Fifth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB, and TrkC; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth domain of Trk receptors TrkA, TrkB, and TrkC, an immunoglobulin (Ig)-like domain which binds to neurotrophin. The Trk family of receptors are tyrosine kinase receptors. They are activated by dimerization, leading to autophosphorylation of intracellular tyrosine residues, and triggering the signal transduction pathway. TrkA, TrkB, and TrkC share significant sequence homology and domain organization. The first three domains are leucine-rich domains while the fourth and fifth domains are Ig-like domains playing a part in ligand binding. TrkA, TrkB, and TrkC mediate the trophic effects of the neurotrophin Nerve Growth Factor (NGF) family. TrkA is recognized by NGF. TrkB is recognized by brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-4. TrkC is recognized by NT-3. NT-3 is promiscuous as in some cell systems it activates TrkA and TrkB receptors. TrkA is a receptor found in all major NGF targets, including the sympathetic, trigeminal, and dorsal root ganglia, cholinergic neurons of the basal forebrain, and the striatum. TrKB transcripts are found throughout multiple structures of the central and peripheral nervous systems. The TrkC gene is expressed throughout the mammalian nervous system. This group belongs to the I-set of IgSF domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644881 304 PPRVVSLVEPEVRLEHCIEFVVRGNPTPTLHWLYNGQPLRESKIIHMDYYQEG---EVSEGCLLFNKPTHYNNGNYTLIA 380
Cdd:cd04971     1 APVIVRLEEPELRHHWCIPFTVRGNPKPTLTWYHNGAVLNESDYIRTEIHYEAatpTEYHGCLKFDNPTHVNNGNYTLVA 80

                          90
                  ....*....|....*.
gi 1958644881 381 KNALGTANQTINGHFL 396
Cdd:cd04971    81 SNEYGQDSKSISAHFM 96

Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1958644881 532 HIKRRDIVLKRELGEGAFGKVFLAECYNLSPTKDKMLVAVK 572
Cdd:cd05094     1 HIKRRDIVLKRELGEGAFGKVFLAECYNLSPTKDKMLVAVK 41

Leucine rich repeat;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958644881 103 TGLQKLTIKNSGLRNIQPRAFAKNPHLRYINLSSNRLTTLSWQLFQTL-SLRELRLEQN 160
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLpSLRYLDLSGN 59

Fifth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB, and TrkC; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth domain of Trk receptors TrkA, TrkB, and TrkC, an immunoglobulin (Ig)-like domain which binds to neurotrophin. The Trk family of receptors are tyrosine kinase receptors. They are activated by dimerization, leading to autophosphorylation of intracellular tyrosine residues, and triggering the signal transduction pathway. TrkA, TrkB, and TrkC share significant sequence homology and domain organization. The first three domains are leucine-rich domains while the fourth and fifth domains are Ig-like domains playing a part in ligand binding. TrkA, TrkB, and TrkC mediate the trophic effects of the neurotrophin Nerve Growth Factor (NGF) family. TrkA is recognized by NGF. TrkB is recognized by brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-4. TrkC is recognized by NT-3. NT-3 is promiscuous as in some cell systems it activates TrkA and TrkB receptors. TrkA is a receptor found in all major NGF targets, including the sympathetic, trigeminal, and dorsal root ganglia, cholinergic neurons of the basal forebrain, and the striatum. TrKB transcripts are found throughout multiple structures of the central and peripheral nervous systems. The TrkC gene is expressed throughout the mammalian nervous system. This group belongs to the I-set of IgSF domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644881 304 PPRVVSLVEPEVRLEHCIEFVVRGNPTPTLHWLYNGQPLRESKIIHMDYYQEG---EVSEGCLLFNKPTHYNNGNYTLIA 380
Cdd:cd04971     1 APVIVRLEEPELRHHWCIPFTVRGNPKPTLTWYHNGAVLNESDYIRTEIHYEAatpTEYHGCLKFDNPTHVNNGNYTLVA 80

                          90
                  ....*....|....*.
gi 1958644881 381 KNALGTANQTINGHFL 396
Cdd:cd04971    81 SNEYGQDSKSISAHFM 96

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkC is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkC to its ligand, neurotrophin 3 (NT3), results in receptor oligomerization and activation of the catalytic domain. TrkC is broadly expressed in the nervous system and in some non-neural tissues including the developing heart. NT3/TrkC signaling plays an important role in the innervation of the cardiac conducting system and the development of smooth muscle cells. Mice deficient with NT3 and TrkC have multiple heart defects. NT3/TrkC signaling is also critical for the development and maintenance of enteric neurons that are important for the control of gut peristalsis. The TrkC subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1958644881 532 HIKRRDIVLKRELGEGAFGKVFLAECYNLSPTKDKMLVAVK 572
Cdd:cd05094     1 HIKRRDIVLKRELGEGAFGKVFLAECYNLSPTKDKMLVAVK 41

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644881  218 NLTVREGDNAVITCNGSGSPLPDVDWIVTGLQSInTHQTNLNWTNVHAI-NLTLVNVTSEDNGfTLTCIAENVVGMSNAS 296
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLL-AESGRFSVSRSGSTsTLTISNVTPEDSG-TYTCAATNSSGSASSG 80

                   ....*
gi 1958644881  297 VALTV 301
Cdd:smart00410  81 TTLTV 85

Leucine rich repeat;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958644881 103 TGLQKLTIKNSGLRNIQPRAFAKNPHLRYINLSSNRLTTLSWQLFQTL-SLRELRLEQN 160
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLpSLRYLDLSGN 59

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644881 304 PPRVVSLVEPE-VRLEhCIefvVRGNPTPTLHWLYNGQPLRESKIIHMDYyqEGEVSEgcLLFNKPTHYNNGNYTLIAKN 382
Cdd:pfam07679   6 KPKDVEVQEGEsARFT-CT---VTGTPDPEVSWFKDGQPLRSSDRFKVTY--EGGTYT--LTISNVQPDDSGKYTCVATN 77

                  ....*
gi 1958644881 383 ALGTA 387
Cdd:pfam07679  78 SAGEA 82

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1958644881 538 IVLKRELGEGAFGKVFLAEcYNLSPTKDKMLVAVK 572
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGT-LKGEGENTKIKVAVK 34

Leucine-rich repeat (LRR) protein [Transcription];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644881  75 DISRN-ITSIH--IENWRGLHTLNAVDMELY---------TGLQKLTIKNSGLRNIqpRAFAKNPHLRYINLSSNRLTTL 142
Cdd:COG4886   188 DLSNNqITDLPepLGNLTNLEELDLSGNQLTdlpeplanlTNLETLDLSNNQLTDL--PELGNLTNLEELDLSNNQLTDL 265

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644881 143 SwQLFQTLSLRELRLEQNffncscDIRWMQLwQEQGEARLDSQSLYCISADGSQLPLFRMNISQCDLPEISVSHVNLTVR 222
Cdd:COG4886   266 P-PLANLTNLKTLDLSNN------QLTDLKL-KELELLLGLNSLLLLLLLLNLLELLILLLLLTTLLLLLLLLKGLLVTL 337

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1958644881 223 EGDNAVITCNGSGSPLPDVDWIVTGLQSINTHQTNLNWTNVHAINLT 269
Cdd:COG4886   338 TTLALSLSLLALLTLLLLLNLLSLLLTLLLTLGLLGLLEATLLTLAL 384

Leucine rich repeat N-terminal domain;

                           10        20
                   ....*....|....*....|....*.
gi 1958644881   31 ACPANCVCSKTEINCRRPDDGnLFPL 56
Cdd:smart00013   1 ACPAPCNCSGTAVDCSGRGLT-EVPL 25

Fifth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB, and TrkC; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth domain of Trk receptors TrkA, TrkB, and TrkC, an immunoglobulin (Ig)-like domain which binds to neurotrophin. The Trk family of receptors are tyrosine kinase receptors. They are activated by dimerization, leading to autophosphorylation of intracellular tyrosine residues, and triggering the signal transduction pathway. TrkA, TrkB, and TrkC share significant sequence homology and domain organization. The first three domains are leucine-rich domains while the fourth and fifth domains are Ig-like domains playing a part in ligand binding. TrkA, TrkB, and TrkC mediate the trophic effects of the neurotrophin Nerve Growth Factor (NGF) family. TrkA is recognized by NGF. TrkB is recognized by brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-4. TrkC is recognized by NT-3. NT-3 is promiscuous as in some cell systems it activates TrkA and TrkB receptors. TrkA is a receptor found in all major NGF targets, including the sympathetic, trigeminal, and dorsal root ganglia, cholinergic neurons of the basal forebrain, and the striatum. TrKB transcripts are found throughout multiple structures of the central and peripheral nervous systems. The TrkC gene is expressed throughout the mammalian nervous system. This group belongs to the I-set of IgSF domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644881 304 PPRVVSLVEPEVRLEHCIEFVVRGNPTPTLHWLYNGQPLRESKIIHMDYYQEG---EVSEGCLLFNKPTHYNNGNYTLIA 380
Cdd:cd04971     1 APVIVRLEEPELRHHWCIPFTVRGNPKPTLTWYHNGAVLNESDYIRTEIHYEAatpTEYHGCLKFDNPTHVNNGNYTLVA 80

                          90
                  ....*....|....*.
gi 1958644881 381 KNALGTANQTINGHFL 396
Cdd:cd04971    81 SNEYGQDSKSISAHFM 96

Leucine rich repeat C-terminal motif; This entry represents the Leucine Rich Repeat C-terminal (LRRCT) capping motif from TRK receptors.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1958644881 163 NCSCDIRWMQLWQEQGEARLDSQSLYCISaDGSQLPLFRMNISQCD 208
Cdd:pfam16920   1 RCSCDIRWLQLWQEEGLAGLGTQQLYCLN-DGSKIPLQSMNIPNCG 45

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkA is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkA to its ligand, nerve growth factor (NGF), results in receptor oligomerization and activation of the catalytic domain. TrkA is expressed mainly in neural-crest-derived sensory and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons of the central nervous system. It is critical for neuronal growth, differentiation and survival. Alternative TrkA splicing has been implicated as a pivotal regulator of neuroblastoma (NB) behavior. Normal TrkA expression is associated with better NB prognosis, while the hypoxia-regulated TrkAIII splice variant promotes NB pathogenesis and progression. Aberrant TrkA expression has also been demonstrated in non-neural tumors including prostate, breast, lung, and pancreatic cancers. The TrkA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1958644881 532 HIKRRDIVLKRELGEGAFGKVFLAECYNLSPTKDKMLVAVK 572
Cdd:cd05092     1 HIKRRDIVLKWELGEGAFGKVFLAECHNLLPEQDKMLVAVK 41

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644881 214 VSHVNLTVREGDNAVITCNGS-GSPLPDVDWIVTGLQSINTHQTNLNWTNVHAINLTLVNVTSEDNGfTLTCIAENVVGM 292
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSAStGSPGPDVTWSKEGGTLIESLKVKHDNGRTTQSSLLISNVTKEDAG-TYTCVVNNPGGS 79

                  ....*..
gi 1958644881 293 SNASVAL 299
Cdd:pfam00047  80 ATLSTSL 86

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644881  218 NLTVREGDNAVITCNGSGSPLPDVDWIVTGLQSInTHQTNLNWTNVHAI-NLTLVNVTSEDNGfTLTCIAENVVGMSNAS 296
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLL-AESGRFSVSRSGSTsTLTISNVTPEDSG-TYTCAATNSSGSASSG 80

                   ....*
gi 1958644881  297 VALTV 301
Cdd:smart00410  81 TTLTV 85

Leucine rich repeat C-terminal domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1958644881  160 NFFNCSCDIRWMQLWQEQGEARLDSQSLYCISADGSQLPLFRMNIS 205
Cdd:smart00082   1 NPFICDCELRWLLRWLQANEHLQDPVDLRCASPSSLRGPLLELLHS 46

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 1958644881 210 PEISVSHVNLTVREGDNAVITCNGSGSPLPDVDWIVTG--LQSINTHQTnlnwTNVHAINLTLVNVTSEDNGfTLTCIAE 287
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAqpLQYAADRST----CEAGVGELHIQDVLPEDHG-TYTCLAK 76

                          90
                  ....*....|....
gi 1958644881 288 NVVGMSNASVALTV 301
Cdd:cd20976    77 NAAGQVSCSAWVTV 90

Fourth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB, and TrkC; The members here are composed of the fourth domain of Trk receptors TrkA, TrkB, and TrkC, an immunoglobulin (Ig)-like domain which binds to neurotrophin. The Trk family of receptors are tyrosine kinase receptors. They are activated by dimerization, leading to autophosphorylation of intracellular tyrosine residues, and triggering the signal transduction pathway. TrkA, TrkB, and TrkC share significant sequence homology and domain organization. The first three domains are leucine-rich domains while the fourth and fifth domains are Ig-like domains playing a part in ligand binding. TrkA, TrkB, and TrkC mediate the trophic effects of the neurotrophin Nerve Growth Factor (NGF) family. TrkA is recognized by NGF. TrKB is recognized by brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-4. TrkC is recognized by NT-3. NT-3 is promiscuous as in some cell systems it activates TrkA and TrkB receptors. TrkA is a receptor found in all major NGF targets, including the sympathetic, trigeminal, and dorsal root ganglia, cholinergic neurons of the basal forebrain, and the striatum. TrKB transcripts are found throughout multiple structures of the central and peripheral nervous systems. The TrkC gene is expressed throughout the mammalian nervous system.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644881 211 EISVSHVNLTVREGDNAVITCNGSGSPLPDVDWIVTGLQSintHQTNLNWTNVHAINLTLVNVTSEDNGFTLTCIAENVV 290
Cdd:cd04972     1 TLKIQMPNASVDVGDDVLLQCQVEGQGLEQAGWILTELEQ---SATVMKSGSLPSLGLTLANVTSDLNRKNVTCWAENDV 77

                          90
                  ....*....|.
gi 1958644881 291 GMSNASVALTV 301
Cdd:cd04972    78 GRAEVSVQVNV 88

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644881 217 VNLTVREGDNAVITCNGSGSPLPDVDWIVTG--LQSINTHQTNLNwtnvhaiNLTLVNVTSEDNGfTLTCIAENVVGMSN 294
Cdd:cd05725     5 QNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDgeLPKGRYEILDDH-------SLKIRKVTAGDMG-SYTCVAENMVGKIE 76

                  ....*..
gi 1958644881 295 ASVALTV 301
Cdd:cd05725    77 ASATLTV 83

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. 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 MuSK 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958644881 218 NLTVREGDNAVITCNGSGSPLPDVDWIVTG--LQSINT-HQTNLNWTnvhaiNLTLVNVTSEDNGFTLtCIAENVVG 291
Cdd:cd20970    11 TVTAREGENATFMCRAEGSPEPEISWTRNGnlIIEFNTrYIVRENGT-----TLTIRNIRRSDMGIYL-CIASNGVP 81

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958644881 325 VRGNPTPTLHWLYNGQPLRESKIIHMDYYQEGEVSegcLLFNKPTHYNNGNYTLIAKNALGTANQT 390
Cdd:cd20973    21 VEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCS---LIISDVCGDDSGKYTCKAVNSLGEATCS 83

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 1958644881 215 SHVNLTVREGDNAVITCNGSGSPLPDVDWIVTGlQSINTHQTNLNWtNVHAINLTLVNVTSEDNGfTLTCIAENVVGMSN 294
Cdd:cd05730     9 SEVNATANLGQSVTLACDADGFPEPTMTWTKDG-EPIESGEEKYSF-NEDGSEMTILDVDKLDEA-EYTCIAENKAGEQE 85

                  ....*...
gi 1958644881 295 ASVALTVY 302
Cdd:cd05730    86 AEIHLKVF 93

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 1958644881 218 NLTVREGDNAVITCNGSGSPLPDVDWIVTGlqsiNTHQTNLNWTNVHAINLTLVNVTSEDNGfTLTCIAENVVGMSNASV 297
Cdd:cd20978    10 NVVVKGGQDVTLPCQVTGVPQPKITWLHNG----KPLQGPMERATVEDGTLTIINVQPEDTG-YYGCVATNEIGDIYTET 84

                  ....
gi 1958644881 298 ALTV 301
Cdd:cd20978    85 LLHV 88

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1958644881 538 IVLKRELGEGAFGKVFLAEcYNLSPTKDKMLVAVK 572
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGT-LKGEGENTKIKVAVK 34

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1958644881  538 IVLKRELGEGAFGKVFLAEcYNLSPTKDKMLVAVK 572
Cdd:smart00219   1 LTLGKKLGEGAFGEVYKGK-LKGKGGKKKVEVAVK 34

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958644881 327 GNPTPTLHWLYNGQPLRESKIIHMDYYQEGEVSEgcLLFNKPTHYNNGNYTLIAKNALGTANQTINGH 394
Cdd:cd05750    26 ENPSPRYRWFKDGKELNRKRPKNIKIRNKKKNSE--LQINKAKLEDSGEYTCVVENILGKDTVTGNVT 91

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644881 219 LTVREGDNAVITCNGSGSPLPDVDWIVTGlQSINTHQTNLNWTNVHAINLTLVNVTSEDNGfTLTCIAENVVGMSNASVA 298
Cdd:cd20949     9 TTVKEGQSATILCEVKGEPQPNVTWHFNG-QPISASVADMSKYRILADGLLINKVTQDDTG-EYTCRAYQVNSIASDMQE 86

                  ...
gi 1958644881 299 LTV 301
Cdd:cd20949    87 RTV 89

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 1958644881 325 VRGNPTPTLHWLYNGQPL-RESKIIHmdyyqegeVSEGCLLFNKPTHYNNGNYTLIAKNALGT 386
Cdd:cd20978    25 VTGVPQPKITWLHNGKPLqGPMERAT--------VEDGTLTIINVQPEDTGYYGCVATNEIGD 79

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958644881 325 VRGNPTPTLHWLYNGQPLRESKiihmDYYQeGEVSEGCLLFNKPTHYNNGNYTLIAKNALGTANQT 390
Cdd:cd20976    25 ARGKPVPRITWIRNAQPLQYAA----DRST-CEAGVGELHIQDVLPEDHGTYTCLAKNAAGQVSCS 85

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958644881 315 VRLEhCiefVVRGNPTPTLHWLYNGQPLRESKIIhmdyyQEGEVSEG--CLLFNKPTHYNNGNYTLIAKNALGTANQT 390
Cdd:cd05729    22 VRLE-C---GAGGNPMPNITWLKDGKEFKKEHRI-----GGTKVEEKgwSLIIERAIPRDKGKYTCIVENEYGSINHT 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958644881 324 VVRGNPTPTLHWLYNGQPLRESKIIHMDYYQegevSEGCLLFNKPTHYNNGNYTLIAKNALGTANQTI 391
Cdd:cd00096     6 SASGNPPPTITWYKNGKPLPPSSRDSRRSEL----GNGTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

Fourth 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 fourth 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644881 210 PEISVSHVNLTVREGDNAVITCNGSGSPLPDVDWIVTGLQSINTHQTNLN-WTNVHAINLTLVNVTS---EDNGFtLTCI 285
Cdd:cd20956     2 PVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVGdYVTSDGDVVSYVNISSvrvEDGGE-YTCT 80

                  ....*.
gi 1958644881 286 AENVVG 291
Cdd:cd20956    81 ATNDVG 86

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958644881 325 VRGNPTPTLHWLYNGQPLR-ESKI--IHMDYYQEGEVSEGCLLFNKpthynnGNYTLIAKNALGTANQT 390
Cdd:cd05857    28 AAGNPTPTMRWLKNGKEFKqEHRIggYKVRNQHWSLIMESVVPSDK------GNYTCVVENEYGSINHT 90

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 1958644881 208 DLPEISVSHVNLTVREGDNAVITCNGSGSPLPDVdwivTGLQSINTHQTNLNWTNVH---------AINLTLVNVTSEDN 278
Cdd:cd04970     1 DATRITLAPSNADITVGENATLQCHASHDPTLDL----TFTWSFNGVPIDLEKIEGHyrrrygkdsNGDLEIVNAQLKHA 76

                          90       100
                  ....*....|....*....|....*..
gi 1958644881 279 GfTLTCIAENVVGMSNASVALTVYYPP 305
Cdd:cd04970    77 G-RYTCTAQTVVDSDSASATLVVRGPP 102

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644881 218 NLTVREGDNAVITCNGSGSPLPDVDWI-VTG-LQSINTHQTNLNWTnvhainLTLVNVTSEDNGfTLTCIAENVVGMSNA 295
Cdd:cd05731     4 STMVLRGGVLLLECIAEGLPTPDIRWIkLGGeLPKGRTKFENFNKT------LKIENVSEADSG-EYQCTASNTMGSARH 76

                  ....*.
gi 1958644881 296 SVALTV 301
Cdd:cd05731    77 TISVTV 82

Sixth immunoglobulin (Ig) domain of contactin-2; The members here are composed of the sixth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. 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-2 is also expressed in retinal amacrine cells (AC) in the developing chick retina, corresponding to the period of formation and maturation of AC processes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644881 208 DLPEISVSHVNLTVREGDNAVITCNGSGSPLPDVD--WIVTG----LQSINTHQTNLNWTNVHAiNLTLVNVTSEDNGfT 281
Cdd:cd05854     1 DATKITLAPSSADINQGENLTLQCHASHDPTMDLTftWSLDDfpidLDKPNGHYRRMEVKETIG-DLVIVNAQLSHAG-T 78

                          90       100
                  ....*....|....*....|....
gi 1958644881 282 LTCIAENVVGMSNASVALTVYYPP 305
Cdd:cd05854    79 YTCTAQTVVDSASASATLVVRGPP 102