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 209572601  30 LGPQMLRELQETNAALQDVRELLRQQVREITFLKNTVMECDAC 72
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 209572601  493 EDADRDGVGDVCQDDFDADKVVDKIDVCPENAEVT 527
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 209572601 127 DVNEC-NAHPCFPRVRCINTSPGFRCEaCPPGYSGPT 162
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 209572601  30 LGPQMLRELQETNAALQDVRELLRQQVREITFLKNTVMECDAC 72
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 209572601   33 QMLRELQETNAALQDVRELLRQQVREITFLKNTVMECDACG 73
Cdd:pfam11598   3 QLATQLTQLTQLLKELKDDMRQQVKETSFLRNTIEECQACG 43

Calcium-binding EGF domain;

                          10        20
                  ....*....|....*....|....*..
gi 209572601  180 DINECETGQHNCVPNSVCINTRGSFQC 206
Cdd:pfam07645   1 DVDECATGTHNCPANTVCVNTIGSFEC 27

Calcium-binding EGF-like domain;

                           10        20        30
                   ....*....|....*....|....*....|....
gi 209572601   180 DINECETGqHNCVPNSVCINTRGSFQCGpCQPGF 213
Cdd:smart00179   1 DIDECASG-NPCQNGGTCVNTVGSYRCE-CPPGY 32

Calcium-binding EGF-like domain;

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 209572601   127 DVNEC-NAHPCFPRVRCINTSPGFRCEaCPPGYSGPTH 163
Cdd:smart00179   1 DIDECaSGNPCQNGGTCVNTVGSYRCE-CPPGYTDGRN 37

MSCRAMM family adhesin clumping factor ClfA; Clumping factor A is an MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules). It is heavily studied in Staphylococcus aureus both for its biological role in adhesion and for its potential for vaccination. Features of the sequence, but also of other MSCRAMM adhesins, include a long run of Ser-Asp dipeptide repeats and a C-terminal cell wall anchoring LPXTG motif.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209572601 304 DRDGIGD---ACDPDADGDGVPNEKDNCPLVRNPDQRNTDEDKWGDACDNCRSQKNDDQKDTDQDGRGDACDDDIDGDRI 380
Cdd:NF033609 609 DSDSASDsdsASDSDSASDSDSASDSDSASDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDS 688

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209572601 381 RNQADNCPRVPNSDQKDSDGDGIGDACDNCPQKSNPDqADVDHDFVGDACDSDQDQDGDGHQDSRDNCPTVPNSAQEDSD 460
Cdd:NF033609 689 DSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSD-SDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSD 767

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 209572601 461 HDGQGDACDDDDDNDGVPDSRDNCRLVPNPGQEDADRDGVGDVCQD-DFDADKVVD 515
Cdd:NF033609 768 SDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDsDSDSDSDSD 823

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 209572601  30 LGPQMLRELQETNAALQDVRELLRQQVREITFLKNTVMECDAC 72
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 209572601  31 GPQMLRELQETNAALQDVRELLRQQVREITFLKNTVMECDACG 73
Cdd:cd16080    2 GRQLLGQMTQLNQVLGEVKDLLRQQVKETSFLRNTIAECQACG 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 209572601   33 QMLRELQETNAALQDVRELLRQQVREITFLKNTVMECDACG 73
Cdd:pfam11598   3 QLATQLTQLTQLLKELKDDMRQQVKETSFLRNTIEECQACG 43

Calcium-binding EGF domain;

                          10        20
                  ....*....|....*....|....*..
gi 209572601  180 DINECETGQHNCVPNSVCINTRGSFQC 206
Cdd:pfam07645   1 DVDECATGTHNCPANTVCVNTIGSFEC 27

Calcium-binding EGF-like domain;

                           10        20        30
                   ....*....|....*....|....*....|....
gi 209572601   180 DINECETGqHNCVPNSVCINTRGSFQCGpCQPGF 213
Cdd:smart00179   1 DIDECASG-NPCQNGGTCVNTVGSYRCE-CPPGY 32

Coiled coil region of thrombospondin-3 (TSP-3); This family contains the N-terminal coiled coil region of TSP-3, which is highly expressed in osteosarcomas and associated with metastasis. TSP-3, along with TSP-5 and type IX collagen, is also expressed in the growth plate and all operate in concert and participate in growth plate organization that directly modulates linear growth. 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-3 knockout mice have been shown to display accelerated endochondral ossification and increased trabecular bone in the femoral head.

                         10        20        30
                 ....*....|....*....|....*....|.
gi 209572601  42 NAALQDVRELLRQQVREITFLKNTVMECDAC 72
Cdd:cd16079   13 NQILGELREDIRDQVKEMSLIRNTIMECQVC 43

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 209572601  184 CETGQHNCVPNSVCINTRGSFQCgPCQPGFVGD 216
Cdd:pfam12947   1 CSDNNGGCHPNATCTNTGGSFTC-TCNDGYTGD 32

MSCRAMM family adhesin clumping factor ClfA; Clumping factor A is an MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules). It is heavily studied in Staphylococcus aureus both for its biological role in adhesion and for its potential for vaccination. Features of the sequence, but also of other MSCRAMM adhesins, include a long run of Ser-Asp dipeptide repeats and a C-terminal cell wall anchoring LPXTG motif.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209572601 304 DRDGIGD---ACDPDADGDGVPNEKDNCPLVRNPDQRNTDEDKWGDACDNCRSQKNDDQKDTDQDGRGDACDDDIDGDRI 380
Cdd:NF033609 609 DSDSASDsdsASDSDSASDSDSASDSDSASDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDS 688

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209572601 381 RNQADNCPRVPNSDQKDSDGDGIGDACDNCPQKSNPDqADVDHDFVGDACDSDQDQDGDGHQDSRDNCPTVPNSAQEDSD 460
Cdd:NF033609 689 DSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSD-SDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSD 767

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 209572601 461 HDGQGDACDDDDDNDGVPDSRDNCRLVPNPGQEDADRDGVGDVCQD-DFDADKVVD 515
Cdd:NF033609 768 SDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDsDSDSDSDSD 823

Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large number of proteins, mostly animal; the list of proteins currently known to contain one or more copies of an EGF-like pattern is large and varied; the functional significance of EGF-like domains in what appear to be unrelated proteins is not yet clear; a common feature is that these repeats are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted (exception: prostaglandin G/H synthase); the domain includes six cysteine residues which have been shown to be involved in disulfide bonds; the main structure is a two-stranded beta-sheet followed by a loop to a C-terminal short two-stranded sheet; Subdomains between the conserved cysteines vary in length; the region between the 5th and 6th cysteine contains two conserved glycines of which at least one is present in most EGF-like domains; a subset of these bind calcium.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 209572601 130 ECNA-HPCFPRVRCINTSPGFRCEaCPPGYSGPTH 163
Cdd:cd00053    1 ECAAsNPCSNGGTCVNTPGSYRCV-CPPGYTGDRS 34