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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116006967 252 PRLKEMKSQESAAGSKLVLRCETSSEYSSLRFKWFKNGNELNRKNKPQNIKIQKKPGKSELRINKASLADSGEYMCKVIS 331
Cdd:cd05895    1 PKLKEMKSQEVAAGSKLVLRCETSSEYPSLRFKWFKNGKEINRKNKPENIKIQKKKKKSELRINKASLADSGEYMCKVSS 80

                         90
                 ....*....|...
gi 116006967 332 KLGNDSASANITI 344
Cdd:cd05895   81 KLGNDSASANVTI 93

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116006967 252 PRLKEMKSQESAAGSKLVLRCETSSEYSSLRFKWFKNGNELNRKNKPQNIKIQKKPGKSELRINKASLADSGEYMCKVIS 331
Cdd:cd05895    1 PKLKEMKSQEVAAGSKLVLRCETSSEYPSLRFKWFKNGKEINRKNKPENIKIQKKKKKSELRINKASLADSGEYMCKVSS 80

                         90
                 ....*....|...
gi 116006967 332 KLGNDSASANITI 344
Cdd:cd05895   81 KLGNDSASANVTI 93

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116006967  254 LKEMKSQESAAGSKLVLRCETSsEYSSLRFKWFKNGNELNRKNKpqnIKIQKKPGKSELRINKASLADSGEYMCKVISKL 333
Cdd:pfam07679   4 TQKPKDVEVQEGESARFTCTVT-GTPDPEVSWFKDGQPLRSSDR---FKVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                          90
                  ....*....|.
gi 116006967  334 GNDSASANITI 344
Cdd:pfam07679  80 GEAEASAELTV 90

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 116006967  371 CVNGGECFMVkdlsnPSRYLCKCPNEFTGDR 401
Cdd:pfam00008   6 CSNGGTCVDT-----PGGYTCICPEGYTGKR 31

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116006967 252 PRLKEMKSQESAAGSKLVLRCETSSEYSSLRFKWFKNGNELNRKNKPQNIKIQKKPGKSELRINKASLADSGEYMCKVIS 331
Cdd:cd05895    1 PKLKEMKSQEVAAGSKLVLRCETSSEYPSLRFKWFKNGKEINRKNKPENIKIQKKKKKSELRINKASLADSGEYMCKVSS 80

                         90
                 ....*....|...
gi 116006967 332 KLGNDSASANITI 344
Cdd:cd05895   81 KLGNDSASANVTI 93

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116006967   258 KSQESAAGSKLVLRCETSSeYSSLRFKWFKNGNELnrKNKPQNIKIQKKPGKSELRINKASLADSGEYMCKVISKLGNDS 337
Cdd:smart00410   2 PSVTVKEGESVTLSCEASG-SPPPEVTWYKQGGKL--LAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSAS 78

                   ....*..
gi 116006967   338 ASANITI 344
Cdd:smart00410  79 SGTTLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116006967  254 LKEMKSQESAAGSKLVLRCETSsEYSSLRFKWFKNGNELNRKNKpqnIKIQKKPGKSELRINKASLADSGEYMCKVISKL 333
Cdd:pfam07679   4 TQKPKDVEVQEGESARFTCTVT-GTPDPEVSWFKDGQPLRSSDR---FKVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                          90
                  ....*....|.
gi 116006967  334 GNDSASANITI 344
Cdd:pfam07679  80 GEAEASAELTV 90

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116006967 251 PPR-LKEMKSQESAAGSKLVLRCETSSEySSLRFKWFKNGNELnrKNKPqNIKIQKKPGKSELRINKASLADSGEYMCKV 329
Cdd:cd20972    1 PPQfIQKLRSQEVAEGSKVRLECRVTGN-PTPVVRWFCEGKEL--QNSP-DIQIHQEGDLHSLIIAEAFEEDTGRYSCLA 76

                         90
                 ....*....|....*
gi 116006967 330 ISKLGNDSASANITI 344
Cdd:cd20972   77 TNSVGSDTTSAEIFV 91

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116006967  251 PPRLK-EMKSQESAAGSKLVLRCETSSeYSSLRFKWFKNGNELNrknKPQNIKIQKKPGKSELRINKASLADSGEYMCKV 329
Cdd:pfam13927   1 KPVITvSPSSVTVREGETVTLTCEATG-SPPPTITWYKNGEPIS---SGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. 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 structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. 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 116006967 261 ESAAGSKLVLRCETSSEYSSLRfkWFKNGNELNRKNKpqnIKIQKKPGKSELRINKASLADSGEYMCKV 329
Cdd:cd20967    8 QVSKGHKIRLTVELADPDAEVK--WYKDGQELQSSSK---VIFESIGAKRTLTVQQASLADAGEYQCVA 71

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116006967 265 GSKLVLRCETS-SEYSSLRFKWFKNGNELNRkNKPqNIKIQKKPGK---SELRINKASLADSGEYMCKVISKLGNDSASA 340
Cdd:cd04970   17 GENATLQCHAShDPTLDLTFTWSFNGVPIDL-EKI-EGHYRRRYGKdsnGDLEIVNAQLKHAGRYTCTAQTVVDSDSASA 94

                 ....
gi 116006967 341 NITI 344
Cdd:cd04970   95 TLVV 98

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116006967 252 PRLKEMKSQESAAGSKLVLRCETSSE-YSSLRFKWFKNGNELNRKNKPQNIKIQKKPGKSELRINKASLADSGEYMCKVI 330
Cdd:cd05732    3 PKITYLENQTAVELEQITLTCEAEGDpIPEITWRRATRGISFEEGDLDGRIVVRGHARVSSLTLKDVQLTDAGRYDCEAS 82

                 ....*....
gi 116006967 331 SKLGNDSAS 339
Cdd:cd05732   83 NRIGGDQQS 91

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R); member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members, VEGFR-1 (also known as Flt-1), VEGFR-2 (also known as KDR or Flk-1) and VEGFR-3 (also known as Flt-4). VEGF_A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF, VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-2 and -1 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116006967 258 KSQESAAGSKLVLRCETSSEYSS-LRFKW-FKNGNELNRKNKPQNIKIQKKPGK---SELRINKASLADSGEYMCKVISK 332
Cdd:cd05862    9 KPVELLVGEKLVLNCTARTELNVgVDFQWdYPGKKEQRRASVRRRRKQQSSEATefsSTLTIDNVTLSDKGLYTCAASSG 88

                         90
                 ....*....|....
gi 116006967 333 LGNDSASANITIVE 346
Cdd:cd05862   89 PMFKKNSTSVIVHE 102

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 116006967 258 KSQESAAGSKLVLRCETSSEySSLRFKWFKNGNELNRKnkpQNIKIQKKPGKSELRINKASLADSGEYMCKVISKLGNDS 337
Cdd:cd05736    8 EFQAKEPGVEASLRCHAEGI-PLPRVQWLKNGMDINPK---LSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEGGVDE 83

                         90
                 ....*....|
gi 116006967 338 ASANITIVES 347
Cdd:cd05736   84 DISSLFVEDS 93

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and related proteins. The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4). VEGF-A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF; VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group also contains alpha-type platelet-derived growth factor receptor precursor (PDGFR)-alpha (CD140a), and PDGFR-beta (CD140b). PDGFRs alpha and beta have an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion that has protein tyrosine kinase activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116006967 250 LPPRLKEMKSQesaaGSKLVLRCETSSEYSS-LRFKWFKNGNELNRKNKPQ-NIKIQKKPGK---SELRINKASLADSGE 324
Cdd:cd05742    6 SPNAEPTVLPQ----GETLVLNCTANVNLNEvVDFQWTYPSEKEGKLALLKpDIKVDWSEPGefvSTLTIPEATLKDSGT 81

                         90       100
                 ....*....|....*....|.
gi 116006967 325 YMCKVISKLGNDSASANITIV 345
Cdd:cd05742   82 YTCAARSGVMKKEKQTSVSVH 102

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 116006967 265 GSKLVLRCETSSEYSSLRFKWFKNGNELNRKNKP----QNIKIQKKPGKSELRINKASLADSGEYMCKVISKLG 334
Cdd:cd20950   12 GNRAVLTCSEPDGSPPSEYTWFKDGVVMPTNPKStrafSNSSYSLDPTTGELVFDPLSASDTGEYSCEARNGYG 85

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. 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 this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus 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 116006967 249 ALPPRLkemksqESAAGSKLVLRCeTSSEYSSLRFKWFKNGNELNRKNKpqniKIQKKPGKSELRINKASLADSGEYMCK 328
Cdd:cd20976    6 SVPKDL------EAVEGQDFVAQC-SARGKPVPRITWIRNAQPLQYAAD----RSTCEAGVGELHIQDVLPEDHGTYTCL 74

                         90
                 ....*....|....*.
gi 116006967 329 VISKLGNDSASANITI 344
Cdd:cd20976   75 AKNAAGQVSCSAWVTV 90

First immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for all FGFs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116006967 256 EMKSQESAAGSKLVLRCETSSEYSSLrfKWFKNGNELNRKNKPQNIKiqkkpgkSELRINKASLADSGEYMCKVISKLGN 335
Cdd:cd04973   15 EVESYSAHPGDLLQLRCRLRDDVQSI--NWTKDGVQLGENNRTRITG-------EEVQIKDAVPRDSGLYACVTSSPSGS 85

                 ..
gi 116006967 336 DS 337
Cdd:cd04973   86 DT 87

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 116006967  371 CVNGGECFMVkdlsnPSRYLCKCPNEFTGDR 401
Cdd:pfam00008   6 CSNGGTCVDT-----PGGYTCICPEGYTGKR 31