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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767979942   11 SPLVTREGDTIELQCQVTGKPKPIILWSRADKEVAmPDGSMQM--ESYDGTLRIVNVSREMSGMYRCQ 76
Cdd:pfam07679   8 KDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLR-SSDRFKVtyEGGTYTLTISNVQPDDSGKYTCV 74

MAM domain, meprin/A5/mu; An extracellular domain found in many receptors. The MAM domain along with the associated Ig domain in type IIB receptor protein tyrosine phosphatases forms a structural unit (termed MIg) with a seamless interdomain interface. It plays a major role in homodimerization of the phosphatase ectoprotein and in cell adhesion. MAM is a beta-sandwich consisting of two five-stranded antiparallel beta-sheets rotated away from each other by approx 25 degrees, and plays a similar role in meprin metalloproteinases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979942  308 CGFEDGNICLFTQDDTDNFDWTkqstatRNTKYTPNTGPNADRSGSKE-GFYMYIETSRPRlEGEKARLLSPvfsiapkn 386
Cdd:pfam00629   1 CDFEDGNLCGWTQDSSDDFDWE------RVSGPSVKTGPSSDHTQGTGsGHFMYVDTSSGA-PGQTARLLSP-------- 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979942  387 PYGPTNTAYCFSFFYHMYGQHIGVLNVYLRLKGQTTiENPLWSSSGNKGQRWNEAHVNIYPITS-FQLIFEGIRGPGIEG 465
Cdd:pfam00629  66 LLPPSRSPQCLRFWYHMSGSGVGTLRVYVRENGGTL-DTLLWSISGDQGPSWKEARVTLSSSTQpFQVVFEGIRGGGSRG 144

                         170
                  ....*....|....*
gi 767979942  466 DIAIDDVSIAEGECA 480
Cdd:pfam00629 145 GIALDDISLSSGPCP 159

Immunoglobulin I-set domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767979942   11 SPLVTREGDTIELQCQVTGKPKPIILWSRADKEVAmPDGSMQM--ESYDGTLRIVNVSREMSGMYRCQ 76
Cdd:pfam07679   8 KDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLR-SSDRFKVtyEGGTYTLTISNVQPDDSGKYTCV 74

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767979942  17 EGDTIELQCQVTGKPKPIILWSRADKEVAMPDGSMQMEsyDGTLRIVNVSREMSGMYRCQTSQYNG 82
Cdd:cd20978   15 GGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVE--DGTLTIINVQPEDTGYYGCVATNEIG 78

MAM domain, meprin/A5/mu; An extracellular domain found in many receptors. The MAM domain along with the associated Ig domain in type IIB receptor protein tyrosine phosphatases forms a structural unit (termed MIg) with a seamless interdomain interface. It plays a major role in homodimerization of the phosphatase ectoprotein and in cell adhesion. MAM is a beta-sandwich consisting of two five-stranded antiparallel beta-sheets rotated away from each other by approx 25 degrees, and plays a similar role in meprin metalloproteinases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979942  308 CGFEDGNICLFTQDDTDNFDWTkqstatRNTKYTPNTGPNADRSGSKE-GFYMYIETSRPRlEGEKARLLSPvfsiapkn 386
Cdd:pfam00629   1 CDFEDGNLCGWTQDSSDDFDWE------RVSGPSVKTGPSSDHTQGTGsGHFMYVDTSSGA-PGQTARLLSP-------- 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979942  387 PYGPTNTAYCFSFFYHMYGQHIGVLNVYLRLKGQTTiENPLWSSSGNKGQRWNEAHVNIYPITS-FQLIFEGIRGPGIEG 465
Cdd:pfam00629  66 LLPPSRSPQCLRFWYHMSGSGVGTLRVYVRENGGTL-DTLLWSISGDQGPSWKEARVTLSSSTQpFQVVFEGIRGGGSRG 144

                         170
                  ....*....|....*
gi 767979942  466 DIAIDDVSIAEGECA 480
Cdd:pfam00629 145 GIALDDISLSSGPCP 159

Immunoglobulin I-set domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767979942   11 SPLVTREGDTIELQCQVTGKPKPIILWSRADKEVAmPDGSMQM--ESYDGTLRIVNVSREMSGMYRCQ 76
Cdd:pfam07679   8 KDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLR-SSDRFKVtyEGGTYTLTISNVQPDDSGKYTCV 74

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767979942    9 EKSPLVTREGDTIELQCQVTGKPKPIILWSRADKEVA-MPDGSMQMESYDGTLRIVNVSREMSGMYRCQTS 78
Cdd:pfam13927   7 SPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISsGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 767979942  21 IELQCQVTGKPKPIILWSRADKEVAM-PDGSMQMESYDGTLRIVNVSREMSGMYRCQ 76
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPsSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767979942  10 KSPLVTREGDTIeLQCQVTGKPKPIILWSRADKEVAMPDGSMQMEsyDGTLRIVNVSREMSGMYRCQTSQYNG 82
Cdd:cd04969   10 KKILAAKGGDVI-IECKPKASPKPTISWSKGTELLTNSSRICILP--DGSLKIKNVTKSDEGKYTCFAVNFFG 79

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and 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, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767979942   9 EKSPLVTReGDTIELQCQVTGKPKPIILWSRADKEvaMPDGSMQMESYDGTLRIVNVSREMSGMYRCQTSQYNG 82
Cdd:cd05731    2 ESSTMVLR-GGVLLLECIAEGLPTPDIRWIKLGGE--LPKGRTKFENFNKTLKIENVSEADSGEYQCTASNTMG 72

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767979942   9 EKSPLVTREGDTIELQCQVTGKPKPIILWSRADKEVAMPDGSMQMESYDGTLRIVNVSREMSGMYRCQTSQYNGF 83
Cdd:cd04978    5 EPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHGY 79

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767979942    8 QEKSPLVTREGDTIELQCQV-TGKPKPIILWSRADKEVAMPDGSMQMESYDG--TLRIVNVSREMSGMYRCQTS 78
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGRTTqsSLLISNVTKEDAGTYTCVVN 74

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 767979942   8 QEKSPLVTREGDTIELQCQVTGKPKPIILWSRADKEVAMPDGSMQMESyDGTLRIVNVSREMSGMYRC 75
Cdd:cd20952    4 QGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLE-NGSLQIKGAEKSDTGEYTC 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979942   3 IYPAAQEKSPlvtreGDTIELQCQVTGKPKPIILWSRADKEVaMPDGSMQME-SYDGT-LRIVNVSREMSGMYRCQTSQY 80
Cdd:cd05736    5 VYPEFQAKEP-----GVEASLRCHAEGIPLPRVQWLKNGMDI-NPKLSKQLTlIANGSeLHISNVRYEDTGAYTCIAKNE 78

                         90
                 ....*....|....*..
gi 767979942  81 NGFNvkprEALVQLIVQ 97
Cdd:cd05736   79 GGVD----EDISSLFVE 91

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767979942  18 GDTIELQCQVTGKPKPIILWSRADKevAMPdGSMQMESYDGTLRIVNVSREMSGMYRCQTSQYNG 82
Cdd:cd05851   16 GQNVTLECFALGNPVPVIRWRKILE--PMP-ATAEISMSGAVLKIFNIQPEDEGTYECEAENIKG 77

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth 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 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, 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, and 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 Slit2 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979942  14 VTREGDTIELQCQVTGKPKPIILWSRADKEVAM-PDGSMQ-----MESYDGTLRIVNVSREMSGMYRCQT 77
Cdd:cd05726   10 VVALGRTVTFQCETKGNPQPAIFWQKEGSQNLLfPYQPPQpssrfSVSPTGDLTITNVQRSDVGYYICQA 79

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). 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 also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767979942  10 KSPLVTREGDTIELQCQVTGKPKPIILWSRADKevAMPDGSMQMESYDGTLRIVNVSREMSGMYRC 75
Cdd:cd05876    2 SSSLVALRGQSLVLECIAEGLPTPTVKWLRPSG--PLPPDRVKYQNHNKTLQLLNVGESDDGEYVC 65

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). 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 human APEG-1 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979942  16 REGDTIELQCQVTGKPKPIILWSRADKEVAMPDGSMQMESYDG--TLRIVNVSREMSGMYRCQTsqYNGFNVKPREALVQ 93
Cdd:cd20975   13 REGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGlcRLRILAAERGDAGFYTCKA--VNEYGARQCEARLE 90

                 .
gi 767979942  94 L 94
Cdd:cd20975   91 V 91

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh 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. This group 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767979942  18 GDTIELQCQVTGKPKPIILWSRAD-------KEVAMPDGSMQMEsyDGTLRIVNVSREMSGMYRCQ 76
Cdd:cd20954   16 GQDVMLHCQADGFPTPTVTWKKATgstpgeyKDLLYDPNVRILP--NGTLVFGHVQKENEGHYLCE 79

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767979942  18 GDTIELQCQVTGKPKPIILWSRADKEV-AMPDGSMQMESYDGTLRIVNVSREMSGMYRCQ 76
Cdd:cd05743    1 GETVEFTCVATGVPTPIINWRLNWGHVpDSARVSITSEGGYGTLTIRDVKESDQGAYTCE 60

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

                         10        20        30        40        50        60
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gi 767979942  13 LVTREGDTIELQCQVTGKPKPIILWSRADKEVaMPDGSMQMESYD--GTLRIVNVSREMSGMYR 74
Cdd:cd05748    2 IVVRAGESLRLDIPIKGRPTPTVTWSKDGQPL-KETGRVQIETTAssTSLVIKNAKRSDSGKYT 64

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

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gi 767979942  15 TREGDTIELQCQVTGKPKPIILWSRADK----EVAMPDGSMQMESYDG--TLRIVNVSREMSGMYRCQTS 78
Cdd:cd05732   13 AVELEQITLTCEAEGDPIPEITWRRATRgisfEEGDLDGRIVVRGHARvsSLTLKDVQLTDAGRYDCEAS 82

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

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gi 767979942  10 KSPLVtrEGDTIELQCQVTG-KPKPIILWSRADKEVAMP-----DGSMQMESYDGTLRIvNVSREMSG-MYRCQ 76
Cdd:cd05761   13 TSPVV--EGDEITLTCTTSGsKPAADIRWFKNDKELKGVkevqeSGAGKTFTVTSTLRF-RVDRDDDGvAVICR 83

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.

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gi 767979942   5 PAAQEKSPLVTREGDTIELQCQVTGKPKPIILWSRaDKEVAMPDGSMQMESYDGTLRIVNVSREMSGMYRCQTSQYNG 82
Cdd:cd05856    6 PAKMRRRVIARPVGSSVRLKCVASGNPRPDITWLK-DNKPLTPPEIGENKKKKWTLSLKNLKPEDSGKYTCHVSNRAG 82

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first 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 767979942   8 QEKSPLVTREGDTIELQCQVTGKPKPIILWSRaDKEVAMPDGS--MQMESYDGT--LRIVNVSREMSGMYRCQTSQYNGF 83
Cdd:cd20974    5 QPLQSVVVLEGSTATFEAHVSGKPVPEVSWFR-DGQVISTSTLpgVQISFSDGRakLSIPAVTKANSGRYSLTATNGSGQ 83

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gi 767979942  84 NVKPREALV 92
Cdd:cd20974   84 ATSTAELLV 92

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. 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. The Ig-like domain of the Twitchin is a member of the I-set 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. 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.

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gi 767979942  16 REGDTIELQCQVTGKPKPIILWSRADKEVAMpdGSMQMESYDGT---LRIVNVSREMSGMYRCQTSQYNG 82
Cdd:cd20949   12 KEGQSATILCEVKGEPQPNVTWHFNGQPISA--SVADMSKYRILadgLLINKVTQDDTGEYTCRAYQVNS 79

First Ig-like domain of Junctional adhesion molecule-1 (JAM1)and similar domains; a member of the V-set of IgSF domains; The members here are composed of the first Ig-like domain of Junctional Adhesion Molecule-1 (JAM1)and similar domains. 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 first Ig-like domain of JAM1 is a member of the V-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C'-C" in the other.

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gi 767979942  17 EGDTIELQCQVTGKP-KPIILWSRADKEVA---MPDGSMQ------MESYDGTLRIVNVSREMSGMYRCQTSQYNGFNvK 86
Cdd:cd20946   13 ENQEVILSCKTPKKTsSPRVEWKKLQRDVTfvvFQNNKIQgdykgrAEILGTNITIKNVTRSDSGKYRCEVSARSDGQ-N 91

                         90
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gi 767979942  87 PREALVQLIVQ 97
Cdd:cd20946   92 LGEVTVTLEVL 102

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and 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 also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. 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 lacks a C" strand.

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gi 767979942   5 PAAQEKSP--LVTREGDTIELQCQVTGKPKPIILWSRADKEVAM---PDGSMQMESydGTLRIVN---VSREMSGMYRCQ 76
Cdd:cd05733    1 PTITEQSPkdYIVDPRDNITIKCEAKGNPQPTFRWTKDGKFFDPakdPRVSMRRRS--GTLVIDNhngGPEDYQGEYQCY 78

                 ..
gi 767979942  77 TS 78
Cdd:cd05733   79 AS 80

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (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 767979942  12 PLVTR--------EGDTIELQCQVTGKPKPIILWSRADKEVaMPDGSMQMESYDGTLRIVNVSREMSGMYRCQTSQYNG 82
Cdd:cd05764    1 PLITRhthelrvlEGQRATLRCKARGDPEPAIHWISPEGKL-ISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAG 78

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

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gi 767979942  15 TREGDTIELQCQVTGKPKPIILWSRA---------DKEvamPDGSMQMESYDG--TLRIVNVSREMSGMYRCQ 76
Cdd:cd05870   13 TVENGAATLSCKAEGEPIPEITWKRAsdghtfsegDKS---PDGRIEVKGQHGesSLHIKDVKLSDSGRYDCE 82