-309, while a member of the CC chemokine family, has been found to have novel biological functions in apoptosis not shown by other chemokines. It also has the ability to block CCR8-mediated HIV-1 infection."


Keizer et al (2000) found that, excluding the N- and C-terminals, protein I-309 is generally well-ordered, but the NMR structure (PDB 1EL0) did show areas of relative disorder.


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