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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571 289 PLITQHTHKLLVLEGQAATLKCKAIGDPSPLIHWVAPDDRLVGNSSRTAVYDNGTLDILITTSQDSGPFTCIAANAAGEA 368
Cdd:cd05764    1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEA 80

                 ....*...
gi 569001571 369 TATVEVSI 376
Cdd:cd05764   81 TARVELHI 88

Leucine rich repeat C-terminal domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 569001571   242 NPLHCNCELLWLRRLERDDDLE------TCGSPGSLKGRYFwHIREEEFVC 286
Cdd:smart00082   1 NPFICDCELRWLLRWLQANEHLqdpvdlRCASPSSLRGPLL-ELLHSEFKC 50

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571 289 PLITQHTHKLLVLEGQAATLKCKAIGDPSPLIHWVAPDDRLVGNSSRTAVYDNGTLDILITTSQDSGPFTCIAANAAGEA 368
Cdd:cd05764    1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEA 80

                 ....*...
gi 569001571 369 TATVEVSI 376
Cdd:cd05764   81 TARVELHI 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569001571  288 PPLITQHTHKLLVLEGQAATLKCKAIGDPSPLIHWVAPDDRLVGNSSR--TAVYDNGTLDILITTSQDSGPFTCI 360
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRsrSLSGSNSTLTISNVTRSDAGTYTCV 75

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571  61 GNFIIHIgrQDFANMTGLVDLTLSRNTISHIQPFSflDLESLRSLHLDSNRLPSLgEDtLRGLVNLQHLIVNNNQLGgiA 140
Cdd:cd21340   33 DNKITKI--ENLEFLTNLTHLYLQNNQIEKIENLE--NLVNLKKLYLGGNRISVV-EG-LENLTNLEELHIENQRLP--P 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571 141 DD--AFEDFLL-----TLEDLDLSYNNLHGLpwDSVRRMVNLHQLSLDHNLLDHIAE--GTFADLQKLARLDLTSNRLQK 211
Cdd:cd21340  105 GEklTFDPRSLaalsnSLRVLNISGNNIDSL--EPLAPLRNLEQLDASNNQISDLEEllDLLSSWPSLRELDLTGNPVCK 182

                 ..
gi 569001571 212 LP 213
Cdd:cd21340  183 KP 184

type III secretion system effector E3 ubiquitin transferase SlrP;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571  74 NMTGLVDLTLSRNTISHIQPfsfldlESLRSLHLDSNRLPSLGEDtLRGlvNLQHLIVNNNQLGGIAddafEDFLLTLED 153
Cdd:PRK15370 179 NKTELRLKILGLTTIPACIP------EQITTLILDNNELKSLPEN-LQG--NIKTLYANSNQLTSIP----ATLPDTIQE 245

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571 154 LDLSYNNLHGLPwdsVRRMVNLHQLSLDHNLLDHIAEGTFADLQKlarLDLTSNRLQKLP---PDPIFARS-QASLLTAT 229
Cdd:PRK15370 246 MELSINRITELP---ERLPSALQSLDLFHNKISCLPENLPEELRY---LSVYDNSIRTLPahlPSGITHLNvQSNSLTAL 319

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 569001571 230 PFAPPLSfsfggnplhcncellwLRRLERDDDLETCgSPGSL 271
Cdd:PRK15370 320 PETLPPG----------------LKTLEAGENALTS-LPASL 344

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571 289 PLITQHTHKLLVLEGQAATLKCKAIGDPSPLIHWVAPDDRLVGNSSRTAVYDNGTLDILITTSQDSGPFTCIAANAAGEA 368
Cdd:cd05764    1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEA 80

                 ....*...
gi 569001571 369 TATVEVSI 376
Cdd:cd05764   81 TARVELHI 88

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571  56 ELRLGGNFIIHIGRqDFANMTGLVDLTLSRNTISHIqPFSFLDLESLRSLHLDSNRLPSLGEdTLRGLVNLQHLIVNNNQ 135
Cdd:COG4886  140 ELDLSNNQLTDLPE-PLGNLTNLKSLDLSNNQLTDL-PEELGNLTNLKELDLSNNQITDLPE-PLGNLTNLEELDLSGNQ 216

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571 136 LGGIaDDAFEDfLLTLEDLDLSYNNLHGLPWdsVRRMVNLHQLSLDHNLLDHIAEgtFADLQKLARLDLTSNRLQKLPPD 215
Cdd:COG4886  217 LTDL-PEPLAN-LTNLETLDLSNNQLTDLPE--LGNLTNLEELDLSNNQLTDLPP--LANLTNLKTLDLSNNQLTDLKLK 290

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 569001571 216 PIFARSQASLLTATPFAPPLSFSFGGNPLHCNCELLWLRRLERDDDLET 264
Cdd:COG4886  291 ELELLLGLNSLLLLLLLLNLLELLILLLLLTTLLLLLLLLKGLLVTLTT 339

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569001571  288 PPLITQHTHKLLVLEGQAATLKCKAIGDPSPLIHWVAPDDRLVGNSSR--TAVYDNGTLDILITTSQDSGPFTCI 360
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRsrSLSGSNSTLTISNVTRSDAGTYTCV 75

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571  61 GNFIIHIgrQDFANMTGLVDLTLSRNTISHIQPFSflDLESLRSLHLDSNRLPSLgEDtLRGLVNLQHLIVNNNQLGgiA 140
Cdd:cd21340   33 DNKITKI--ENLEFLTNLTHLYLQNNQIEKIENLE--NLVNLKKLYLGGNRISVV-EG-LENLTNLEELHIENQRLP--P 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571 141 DD--AFEDFLL-----TLEDLDLSYNNLHGLpwDSVRRMVNLHQLSLDHNLLDHIAE--GTFADLQKLARLDLTSNRLQK 211
Cdd:cd21340  105 GEklTFDPRSLaalsnSLRVLNISGNNIDSL--EPLAPLRNLEQLDASNNQISDLEEllDLLSSWPSLRELDLTGNPVCK 182

                 ..
gi 569001571 212 LP 213
Cdd:cd21340  183 KP 184

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571  150 TLEDLDLSYNNLHGLPWDSVRRMVNLHQLSLDHNLLDHIAEGTFADLQKLARLDLTSNRL 209
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569001571  101 SLRSLHLDSNRLPSLGEDTLRGLVNLQHLIVNNNQLGGIADDAFEDfLLTLEDLDLSYNNL 161
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSG-LPSLRYLDLSGNRL 61

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. 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 569001571 291 ITQHTHKLLVLEGQAATLKCKAIGDPSPLIHWVAPDDrLVGNSSRTAVYDNGTLDILITTSQDSGPFTCI 360
Cdd:cd20968    2 ITRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDD-LIKENNRIAVLESGSLRIHNVQKEDAGQYRCV 70

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569001571 298 LLVLEGQAATLKCKAIGDPSPLIHWVAPDDRLVGNSSrTAVYDNGTLDILITTSQDSGPFTCI 360
Cdd:cd05876    5 LVALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRV-KYQNHNKTLQLLNVGESDDGEYVCL 66

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569001571 290 LITQHTHKLLVLEGQAATLKCKAIGDPSPLIHWVAPDDRLVGNSSRTAVYDNGTLDILITTSQDSGPFTCI 360
Cdd:cd20952    1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCV 71

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. 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 Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569001571 302 EGQAATLKCKAIGDPSPLIHWVAPDDRLVGNSS--RTAVYDNGTLDILITTSQDSGPFTCI 360
Cdd:cd20969   16 EGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSngRLTVFPDGTLEVRYAQVQDNGTYLCI 76

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569001571 297 KLLVLEGQAATLKCKAIGDPSPLIHWVAPDDRLVgNSSRTAVYDNGTLDILITTSQDSGPFTC 359
Cdd:cd05852   11 KILAAKGGRVIIECKPKAAPKPKFSWSKGTELLV-NNSRISIWDDGSLEILNITKLDEGSYTC 72

type III secretion system effector E3 ubiquitin transferase SlrP;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571  74 NMTGLVDLTLSRNTISHIQPfsfldlESLRSLHLDSNRLPSLGEDtLRGlvNLQHLIVNNNQLGGIAddafEDFLLTLED 153
Cdd:PRK15370 179 NKTELRLKILGLTTIPACIP------EQITTLILDNNELKSLPEN-LQG--NIKTLYANSNQLTSIP----ATLPDTIQE 245

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571 154 LDLSYNNLHGLPwdsVRRMVNLHQLSLDHNLLDHIAEGTFADLQKlarLDLTSNRLQKLP---PDPIFARS-QASLLTAT 229
Cdd:PRK15370 246 MELSINRITELP---ERLPSALQSLDLFHNKISCLPENLPEELRY---LSVYDNSIRTLPahlPSGITHLNvQSNSLTAL 319

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 569001571 230 PFAPPLSfsfggnplhcncellwLRRLERDDDLETCgSPGSL 271
Cdd:PRK15370 320 PETLPPG----------------LKTLEAGENALTS-LPASL 344

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569001571 289 PLITQHTHKLLVLEGQAATLKCKAIGDPSPLIHWVApDDRLVGNSSRTAVY--DNGTLDILIT--TSQDSGPFTCI 360
Cdd:cd05744    1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQL-NGKPVRPDSAHKMLvrENGRHSLIIEpvTKRDAGIYTCI 75

Leucine rich repeat;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 569001571  174 NLHQLSLDHNLLDHIAEGTFADLQKLARLDLTSNRLQKLPPD 215
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPG 43

leucine-rich repeat receptor-like protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571  74 NMTGLVDLTLSRNTISHIQPFSFLDLESLRSLHLDSNRLPSLGEDTLRGLVNLQHLIVNNNQL-GGIADDAFEDFLLTLe 152
Cdd:PLN00113 282 SLQKLISLDLSDNSLSGEIPELVIQLQNLEILHLFSNNFTGKIPVALTSLPRLQVLQLWSNKFsGEIPKNLGKHNNLTV- 360

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569001571 153 dLDLSYNNLHGLPWDSVRRMVNLHQLSLDHNLLDHIAEGTFADLQKLARLDLTSNRLQ-KLPPD 215
Cdd:PLN00113 361 -LDLSTNNLTGEIPEGLCSSGNLFKLILFSNSLEGEIPKSLGACRSLRRVRLQDNSFSgELPSE 423

leucine-rich repeat receptor-like protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571  36 TLCPS----KGLLF-------VPPDID--RRTVELRLGGNFIIHIGRQDFANMTGLVDLTLSRNTISHIQPFSFLDLESL 102
Cdd:PLN00113 375 GLCSSgnlfKLILFsnslegeIPKSLGacRSLRRVRLQDNSFSGELPSEFTKLPLVYFLDISNNNLQGRINSRKWDMPSL 454

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571 103 RSLHLDSNRLpSLGEDTLRGLVNLQHLIVNNNQLGGIADDAFEDFLlTLEDLDLSYNNLHGLPWDSVRRMVNLHQLSLDH 182
Cdd:PLN00113 455 QMLSLARNKF-FGGLPDSFGSKRLENLDLSRNQFSGAVPRKLGSLS-ELMQLKLSENKLSGEIPDELSSCKKLVSLDLSH 532

                        170       180       190
                 ....*....|....*....|....*....|....
gi 569001571 183 NLLDHIAEGTFADLQKLARLDLTSNRLQ-KLPPD 215
Cdd:PLN00113 533 NQLSGQIPASFSEMPVLSQLDLSQNQLSgEIPKN 566

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third 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. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569001571 288 PPLITQHTHKLLVLEGQAATLKCKAIGDPSPLIHWVAPDDRLVgnSSRTAVYDNGTLDILITTSQDSGPFTCI 360
Cdd:cd04968    1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPS--SQWEITTSEPVLEIPNVQFEDEGTYECE 71

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001571  57 LRLGGNFIIHIgrQDFANMTGLVDLTLSRNTISHIQPFSFLD------LESLRSLHLDSNRLPSLGEdtLRGLVNLQHLI 130
Cdd:cd21340   73 LYLGGNRISVV--EGLENLTNLEELHIENQRLPPGEKLTFDPrslaalSNSLRVLNISGNNIDSLEP--LAPLRNLEQLD 148

                         90       100       110
                 ....*....|....*....|....*....|..
gi 569001571 131 VNNNQLGGIADdaFEDFLLT---LEDLDLSYN 159
Cdd:cd21340  149 ASNNQISDLEE--LLDLLSSwpsLRELDLTGN 178

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 569001571 288 PPLITQHTHKLLVLEGQAATLKCKAIGDPSPLIHWVApDDRLVGNSSRTAVYDNGTLDILITTS---QDSGPFTCIAANA 364
Cdd:cd20972    1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFC-EGKELQNSPDIQIHQEGDLHSLIIAEafeEDTGRYSCLATNS 79

                         90
                 ....*....|..
gi 569001571 365 AGEATATVEVSI 376
Cdd:cd20972   80 VGSDTTSAEIFV 91

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 569001571 288 PPLITQHTHKLLVLEGQAATLKCKAIGDPSPLIHWVAPDDRLVGNSSR-TAVYDNGTLDILITTSQDSGPFTCIAANAAG 366
Cdd:cd20976    1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRsTCEAGVGELHIQDVLPEDHGTYTCLAKNAAG 80

                         90
                 ....*....|
gi 569001571 367 EATATVEVSI 376
Cdd:cd20976   81 QVSCSAWVTV 90

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. 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 569001571 289 PLITQHTHKLLVLEGQAATLKCKAIGDPSPLIHW------VAPDdrlvgNSSRTAVYDNGTLDILI--TTSQDSGPFTCI 360
Cdd:cd20990    1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWqldgkpIRPD-----SAHKMLVRENGVHSLIIepVTSRDAGIYTCI 75

                         90
                 ....*....|....*.
gi 569001571 361 AANAAGEATATVEVSI 376
Cdd:cd20990   76 ATNRAGQNSFNLELVV 91

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 569001571 302 EGQAATLKCKAIGDPSPLIHWVAPDDRLVGNsSRTAVYDNGTLDILITTSQDSGPFTC 359
Cdd:cd05745    1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSVD-RRHLVLSSGTLRISRVALHDQGQYEC 57

leucine-rich repeat receptor-like protein kinase; Provisional