SCYIntercrine alpha family (small cytokine C-X-C) (chemokine CXC).
|SMART accession number:||SM00199|
|Description:||Family of cytokines involved in cell-specific chemotaxis, mediation of cell growth, and the inflammatory response.|
|Interpro abstract (IPR001811):|
Many low-molecular weight factors secreted by cells including fibroblasts, macrophages and endothelial cells, in response to a variety of stimuli such as growth factors, interferons, viral transformation and bacterial products, are structurally related [(PUBMED:1910690), (PUBMED:2149646), (PUBMED:2687068)]. Most members of this family of proteins seem to have mitogenic, chemotactic or inflammatory activities. These small cytokines are also called intercrines or chemokines. They are cationic proteins of 70 to 100 amino acid residues that share four conserved cysteine residues involved in two disulphide bonds, as shown in the following schematic representation:
Chemokines can be sorted into main groups based on the spacing of the two amino-terminal cysteines. In the first group (see IPR001089), the two cysteines are separated by a single residue (C-x-C), while in the second group (see IPR000827), they are adjacent (C-C).
|GO process:||immune response (GO:0006955)|
|GO component:||extracellular region (GO:0005576)|
|GO function:||chemokine activity (GO:0008009)|
Click on the following links for more information.
- Evolution (species in which this domain is found)
Click on to expand nodes. To display all proteins with a SCY domain in a specific node, click on it.
This tree shows only several representative species. The complete taxonomic breakdown of all proteins with SCY domain is also avaliable.
- Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Baggiolini M, Dewald B, Moser B
- Human chemokines: an update.
- Annu Rev Immunol. 1997; 15: 675-705
- Display abstract
Interleukin 8, the first chemokine to be characterized, was discovered nearly ten years ago. Today, more than 30 human chemokines are known. They are often upregulated in inflammation and act mainly on leukocytes inducing migration and release responses. The present review deals largely with the new developments of the last three years. Several structural studies have shown that most chemokines form dimers. The dimers, however, dissociate upon dilution, and the monomers constitute the biologically active form. Chemokine activities are mediated by seven-transmembrane-domain, G protein coupled receptors, five of which were discovered in the past three years. The primary receptor-binding domain of all chemokines is near the NH2 terminus, and antagonists can be obtained by truncation or substitutions in this region. Major progress has been made in the understanding of chemokine actions on T lymphocytes that respond to several CC chemokines but also to IP10 and Mig, two CXC chemokines that selectively attract T cells via a novel receptor. Effects of chemokines on angiogenesis and tumor growth have been reported, but the data are still contradictory and the mechanisms unknown. Of considerable interest is the recent discovery that some chemokines function as HIV-suppressive factors by interacting with chemokine receptors which, together with CD4, were recognized as the binding sites for HIV-1.
- Neville LF, Mathiak G, Bagasra O
- The immunobiology of interferon-gamma inducible protein 10 kD (IP-10): a novel, pleiotropic member of the C-X-C chemokine superfamily.
- Cytokine Growth Factor Rev. 1997; 8: 207-19
- Display abstract
Interferon-gamma inducible protein 10 kD (IP-10) is a highly inducible, primary response gene that belongs to the C-X-C chemokine superfamily. Despite the original cloning of IP-10 in 1985, its biological functions are still unclear although accumulating reports indicate that it is a pleiotropic molecule capable of eliciting potent biological effects, including stimulation of monocytes, natural killer and T-cell migration, regulation of T-cell and bone marrow progenitor maturation, modulation of adhesion molecule expression as well as inhibition of angiogenesis. More interest is now likely to be focused on IP-10 due to the recent cloning of an IP-10 receptor. This paper aims to highlight our current knowledge of IP-10 and its homologues as well as defining its likely involvement in regulating fibroproliferation following inflammatory lung injury.
- Baggiolini M, Dewald B, Moser B
- Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines.
- Adv Immunol. 1994; 55: 97-179
- Baggiolini M, Clark-Lewis I
- Interleukin-8, a chemotactic and inflammatory cytokine.
- FEBS Lett. 1992; 307: 97-101
- Display abstract
Interleukin-8 (IL-8) belongs to a family of small, structurally related cytokines similar to platelet factor 4. It is produced by phagocytes and mesenchymal cells exposed to inflammatory stimuli (e.g., interleukin-1 or tumor necrosis factor) and activates neutrophils inducing chemotaxis, exocytosis and the respiratory burst. In vivo, IL-8 elicits a massive neutrophil accumulation at the site of injection. Five neutrophil-activating cytokines similar to IL-8 in structure and function have been identified recently. IL-8 and the related cytokines are produced in several tissues upon infection, inflammation, ischemia, trauma etc., and are thought to be the main cause of local neutrophil accumulation.
- Clore GM, Appella E, Yamada M, Matsushima K, Gronenborn AM
- Three-dimensional structure of interleukin 8 in solution.
- Biochemistry. 1990; 29: 1689-96
- Display abstract
The solution structure of the interleukin 8 (IL-8) dimer has been solved by nuclear magnetic resonance (NMR) spectroscopy and hybrid distance geometry-dynamical simulated annealing calculations. The structure determination is based on a total of 1880 experimental distance restraints (of which 82 are intersubunit) and 362 torsion angle restraints (comprising phi, psi, and chi 1 torsion angles). A total of 30 simulated annealing structures were calculated, and the atomic rms distribution about the mean coordinate positions (excluding residues 1-5 of each subunit) is 0.41 +/- 0.08 A for the backbone atoms and 0.90 +/- 0.08 A for all atoms. The three-dimensional solution structure of the IL-8 dimer reveals a structural motif in which two symmetry-related antiparallel alpha-helices, approximately 24 A long and separated by about 14 A, lie on top of a six-stranded antiparallel beta-sheet platform derived from two three-stranded Greek keys, one from each monomer unit. The general architecture is similar to that of the alpha 1/alpha 2 domains of the human class I histocompatibility antigen HLA-A2. It is suggested that the two alpha-helices form the binding site for the cellular receptor and that the specificity of IL-8, as well as that of a number of related proteins involved in cell-specific chemotaxis, mediation of cell growth, and the inflammatory response, is achieved by the distinct distribution of charged and polar residues at the surface of the helices.
- Metabolism (metabolic pathways involving proteins which contain this domain)
% proteins involved KEGG pathway ID Description 79.37 map04060 Cytokine-cytokine receptor interaction 14.68 map04620 Toll-like receptor signaling pathway 3.97 map04670 Leukocyte transendothelial migration 1.98 map05219 Bladder cancer
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with SCY domain which could be assigned to a KEGG orthologous group, and not all proteins containing SCY domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of SCY domains in PDB
PDB code Main view Title 1a15 Sdf-1alpha 1b2t Solution structure of the cx3c chemokine domain of fractalkine 1b3a Total chemical synthesis and high-resolution crystal structure of the potent anti-hiv protein aop-rantes 1b50 Nmr structure of human mip-1a d26a, 10 structures 1b53 Nmr structure of human mip-1a d26a, minimized average structure 1bo0 Monocyte chemoattractant protein-3, nmr, minimized average structure 1cm9 Crystal structure of viral macrophage inflammatory protein- ii 1dok Monocyte chemoattractant protein 1, p-form 1dol Monocyte chemoattractant protein 1, i-form 1dom Solution structure of the monocyte chemoattractant protein- dimer using heteronuclear, nmr, minimized average structure 1don Solution structure of the monocyte chemoattractant protein- dimer using heteronuclear, nmr, 20 structures 1eig Solution structure of the human chemokine eotaxin-2 1eih Solution structure of the human chemokine eotaxin-2 1el0 Solution structure of the human cc chemokine, i-309 1eot Solution nmr structure of eotaxin, minimized average structure 1eqt Met-rantes 1esr Crystal structure of human monocyte chemotactic protein-2 1f2l Crystal structure of chemokine domain of fractalkine 1f9p Crystal structure of connective tissue activating peptide- iii(ctap-iii) complexed with polyvinylsulfonic acid 1f9q Crystal structure of platelet factor 4 1f9r Crystal structure of platelet factor 4 mutant 1 1f9s Crystal structure of platelet factor 4 mutant 2 1g2s Solution structure of eotaxin-3 1g2t Solution structure of eotaxin-3 1g91 Solution structure of myeloid progenitor inhibitory factor- (mpif-1) 1ha6 Nmr solution structure of murine ccl20/mip-3a chemokine 1hfg Nmr solution structure of vmip-ii 1-71 from kaposi's sarcoma-associated herpesvirus (minimized average structure). 1hfn Nmr solution structures of vmip-ii 1-71 from kaposi's sarcoma-associated herpesvirus. 1hhv Solution structure of virus chemokine vmip-ii 1hrj Human rantes, nmr, 13 structures 1hum Solution structure of the chemokine hmip-1beta(slash)act-2 by multi-dimensional nmr: a novel chemokine dimer 1hun Solution structure of the chemokine hmip-1beta(slash)act-2 by multi-dimensional nmr: a novel chemokine dimer 1icw Interleukin-8, mutant with glu 38 replaced by cys and cys replaced by ala 1ikl Nmr study of monomeric human interleukin-8 (minimized average structure) 1ikm Nmr study of monomeric human interleukin-8 (30 structures) 1il8 Three-dimensional structure of interleukin 8 in solution 1ilp Cxcr-1 n-terminal peptide bound to interleukin-8 1ilq Cxcr-1 n-terminal peptide bound to interleukin-8 (minimized mean) 1j8i Solution structure of human lymphotactin 1j9o Solution structure of human lymphotactin 1je4 Solution structure of the monomeric variant of the chemokine mip-1beta 1lv9 Cxcr3 binding chemokine ip-10/cxcl10 1m8a Human mip-3alpha/ccl20 1mgs The solution structure of melanoma growth stimulating activity 1mi2 Solution structure of murine macrophage inflammatory protein-2, nmr, 20 structures 1ml0 Viral chemokine binding protein m3 from murine gammaherpesvirus68 in complex with the p8a variant of cc- chemokine mcp-1 1msg Solution structure of gro(slash)melanoma growth stimulatory activity determined by 1h nmr spectroscopy 1msh Solution structure of gro(slash)melanoma growth stimulatory activity determined by 1h nmr spectroscopy 1nap The crystal structure of recombinant human neutrophil- activating peptide-2 (m6l) at 1.9-angstroms resolution 1ncv Determination cc-chemokine mcp-3, nmr, 7 structures 1nr2 High resolution crystal structures of thymus and activation- regulated chemokine 1nr4 High resolution crystal structures of thymus and activation- regulated chemokine 1o7y Crystal structure of ip-10 m-form 1o7z Crystal structure of ip-10 t-form 1o80 Crystal structure of ip-10 h-form 1pfm Pf4-m2 chimeric mutant with the first 10 n-terminal residues of r-pf4 replaced by the n-terminal residues of the il8 sequence. models 1-15 of a 27-model set. 1pfn Pf4-m2 chimeric mutant with the first 10 n-terminal residues of r-pf4 replaced by the n-terminal residues of the il8 sequence. models 16-27 of a 27-model set. 1plf The three-dimensional structure of bovine platelet factor 4 at 3.0 angstroms resolution 1qe6 Interleukin-8 with an added disulfide between residues 5 and 33 (l5c/h33c) 1qg7 Stroma cell-derived factor-1alpha (sdf-1alpha) 1qnk Truncated human grob[5-73], nmr, 20 structures 1rhp Crystal structure of recombinant human platelet factor 4 1rjt Nmr structure of cxc chemokine cxcl11/itac 1rod Chimeric protein of interleukin 8 and human melanoma growth stimulating activity protein, nmr 1rtn Proton nmr assignments and solution conformation of rantes, a chemokine of the cc type 1rto Proton nmr assignments and solution conformation of rantes, a chemokine of the cc type 1sdf Solution structure of stromal cell-derived factor-1 (sdf-1), nmr, minimized average structure 1tvx Neutrophil activating peptide-2 variant form m6l with five additional amino terminal residues (dsdly) 1u4l Human rantes complexed to heparin-derived disaccharide i-s 1u4m Human rantes complexed to heparin-derived disaccharide iii-s 1u4p Crystal structure of human rantes mutant k45e 1u4r Crystal structure of human rantes mutant 44-aana-47 1vmc Stroma cell-derived factor-1alpha (sdf-1alpha) 1vmp Structure of the anti-hiv chemokine vmip-ii 1zxt Crystal structure of a viral chemokine 2bdn Crystal structure of human mcp-1 bound to a blocking antibody, 11k2 2d1h Crystal structure of st1889 protein from thermoacidophilic archaeon sulfolobus tokodaii 2eot Solution structure of eotaxin, an ensemble of 32 nmr solution structures 2ffk Solution structure of the complex between poxvirus-encoded cc chemokine inhibitor vcci and human mip-1beta, minimized average structure 2fht Crystal structure of viral macrophage inflammatory protein- ii 2fin Solution structure of the complex between poxvirus-encoded cc chemokine inhibitor vcci and human mip-1beta, ensemble structure 2fj2 Crystal structure of viral macrophage inflammatory protein- ii 2hcc Solution structure of the human chemokine hcc-2, nmr, 30 structures 2hci Structure of human mip-3a chemokine 2hdl Solution structure of brak/cxcl14 2hdm Solution structure of v21c/v59c lymphotactin/xcl1 2il8 Three-dimensional structure of interleukin 8 in solution 2j7z Crystal structure of recombinant human stromal cell-derived factor-1alpha 2jp1 Solution structure of the alternative conformation of xcl1/lymphotactin 2jyo Nmr solution structure of human mip-3alpha/ccl20 2k01 Structure of a locked sdf1 dimer 2k03 Structure of sdf1 in complex with the cxcr4 n-terminus containing a sulfotyrosine at postition 21 2k04 Structure of sdf1 in complex with the cxcr4 n-terminus containing no sulfotyrosines 2k05 Structure of sdf1 in complex with the cxcr4 n-terminus containing sulfotyrosines at postitions 7, 12 and 21 2kec Structure of sdf-1/cxcl12 2ked Structure of sdf-1/cxcl12 2kee Structure of sdf-1/cxcl12 2nwg Structure of cxcl12:heparin disaccharide complex 2nyz Viral chemokine binding protein m3 from murine gammaherpesvirus68 in complex with the c- chemokine xcl1 2nz1 Viral chemokine binding protein m3 from murine gammaherpesvirus68 in complex with the cc-chemokine ccl2/mcp-1 2q8r Structural and functional characterization of cc chemokine ccl14 2q8t Crystal structure of the cc chemokine ccl14 2r3z Crystal structure of mouse ip-10 2ra4 Crystal structure of human monocyte chemoattractant protein (mcp-4/ccl13) 2sdf Solution nmr structure of stromal cell-derived factor-1 (sdf-1), 30 structures 2vxw Structural and functional studies of the potent anti-hiv chemokine variant p2-rantes 3ifd Human synthetic monocyte chemoattractant protein 1 (mcp-1) 3il8 Crystal structure of interleukin 8: symbiosis of nmr and crystallography
- Links (links to other resources describing this domain)
BLOCKS SMALL_CYTOKINES_CXC PFAM il8 INTERPRO IPR001811 PROSITE SCY_DOMAIN