UPA domain; The UPA domain is conserved in UNC5, PIDD, and Ankyrins. It has a beta sandwich structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2055392    645 ATKRLRLLLFAPVACTSLEYNIRVYCLHDTHDALKEVVQLEKQLGGQLIQEPRVLHFKDSYHNLRLSIHDVPSSLWKSKL 724
Cdd:pfam17217   1 AIKRLRLAVFAPAACTSLEYSLRVYCLDDTPDALKEVVQLEKQLGGQLLEEPKTLHFKDSTHNLRLSIHDIPPSLWKSKL 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2055392    725 LVSYQEIPFYHIWNGTQQYLHCTFTLERINASTSDLACKVWVWQVEGDGQSFNINFNI 782
Cdd:pfam17217  81 FAKYQEIPFYHVWSGNQNPLHCTFTLERYSLATTELSCKICVRQVEGEGQIFQLYTTL 138

Domain present in ZO-1 and Unc5-like netrin receptors; Domain of unknown function.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2055392     495 TSNMAYGTFNFLGGRLMIPNTGISLLIPPDAIPRGKIYEIYLTLHKPEDVRLPLAGCQTLLSPVVSCGPPGVLLTRPVIL 574
Cdd:smart00218   1 PSFLVSGTFDARGGRLRGPRTGVRLIIPPGAIPQGTRYTCYLVVHKTLSTPPPLEEGETLLSPVVECGPHGALFLRPVIL 80

                           90       100
                   ....*....|....*....|....
gi 2055392     575 AMDHCGEPSPDSWSLRLKKQSCEG 598
Cdd:smart00218  81 EVPHCASLRPRDWEIVLLRSENGG 104

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2055392  153 QEPLAKEVSLEQGIVLPCRPPEGIPPAEVEWLRNEDLVDpSLDPNVYITREHSLVVRQARLADTANYTCVAKNIVARRRS 232
Cdd:cd05724   2 VEPSDTQVAVGEMAVLECSPPRGHPEPTVSWRKDGQPLN-LDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERES 80

                ....*..
gi 2055392  233 TSAAVIV 239
Cdd:cd05724  81 RAARLSV 87

UPA domain; The UPA domain is conserved in UNC5, PIDD, and Ankyrins. It has a beta sandwich structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2055392    645 ATKRLRLLLFAPVACTSLEYNIRVYCLHDTHDALKEVVQLEKQLGGQLIQEPRVLHFKDSYHNLRLSIHDVPSSLWKSKL 724
Cdd:pfam17217   1 AIKRLRLAVFAPAACTSLEYSLRVYCLDDTPDALKEVVQLEKQLGGQLLEEPKTLHFKDSTHNLRLSIHDIPPSLWKSKL 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2055392    725 LVSYQEIPFYHIWNGTQQYLHCTFTLERINASTSDLACKVWVWQVEGDGQSFNINFNI 782
Cdd:pfam17217  81 FAKYQEIPFYHVWSGNQNPLHCTFTLERYSLATTELSCKICVRQVEGEGQIFQLYTTL 138

Domain present in ZO-1 and Unc5-like netrin receptors; Domain of unknown function.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2055392     495 TSNMAYGTFNFLGGRLMIPNTGISLLIPPDAIPRGKIYEIYLTLHKPEDVRLPLAGCQTLLSPVVSCGPPGVLLTRPVIL 574
Cdd:smart00218   1 PSFLVSGTFDARGGRLRGPRTGVRLIIPPGAIPQGTRYTCYLVVHKTLSTPPPLEEGETLLSPVVECGPHGALFLRPVIL 80

                           90       100
                   ....*....|....*....|....
gi 2055392     575 AMDHCGEPSPDSWSLRLKKQSCEG 598
Cdd:smart00218  81 EVPHCASLRPRDWEIVLLRSENGG 104

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2055392     245 WSTWTEWSVCSASCGRGWQKRSRSCTNPAPLNGGAFCEGQNVQKTACAT-LCP 296
Cdd:smart00209   1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPPPQNGGGPCTGEDVETRACNEqPCP 53

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2055392  153 QEPLAKEVSLEQGIVLPCRPPEGIPPAEVEWLRNEDLVDpSLDPNVYITREHSLVVRQARLADTANYTCVAKNIVARRRS 232
Cdd:cd05724   2 VEPSDTQVAVGEMAVLECSPPRGHPEPTVSWRKDGQPLN-LDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERES 80

                ....*..
gi 2055392  233 TSAAVIV 239
Cdd:cd05724  81 RAARLSV 87

Thrombospondin type 1 domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2055392    246 STWTEWSVCSASCGRGWQKRSRSCTNPAPlnGGAFCEGQNVQKTAC 291
Cdd:pfam00090   1 SPWSPWSPCSVTCGKGIQVRQRTCKSPFP--GGEPCTGDDIETQAC 44

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2055392     166 IVLPCRPPeGIPPAEVEWLRNeDLVDPSLDPNVYITRE---HSLVVRQARLADTANYTCVAKN 225
Cdd:smart00410  12 VTLSCEAS-GSPPPEVTWYKQ-GGKLLAESGRFSVSRSgstSTLTISNVTPEDSGTYTCAATN 72

UPA domain; The UPA domain is conserved in UNC5, PIDD, and Ankyrins. It has a beta sandwich structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2055392    645 ATKRLRLLLFAPVACTSLEYNIRVYCLHDTHDALKEVVQLEKQLGGQLIQEPRVLHFKDSYHNLRLSIHDVPSSLWKSKL 724
Cdd:pfam17217   1 AIKRLRLAVFAPAACTSLEYSLRVYCLDDTPDALKEVVQLEKQLGGQLLEEPKTLHFKDSTHNLRLSIHDIPPSLWKSKL 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2055392    725 LVSYQEIPFYHIWNGTQQYLHCTFTLERINASTSDLACKVWVWQVEGDGQSFNINFNI 782
Cdd:pfam17217  81 FAKYQEIPFYHVWSGNQNPLHCTFTLERYSLATTELSCKICVRQVEGEGQIFQLYTTL 138

Domain present in ZO-1 and Unc5-like netrin receptors; Domain of unknown function.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2055392     495 TSNMAYGTFNFLGGRLMIPNTGISLLIPPDAIPRGKIYEIYLTLHKPEDVRLPLAGCQTLLSPVVSCGPPGVLLTRPVIL 574
Cdd:smart00218   1 PSFLVSGTFDARGGRLRGPRTGVRLIIPPGAIPQGTRYTCYLVVHKTLSTPPPLEEGETLLSPVVECGPHGALFLRPVIL 80

                           90       100
                   ....*....|....*....|....
gi 2055392     575 AMDHCGEPSPDSWSLRLKKQSCEG 598
Cdd:smart00218  81 EVPHCASLRPRDWEIVLLRSENGG 104

Death domain found in Uncoordinated-5 homolog family; Death Domain (DD) found in Uncoordinated-5 (UNC-5) homolog family, which includes Unc5A, B, C and D in vertebrates. UNC5 proteins are receptors for secreted netrins (netrin-1, -3 and -4) that are involved in diverse processes like axonal guidance, neuronal migration, blood vessel patterning, and apoptosis. They are transmembrane proteins with an extracellular domain consisting of two immunoglobulin repeats, two thrombospondin type-I modules and an intracellular region containing a ZU-5 domain, UPA domain and a DD. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2055392  811 IPFLIRQKIIASLDPPCSRGADWRTLAQKLHLDSHLSFFASKPSPTAMILNLWEARHFPNGNLGQLAAAVAGLGQPDA 888
Cdd:cd08781   1 LPYSIRQKLCSLLDPPNARGNDWRLLAQKLSVDRYINYFATKPSPTEVILDLWEARNRDDGALNSLAAILREMGRHDA 78

Death domain found in Uncoordinated-5B; Death Domain (DD) found in Uncoordinated-5B (UNC5B). UNC5B is part of the UNC-5 homolog family. It is a receptor for the secreted netrin-1 and plays a role in axonal guidance, angiogenesis, and apoptosis. UNC5B signaling is involved in the netrin-1-induced proliferation and migration of renal proximal tubular cells. It is also required for vascular patterning during embryonic development, and its activation inhibits sprouting angiogenesis. UNC5 proteins are transmembrane proteins with an extracellular domain consisting of two immunoglobulin repeats, two thrombospondin type-I modules and an intracellular region containing a ZU-5 domain, UPA domain and a DD. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2055392  811 IPFLIRQKIIASLDPPCSRGADWRTLAQKLHLDSHLSFFASKPSPTAMILNLWEARHFPNGNLGQLAAAVAGLGQPD 887
Cdd:cd08802   1 IPLSIRQKICNSLDAPNSRGNDWRLLAQKLSMDRYLNYFATKASPTGVILDLWEARHQDDGDLNSLASALEEMGKSE 77

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2055392     245 WSTWTEWSVCSASCGRGWQKRSRSCTNPAPLNGGAFCEGQNVQKTACAT-LCP 296
Cdd:smart00209   1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPPPQNGGGPCTGEDVETRACNEqPCP 53

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2055392  153 QEPLAKEVSLEQGIVLPCRPPEGIPPAEVEWLRNEDLVDpSLDPNVYITREHSLVVRQARLADTANYTCVAKNIVARRRS 232
Cdd:cd05724   2 VEPSDTQVAVGEMAVLECSPPRGHPEPTVSWRKDGQPLN-LDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERES 80

                ....*..
gi 2055392  233 TSAAVIV 239
Cdd:cd05724  81 RAARLSV 87

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2055392  174 EGIPPAEVEWLRNEDLVDPSLDPNVYITRE----HSLVVRQARLADTANYTCVAKNIvARRRSTSAAVIV 239
Cdd:cd20951  25 QGKPDPEVKWYKNGVPIDPSSIPGKYKIESeygvHVLHIRRVTVEDSAVYSAVAKNI-HGEASSSASVVV 93

Death domain of Myeloid Differentation primary response protein MyD88; Death Domain (DD) of Myeloid Differentiation primary response protein 88 (MyD88). MyD88 is an adaptor protein involved in interleukin-1 receptor (IL-1R)- and Toll-like receptor (TLR)-induced activation of nuclear factor-kappaB (NF-kB) and mitogen activated protein kinase pathways that lead to the induction of proinflammatory cytokines. It is a key component in the signaling pathway of pathogen recognition in the innate immune system. MyD88 contains an N-terminal DD and a C-terminal Toll/IL-1 Receptor (TIR) homology domain that mediates interaction with TLRs and IL-1R. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2055392  816 RQKIIASLDPPCSRGADWRTLAQKLHLDS-HLSFFASKPSPTAMILNLWEARHfPNGNLGQL 876
Cdd:cd08312   2 RKKLSLYLNPEKVVANDWRGLAELMGFDYlEIRNFERQSSPTERLLEDWETRP-PGATVGNL 62

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2055392    151 FEQEPLAKEVSLEQGIVLPCRPpEGIPPAEVEWLRNEDLVDPSldPNVYITRE---HSLVVRQARLADTANYTCVAKNIV 227
Cdd:pfam07679   3 FTQKPKDVEVQEGESARFTCTV-TGTPDPEVSWFKDGQPLRSS--DRFKVTYEggtYTLTISNVQPDDSGKYTCVATNSA 79

                          90
                  ....*....|..
gi 2055392    228 ArRRSTSAAVIV 239
Cdd:pfam07679  80 G-EAEASAELTV 90

Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an alternative disulphide binding pattern compared to the canonical TSP1 domain.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 2055392    246 STWTEWSVCSASCGRGWQKRSRSCTNPaPLNGGAFC 281
Cdd:pfam19028   4 SEWSEWSECSVTCGGGVQTRTRTVIVE-PQNGGRPC 38

Death domain of Nuclear Factor-KappaB precursor proteins; Death Domain (DD) of Nuclear Factor-KappaB (NF-kB) precursor proteins. The NF-kB family of transcription factors play a central role in cardiovascular growth, stress response, and inflammation by controlling the expression of a network of different genes. There are five NF-kB proteins, all containing an N-terminal REL Homology Domain (RHD). Two of these, NF-kB1 and NF-kB2 are produced from the processing of the precursor proteins p105 and p100, respectively. In addition to RHD, p105 and p100 contain ANK repeats and a C-terminal DD. NF-kBs are regulated by the Inhibitor of NF-kB (IkB) Kinase (IKK) complex through classical and non-canonical pathways, which differ in the IKK subunits involved and downstream targets. IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. The precursor proteins p105 and p100 function as IkBs and as NF-kB proteins after being processed by the proteasome. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2055392  823 LDPPCsrgaDWRTLAQKLHLDSHLSFFASKPSPTAMILNLWEARhfpNGNLGQLAAAVAGLGQPDA 888
Cdd:cd08310   9 LDVGK----DWRELAELLGLGHLVESIEQSSSPTKLLLDYYEAQ---GGTLEKLREALRALGETDA 67

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2055392  151 FEQEPL-AKEVSLEQGIVLPCRPpEGIPPAEVEWLRNEDLVdpSLDPNVYITREHSLVVRQARLADTANYTCVAKNIVAR 229
Cdd:cd20978   3 FIQKPEkNVVVKGGQDVTLPCQV-TGVPQPKITWLHNGKPL--QGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGD 79

                ....
gi 2055392  230 RRST 233
Cdd:cd20978  80 IYTE 83

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2055392     166 IVLPCRPPeGIPPAEVEWLRNeDLVDPSLDPNVYITRE---HSLVVRQARLADTANYTCVAKN 225
Cdd:smart00410  12 VTLSCEAS-GSPPPEVTWYKQ-GGKLLAESGRFSVSRSgstSTLTISNVTPEDSGTYTCAATN 72

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2055392    245 WSTwTEWSVCSASCGRGWQKRSRSCTNPAP--LNGGAFCEGQ 284
Cdd:pfam19030   1 WVA-GPWGECSVTCGGGVQTRLVQCVQKGGgsIVPDSECSAQ 41

Second immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins. L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1 that involves abnormalities of axonal growth. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2055392  158 KEVSLEQG--IVLPCRPPEGIPPAEVEWLrNEDLVDPSLDPNVYITREHSLVVRQARLADTAN-YTCVA 223
Cdd:cd05845   5 DPVEVEEGdpVVLPCNPPKGAPPPRIYWM-NSSLEHITQDERVSMGQNGDLYFSNVMEQDSHPdYICHA 72

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

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gi 2055392  153 QEPLAKEVSLEQGIVLPCRPPEGIPPAEVEWLRNEDLVDPSLDPNVYI--TREHS-LVVRQARLADTANYTCVAKNIVAr 229
Cdd:cd05750   4 KEMKSQTVQEGSKLVLKCEATSENPSPRYRWFKDGKELNRKRPKNIKIrnKKKNSeLQINKAKLEDSGEYTCVVENILG- 82

                        90
                ....*....|
gi 2055392  230 RRSTSAAVIV 239
Cdd:cd05750  83 KDTVTGNVTV 92

Second Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the second Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

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gi 2055392  165 GIVLPCRPPEGIPPAEVEWLRNEDLVDPSLDPNVYITREH-SLVVRQARLADTANYTCVAKNIV 227
Cdd:cd05727  12 GVVLFCDPPPHYPDLSYRWLLNEFPNFIPEDGRRFVSQTNgNLYIAKVEASDRGNYSCFVSSPS 75

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

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gi 2055392  153 QEPLAKEVSLEQGIVLPCRPpEGIPPAEVEWLRNEDLVDPSLDPNVYITREHSLVVRQARLADTANYTCVAKN 225
Cdd:cd20970   7 QPSFTVTAREGENATFMCRA-EGSPEPEISWTRNGNLIIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASN 78

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

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gi 2055392    159 EVSLEQGIVLPCRPPEGIPPAEVEWLRnEDLVDPSLD---PNVYITREHSLVVRQARLADTANYTCVAKN 225
Cdd:pfam00047   7 TVLEGDSATLTCSASTGSPGPDVTWSK-EGGTLIESLkvkHDNGRTTQSSLLISNVTKEDAGTYTCVVNN 75

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

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gi 2055392  155 PLAKEVSLEQGIVLPCRPpEGIPPAEVEWLRNEDLVDPslDPNVYITREHSLVVRQARLADTANYTCVAKNIVARRRSTS 234
Cdd:cd20968   6 PTNVTIIEGLKAVLPCTT-MGNPKPSVSWIKGDDLIKE--NNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIAYSKP 82

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gi 2055392  235 AAVIV 239
Cdd:cd20968  83 VTIEV 87

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-2 (KDR/Flk-1) is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A; VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGF-A also interacts with VEGFR-1, which it binds more strongly than VEGFR-2. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

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gi 2055392  175 GIPPAEVEWLRNEDLvdpsLDPNVYITREHSLVVRQARLADTANYTCVAKN 225
Cdd:cd05864  28 GYPPPEIKWYKNGIP----IESNHTIKAGHVLTIMEVTEKDAGNYTVVLTN 74