HYR domain; This domain is known as the HYR (Hyalin Repeat) domain, after the protein hyalin that is composed exclusively of this repeat. This domain probably corresponds to a new superfamily in the immunoglobulin fold. The function of this domain is uncertain it may be involved in cell adhesion.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392886540  2235 KDRLPPTVlRCPKNIRKGTTEDFTKVEWPDEDVAFFDNIG-VIRIEVNYHNGQQFGVGITTVRYVGFDAAGNSAECTFDV 2313
Cdd:pfam02494    1 VDTTPPTV-KCPNNIVRTVELGTSTVRVFFTEPTAFDNSGqAILVSRTAQPGDFFPVGTTTVTYVAYDNSGNRASCTFTV 79

                   ..
gi 392886540  2314 TI 2315
Cdd:pfam02494   80 TV 81

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

                          10        20        30
                  ....*....|....*....|....*....|...
gi 392886540  185 CLSGTFRCAdNSKCIPASLKDDGFKDCQDGSDE 217
Cdd:cd00112     1 CPPNEFRCA-NGRCIPSSWVCDGEDDCGDGSDE 32

Tyrosine-protein kinase ephrin type A/B receptor-like; This family has repeats of a region rich in cysteines. It is found in various ephrin type A and B receptors, which have tyrosine kinase activity.

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 392886540  2640 CRECTFGFYK-TGVRGPCIQCPRGLTTTSQASTSINSC 2676
Cdd:pfam07699   11 CIPCPRGTYQpEEGQLSCLACPLGTTTDSPGATSISDC 48

Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) interactions with TNF superfamily (TNFSF) ligands (TNFL) control key cellular processes such as differentiation, proliferation, apoptosis, and cell growth. Dysregulation of these pathways has been shown to result in a wide range of pathological conditions, including autoimmune diseases, inflammation, cancer, and viral infection. There are 29 very diverse family members of TNFRSF reported in humans: 22 are type I transmembrane receptors (single pass with the N terminus on extracellular side of the cell membrane) and have a clear signal peptide; the remaining 7 members are either type III transmembrane receptors (single pass with the N terminus on extracellular side of the membrane but no signal sequence; TNFR13B, TNFR13C, TNFR17, and XEDAR), or attached to the membrane via a glycosylphosphatidylinositol (GPI) linker (TNFR10C), or secreted as soluble receptors (TNFR11B and TNFR6B). All TNFRs contain relatively short cysteine-rich domains (CRDs) in the ectodomain, and are involved in interaction with the TNF homology domain (THD) of their ligands. TNFRs often have multiple CRDs (between one and six), with the most frequent configurations of three or four copies; most CRDs possess three disulfide bridges, but could have between one and four. Localized or genome-wide duplication and evolution of the TNFRSF members appear to have paralleled the emergence of the adaptive immune system; teleosts (i.e. ray-finned, bony fish), which possess an immune system with B and T cells, possess primary and secondary lymphoid organs, and are capable of adaptive responses to pathogens also display several characteristics that are different from the mammalian immune system, making teleost TNFSF orthologs and paralogs of interest to better understand immune system evolution and the immunological pathways elicited to pathogens.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392886540 2510 ICVKCPEGTFANKE-SNKCIDCPINTYrnSTNLDQLKCTACpgttvtgdvtgavdeSQCYvncpiGQFESKGLCNPCPEG 2588
Cdd:cd13410     5 SCSNCPAGTFCGKNkDQTCIPCPPNSF--SSTGGQQTCDIC---------------RKCE-----GVFRTKKPCSSTSNA 62

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 392886540 2589 TFGPTTGLRkciCCGfdlstfgegkTNLADCTKTCEAGQEMIREDgnsipfCRECTFGFYKTGVRGPCI 2657
Cdd:cd13410    63 ECECVPGFH---CLG----------PGCSMCEPDCKQGQELTKEG------CKDCSFGTFNDQEGGVCR 112

HYR domain; This domain is known as the HYR (Hyalin Repeat) domain, after the protein hyalin that is composed exclusively of this repeat. This domain probably corresponds to a new superfamily in the immunoglobulin fold. The function of this domain is uncertain it may be involved in cell adhesion.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392886540  2235 KDRLPPTVlRCPKNIRKGTTEDFTKVEWPDEDVAFFDNIG-VIRIEVNYHNGQQFGVGITTVRYVGFDAAGNSAECTFDV 2313
Cdd:pfam02494    1 VDTTPPTV-KCPNNIVRTVELGTSTVRVFFTEPTAFDNSGqAILVSRTAQPGDFFPVGTTTVTYVAYDNSGNRASCTFTV 79

                   ..
gi 392886540  2314 TI 2315
Cdd:pfam02494   80 TV 81

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

                          10        20        30
                  ....*....|....*....|....*....|...
gi 392886540  185 CLSGTFRCAdNSKCIPASLKDDGFKDCQDGSDE 217
Cdd:cd00112     1 CPPNEFRCA-NGRCIPSSWVCDGEDDCGDGSDE 32

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....
gi 392886540    851 DRDECEEKSDyCDSFATCNNTDGGFECHCPVGYH 884
Cdd:smart00179    1 DIDECASGNP-CQNGGTCVNTVGSYRCECPPGYT 33

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 392886540  851 DRDECEEKSDyCDSFATCNNTDGGFECHCPVGYHLYN 887
Cdd:cd00054     1 DIDECASGNP-CQNGGTCVNTVGSYRCSCPPGYTGRN 36

Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system; SUSHI repeats (short complement-like repeat, SCR) are abundant in complement control proteins. The complement control protein (CCP) modules (also known as short consensus repeats SCRs or SUSHI repeats) contain approximately 60 amino acid residues and have been identified in several proteins of the complement system. Typically, 2 to 4 modules contribute to a binding site, implying that the orientation of the modules to each other is critical for function.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 392886540 1066 FEYQTVIYFKCENGYMLspgSGSESITCIRYDdeyQWSDAIPVCI 1110
Cdd:cd00033    19 YSYGSTVTYSCNEGYTL---VGSSTITCTENG---GWSPPPPTCE 57

Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR); The complement control protein (CCP) modules (also known as short consensus repeats SCRs or SUSHI repeats) contain approximately 60 amino acid residues and have been identified in several proteins of the complement system. A missense mutation in seventh CCP domain causes deficiency of the b subunit of factor XIII.

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*...
gi 392886540    604 KLPTVVDGYIINVFLRYILGSKVVIDCSQGFALSSlPYIIQCNSNGQW 651
Cdd:smart00032    3 PPPDIENGTVTSSSGTYSYGDTVTYSCDPGYTLIG-SSTITCLENGTW 49

Low-density lipoprotein receptor domain class A;

                           10        20        30
                   ....*....|....*....|....*....|...
gi 392886540   185 CLSGTFRCAdNSKCIPASLKDDGFKDCQDGSDE 217
Cdd:pfam00057    3 CSPNEFQCG-SGECIPRSWVCDGDPDCGDGSDE 34

HYR domain; This domain is known as the HYR (Hyalin Repeat) domain, after the protein hyalin that is composed exclusively of this repeat. This domain probably corresponds to a new superfamily in the immunoglobulin fold. The function of this domain is uncertain it may be involved in cell adhesion.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392886540  2235 KDRLPPTVlRCPKNIRKGTTEDFTKVEWPDEDVAFFDNIG-VIRIEVNYHNGQQFGVGITTVRYVGFDAAGNSAECTFDV 2313
Cdd:pfam02494    1 VDTTPPTV-KCPNNIVRTVELGTSTVRVFFTEPTAFDNSGqAILVSRTAQPGDFFPVGTTTVTYVAYDNSGNRASCTFTV 79

                   ..
gi 392886540  2314 TI 2315
Cdd:pfam02494   80 TV 81

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure

                          10        20        30
                  ....*....|....*....|....*....|...
gi 392886540  185 CLSGTFRCAdNSKCIPASLKDDGFKDCQDGSDE 217
Cdd:cd00112     1 CPPNEFRCA-NGRCIPSSWVCDGEDDCGDGSDE 32

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....
gi 392886540    851 DRDECEEKSDyCDSFATCNNTDGGFECHCPVGYH 884
Cdd:smart00179    1 DIDECASGNP-CQNGGTCVNTVGSYRCECPPGYT 33

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 392886540  851 DRDECEEKSDyCDSFATCNNTDGGFECHCPVGYHLYN 887
Cdd:cd00054     1 DIDECASGNP-CQNGGTCVNTVGSYRCSCPPGYTGRN 36

Tyrosine-protein kinase ephrin type A/B receptor-like; This family has repeats of a region rich in cysteines. It is found in various ephrin type A and B receptors, which have tyrosine kinase activity.

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 392886540  2640 CRECTFGFYK-TGVRGPCIQCPRGLTTTSQASTSINSC 2676
Cdd:pfam07699   11 CIPCPRGTYQpEEGQLSCLACPLGTTTDSPGATSISDC 48

Tumor necrosis factor receptor superfamily member 9 (TNFRSF9), also known as CD137; TNFRSF9 (also known as CD137, ILA, 4-1BB) plays a role in the immunobiology of human cancer where it is preferentially expressed on tumor-reactive subset of tumor-infiltrating lymphocytes. It can be expressed by activated T cells, but to a larger extent on CD8 than on CD4 T cells. In addition, CD137 expression is found on dendritic cells, follicular dendritic cells, natural killer cells, granulocytes and cells of blood vessel walls at sites of inflammation. It transduces signals that lead to the activation of NF-kappaB, mediated by the TRAF adaptor proteins. CD137 contributes to the clonal expansion, survival, and development of T cells. It can also induce proliferation in peripheral monocytes, enhance T cell apoptosis induced by TCR/CD3 triggered activation, and regulate CD28 co-stimulation to promote Th1 cell responses. CD137 is modulated by SAHA treatment in breast cancer cells, suggesting that the combination of SAHA with this receptor could be a new therapeutic approach for the treatment of tumors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392886540 2510 ICVKCPEGTFANKE-SNKCIDCPINTYrnSTNLDQLKCTACpgttvtgdvtgavdeSQCYvncpiGQFESKGLCNPCPEG 2588
Cdd:cd13410     5 SCSNCPAGTFCGKNkDQTCIPCPPNSF--SSTGGQQTCDIC---------------RKCE-----GVFRTKKPCSSTSNA 62

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 392886540 2589 TFGPTTGLRkciCCGfdlstfgegkTNLADCTKTCEAGQEMIREDgnsipfCRECTFGFYKTGVRGPCI 2657
Cdd:cd13410    63 ECECVPGFH---CLG----------PGCSMCEPDCKQGQELTKEG------CKDCSFGTFNDQEGGVCR 112

Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system; SUSHI repeats (short complement-like repeat, SCR) are abundant in complement control proteins. The complement control protein (CCP) modules (also known as short consensus repeats SCRs or SUSHI repeats) contain approximately 60 amino acid residues and have been identified in several proteins of the complement system. Typically, 2 to 4 modules contribute to a binding site, implying that the orientation of the modules to each other is critical for function.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 392886540  603 CKLPTVVD-GYIINVFLRYILGSKVVIDCSQGFALSSlPYIIQCNSNGQW 651
Cdd:cd00033     1 CPPPPVPEnGTVTGSKGSYSYGSTVTYSCNEGYTLVG-SSTITCTENGGW 49