Ras-associating (RA) domain found in Ankyrin repeat and fibronectin type-III domain-containing protein 1 (ANKFN1) and similar proteins; ANKFN1 is a multi-domain protein, with unknown function, that contains two ankyrin repeats and one fibronectin type-III domain. Except for the mammalian homologs, most metazon ANKFN1 harbor a RA domain at the C-terminus. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1941228228 1374 IIQVYAAYETGLASGTSLKLHVTPKTTAREVVDLVVKQLNMAVVLKGKDGPIYTPDKLENFCLVAVIGARERCLRDDFKP 1453
Cdd:cd17117      1 ILRVYAAYETGLPKGTSVKLHVTPKTTAREVVNLVVQQLNKAVRSKGKGGPVYSEDQLDDFCLVAVVGARERCLRDDFQP 80

                           90
                   ....*....|....*..
gi 1941228228 1454 LQLQNPWKKGKLYVRQK 1470
Cdd:cd17117     81 LQLQNPWTKGRLYVRLK 97

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1941228228  500 PDEPSAVTVDVSGQNSVSISILEPLE--GPIgTKFKVQWSSKADfsnimgereiTQWTSYQGVMGAT--CRISDLTQGRR 575
Cdd:cd00063      1 PSPPTNLRVTDVTSTSVTLSWTPPEDdgGPI-TGYVVEYREKGS----------GDWKEVEVTPGSEtsYTLTGLKPGTE 69

                           90       100
                   ....*....|....*....|..
gi 1941228228  576 YFFRACCGNVKGWGPYHTTVPA 597
Cdd:cd00063     70 YEFRVRAVNGGGESPPSESVTV 91

Ras-associating (RA) domain found in Ankyrin repeat and fibronectin type-III domain-containing protein 1 (ANKFN1) and similar proteins; ANKFN1 is a multi-domain protein, with unknown function, that contains two ankyrin repeats and one fibronectin type-III domain. Except for the mammalian homologs, most metazon ANKFN1 harbor a RA domain at the C-terminus. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1941228228 1374 IIQVYAAYETGLASGTSLKLHVTPKTTAREVVDLVVKQLNMAVVLKGKDGPIYTPDKLENFCLVAVIGARERCLRDDFKP 1453
Cdd:cd17117      1 ILRVYAAYETGLPKGTSVKLHVTPKTTAREVVNLVVQQLNKAVRSKGKGGPVYSEDQLDDFCLVAVVGARERCLRDDFQP 80

                           90
                   ....*....|....*..
gi 1941228228 1454 LQLQNPWKKGKLYVRQK 1470
Cdd:cd17117     81 LQLQNPWTKGRLYVRLK 97

Ankyrin repeats (3 copies);

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1941228228  333 ESLLSPSSGRRTKQNRGITALFSAVEHGHLDKARTILESTDVDVnslNSDGLSPLDVAVLSNNRSMTKMLLQHGA 407
Cdd:pfam12796   14 KLLLENGADANLQDKNGRTALHLAAKNGHLEIVKLLLEHADVNL---KDNGRTALHYAARSGHLEIVKLLLEKGA 85

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.)

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1941228228  1373 GIIQVYAAYetgLASGTSLKLHVTPKTTAREVVDLVVKQLNMAvvlkgkDGPiytpdklENFCLVAVI-GARERCLRDDF 1451
Cdd:smart00314    3 FVLRVYVDD---LPGGTYKTLRVSSRTTARDVIQQLLEKFHLT------DDP-------EEYVLVEVLpDGKERVLPDDE 66

                            90       100
                    ....*....|....*....|....
gi 1941228228  1452 KPLQLQNPWKKGKL---YVRQKHD 1472
Cdd:smart00314   67 NPLQLQKLWPRRGPnlrFVLRKRD 90

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1941228228  500 PDEPSAVTVDVSGQNSVSISILEPLE--GPIgTKFKVQWSSKADfsnimgereiTQWTSYQGVMGAT--CRISDLTQGRR 575
Cdd:cd00063      1 PSPPTNLRVTDVTSTSVTLSWTPPEDdgGPI-TGYVVEYREKGS----------GDWKEVEVTPGSEtsYTLTGLKPGTE 69

                           90       100
                   ....*....|....*....|..
gi 1941228228  576 YFFRACCGNVKGWGPYHTTVPA 597
Cdd:cd00063     70 YEFRVRAVNGGGESPPSESVTV 91

Transient Receptor Potential channel, Vanilloid subfamily (TRPV), types 5 and 6; TRPV5 and TRPV6 (TRPV5/6) are two homologous members within the vanilloid subfamily of the transient receptor potential (TRP) family. TRPV5 and TRPV6 show only 30-40% homology with other members of the TRP family and have unique properties that differentiates them from other TRP channels. They mediate calcium uptake in epithelia and their expression is dramatically increased in numerous types of cancer. The structure of TRPV5/6 shows the typical topology features of all TRP family members, such as six transmembrane regions, a short hydrophobic stretch between transmembrane segments 5 and 6, which is predicted to form the Ca2+ pore, and large intracellular N- and C-terminal domains. The N-terminal domain of TRPV5/6 contains three ankyrin repeats. This structural element is present in several proteins and plays a role in protein-protein interactions. The N- and C-terminal tails of TRPV5/6 each contain an internal PDZ motif which can function as part of a molecular scaffold via interaction with PDZ-domain containing proteins. A major difference between the properties of TRPV5 and TRPV6 is in their tissue distribution: TRPV5 is predominantly expressed in the distal convoluted tubules (DCT) and connecting tubules (CNT) of the kidney, with limited expression in extrarenal tissues. In contrast, TRPV6 has a broader expression pattern such as expression in the intestine, kidney, placenta, epididymis, exocrine tissues, and a few other tissues.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1941228228  335 LLSPSSGRRTKQNRGITALFSAVEHGHLDKARTILESTDVDVN-SLNSD---GLSPLDVAVLSNNRSMTKMLLQHGA 407
Cdd:cd22192     37 LKCPSCDLFQRGALGETALHVAALYDNLEAAVVLMEAAPELVNePMTSDlyqGETALHIAVVNQNLNLVRELIARGA 113

Ras-associating (RA) domain found in Ankyrin repeat and fibronectin type-III domain-containing protein 1 (ANKFN1) and similar proteins; ANKFN1 is a multi-domain protein, with unknown function, that contains two ankyrin repeats and one fibronectin type-III domain. Except for the mammalian homologs, most metazon ANKFN1 harbor a RA domain at the C-terminus. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1941228228 1374 IIQVYAAYETGLASGTSLKLHVTPKTTAREVVDLVVKQLNMAVVLKGKDGPIYTPDKLENFCLVAVIGARERCLRDDFKP 1453
Cdd:cd17117      1 ILRVYAAYETGLPKGTSVKLHVTPKTTAREVVNLVVQQLNKAVRSKGKGGPVYSEDQLDDFCLVAVVGARERCLRDDFQP 80

                           90
                   ....*....|....*..
gi 1941228228 1454 LQLQNPWKKGKLYVRQK 1470
Cdd:cd17117     81 LQLQNPWTKGRLYVRLK 97

Ankyrin repeats (3 copies);

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1941228228  333 ESLLSPSSGRRTKQNRGITALFSAVEHGHLDKARTILESTDVDVnslNSDGLSPLDVAVLSNNRSMTKMLLQHGA 407
Cdd:pfam12796   14 KLLLENGADANLQDKNGRTALHLAAKNGHLEIVKLLLEHADVNL---KDNGRTALHYAARSGHLEIVKLLLEKGA 85

Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in various functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. RA-containing proteins include RalGDS, AF6, RIN, RASSF1, SNX27, CYR1, STE50, and phospholipase C epsilon.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1941228228 1374 IIQVYAAYETGLASGTSLklHVTPKTTAREVVDLVVKQLNmavvlkgkdgpiyTPDKLENFCL--VAVIGARERCLRDDF 1451
Cdd:cd17043      1 VLKVYDDDLAPGSAYKSI--LVSSTTTAREVVQLLLEKYG-------------LEEDPEDYSLyeVSEKQETERVLHDDE 65

                           90
                   ....*....|....*..
gi 1941228228 1452 KPLQLQNPWKKGKLYVR 1468
Cdd:cd17043     66 CPLLIQLEWGPQGTEFR 82

Ankyrin repeats (many copies);

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1941228228  351 TALFSAVEHGHLDKARTILESTdVDVNSLNSDGLSPLDVAVLSNNRSMTKMLL 403
Cdd:pfam13637    3 TALHAAAASGHLELLRLLLEKG-ADINAVDGNGETALHFAASNGNVEVLKLLL 54

Ankyrin repeat [Signal transduction mechanisms];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1941228228  345 KQNRGITALFSAVEHGHLDKARTILEStDVDVNSLNSDGLSPLDVAVLSNNRSMTKMLLQHGATEGSQFKSADSLGNHLN 424
Cdd:COG0666    182 RDNDGETPLHLAAENGHLEIVKLLLEA-GADVNAKDNDGKTALDLAAENGNLEIVKLLLEAGADLNAKDKDGLTALLLAA 260

                           90
                   ....*....|....*..
gi 1941228228  425 GLLHDAENRIHDLSTAD 441
Cdd:COG0666    261 AAGAALIVKLLLLALLL 277

ankyrin repeat protein; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1941228228  329 INRRESLLSPSSGRRTKQNRGITALFSAVEHGHLDKARTILESTdVDVNSLNSDGLSPLDVAVLSNNRSMTKMLLQHGAT 408
Cdd:PHA03100   172 KNRVNYLLSYGVPINIKDVYGFTPLHYAVYNNNPEFVKYLLDLG-ANPNLVNKYGDTPLHIAILNNNKEIFKLLLNNGPS 250

                   .
gi 1941228228  409 E 409
Cdd:PHA03100   251 I 251

Ankyrin repeats (3 copies);

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1941228228  353 LFSAVEHGHLDKARTILEStDVDVNSLNSDGLSPLDVAVLSNNRSMTKMLLQHGATE 409
Cdd:pfam12796    1 LHLAAKNGNLELVKLLLEN-GADANLQDKNGRTALHLAAKNGHLEIVKLLLEHADVN 56

Transient Receptor Potential channel, Vanilloid subfamily (TRPV), types 5 and 6; TRPV5 and TRPV6 (TRPV5/6) are two homologous members within the vanilloid subfamily of the transient receptor potential (TRP) family. TRPV5 and TRPV6 show only 30-40% homology with other members of the TRP family and have unique properties that differentiates them from other TRP channels. They mediate calcium uptake in epithelia and their expression is dramatically increased in numerous types of cancer. The structure of TRPV5/6 shows the typical topology features of all TRP family members, such as six transmembrane regions, a short hydrophobic stretch between transmembrane segments 5 and 6, which is predicted to form the Ca2+ pore, and large intracellular N- and C-terminal domains. The N-terminal domain of TRPV5/6 contains three ankyrin repeats. This structural element is present in several proteins and plays a role in protein-protein interactions. The N- and C-terminal tails of TRPV5/6 each contain an internal PDZ motif which can function as part of a molecular scaffold via interaction with PDZ-domain containing proteins. A major difference between the properties of TRPV5 and TRPV6 is in their tissue distribution: TRPV5 is predominantly expressed in the distal convoluted tubules (DCT) and connecting tubules (CNT) of the kidney, with limited expression in extrarenal tissues. In contrast, TRPV6 has a broader expression pattern such as expression in the intestine, kidney, placenta, epididymis, exocrine tissues, and a few other tissues.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1941228228  335 LLSPSSGRRTKQNRGITALFSAVEHGHLDKARTILESTDVDVN-SLNSD---GLSPLDVAVLSNNRSMTKMLLQHGA 407
Cdd:cd22192     37 LKCPSCDLFQRGALGETALHVAALYDNLEAAVVLMEAAPELVNePMTSDlyqGETALHIAVVNQNLNLVRELIARGA 113