polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) Polycystin is a huge protein of 4303aas. Its repeated leucine-rich (LRR) segment is found in many proteins. It contains 16 polycystic kidney disease (PKD) domains, one LDL-receptor class A domain, one C-type lectin family domain, and 16-18 putative TMSs in positions between residues 2200 and 4100. Polycystin-L has been shown to be a cation (Na+, K+ and Ca2+) channel that is activated by Ca2+. Two members of the PCC family (polycystin 1 and 2) are mutated in autosomal dominant polycystic kidney disease, and polycystin-L is deleted in mice with renal and retinal defects. Note: this model is restricted to the amino half.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 238859612   154 INNNRLRTLEPGTFDALSALSHLQLYHNPFHCSCGLVWLQAWAASTRVSLPEPDSIACASPPELQGVPVHRLPAL 228
Cdd:TIGR00864    2 ISNNKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEEKGVKVRQPEAALCAGPGALAGQPLLGIPLL 76

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
                  ....*....|....*....|...
gi 238859612  351 AGIYTCRAHNELGTNSTSLRVTV 373
Cdd:pfam07679  68 SGKYTCVATNSAGEAEASAELTV 90

polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) Polycystin is a huge protein of 4303aas. Its repeated leucine-rich (LRR) segment is found in many proteins. It contains 16 polycystic kidney disease (PKD) domains, one LDL-receptor class A domain, one C-type lectin family domain, and 16-18 putative TMSs in positions between residues 2200 and 4100. Polycystin-L has been shown to be a cation (Na+, K+ and Ca2+) channel that is activated by Ca2+. Two members of the PCC family (polycystin 1 and 2) are mutated in autosomal dominant polycystic kidney disease, and polycystin-L is deleted in mice with renal and retinal defects. Note: this model is restricted to the amino half.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 238859612   154 INNNRLRTLEPGTFDALSALSHLQLYHNPFHCSCGLVWLQAWAASTRVSLPEPDSIACASPPELQGVPVHRLPAL 228
Cdd:TIGR00864    2 ISNNKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEEKGVKVRQPEAALCAGPGALAGQPLLGIPLL 76

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 238859612  52 NVTTLSLSANKITVLRrgAFVNVTQVTSLWLAHSEVRTVESgaLAVLSQLKNLDLSHNLISNFpwSDLRNLSALQLLKMN 131
Cdd:cd21340   25 NLKVLYLYDNKITKIE--NLEFLTNLTHLYLQNNQIEKIEN--LENLVNLKKLYLGGNRISVV--EGLENLTNLEELHIE 98

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 238859612 132 HNRLGS------LPRDALGALPDLRSLRINNNRLRTLEPgtFDALSALSHLQLYHN 181
Cdd:cd21340   99 NQRLPPgekltfDPRSLAALSNSLRVLNISGNNIDSLEP--LAPLRNLEQLDASNN 152

leucine-rich repeat receptor-like protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 238859612  99 SQLKNLDLSHNLISNFPWSDLRNLSALQLLKMNHNRL-GSLPrDALGALPDLRSLRINNNRLRTLEPGTFDALSALSHLQ 177
Cdd:PLN00113 475 KRLENLDLSRNQFSGAVPRKLGSLSELMQLKLSENKLsGEIP-DELSSCKKLVSLDLSHNQLSGQIPASFSEMPVLSQLD 553

                 ....
gi 238859612 178 LYHN 181
Cdd:PLN00113 554 LSQN 557

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 238859612 248 TPLRAGLAFMLHCVAEGHPTPRLQWQlqipggtvvlvppvlskeEDGgdkvedgegdgdEDLPTQTEaptptpapawpap 327
Cdd:cd20952    9 QTVAVGGTVVLNCQATGEPVPTISWL------------------KDG------------VPLLGKDE------------- 45

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 238859612 328 patpRFLALANGSLLVPLLSAKEAGIYTCRAHNELGTNSTSLRVTV 373
Cdd:cd20952   46 ----RITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 238859612  36 DCAYKELREVPE---GLPaNVTTLSLSANKITVLRrGAFVNVTQVTSLWLAHSEVRTVeSGALAVLSQLKNLDLSHNLIS 112
Cdd:COG4886  165 DLSNNQLTDLPEelgNLT-NLKELDLSNNQITDLP-EPLGNLTNLEELDLSGNQLTDL-PEPLANLTNLETLDLSNNQLT 241

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 238859612 113 NFPWsdLRNLSALQLLKMNHNRLGSLPrdALGALPDLRSLRINNNRLRTLEPGTFDALSALSHLQLYHNPFH 184
Cdd:COG4886  242 DLPE--LGNLTNLEELDLSNNQLTDLP--PLANLTNLKTLDLSNNQLTDLKLKELELLLGLNSLLLLLLLLN 309

polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) Polycystin is a huge protein of 4303aas. Its repeated leucine-rich (LRR) segment is found in many proteins. It contains 16 polycystic kidney disease (PKD) domains, one LDL-receptor class A domain, one C-type lectin family domain, and 16-18 putative TMSs in positions between residues 2200 and 4100. Polycystin-L has been shown to be a cation (Na+, K+ and Ca2+) channel that is activated by Ca2+. Two members of the PCC family (polycystin 1 and 2) are mutated in autosomal dominant polycystic kidney disease, and polycystin-L is deleted in mice with renal and retinal defects. Note: this model is restricted to the amino half.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 238859612   154 INNNRLRTLEPGTFDALSALSHLQLYHNPFHCSCGLVWLQAWAASTRVSLPEPDSIACASPPELQGVPVHRLPAL 228
Cdd:TIGR00864    2 ISNNKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEEKGVKVRQPEAALCAGPGALAGQPLLGIPLL 76

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 238859612  120 RNLSALQLlkmNHNRLGSLPRDALGALPDLRSLRINNNRLRTLEPGTFDALSALSHLQLYHNPF 183
Cdd:pfam13855   1 PNLRSLDL---SNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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 238859612  52 NVTTLSLSANKITVLRrgAFVNVTQVTSLWLAHSEVRTVESgaLAVLSQLKNLDLSHNLISNFpwSDLRNLSALQLLKMN 131
Cdd:cd21340   25 NLKVLYLYDNKITKIE--NLEFLTNLTHLYLQNNQIEKIEN--LENLVNLKKLYLGGNRISVV--EGLENLTNLEELHIE 98

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 238859612 132 HNRLGS------LPRDALGALPDLRSLRINNNRLRTLEPgtFDALSALSHLQLYHN 181
Cdd:cd21340   99 NQRLPPgekltfDPRSLAALSNSLRVLNISGNNIDSLEP--LAPLRNLEQLDASNN 152

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 238859612  36 DCAYKELREVPEGLPA--NVTTLSLSANKITVLRrgAFVNVTQVTSLWLAHSEVRTVESgaLAVLSQLKNLDLSHNLISN 113
Cdd:COG4886  211 DLSGNQLTDLPEPLANltNLETLDLSNNQLTDLP--ELGNLTNLEELDLSNNQLTDLPP--LANLTNLKTLDLSNNQLTD 286

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 238859612 114 FPWSDLRNLSALQLLKMNHNRLGSLPrdALGALPDLRSLRINNNRLRTLEPGTFDALSALSHLQLYHNPFH 184
Cdd:COG4886  287 LKLKELELLLGLNSLLLLLLLLNLLE--LLILLLLLTTLLLLLLLLKGLLVTLTTLALSLSLLALLTLLLL 355

hypothetical protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 238859612  98 LSQLKNLDLSHNLI-SNFPWSdLRNLSALQLLKMNHNRL-GSLPrDALGALPDLRSLRINNNRLRTLEPGTFDAL 170
Cdd:PLN03150 441 LRHLQSINLSGNSIrGNIPPS-LGSITSLEVLDLSYNSFnGSIP-ESLGQLTSLRILNLNGNSLSGRVPAALGGR 513

Leucine-rich repeat;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 238859612   96 AVLSQLKNLDLSHNLI---SNFPWsdlrnLSALQLLKMNHNRLGSLPRDALGALPDLRSLRINNNRLRTLepGTFDALSA 172
Cdd:pfam14580  39 ATLDQFDTIDFSDNEIrklDGFPL-----LRRLKTLLLNNNRICRIGEGLGEALPNLTELILTNNNLQEL--GDLDPLAS 111

                          90
                  ....*....|...
gi 238859612  173 LSHLQ---LYHNP 182
Cdd:pfam14580 112 LKKLTflsLLRNP 124

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 238859612 248 TPLRAGLAFMLHCVAEGHPTPRLQWQlqipggtvvlvppvlskeEDGgdkvedgegdgdEDLPTQTEaptptpapawpap 327
Cdd:cd20952    9 QTVAVGGTVVLNCQATGEPVPTISWL------------------KDG------------VPLLGKDE------------- 45

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 238859612 328 patpRFLALANGSLLVPLLSAKEAGIYTCRAHNELGTNSTSLRVTV 373
Cdd:cd20952   46 ----RITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

leucine-rich repeat receptor-like protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 238859612  76 QVTSLWLAHSEVRTVESGALAVLSQLKNLDLSHNLISNFPWSDLRNLSALQLLKMNHNRL-GSLPrDALGALPDLRSLRI 154
Cdd:PLN00113 476 RLENLDLSRNQFSGAVPRKLGSLSELMQLKLSENKLSGEIPDELSSCKKLVSLDLSHNQLsGQIP-ASFSEMPVLSQLDL 554

                         90       100       110
                 ....*....|....*....|....*....|..
gi 238859612 155 NNNRLRTLEPGTFDALSALSHLQLYHNPFHCS 186
Cdd:PLN00113 555 SQNQLSGEIPKNLGNVESLVQVNISHNHLHGS 586

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup 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. 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. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin 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. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 238859612 250 LRAGLAFMLHCVAEGHPTPRLQWQlqipggtvvlvppvlskeEDGGDKVEDGEGDGDEDLPTQTEaptptpapawpappa 329
Cdd:cd05763   11 IRAGSTARLECAATGHPTPQIAWQ------------------KDGGTDFPAARERRMHVMPEDDV--------------- 57

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 238859612 330 tprflalangsLLVPLLSAKEAGIYTCRAHNELGTNSTSLRVTV 373
Cdd:cd05763   58 -----------FFIVDVKIEDTGVYSCTAQNSAGSISANATLTV 90

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 238859612 256 FMLHCVAEGHPTPRLQWQLqipGGTVVLVPPVLSKEEDGGdkvedgegdgdedlptqteaptptpapawpappatprfla 335
Cdd:cd00096    1 VTLTCSASGNPPPTITWYK---NGKPLPPSSRDSRRSELG---------------------------------------- 37

                         90       100       110
                 ....*....|....*....|....*....|...
gi 238859612 336 laNGSLLVPLLSAKEAGIYTCRAHNELGTNSTS 368
Cdd:cd00096   38 --NGTLTISNVTLEDSGTYTCVASNSAGGSASA 68