Conserved Protein Domain Family
EFh_SPARC_FSTL1

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cd16233: EFh_SPARC_FSTL1 
EF-hand, extracellular calcium-binding (EC) motif, found in follistatin-related protein 1 (FRP-1)
FRP-1, also termed follistatin-like protein 1 (fstl-1), TGF-beta-stimulated clone 36 (TSC-36/Flik), or TGF-beta inducible protein, is a secreted glycoprotein that is overexpressed in certain inflammatory diseases and has been implicated in many autoimmune diseases. FRP-1 functions as an important proinflammatory factor in the pathogenesis of osteoarthritis (OA) by activating the canonical NF-kappaB-mediated inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), and enhancing fibroblast like synoviocytes proliferation. It also acts as a critical mediator of collagen-induced arthritis (CIA), juvenile rheumatoid arthritis (JRA), as well as Lyme arthritis observed after Borrelia burgdorferi infection. Meanwhile, it enhances nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-mediated IL-1beta secretion from monocytes and macrophages. Moreover, FRP-1 shows critical functions in the nervous system. It differentially regulates transforming growth factor beta (TGF-beta) and bone morphogenetic protein (BMP) signaling, leading to epithelial injury and fibroblast activation. Furthermore, FRP-1 functions as a cardiokine with cardioprotective properties. It may play a potential role in ischemic stroke through decreasing neuronal apoptosis and improving neurological deficits via disco-interacting protein 2 homolog A (DIP2A)/Akt pathway after middle cerebral artery occlusion (MCAO). Plasma FRP-1 is elevated in Kawasaki disease (KD) and thus may play a possible role in the formation of coronary artery aneurysm (CAA). FRP-1 contains a follistatin-like (FS) domain, an extracellular calcium-binding (EC) domain including a pair of EF hands, and a von Willebrand factor type C (VWC) domain. The EC domain does not undergo characteristic structural changes upon calcium addition or depletion and therefore is not a functional calcium binding domain.
Statistics
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PSSM-Id: 320012
View PSSM: cd16233
Aligned: 7 rows
Threshold Bit Score: 181.503
Threshold Setting Gi: 676440959
Created: 18-Nov-2014
Updated: 18-Aug-2016
Structure
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Aligned Rows:
 
Feature 1:putative Ca binding site [ion binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                     #   #      #                       
gi 2498390   113 CYQSNRDELRRRIIQWLEAEIIPDGwfsk-gsnYSEILDKYFKNFDn-GDSRLDSSEFLKFVEQNEtainittyp-dqen 189
gi 591374896 112 CYQSDRDELRRRIIQWLEAEIIPDGwfsk-gsnYSEVLDKYFKSFDg-GDSRLDSNEFLKFVEQNEtainittyv-dqet 188
gi 148238293 110 CYQSDRDEMRRRVIHWLQTEIIPDGwfsk-gsdYSEILDRYFKKFDd-GDSHLDSAELQSFLEQSQstnittyk--deet 185
gi 657588228  10 CFLSDRDWLRDRVIQWVQKETQSDQvsln-assASGLLQTYFQTYDn-GDSQLDSKEFLRFLKHNEtalnltfsn-tlet 86
gi 259013366 139 CFQSDRDILRQKLIDWMIQQEIPAGwftd-grsYKDIIQMFFDKYDetSDGKLDSNELLHFVEGNEtvsnvthn--sege 215
gi 676440959  86 CYQIQRDELRQLLVDWLKTEVTKVCgltlsdksYSDIVHETFSKCDvdKDGSLDGDELLKCTEKKPahtnltlcqsqqgm 165
gi 88900441  112 CYVADRNELRRRVIEWLQTEVVPDGwftk-gsnFTDILLKYFKNYDn-GDSQLDSAELLKFIQHNEtavqmssya-eeen 188
                         90       100       110
                 ....*....|....*....|....*....|....*..
Feature 1                        # # #      #         
gi 2498390   190 nkllRGLCVDALIELSDENADWKLSFQEFLKCLNPSF 226
gi 591374896 189 nkllRGLCVDALIELSDENADWKLSFNEFLKCLNPSF 225
gi 148238293 186 nrmlKSLCVEALIELSDENADWKLNKNEFLKCLNPDF 222
gi 657588228  87 nlllRSLCVDALIELSDENADWKLSLSEFINCLTPSF 123
gi 259013366 216 nailRGLCVDALIDISDDDADWALNLEEFQNCMNPEF 252
gi 676440959 166 skyfRGLCMDALINMGDGDDNWVLNEEEFIKILSLHF 202
gi 88900441  189 nrllRSLCVDALIELSDENADWKLSFDEFLNCLKPGF 225

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