Death domain similar to that found in Mucosa-associated lymphoid tissue-lymphoma-translocation gene 1; Death domain (DD) similar to that found in Malt1 (mucosa-associated lymphoid tissue-lymphoma-translocation gene 1). Malt1, together with Bcl10 (B-cell lymphoma 10), are the integral components of the CBM signalosome. They associate with CARD9 to form M-CBM (CBM complex in myeloid immune cells) and with CARMA1 to form L-CBM (CBM complex in lymphoid immune cells), to mediate activation of NF-kB and MAPK by ITAM-coupled receptors expressed on immune cells. 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564393882  36 LNRLPEPLLRRLSESLDRAPEgRGWRQLAELAGSRGRLRLSCLDLEQCSLKVLEPEGSPSLCLLKLMGEKGCTVPELSDF 115
Cdd:cd08783    1 INSLQEPVLRRLCELLDQASD-KGWRKLAEAVGSDPRFKISSQELEQCSLKVLEPEGSPSRCLLKLMGERGCTLKDLTDF 79

                         90
                 ....*....|....*..
gi 564393882 116 LQALEHTEVLQLLNPPG 132
Cdd:cd08783   80 LQTMGHTEALQLLKPPG 96

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564393882  130 PPglKITVNPESKAVLAGQFVKLCCRATGHPFVQYQWFKMNKEIP---------YGNSSELIFNTVHVKDAGFYVCRVNN 200
Cdd:pfam13927   1 KP--VITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISsgstrsrslSGSNSTLTISNVTRSDAGTYTCVASN 78

Death domain similar to that found in Mucosa-associated lymphoid tissue-lymphoma-translocation gene 1; Death domain (DD) similar to that found in Malt1 (mucosa-associated lymphoid tissue-lymphoma-translocation gene 1). Malt1, together with Bcl10 (B-cell lymphoma 10), are the integral components of the CBM signalosome. They associate with CARD9 to form M-CBM (CBM complex in myeloid immune cells) and with CARMA1 to form L-CBM (CBM complex in lymphoid immune cells), to mediate activation of NF-kB and MAPK by ITAM-coupled receptors expressed on immune cells. 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564393882  36 LNRLPEPLLRRLSESLDRAPEgRGWRQLAELAGSRGRLRLSCLDLEQCSLKVLEPEGSPSLCLLKLMGEKGCTVPELSDF 115
Cdd:cd08783    1 INSLQEPVLRRLCELLDQASD-KGWRKLAEAVGSDPRFKISSQELEQCSLKVLEPEGSPSRCLLKLMGERGCTLKDLTDF 79

                         90
                 ....*....|....*..
gi 564393882 116 LQALEHTEVLQLLNPPG 132
Cdd:cd08783   80 LQTMGHTEALQLLKPPG 96

Caspase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564393882  351 KVALLIGNMNYWEH-PKLKAPLVDVYELTNLLRQLDFKVVSLLDLTEYEMCNAVDEFLLLL-----DKGVYGLLYYAGHG 424
Cdd:pfam00656   2 GLALIIGNNNYPGTkAPLRGCDNDAEALAKTLKSLGFEVRVFEDLTAEEIRRALRDFAARAdhsdgDSFVVVLLYYSGHG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564393882  425 YENFGN------SFMVPVDAPNpyrseNCLCVQNILKLMQEKetgLNVFLLDMCRkRNDYDDTIpildalkVTANIVFGY 498
Cdd:pfam00656  82 EQVPGGdiygtdEYLVPVDALT-----NLFTGDDCLPSLVGK---PKLFIIDACR-GNLEDGGV-------VEADFLVAY 145

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564393882  499 ATCQGAEAFEiqhSGLANGIFMKFLKDRLLEDKK---ITVLLDEVAEDMgkCHLTKGRQALEIRSS 561
Cdd:pfam00656 146 STAPGQVSWR---NTGSGSWFIQALCQVLREYGHgldLLSLLTKVRRRV--AEATGKKQMPCLSSS 206

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564393882  235 KLRICVEPQSQKLAPGSALLLQCVAIGSPVPHYQWFKDESPLAHETKKHY---------TVPYVDLEHEGTYWCHVYN 303
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRslsgsnstlTISNVTRSDAGTYTCVASN 78

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564393882 253 LLLQCVAIGSPVPHYQWFKDESPLAHETKKHY---------TVPYVDLEHEGTYWCHVYNDRDSQDSKKV 313
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRrselgngtlTISNVTLEDSGTYTCVASNSAGGSASASV 70

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564393882   242 PQSQKLAPGSALLLQCVAIGSPVPHYQWFKDESPLAHETKK----------HYTVPYVDLEHEGTYWCHVYND 304
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRfsvsrsgstsTLTISNVTPEDSGTYTCAATNS 73

Death domain similar to that found in Mucosa-associated lymphoid tissue-lymphoma-translocation gene 1; Death domain (DD) similar to that found in Malt1 (mucosa-associated lymphoid tissue-lymphoma-translocation gene 1). Malt1, together with Bcl10 (B-cell lymphoma 10), are the integral components of the CBM signalosome. They associate with CARD9 to form M-CBM (CBM complex in myeloid immune cells) and with CARMA1 to form L-CBM (CBM complex in lymphoid immune cells), to mediate activation of NF-kB and MAPK by ITAM-coupled receptors expressed on immune cells. 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564393882  36 LNRLPEPLLRRLSESLDRAPEgRGWRQLAELAGSRGRLRLSCLDLEQCSLKVLEPEGSPSLCLLKLMGEKGCTVPELSDF 115
Cdd:cd08783    1 INSLQEPVLRRLCELLDQASD-KGWRKLAEAVGSDPRFKISSQELEQCSLKVLEPEGSPSRCLLKLMGERGCTLKDLTDF 79

                         90
                 ....*....|....*..
gi 564393882 116 LQALEHTEVLQLLNPPG 132
Cdd:cd08783   80 LQTMGHTEALQLLKPPG 96

Caspase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564393882  351 KVALLIGNMNYWEH-PKLKAPLVDVYELTNLLRQLDFKVVSLLDLTEYEMCNAVDEFLLLL-----DKGVYGLLYYAGHG 424
Cdd:pfam00656   2 GLALIIGNNNYPGTkAPLRGCDNDAEALAKTLKSLGFEVRVFEDLTAEEIRRALRDFAARAdhsdgDSFVVVLLYYSGHG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564393882  425 YENFGN------SFMVPVDAPNpyrseNCLCVQNILKLMQEKetgLNVFLLDMCRkRNDYDDTIpildalkVTANIVFGY 498
Cdd:pfam00656  82 EQVPGGdiygtdEYLVPVDALT-----NLFTGDDCLPSLVGK---PKLFIIDACR-GNLEDGGV-------VEADFLVAY 145

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564393882  499 ATCQGAEAFEiqhSGLANGIFMKFLKDRLLEDKK---ITVLLDEVAEDMgkCHLTKGRQALEIRSS 561
Cdd:pfam00656 146 STAPGQVSWR---NTGSGSWFIQALCQVLREYGHgldLLSLLTKVRRRV--AEATGKKQMPCLSSS 206

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564393882  235 KLRICVEPQSQKLAPGSALLLQCVAIGSPVPHYQWFKDESPLAHETKKHY---------TVPYVDLEHEGTYWCHVYN 303
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRslsgsnstlTISNVTRSDAGTYTCVASN 78

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564393882 253 LLLQCVAIGSPVPHYQWFKDESPLAHETKKHY---------TVPYVDLEHEGTYWCHVYNDRDSQDSKKV 313
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRrselgngtlTISNVTLEDSGTYTCVASNSAGGSASASV 70

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. 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. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564393882 236 LRICVEPQSQKLAPGSALLLQCVAIGSPVPHYQWFKDESPLAHETKKHYT------VPYVDLEHEGTYWCHVYNDRDS 307
Cdd:cd20957    2 LSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILsedvlvIPSVKREDKGMYQCFVRNDGDS 79

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564393882 250 GSALLLQCVAIGSPVPHYQWFKDESPLAHET-----KKHYTVPYVDL--EHEGTYWCHVYN 303
Cdd:cd05856   19 GSSVRLKCVASGNPRPDITWLKDNKPLTPPEigenkKKKWTLSLKNLkpEDSGKYTCHVSN 79

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564393882   242 PQSQKLAPGSALLLQCVAIGSPVPHYQWFKDESPLAHETKK----------HYTVPYVDLEHEGTYWCHVYND 304
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRfsvsrsgstsTLTISNVTPEDSGTYTCAATNS 73

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564393882  242 PQSQKLAPGSALLLQCVAIGSPVPHYQWFKDESPLA-------HETKKHYT--VPYVDLEHEGTYWCHVYNdRDSQDSKK 312
Cdd:pfam07679   7 PKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRssdrfkvTYEGGTYTltISNVQPDDSGKYTCVATN-SAGEAEAS 85

                  ....*
gi 564393882  313 VEIII 317
Cdd:pfam07679  86 AELTV 90

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of 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, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -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, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -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 Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564393882 238 ICVEPQSQKLAPGSALLLQCVAIGSPVPHYQWFKDESPLAHETKKHYTVP-------YVDLEHEGTYWC 299
Cdd:cd20952    2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLEngslqikGAEKSDTGEYTC 70

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, 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 found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564393882 135 ITVNPESKAVLAGQFVKLCCRATGHPFVQYQWFKMNKEIPY---------GNSSELIFNTVHVKDAGFYVCRVNN 200
Cdd:cd05736    3 IRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPklskqltliANGSELHISNVRYEDTGAYTCIAKN 77

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564393882 238 ICVEPQSQKLAPGSALLLQCVAIGSPVPHYQWFK-DESPLA----HETKKHYTVPYVDLEHEGTYWCHVYNDR 305
Cdd:cd04968    4 KVRFPADTYALKGQTVTLECFALGNPVPQIKWRKvDGSPSSqweiTTSEPVLEIPNVQFEDEGTYECEAENSR 76

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564393882  240 VEPQSQKLAPGSALLLQC-VAIGSPVPHYQWFKD--ESPLAHETKKHY--------TVPYVDLEHEGTYWChVYNDRDSQ 308
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCsASTGSPGPDVTWSKEggTLIESLKVKHDNgrttqsslLISNVTKEDAGTYTC-VVNNPGGS 79

                  ....*..
gi 564393882  309 DSKKVEI 315
Cdd:pfam00047  80 ATLSTSL 86

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 564393882 242 PQSQKLAPGSALLLQCVAIGSPVPHYQWFKDESPLAHE 279
Cdd:cd05739    4 PSNHEVMPGGSVNLTCVAVGAPMPYVKWMKGGEELTKE 41

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, 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 found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564393882 238 ICVEPQSQKLAPGSALLLQCVAIGSPVPHYQWFKDESPLAHETKKHYT---------VPYVDLEHEGTYWCHVYN----D 304
Cdd:cd05736    3 IRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKLSKQLTliangselhISNVRYEDTGAYTCIAKNeggvD 82

                 ..
gi 564393882 305 RD 306
Cdd:cd05736   83 ED 84

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564393882 136 TVNPESKavLAGQfVKLCCRATGHPFVQYQWFKMNKEIPYGNS-------SELIFNTVHVKDAGFYVCRVNNN 201
Cdd:cd05849   11 TIYPEES--TEGK-VSVNCRARANPFPIYKWRKNNLDIDLTNDrysmvggNLVINNPDKYKDAGRYVCIVSNI 80

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

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gi 564393882 140 ESKAVLAGQFVKLCCRATG-HPFVQYQWFKMNKEIPYGN------------SSELIFNTVHVKDAGFYVCRVNN 200
Cdd:cd05895    7 KSQEVAAGSKLVLRCETSSeYPSLRFKWFKNGKEINRKNkpenikiqkkkkKSELRINKASLADSGEYMCKVSS 80

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 564393882 235 KLRicvEPQSQKLAPGSALLLQCVAIG-SPVPHYQWFKDESPLAHETKKHYTVP-----------YVDLEHEGTYWCHVY 302
Cdd:cd05750    2 KLK---EMKSQTVQEGSKLVLKCEATSeNPSPRYRWFKDGKELNRKRPKNIKIRnkkknselqinKAKLEDSGEYTCVVE 78

                         90
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gi 564393882 303 NdRDSQDSKKVEIII 317
Cdd:cd05750   79 N-ILGKDTVTGNVTV 92

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

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gi 564393882 142 KAVLAGQFVKLCCRATGHPFVQYQWFKMNKEI-------PYGNSSE---LIFNTVHVKDAGFYVCRVNN 200
Cdd:cd05729   14 HALPAANKVRLECGAGGNPMPNITWLKDGKEFkkehrigGTKVEEKgwsLIIERAIPRDKGKYTCIVEN 82

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The 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 second Ig-like domain of JAM1 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, the A strand of the I-set is discontinuous but lacks 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.

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gi 564393882 136 TVNPESKAVLAGQFVKLCCRATGHPFVQYQWFKMNKEIP--------YGNSS--------ELIFNTVHVKDAGFYVCRVN 199
Cdd:cd20950    2 TVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDGVVMPtnpkstraFSNSSysldpttgELVFDPLSASDTGEYSCEAR 81

                 .
gi 564393882 200 N 200
Cdd:cd20950   82 N 82

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of 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 (Slit1, Slit2, Slit3), 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 Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 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 Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

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gi 564393882 237 RICVEPQSQKLAPGSALLLQCVAIGSPVPHYQWFKDESPLahETKK------HYTVPYVDL------------EHEGTYW 298
Cdd:cd07693    2 RIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPL--ETDKddprshRIVLPSGSLfflrvvhgrkgrSDEGVYV 79

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gi 564393882 299 CHVYN 303
Cdd:cd07693   80 CVAHN 84

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. 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. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

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gi 564393882 133 LKITVNPESKAVLAGQFVKLCCRATGHPFVQYQWFKMNKEIPYGNSSELIF-NTVHVK-----DAGFYVCRVNN 200
Cdd:cd20957    2 LSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSeDVLVIPsvkreDKGMYQCFVRN 75

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

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gi 564393882 249 PGSALLLQCVAIGSPVPHYQWFKDESPLAHETKKH--------YTVPYVDLEHEGTYWCHVYN 303
Cdd:cd05760   15 PSSRVTLRCHIDGHPRPTYQWFRDGTPLSDGQGNYsvsskertLTLRSAGPDDSGLYYCCAHN 77

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk 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. 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 titin Z1z2 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 564393882 241 EPQSQKLAPGSALLLQCVAIGSPVPHYQWFKDESPLA-------HETKKHYTVPYVDL--EHEGTYWCHVYNDRDSqDSK 311
Cdd:cd20972    7 KLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQnspdiqiHQEGDLHSLIIAEAfeEDTGRYSCLATNSVGS-DTT 85

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gi 564393882 312 KVEIII 317
Cdd:cd20972   86 SAEIFV 91