Ly6/PLAUR domain-containing protein 6, Lypd6; UPAR_LY6_2 is a family of higher eukaryotic proteins expressed in neurons. It modulates nicotinic acetylcholine receptors by selectively increasing Ca2+-influx through this ion channel. The family carries an LU protein domain - about 80 amino acids long characterized by a conserved pattern of 10 cysteine residues. The family is a positive feedback regulator of Wnt/beta-catenin signalling, eg for patterning of the mesoderm and neuroectoderm in zebrafish gastrulation, where Lypd6 is GPI-anchored to the plasma-membrane and interacts with the Wnt receptor Frizzled8 and the co-receptor Lrp6.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55583936    40 TTPYPGGFKCFTCEKAADNYECNRWAPDIYCPRDTRYCYTQHTMEVTGNSISVTKRCVPLEECLSTGCRDSEHEGYKICT 119
Cdd:pfam16975   1 TTPYPSGFKCFTCEAADDNYCCNRWAPDWCCPRTTYYCTTHHFMSHGGSSVSVTKRCATEEECLVGGCHHRDDGGHEVCS 80

                          90       100
                  ....*....|....*....|....*.
gi 55583936   120 SCCEGNICNLPLPRNETDATFATTSP 145
Cdd:pfam16975  81 SCCEGNICNVVLPNNTTAAVFATTSP 106

Ly6/PLAUR domain-containing protein 6, Lypd6; UPAR_LY6_2 is a family of higher eukaryotic proteins expressed in neurons. It modulates nicotinic acetylcholine receptors by selectively increasing Ca2+-influx through this ion channel. The family carries an LU protein domain - about 80 amino acids long characterized by a conserved pattern of 10 cysteine residues. The family is a positive feedback regulator of Wnt/beta-catenin signalling, eg for patterning of the mesoderm and neuroectoderm in zebrafish gastrulation, where Lypd6 is GPI-anchored to the plasma-membrane and interacts with the Wnt receptor Frizzled8 and the co-receptor Lrp6.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55583936    40 TTPYPGGFKCFTCEKAADNYECNRWAPDIYCPRDTRYCYTQHTMEVTGNSISVTKRCVPLEECLSTGCRDSEHEGYKICT 119
Cdd:pfam16975   1 TTPYPSGFKCFTCEAADDNYCCNRWAPDWCCPRTTYYCTTHHFMSHGGSSVSVTKRCATEEECLVGGCHHRDDGGHEVCS 80

                          90       100
                  ....*....|....*....|....*.
gi 55583936   120 SCCEGNICNLPLPRNETDATFATTSP 145
Cdd:pfam16975  81 SCCEGNICNVVLPNNTTAAVFATTSP 106

Ly6/PLAUR domain-containing protein 6, Lypd6; UPAR_LY6_2 is a family of higher eukaryotic proteins expressed in neurons. It modulates nicotinic acetylcholine receptors by selectively increasing Ca2+-influx through this ion channel. The family carries an LU protein domain - about 80 amino acids long characterized by a conserved pattern of 10 cysteine residues. The family is a positive feedback regulator of Wnt/beta-catenin signalling, eg for patterning of the mesoderm and neuroectoderm in zebrafish gastrulation, where Lypd6 is GPI-anchored to the plasma-membrane and interacts with the Wnt receptor Frizzled8 and the co-receptor Lrp6.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55583936    40 TTPYPGGFKCFTCEKAADNYECNRWAPDIYCPRDTRYCYTQHTMEVTGNSISVTKRCVPLEECLSTGCRDSEHEGYKICT 119
Cdd:pfam16975   1 TTPYPSGFKCFTCEAADDNYCCNRWAPDWCCPRTTYYCTTHHFMSHGGSSVSVTKRCATEEECLVGGCHHRDDGGHEVCS 80

                          90       100
                  ....*....|....*....|....*.
gi 55583936   120 SCCEGNICNLPLPRNETDATFATTSP 145
Cdd:pfam16975  81 SCCEGNICNVVLPNNTTAAVFATTSP 106

extracellular domain (ECD) found in the Ly6/PLAUR domain-containing protein 6 (LYPD6)-like family; The LYPD6-like family includes LYPD6 and LYPD6B. LYPD6 acts as a modulator of nicotinic acetylcholine receptors (nAChRs) function in the brain. It inhibits nicotine-induced Ca(2+) influx through nAChRs. It functions as a positive regulator of Wnt/beta-catenin signaling. LYPD6B (also called LYPD7) may act as a modulator of nicotinic acetylcholine receptors (nAChRs) activity. In vitro it acts on nAChRs in a subtype- and stoichiometry-dependent manner. LYPD6B modulates specifically alpha-3(3):beta-4(2) nAChRs by enhancing the sensitivity to ACh, decreasing ACh-induced maximal current response and increasing the rate of desensitization to ACh; has no effect on alpha-7 homomeric nAChRs; modulates alpha-3(2):alpha-5:beta-4(2) nAChRs in the context of CHRNA5/alpha-5 variant Asn-398, but not its wild-type sequence. LYPD6B also activates AP1 (PMA)-mediated transcriptional activation. Members in this family contain an extracellular domain (ECD) that belongs to Ly-6 antigen/uPA receptor-like (LU) superfamily and exhibits a snake toxin-like fold (also known as three-finger toxin/3FTx fold or three-fingered protein/TFP domain fold).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55583936  47 FKCFTCEKAADNYECNRWAPDIYCPRDTRYCYTQHTMEVTGNSISVTKRCVPLEECL--STGCRDSEHEGYKICTSCCEG 124
Cdd:cd23567   1 ITCFTCENKTDNYECNRWAIDRPCPQGTSYCYTVHVMDSRGRSVSVTKKCATPSECTpnTVGCRDSTDTGHTVCISCCDG 80

                ....*...
gi 55583936 125 NICNLPLP 132
Cdd:cd23567  81 SYCNVEVP 88

three-fingered protein (TFP) fold found in Ly6/uPAR (LU) and snake toxin superfamily; The LU (also known as Ly-6 antigen/uPA receptor)-like extracellular domain (ECD) occurs singly in GPI-linked cell-surface glycoproteins (Ly-6 family, CD59, thymocyte B cell antigen, Sgp-2) or as three-fold repeated domain in urokinase-type plasminogen activator receptor. It is a structural domain involved in protein-protein interactions, tolerating an unusual degree of variation and binding with high specificity to a broad spectrum of targets. The snake toxin domain is present in short and long neurotoxins, cytotoxins, and short toxins, and in other miscellaneous venom peptides. The toxin acts by binding to the nicotinic acetylcholine receptors in the postsynaptic membrane of skeletal muscles and preventing the binding of acetylcholine, thereby blocking the excitation of muscles. Both the LU-like ECD and the snake toxin domain belong to three-fingered protein (TFP) fold, which is characterized by containing 70 to 100 amino acids including eight to ten cysteine residues spaced at conserved distances.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55583936  48 KCFTCEKAADNYECNRWAPDIYCPRDTRYCYTQhTMEVTGNSISVTKRCVPLEECLSTGCRDSEHEGYKICTSCCEGNIC 127
Cdd:cd00117   2 KCYQCNSSNDPNCCNSSPTLVTCSSPETFCRKI-VGKVGGGETLVIRGCATECECGCTECCSGTGTSGTTCTSCCDTDLC 80

                .
gi 55583936 128 N 128
Cdd:cd00117  81 N 81

extracellular domain (ECD) found in Ciona intestinalis globin CinHb4 and similar proteins; Four distinct globin genes have been identified in the Ciona genome. CinHb4 is encoded by the fourth globin gene. It shows an unusual extension at its N-terminus, which reveals a conserved region with similarity to the extracellular domain (ECD) of the TGF-beta receptor type I/II protein family involved in signal transduction. The functional relevance of these matches is currently unknown. The ECD belongs to Ly-6 antigen/uPA receptor-like (LU) superfamily and exhibits a snake toxin-like fold (also known as three-finger toxin/3FTx fold or three-fingered protein/TFP domain fold).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55583936  47 FKCFTCEKAADNYECNRWAPDIYCPRDTRYCYTQhTMEVTGNSISVTKRCVPLEECL------------STGCRDSEHeg 114
Cdd:cd23539   1 LSCWTCDNASSNEECLANGTLVTCQSNEESCQTE-VRRRGGGVYLISKGCKQRQACEnnkkqnfkaawnPTQCNPESP-- 77

                        90
                ....*....|....
gi 55583936 115 YKICTSCCEGNICN 128
Cdd:cd23539  78 NSVCRCCCSTDLCN 91