Neuregulin intracellular region;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463556  264 TKKQRKKLHDRLRQSLRSERNNMmNIANGPHHPNPPPENVQLVNqYVSKNVISSEHIVEREAETSFSTSHYTSTAHHSTT 343
Cdd:pfam02158   1 TKKQRKKMHDHLRQNLRSERNNR-NLANGPNHPNPPPEEIQMVN-YISKNVPATEHVIRHEAETSFSGSHYTSTSHHSTT 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463556  344 VTQTPSH---SWSNGHTESILSESHSVIVMSSVENSRHSSPTG-GPRGRLNGTGGPRECNSFLRHARETPDSYRDSPHSE 419
Cdd:pfam02158  79 VTHTSSHeerTWSNERTESVTSDSQSGIMSSSVETSKCSSPACmEARGRRNAAGGPRDPNSYLRQYRDSPDSLRDSPHSE 158

                  ..
gi 236463556  420 RH 421
Cdd:pfam02158 159 RY 160

epidermal growth factor-like protein (EGF-like protein); Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463556 182 CAEKEKTFCVNGgECFMVKDLSNpsrYLCKCPNEFTGDRCQNYVMASFYKAEEL-YQKRVLTITGICIALLVVGIMCVVA 260
Cdd:PHA03099  45 CGPEGDGYCLHG-DCIHARDIDG---MYCRCSHGYTGIRCQHVVLVDYQRSEKPnTTTSYIPSPGIVLVLVGIIITCCLL 120

                         90
                 ....*....|.
gi 236463556 261 YCKTKKQRKKL 271
Cdd:PHA03099 121 SVYRFTRRTKL 131

Neuregulin intracellular region;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463556  264 TKKQRKKLHDRLRQSLRSERNNMmNIANGPHHPNPPPENVQLVNqYVSKNVISSEHIVEREAETSFSTSHYTSTAHHSTT 343
Cdd:pfam02158   1 TKKQRKKMHDHLRQNLRSERNNR-NLANGPNHPNPPPEEIQMVN-YISKNVPATEHVIRHEAETSFSGSHYTSTSHHSTT 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463556  344 VTQTPSH---SWSNGHTESILSESHSVIVMSSVENSRHSSPTG-GPRGRLNGTGGPRECNSFLRHARETPDSYRDSPHSE 419
Cdd:pfam02158  79 VTHTSSHeerTWSNERTESVTSDSQSGIMSSSVETSKCSSPACmEARGRRNAAGGPRDPNSYLRQYRDSPDSLRDSPHSE 158

                  ..
gi 236463556  420 RH 421
Cdd:pfam02158 159 RY 160

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463556    43 KSQESAAGSKLVLRCETSSeYSSLRFKWFKNGNELnrKNKPQNIKIQKKPGKSELRINKASLADSGEYMCKVISKLGNDS 122
Cdd:smart00410   2 PSVTVKEGESVTLSCEASG-SPPPEVTWYKQGGKL--LAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSAS 78

                   ....*..
gi 236463556   123 ASANITI 129
Cdd:smart00410  79 SGTTLTV 85

IL-1 receptor-like protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 236463556  60 SSEYSSLRFKWFKNGNELnrknkPQNIKIQKKPGKSELRINKASLADSGEYMCKVisKLGNDSASANIT 128
Cdd:PHA02826 158 SSTFKDYTLTWYKNGNIV-----LYTDRIQLRNNNSTLVIKSATHDDSGIYTCNL--RFNKNSNNYNIT 219

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 236463556  190 CVNGGECFMVkdlsnPSRYLCKCPNEFTGDR 220
Cdd:pfam00008   6 CSNGGTCVDT-----PGGYTCICPEGYTGKR 31

Neuregulin intracellular region;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463556  264 TKKQRKKLHDRLRQSLRSERNNMmNIANGPHHPNPPPENVQLVNqYVSKNVISSEHIVEREAETSFSTSHYTSTAHHSTT 343
Cdd:pfam02158   1 TKKQRKKMHDHLRQNLRSERNNR-NLANGPNHPNPPPEEIQMVN-YISKNVPATEHVIRHEAETSFSGSHYTSTSHHSTT 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463556  344 VTQTPSH---SWSNGHTESILSESHSVIVMSSVENSRHSSPTG-GPRGRLNGTGGPRECNSFLRHARETPDSYRDSPHSE 419
Cdd:pfam02158  79 VTHTSSHeerTWSNERTESVTSDSQSGIMSSSVETSKCSSPACmEARGRRNAAGGPRDPNSYLRQYRDSPDSLRDSPHSE 158

                  ..
gi 236463556  420 RH 421
Cdd:pfam02158 159 RY 160

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463556  37 PRLKEMKSQESAAGSKLVLRCETSSEYSSLRFKWFKNGNELNRKnKPQNIKIQKKPGKSELRINKASLADSGEYMCKVIS 116
Cdd:cd05750    1 PKLKEMKSQTVQEGSKLVLKCEATSENPSPRYRWFKDGKELNRK-RPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVEN 79

                         90
                 ....*....|...
gi 236463556 117 KLGNDSASANITI 129
Cdd:cd05750   80 ILGKDTVTGNVTV 92

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463556   39 LKEMKSQESAAGSKLVLRCETSsEYSSLRFKWFKNGNELNRKNKpqnIKIQKKPGKSELRINKASLADSGEYMCKVISKL 118
Cdd:pfam07679   4 TQKPKDVEVQEGESARFTCTVT-GTPDPEVSWFKDGQPLRSSDR---FKVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                          90
                  ....*....|.
gi 236463556  119 GNDSASANITI 129
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 236463556  36 PPR-LKEMKSQESAAGSKLVLRCETSSEySSLRFKWFKNGNELnrKNKPqNIKIQKKPGKSELRINKASLADSGEYMCKV 114
Cdd:cd20972    1 PPQfIQKLRSQEVAEGSKVRLECRVTGN-PTPVVRWFCEGKEL--QNSP-DIQIHQEGDLHSLIIAEAFEEDTGRYSCLA 76

                         90
                 ....*....|....*
gi 236463556 115 ISKLGNDSASANITI 129
Cdd:cd20972   77 TNSVGSDTTSAEIFV 91

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 236463556  53 LVLRCETSSeYSSLRFKWFKNGNELNRKNKPqniKIQKKPGKSELRINKASLADSGEYMCKVISKL-GNDSASA 125
Cdd:cd00096    1 VTLTCSASG-NPPPTITWYKNGKPLPPSSRD---SRRSELGNGTLTISNVTLEDSGTYTCVASNSAgGSASASV 70

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 236463556  46 ESAAGSKLVLRCETSSEYSSLRfkWFKNGNELNRKNKpqnIKIQKKPGKSELRINKASLADSGEYMCKV 114
Cdd:cd20967    8 QVSKGHKIRLTVELADPDAEVK--WYKDGQELQSSSK---VIFESIGAKRTLTVQQASLADAGEYQCVA 71

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463556  48 AAGSKLVLRCETSSEYSSLrFKWFKNGNELNRKNkpQNIKIQKKpgkSELRINKASLADSGEYMCKVISKLGNDSASANI 127
Cdd:cd20952   12 AVGGTVVLNCQATGEPVPT-ISWLKDGVPLLGKD--ERITTLEN---GSLQIKGAEKSDTGEYTCVALNLSGEATWSAVL 85

                 ..
gi 236463556 128 TI 129
Cdd:cd20952   86 DV 87

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. 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 telokin Ig domain 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 236463556  40 KEMKSQESAAGSKLVLRCETSSeYSSLRFKWFKNGNELNRKNKPQNIkiQKKPGKSELRINKASLADSGEYMCKVISKLG 119
Cdd:cd20973    2 QTLRDKEVVEGSAARFDCKVEG-YPDPEVKWMKDDNPIVESRRFQID--QDEDGLCSLIISDVCGDDSGKYTCKAVNSLG 78

                         90
                 ....*....|
gi 236463556 120 NDSASANITI 129
Cdd:cd20973   79 EATCSAELTV 88

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 236463556  37 PRLKEMKSQESAAGSKLVLRCETSSE-YSSLRFKWFKNGNELNRKNKPQNIKIQKKPGKSELRINKASLADSGEYMCKVI 115
Cdd:cd05732    3 PKITYLENQTAVELEQITLTCEAEGDpIPEITWRRATRGISFEEGDLDGRIVVRGHARVSSLTLKDVQLTDAGRYDCEAS 82

                 ....*....
gi 236463556 116 SKLGNDSAS 124
Cdd:cd05732   83 NRIGGDQQS 91

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 236463556  43 KSQESAAGSKLVLRCETSSEySSLRFKWFKNGNELNRKnkpQNIKIQKKPGKSELRINKASLADSGEYMCKVISKLGNDS 122
Cdd:cd05736    8 EFQAKEPGVEASLRCHAEGI-PLPRVQWLKNGMDINPK---LSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEGGVDE 83

                         90
                 ....*....|
gi 236463556 123 ASANITIVES 132
Cdd:cd05736   84 DISSLFVEDS 93

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463556  37 PRLKEMKSQESAAGSKLVLRCETSSE-YSSLRFKWFKNGNELNRKNKPQN--IKIQKKPGKSELRINKASLADSGEYMCK 113
Cdd:cd05870    3 PHIIQLKNETTVENGAATLSCKAEGEpIPEITWKRASDGHTFSEGDKSPDgrIEVKGQHGESSLHIKDVKLSDSGRYDCE 82

                         90
                 ....*....|....*.
gi 236463556 114 VISKLGNDSASANITI 129
Cdd:cd05870   83 AASRIGGHQKSMYLDI 98

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 236463556  43 KSQESAAGSKLVLRCETSSEYSS-LRFKW-FKNGNELNRKNKPQNIKIQKKPGK---SELRINKASLADSGEYMCKVISK 117
Cdd:cd05862    9 KPVELLVGEKLVLNCTARTELNVgVDFQWdYPGKKEQRRASVRRRRKQQSSEATefsSTLTIDNVTLSDKGLYTCAASSG 88

                         90
                 ....*....|....
gi 236463556 118 LGNDSASANITIVE 131
Cdd:cd05862   89 PMFKKNSTSVIVHE 102

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 236463556  35 LPPRLKEMKSQesaaGSKLVLRCETSSEYSS-LRFKWFKNGNELNRKNKPQ-NIKIQKKPGK---SELRINKASLADSGE 109
Cdd:cd05742    6 SPNAEPTVLPQ----GETLVLNCTANVNLNEvVDFQWTYPSEKEGKLALLKpDIKVDWSEPGefvSTLTIPEATLKDSGT 81

                         90       100
                 ....*....|....*....|.
gi 236463556 110 YMCKVISKLGNDSASANITIV 130
Cdd:cd05742   82 YTCAARSGVMKKEKQTSVSVH 102

epidermal growth factor-like protein (EGF-like protein); Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463556 182 CAEKEKTFCVNGgECFMVKDLSNpsrYLCKCPNEFTGDRCQNYVMASFYKAEEL-YQKRVLTITGICIALLVVGIMCVVA 260
Cdd:PHA03099  45 CGPEGDGYCLHG-DCIHARDIDG---MYCRCSHGYTGIRCQHVVLVDYQRSEKPnTTTSYIPSPGIVLVLVGIIITCCLL 120

                         90
                 ....*....|.
gi 236463556 261 YCKTKKQRKKL 271
Cdd:PHA03099 121 SVYRFTRRTKL 131

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463556   43 KSQESAAGSKLVLRCETSSEYS--SLRFKW---------------FKNGNELNRKnkPQNIKIQKKPGKS--ELRINKAS 103
Cdd:pfam07686   4 REVTVALGGSVTLPCTYSSSMSeaSTSVYWyrqppgkgptfliayYSNGSEEGVK--KGRFSGRGDPSNGdgSLTIQNLT 81

                          90
                  ....*....|....
gi 236463556  104 LADSGEYMCKVISK 117
Cdd:pfam07686  82 LSDSGTYTCAVIPS 95