Coiled coil region of thrombospondin-5 (TSP-5); This family contains the N-terminal coiled coil region of TSP-5, also known as cartilage oligomeric matrix protein (COMP). It forms a pentameric left-handed coiled coil (COMPcc) with a channel that is a unique carrier for lipophilic compounds. It is known to bind hydrophilic signaling molecules such as vitamin D3 and vitamin A, making it a possible targeted drug delivery system. TSP-5/COMP is expressed in all types of cartilage as well as in the vitreous of the eye, tendons, vascular smooth muscle cells, and heart. The pentamer is stabilized by inter-subunit disulfide bonds formed between cysteine residues adjacent to the C-terminal end of the coiled coil region. TSP-5 is essential for modulating the phenotypic transition of vascular smooth muscle cells and vascular remodeling. Mutations in TSP-5 result in two different inherited chondrodysplasias and osteoarthritic phenotypes: pseudoachondroplasia and multiple epithelial dysplasia. Deficiency of TSP-5 causes dilated cardiomyopathy (DCM), a common cause of congestive heart failure. Early increase in serum TSP-5 is associated with joint damage progression in patients with rheumatoid arthritis, thus representing a novel indicator of an activated destructive process in the joint.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1907186924  29 LAPQMLRELQETNAALQDVRELLRQQVKEITFLKNTVMECDAC 71
Cdd:cd16077     1 LAPQMLSEMQETNQALAEVKELLKQQVKEITFLKNTVMECDAC 43

Thrombospondin type 3 repeat; The thrombospondin repeat is a short aspartate rich repeat which binds to calcium ions. The repeat was initially identified in thrombospondin proteins that contained 7 of these repeats. The repeat lacks defined secondary structure.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1907186924 491 EDNDRDGVGDACQGDFDADKVIDKIDVCPENAEVT 525
Cdd:pfam02412   1 TDSDSDGVGDACDNDFDNDGVPDLLDNCPNNANID 35

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1907186924 125 DVNEC-NAHPCFPRVRCINTSPGFHCEaCPPGFSGPT 160
Cdd:cd00054     1 DIDECaSGNPCQNGGTCVNTVGSYRCS-CPPGYTGRN 36

Coiled coil region of thrombospondin-5 (TSP-5); This family contains the N-terminal coiled coil region of TSP-5, also known as cartilage oligomeric matrix protein (COMP). It forms a pentameric left-handed coiled coil (COMPcc) with a channel that is a unique carrier for lipophilic compounds. It is known to bind hydrophilic signaling molecules such as vitamin D3 and vitamin A, making it a possible targeted drug delivery system. TSP-5/COMP is expressed in all types of cartilage as well as in the vitreous of the eye, tendons, vascular smooth muscle cells, and heart. The pentamer is stabilized by inter-subunit disulfide bonds formed between cysteine residues adjacent to the C-terminal end of the coiled coil region. TSP-5 is essential for modulating the phenotypic transition of vascular smooth muscle cells and vascular remodeling. Mutations in TSP-5 result in two different inherited chondrodysplasias and osteoarthritic phenotypes: pseudoachondroplasia and multiple epithelial dysplasia. Deficiency of TSP-5 causes dilated cardiomyopathy (DCM), a common cause of congestive heart failure. Early increase in serum TSP-5 is associated with joint damage progression in patients with rheumatoid arthritis, thus representing a novel indicator of an activated destructive process in the joint.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1907186924  29 LAPQMLRELQETNAALQDVRELLRQQVKEITFLKNTVMECDAC 71
Cdd:cd16077     1 LAPQMLSEMQETNQALAEVKELLKQQVKEITFLKNTVMECDAC 43

Cartilage oligomeric matrix protein; This family of proteins represents the five-stranded coiled-coil domain of cartilage oligomeric matrix protein (COMP). This region has a binding site between two internal rings formed by Leu37 and Thr40

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1907186924  32 QMLRELQETNAALQDVRELLRQQVKEITFLKNTVMECDACG 72
Cdd:pfam11598   3 QLATQLTQLTQLLKELKDDMRQQVKETSFLRNTIEECQACG 43

Calcium-binding EGF domain;

                          10        20
                  ....*....|....*....|....*..
gi 1907186924 178 DINECETGQHNCVPNSVCVNTRGSFQC 204
Cdd:pfam07645   1 DVDECATGTHNCPANTVCVNTIGSFEC 27

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1907186924 178 DINECETGqHNCVPNSVCVNTRGSFQCGpCQPGFVGD 214
Cdd:cd00054     1 DIDECASG-NPCQNGGTCVNTVGSYRCS-CPPGYTGR 35

Calcium-binding EGF-like domain;

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1907186924  125 DVNEC-NAHPCFPRVRCINTSPGFHCEaCPPGFSGPTH 161
Cdd:smart00179   1 DIDECaSGNPCQNGGTCVNTVGSYRCE-CPPGYTDGRN 37

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1907186924 129 CNAHPCFPRVRCINTSPGFHCEaCPPGFSGPT 160
Cdd:pfam00008   1 CAPNPCSNGGTCVDTPGGYTCI-CPEGYTGKR 31

Coiled coil region of thrombospondin-5 (TSP-5); This family contains the N-terminal coiled coil region of TSP-5, also known as cartilage oligomeric matrix protein (COMP). It forms a pentameric left-handed coiled coil (COMPcc) with a channel that is a unique carrier for lipophilic compounds. It is known to bind hydrophilic signaling molecules such as vitamin D3 and vitamin A, making it a possible targeted drug delivery system. TSP-5/COMP is expressed in all types of cartilage as well as in the vitreous of the eye, tendons, vascular smooth muscle cells, and heart. The pentamer is stabilized by inter-subunit disulfide bonds formed between cysteine residues adjacent to the C-terminal end of the coiled coil region. TSP-5 is essential for modulating the phenotypic transition of vascular smooth muscle cells and vascular remodeling. Mutations in TSP-5 result in two different inherited chondrodysplasias and osteoarthritic phenotypes: pseudoachondroplasia and multiple epithelial dysplasia. Deficiency of TSP-5 causes dilated cardiomyopathy (DCM), a common cause of congestive heart failure. Early increase in serum TSP-5 is associated with joint damage progression in patients with rheumatoid arthritis, thus representing a novel indicator of an activated destructive process in the joint.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1907186924  29 LAPQMLRELQETNAALQDVRELLRQQVKEITFLKNTVMECDAC 71
Cdd:cd16077     1 LAPQMLSEMQETNQALAEVKELLKQQVKEITFLKNTVMECDAC 43

Coiled coil region of thrombospondin-4 (TSP-4); This family contains the N-terminal coiled coil region of TSP-4, which is abundantly expressed in tendon and muscle, as well as in neural and osteogenic tissues, and has also been detected in brain capillaries. It forms a pentameric left-handed coiled coil with a channel that is a unique carrier for lipophilic compounds. The pentamer is stabilized by inter-subunit disulfide bonds formed between cysteine residues adjacent to the C-terminal end of the coiled coil region. TSP-4 regulates the composition of the deposition of extracellular matrix (ECM) in tendon and skeletal muscle. The absence of TSP-4 alters the organization, composition and physiological functions of these tissues. TSP-4 deficiency causes incorrect modification of heparan-sulfate (HS), resulting in decreased activity of lipoprotein lipase (LpL) and loss of beta-glycan; HS is involved in a wide variety of cellular functions, LpL is an endothelial enzyme responsible for the uptake and hydrolysis of lipoproteins, and beta-glycan has inhibiting effect on TGF-beta signaling in skeletal muscle. The human gene THBS4 that encodes for TSP-4 contains a single nucleotide polymorphism (SNP), which is expressed at high frequency in Caucasians and associated with a significantly increased risk of premature myocardial infarction. TSP-4 also binds stromal interaction molecule 1 (STIM1), a transmembrane protein that functions in the endoplasmic reticulum (ER), and regulates calcium channel activity. Studies show that TSP-4 may act as an organizer of adhesive and axon outgrowth-promoting molecules in the ECM to optimize retinal ganglion cell responses. TSP-4 is also involved in the post-translational modification of collagen and may assist in collagen fibril assembly.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1907186924  32 QMLRELQETNAALQDVRELLRQQVKEITFLKNTVMECDACG 72
Cdd:cd16080     4 QLLGQMTQLNQVLGEVKDLLRQQVKETSFLRNTIAECQACG 44

Cartilage oligomeric matrix protein; This family of proteins represents the five-stranded coiled-coil domain of cartilage oligomeric matrix protein (COMP). This region has a binding site between two internal rings formed by Leu37 and Thr40

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1907186924  32 QMLRELQETNAALQDVRELLRQQVKEITFLKNTVMECDACG 72
Cdd:pfam11598   3 QLATQLTQLTQLLKELKDDMRQQVKETSFLRNTIEECQACG 43

Calcium-binding EGF domain;

                          10        20
                  ....*....|....*....|....*..
gi 1907186924 178 DINECETGQHNCVPNSVCVNTRGSFQC 204
Cdd:pfam07645   1 DVDECATGTHNCPANTVCVNTIGSFEC 27

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1907186924 178 DINECETGqHNCVPNSVCVNTRGSFQCGpCQPGFVGD 214
Cdd:cd00054     1 DIDECASG-NPCQNGGTCVNTVGSYRCS-CPPGYTGR 35

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1907186924 125 DVNEC-NAHPCFPRVRCINTSPGFHCEaCPPGFSGPT 160
Cdd:cd00054     1 DIDECaSGNPCQNGGTCVNTVGSYRCS-CPPGYTGRN 36

EGF domain; This family includes a variety of EGF-like domain homologs. This family includes the C-terminal domain of the malaria parasite MSP1 protein.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 1907186924 182 CETGQHNCVPNSVCVNTRGSFQCgPCQPGFVGD 214
Cdd:pfam12947   1 CSDNNGGCHPNATCTNTGGSFTC-TCNDGYTGD 32

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1907186924 129 CNAHPCFPRVRCINTSPGFHCEaCPPGFSGPT 160
Cdd:pfam00008   1 CAPNPCSNGGTCVDTPGGYTCI-CPEGYTGKR 31