Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1407503533  210 PYIVMNPEMKARRAGQSVSLCCKATGKPSPdKYFWYHNNTLLDP------SLYKHESKLVLRNLQQDQAGEYFCKA 279
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPP-TITWYKNGEPISSgstrsrSLSGSNSTLTISNVTRSDAGTYTCVA 76

Mucin-2 protein WxxW repeating region; This family is repeating region found on mucins 2 and 5. The function is not known, but the repeat can be present in up to 32 copies, as in Swiss:C3Y5K5, from Branchiostoma floridae. The region carries a highly conserved WxxW sequence motif and also has at least six well conserved cysteine residues.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1407503533    1 MPAGSTGQVVHGSPREGFWCLNREQRPGQnCSNYTVRFLC 40
Cdd:pfam13330   47 VPASETGQVVTCDVTTGLVCRNADQQPDG-CLDYEVRFLC 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1407503533  210 PYIVMNPEMKARRAGQSVSLCCKATGKPSPdKYFWYHNNTLLDP------SLYKHESKLVLRNLQQDQAGEYFCKA 279
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPP-TITWYKNGEPISSgstrsrSLSGSNSTLTISNVTRSDAGTYTCVA 76

Mucin-2 protein WxxW repeating region; This family is repeating region found on mucins 2 and 5. The function is not known, but the repeat can be present in up to 32 copies, as in Swiss:C3Y5K5, from Branchiostoma floridae. The region carries a highly conserved WxxW sequence motif and also has at least six well conserved cysteine residues.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1407503533    1 MPAGSTGQVVHGSPREGFWCLNREQRPGQnCSNYTVRFLC 40
Cdd:pfam13330   47 VPASETGQVVTCDVTTGLVCRNADQQPDG-CLDYEVRFLC 85

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 1407503533  210 PYIVMNPE-MKARRAGQSVSLCCKATGKPSPdKYFWYHNNTLLDPSLYK---HESKLVLRNLQQDQAGEYFCKAQSDAGA 285
Cdd:cd20978      1 PKFIQKPEkNVVVKGGQDVTLPCQVTGVPQP-KITWLHNGKPLQGPMERatvEDGTLTIINVQPEDTGYYGCVATNEIGD 79

                   ....*.
gi 1407503533  286 VKSKVT 291
Cdd:cd20978     80 IYTETL 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1407503533  210 PYIVMNPEMKARRAGQSVSLCCKATGKPSPdKYFWYHNNTLLDP------SLYKHESKLVLRNLQQDQAGEYFCKA 279
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPP-TITWYKNGEPISSgstrsrSLSGSNSTLTISNVTRSDAGTYTCVA 76

Mucin-2 protein WxxW repeating region; This family is repeating region found on mucins 2 and 5. The function is not known, but the repeat can be present in up to 32 copies, as in Swiss:C3Y5K5, from Branchiostoma floridae. The region carries a highly conserved WxxW sequence motif and also has at least six well conserved cysteine residues.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1407503533    1 MPAGSTGQVVHGSPREGFWCLNREQRPGQnCSNYTVRFLC 40
Cdd:pfam13330   47 VPASETGQVVTCDVTTGLVCRNADQQPDG-CLDYEVRFLC 85

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1407503533  210 PYIVMNPEMKARRAGQSVSLCCKATGKPSPDkYFWYHNNTLLDPS-----LYKH-ESKLVLRNLQQDQAGEYFCKAQSDA 283
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPE-VSWFKDGQPLRSSdrfkvTYEGgTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|..
gi 1407503533  284 GAVKSKVTqLTV 295
Cdd:pfam07679   80 GEAEASAE-LTV 90

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 1407503533  227 VSLCCKATGKPSPdKYFWYHNNTLLDPS------LYKHESKLVLRNLQQDQAGEYFCKAQSDAGAVKSKVT 291
Cdd:cd00096      1 VTLTCSASGNPPP-TITWYKNGKPLPPSsrdsrrSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 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 1407503533  210 PYIVMNPEMKARRAGQSVSLCCKATGKPSPdKYFWYHNNTLLDPSLYK------HESKLVLRNLQQDQAGEYFCKAQSDA 283
Cdd:cd05736      1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLP-RVQWLKNGMDINPKLSKqltliaNGSELHISNVRYEDTGAYTCIAKNEG 79

                   .
gi 1407503533  284 G 284
Cdd:cd05736     80 G 80

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1407503533  222 RAGQSVSLCCKATGKPSPdKYFWYHNNTLLDPSlykheSKLVLRNLQQDQAGEYFCKAQSDAGAVKSKVTQLTV 295
Cdd:pfam13895   12 TEGEPVTLTCSAPGNPPP-SYTWYKDGSAISSS-----PNFFTLSVSAEDSGTYTCVARNGRGGKVSNPVELTV 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        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1407503533  214 MNPEMKARRAGQSVSLCCKATGKPSPDkYFWYHNNTLLDPSLYKHESK----LVLRNLQQDQAGEYFCKAQSDAGAV 286
Cdd:cd05856      9 MRRRVIARPVGSSVRLKCVASGNPRPD-ITWLKDNKPLTPPEIGENKKkkwtLSLKNLKPEDSGKYTCHVSNRAGEI 84

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). 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 1407503533  210 PYIVMNPEMKARRAGQSVSLCCKATGKPSPDkYFWYHNNTLLDP----SLYKHES---KLVLRNLQQDQAGEYFCKAQSD 282
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPD-LFWQLNGKPVRPdsahKMLVRENgrhSLIIEPVTKRDAGIYTCIARNR 79

                           90
                   ....*....|...
gi 1407503533  283 AGAVKSKvTQLTV 295
Cdd:cd05744     80 AGENSFN-AELVV 91

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 1407503533  222 RAGQSVSLCCKATGKPSPDKYFWYHNNTLLDPSLYKHESK-------LVLRNLQQDQAGEYFCKAqSDAGAVKSKVTQL 293
Cdd:pfam00047    9 LEGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHDNgrttqssLLISNVTKEDAGTYTCVV-NNPGGSATLSTSL 86

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1407503533  210 PYIVMNPEMKARRAGQSVSLCCKATGKPSPdKYFWYHNNTLLDPSLYK-----------HESKLVLRNLQQDQAGEYFCK 278
Cdd:cd05734      2 PRFVVQPNDQDGIYGKAVVLNCSADGYPPP-TIVWKHSKGSGVPQFQHivplngriqllSNGSLLIKHVLEEDSGYYLCK 80

                           90
                   ....*....|....*..
gi 1407503533  279 AQSDAGAVKSKVTQLTV 295
Cdd:cd05734     81 VSNDVGADISKSMYLTV 97

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1407503533  216 PEMKARRA--------GQSVSLCCKATGKPSPDkYFWYHNNTLLDPSLYKHE-----SKLVLRNLQQDQAGEYFCKAQSD 282
Cdd:cd05730      2 PTIRARQSevnatanlGQSVTLACDADGFPEPT-MTWTKDGEPIESGEEKYSfnedgSEMTILDVDKLDEAEYTCIAENK 80

                   ..
gi 1407503533  283 AG 284
Cdd:cd05730     81 AG 82

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. 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' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1407503533  220 ARRAGQSVSLCCKATGKPSPDkYFWYHNNTLLdpslyKHESKLVLRNLQQDQAGEYFCKAQSDAGAvKSKVTQLTV 295
Cdd:cd20948      6 YYLSGENLNLSCHAASNPPAQ-YSWTINGTFQ-----TSSQELFLPAITENNEGTYTCSAHNSLTG-KNISLVLSV 74

Second immunoglobulin (Ig)-like domain of Axl/Tyro3 family receptor tyrosine kinases (RTKs); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in the Axl/Tyro3 family of receptor tyrosine kinases (RTKs). This family includes Axl (also known as Ark, Ufo, and Tyro7), Tyro3 (also known as Sky, Rse, Brt, Dtk, and Tif), and Mer (also known as Nyk, c-Eyk, and Tyro12). Axl/Tyro3 family receptors have an extracellular portion with two Ig-like domains followed by two fibronectin-types III (FNIII) domains, a membrane-spanning single helix, and a cytoplasmic tyrosine kinase domain. Axl, Tyro3, and Mer are widely expressed in adult tissues, though they show higher expression in the brain, lymphatic and vascular systems, and testis. Axl, Tyro3, and Mer bind the vitamin K dependent protein Gas6 with high affinity, and in doing so activate their tyrosine kinase activity. Axl/Gas6 signaling may play a part in cell adhesion processes, prevention of apoptosis, and cell proliferation.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1407503533  211 YIVMNPEMKARRAGQSVSLCCKATGKPSPDKYFWYHNNTLLDPSLYKHESKLVLRNLQQDQAgeYFCKAQSDAGAVKSKV 290
Cdd:cd05749      1 HFTVEPEDLAVTANTPFNLTCQAVGPPEPVEILWWQGGSPLGGPPAPSPSVLNVPGLNETTK--FSCEAHNAKGLTSSRT 78

                   ....
gi 1407503533  291 TQLT 294
Cdd:cd05749     79 ATVT 82

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1407503533  214 MNPEMKARRAGQSVSLCCKATGKPSPD-------KYFWYHNNTlldpSLYKHESK---LVLRNLQQDQAGEYFCKAQSDA 283
Cdd:cd05729      9 MEEREHALPAANKVRLECGAGGNPMPNitwlkdgKEFKKEHRI----GGTKVEEKgwsLIIERAIPRDKGKYTCIVENEY 84

                   ...
gi 1407503533  284 GAV 286
Cdd:cd05729     85 GSI 87

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1407503533  210 PYIVMNPEMKARRAGQS-VSLCCKATGKPSPdKYFWYHNNTLL-----DPSLYKHESKLVLRNLQQDQAGEYFCKAQSDA 283
Cdd:cd05760      1 PVVLKHPASAAEIQPSSrVTLRCHIDGHPRP-TYQWFRDGTPLsdgqgNYSVSSKERTLTLRSAGPDDSGLYYCCAHNAF 79

                   ....*
gi 1407503533  284 GAVKS 288
Cdd:cd05760     80 GSVCS 84