Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065 1894 EDAPAVISDFIYQGASLHNQTDRTGETALHLAARYSRSDAAKRLLEASADANIQDNMGRTPLHAAVSADAQGVFQILLRN 1973
Cdd:COG0666    63 LAGDLLVALLLLAAGADINAKDDGGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLLLEA 142

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065 1974 RAtDLDARMHDGTTPLILAARLAVEGMLEDLINSHADVNAVDDLGKSALHWAAAVNNVDAAVVLLKNGANKDMQNNKEET 2053
Cdd:COG0666   143 GA-DVNAQDNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKT 221

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 224967065 2054 PLFLAAREGSYETAKVLLDHFANRDITDHMDRLPRDIAQERMHHDIVRLLDEYNL 2108
Cdd:COG0666   222 ALDLAAENGNLEIVKLLLEAGADLNAKDKDGLTALLLAAAAGAALIVKLLLLALL 276

NOTCH protein; NOTCH signalling plays a fundamental role during a great number of developmental processes in multicellular animals. NOD and NODP represent a region present in many NOTCH proteins and NOTCH homologs in multiple species such as NOTCH2 and NOTCH3, LIN12, SC1 and TAN1. The role of the NOD and NODP domains remains to be elucidated.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 224967065  1661 IRGSIVYLEIDNRQCVQSSSQCFQSATDVAAFLGALASLGSLNIPYKIEAVKSEPVEPP 1719
Cdd:pfam07684    1 VIGSVVYLEIDNRKCSQSSDECFSTAQSAADFLAALAAKGGLDLPYPIKEVRSEPPPPP 59

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 224967065  869 DINECV-KSPCRHGASCQNTNGSYRCLCQAGYTGRNCE 905
Cdd:cd00054     1 DIDECAsGNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 224967065  412 DVDECALGaNPCEHAGKCLNTLGSFECQCLQGYTGPRCE 450
Cdd:cd00054     1 DIDECASG-NPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 224967065  528 DVDECAST-PCKNGAKCLDGPNTYTCVCTEGYTGTHCE 564
Cdd:cd00054     1 DIDECASGnPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 224967065  295 DVDECQlMPNACQNGGTCHNTHGGYNCVCVNGWTGEDC 332
Cdd:cd00054     1 DIDECA-SGNPCQNGGTCVNTVGSYRCSCPPGYTGRNC 37

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065  2183 SSSMLSPVDSLESPHgyLSDVASPPLLPSPFQ-QSPSMPLS--------HLPGMPDTHlgiSHLNVAAKPemaalaggsr 2253
Cdd:pfam03154  191 TTQAATAGPTPSAPS--VPPQGSPATSQPPNQtQSTAAPHTliqqtptlHPQRLPSPH---PPLQPMTQP---------- 255

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065  2254 lafePPPPRLSHLPVAssastvlstngtgamnftvgaPASLNGQCEWLPR-LQNGM------VPSQYNPLRP----GVTP 2322
Cdd:pfam03154  256 ----PPPSQVSPQPLP---------------------QPSLHGQMPPMPHsLQTGPshmqhpVPPQPFPLTPqssqSQVP 310

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065  2323 GTLSTQAAGLQHSMMGPLHSSLSTNTLSPIIYQGLPNTRLAtQPHLvqtQQVQPQNLQLQPQNLQPPSQPHLSVSSAAng 2402
Cdd:pfam03154  311 PGPSPAAPGQSQQRIHTPPSQSQLQSQQPPREQPLPPAPLS-MPHI---KPPPTTPIPQLPNPQSHKHPPHLSGPSPF-- 384

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065  2403 hlgrSFLSGEPSQADVQPLgpSSLPVH----------TILPQeSQALPTslPSSMVPPMTTTQFLTPPSQHSYSSSPVDN 2472
Cdd:pfam03154  385 ----QMNSNLPPPPALKPL--SSLSTHhppsahppplQLMPQ-SQQLPP--PPAQPPVLTQSQSLPPPAASHPPTSGLHQ 455

                          330       340
                   ....*....|....*....|
gi 224967065  2473 TPShQLQVPEHPFLTPSPES 2492
Cdd:pfam03154  456 VPS-QSPFPQHPFVPGGPPP 474

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 224967065 1146 VDEC-SPNPCQNGATCTDYLGGFSCKCVAGYHGSNC 1180
Cdd:cd00054     2 IDECaSGNPCQNGGTCVNTVGSYRCSCPPGYTGRNC 37

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 224967065  678 NIDECA-GSPCHNGGTCEDGIAGFTCRCPEGYHDPTC 713
Cdd:cd00054     1 DIDECAsGNPCQNGGTCVNTVGSYRCSCPPGYTGRNC 37

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 224967065  452 DVNEC-ISNPCQNDATCLDQIGEFQCICMPGYEGVYCE 488
Cdd:cd00054     1 DIDECaSGNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 224967065  907 DIDDCR-PNPCHNGGSCTDGINTAFCDCLPGFQGAFCE 943
Cdd:cd00054     1 DIDECAsGNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 224967065  988 TESSCFNGGTCVDGINSFTCLCPPGFTGSYCQ 1019
Cdd:cd00054     7 SGNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 224967065  142 DPCAS-NPCANGGQCLPFESSYICRCPPGFHGPTC 175
Cdd:cd00054     3 DECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNC 37

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 224967065  566 DIDECD-PDPCHY-GSCKDGVATFTCLCQPGYTGHHCE 601
Cdd:cd00054     1 DIDECAsGNPCQNgGTCVNTVGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 224967065  490 NTDECAS-SPCLHNGHCMDKINEFQCQCPKGFNGHLCQ 526
Cdd:cd00054     1 DIDECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 224967065  335 NIDDCASAA-CFQGATCHDRVASFYCECPHGRTGLLC 370
Cdd:cd00054     1 DIDECASGNpCQNGGTCVNTVGSYRCSCPPGYTGRNC 37

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20
                  ....*....|....*....|....*...
gi 224967065 1067 PCKNGGRCWQTNTQYHCECRSGWTGVNC 1094
Cdd:cd00054    10 PCQNGGTCVNTVGSYRCSCPPGYTGRNC 37

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065 1894 EDAPAVISDFIYQGASLHNQTDRTGETALHLAARYSRSDAAKRLLEASADANIQDNMGRTPLHAAVSADAQGVFQILLRN 1973
Cdd:COG0666    63 LAGDLLVALLLLAAGADINAKDDGGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLLLEA 142

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065 1974 RAtDLDARMHDGTTPLILAARLAVEGMLEDLINSHADVNAVDDLGKSALHWAAAVNNVDAAVVLLKNGANKDMQNNKEET 2053
Cdd:COG0666   143 GA-DVNAQDNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKT 221

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 224967065 2054 PLFLAAREGSYETAKVLLDHFANRDITDHMDRLPRDIAQERMHHDIVRLLDEYNL 2108
Cdd:COG0666   222 ALDLAAENGNLEIVKLLLEAGADLNAKDKDGLTALLLAAAAGAALIVKLLLLALL 276

NOTCH protein; NOTCH signalling plays a fundamental role during a great number of developmental processes in multicellular animals. NOD and NODP represent a region present in many NOTCH proteins and NOTCH homologs in multiple species such as NOTCH2 and NOTCH3, LIN12, SC1 and TAN1. The role of the NOD and NODP domains remains to be elucidated.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 224967065  1661 IRGSIVYLEIDNRQCVQSSSQCFQSATDVAAFLGALASLGSLNIPYKIEAVKSEPVEPP 1719
Cdd:pfam07684    1 VIGSVVYLEIDNRKCSQSSDECFSTAQSAADFLAALAAKGGLDLPYPIKEVRSEPPPPP 59

ankyrin repeat protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065 1907 GASLHNQTDRTGETALHLAARYSRSDAAKRLLEASADANIQDNMGRTPLHAAVSADAQGVFQILLRNRATdLDARMHDGT 1986
Cdd:PHA02878  157 GADINMKDRHKGNTALHYATENKDQRLTELLLSYGANVNIPDKTNNSPLHHAVKHYNKPIVHILLENGAS-TDARDKCGN 235

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065 1987 TPL-ILAARLAVEGMLEDLINSHADVNAVDD-LGKSALHwaAAVNNVDAAVVLLKNGANKDMQNNKEETPLFLAAREGS- 2063
Cdd:PHA02878  236 TPLhISVGYCKDYDILKLLLEHGVDVNAKSYiLGLTALH--SSIKSERKLKLLLEYGADINSLNSYKLTPLSSAVKQYLc 313

                         170       180
                  ....*....|....*....|.
gi 224967065 2064 YETAKVLLDH-----FANRDI 2079
Cdd:PHA02878  314 INIGRILISNicllkRIKPDI 334

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065 1918 GETALHLAARYSRSDAAKRLLEASADAnIQDNM------GRTPLHAAVSADAQGVFQILLRNRATDLDAR---------- 1981
Cdd:cd22192    51 GETALHVAALYDNLEAAVVLMEAAPEL-VNEPMtsdlyqGETALHIAVVNQNLNLVRELIARGADVVSPRatgtffrpgp 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065 1982 ---MHDGTTPLILAARLAVEGMLEDLINSHADVNAVDDLGKSALHWAAAVNNVDAAVV----LLKNGANKD------MQN 2048
Cdd:cd22192   130 knlIYYGEHPLSFAACVGNEEIVRLLIEHGADIRAQDSLGNTVLHILVLQPNKTFACQmydlILSYDKEDDlqpldlVPN 209

                         170
                  ....*....|....
gi 224967065 2049 NKEETPLFLAAREG 2062
Cdd:cd22192   210 NQGLTPFKLAAKEG 223

Domain found in Notch and Lin-12; The Notch protein is essential for the proper differentiation of the Drosophila ectoderm. This protein contains 3 NL domains.

                            10        20        30
                    ....*....|....*....|....*....|....*...
gi 224967065   1442 PPQIEEACELPECQVDAGNKVCNLQCNNHACGWDGGDC 1479
Cdd:smart00004    1 PQDPWSRCEDAQCWDKFGDGVCDEECNNAECLWDGGDC 38

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 224967065    869 DINECV-KSPCRHGASCQNTNGSYRCLCQAGYT-GRNCE 905
Cdd:smart00179    1 DIDECAsGNPCQNGGTCVNTVGSYRCECPPGYTdGRNCE 39

LNR domain; The LNR (Lin-12/Notch repeat) domain is found in three tandem copies in Notch related proteins. The structure of the domain has been determined by NMR and was shown to contain three disulphide bonds and coordinate a calcium ion. Three repeats are also found in the PAPP-A peptidase.

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 224967065  1525 EGQCNPlydQYCKDHFSDGHCDQGCNSAECEWDGLDC 1561
Cdd:pfam00066    1 WPNCPY---PYCWDKFGNGVCDEECNNAECLWDGGDC 34

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 224967065 1021 DVNECDSR-PCLHGGTCQDSYGTYKCTCPQGYTGLNCQ 1057
Cdd:cd00054     1 DIDECASGnPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

LNR domain; The LNR (Lin-12/Notch repeat) domain is found in three tandem copies in Notch related proteins. The structure of the domain has been determined by NMR and was shown to contain three disulphide bonds and coordinate a calcium ion. Three repeats are also found in the PAPP-A peptidase.

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 224967065  1446 EEACELPECQVDAGNKVCNLQCNNHACGWDGGDCS 1480
Cdd:pfam00066    1 WPNCPYPYCWDKFGNGVCDEECNNAECLWDGGDCS 35

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065  2183 SSSMLSPVDSLESPHgyLSDVASPPLLPSPFQ-QSPSMPLS--------HLPGMPDTHlgiSHLNVAAKPemaalaggsr 2253
Cdd:pfam03154  191 TTQAATAGPTPSAPS--VPPQGSPATSQPPNQtQSTAAPHTliqqtptlHPQRLPSPH---PPLQPMTQP---------- 255

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065  2254 lafePPPPRLSHLPVAssastvlstngtgamnftvgaPASLNGQCEWLPR-LQNGM------VPSQYNPLRP----GVTP 2322
Cdd:pfam03154  256 ----PPPSQVSPQPLP---------------------QPSLHGQMPPMPHsLQTGPshmqhpVPPQPFPLTPqssqSQVP 310

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065  2323 GTLSTQAAGLQHSMMGPLHSSLSTNTLSPIIYQGLPNTRLAtQPHLvqtQQVQPQNLQLQPQNLQPPSQPHLSVSSAAng 2402
Cdd:pfam03154  311 PGPSPAAPGQSQQRIHTPPSQSQLQSQQPPREQPLPPAPLS-MPHI---KPPPTTPIPQLPNPQSHKHPPHLSGPSPF-- 384

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065  2403 hlgrSFLSGEPSQADVQPLgpSSLPVH----------TILPQeSQALPTslPSSMVPPMTTTQFLTPPSQHSYSSSPVDN 2472
Cdd:pfam03154  385 ----QMNSNLPPPPALKPL--SSLSTHhppsahppplQLMPQ-SQQLPP--PPAQPPVLTQSQSLPPPAASHPPTSGLHQ 455

                          330       340
                   ....*....|....*....|
gi 224967065  2473 TPShQLQVPEHPFLTPSPES 2492
Cdd:pfam03154  456 VPS-QSPFPQHPFVPGGPPP 474

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 224967065 1184 INECLSQ-PCQNGGTCIDLTNSYKCSCPRGTQGVHCE 1219
Cdd:cd00054     2 IDECASGnPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 224967065 1146 VDEC-SPNPCQNGATCTDYLGGFSCKCVAGYHGSNC 1180
Cdd:cd00054     2 IDECaSGNPCQNGGTCVNTVGSYRCSCPPGYTGRNC 37

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 224967065  678 NIDECA-GSPCHNGGTCEDGIAGFTCRCPEGYHDPTC 713
Cdd:cd00054     1 DIDECAsGNPCQNGGTCVNTVGSYRCSCPPGYTGRNC 37

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 224967065  178 DVNECSQNpGLCRHGGTCHNEIGSYRCACRATHTGPHCE 216
Cdd:cd00054     1 DIDECASG-NPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 224967065  452 DVNEC-ISNPCQNDATCLDQIGEFQCICMPGYEGVYCE 488
Cdd:cd00054     1 DIDECaSGNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....
gi 224967065    678 NIDECA-GSPCHNGGTCEDGIAGFTCRCPEGYHD 710
Cdd:smart00179    1 DIDECAsGNPCQNGGTCVNTVGSYRCECPPGYTD 34

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 224967065   1021 DVNECDSR-PCLHGGTCQDSYGTYKCTCPQGYT-GLNCQ 1057
Cdd:smart00179    1 DIDECASGnPCQNGGTCVNTVGSYRCECPPGYTdGRNCE 39

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 224967065 1221 NVDDChppldpASRSPkCFNNGTCVDQVGGYTCTCPPGFVGERCE 1265
Cdd:cd00054     1 DIDEC------ASGNP-CQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 224967065  907 DIDDCR-PNPCHNGGSCTDGINTAFCDCLPGFQGAFCE 943
Cdd:cd00054     1 DIDECAsGNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 224967065  755 NECES-NPCVNGGTCKDMTSGYVCTCREGFSGPNCQ 789
Cdd:cd00054     3 DECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 224967065  603 NINECHSQ-PCRHGGTCQDRDNSYLCLCLKGTTGPNCE 639
Cdd:cd00054     1 DIDECASGnPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065 2111 SPQLHGTALGGTPTLSPtlcSPNGYLGNLKSATQGKKARKPSTKGLACGSkEAKDLKARRKKSQDGKGCLLDSSSMLSPV 2190
Cdd:PHA03247 2630 SPSPAANEPDPHPPPTV---PPPERPRDDPAPGRVSRPRRARRLGRAAQA-SSPPQRPRRRAARPTVGSLTSLADPPPPP 2705

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065 2191 DSLES-PHGYLSDVASPPLLPSPFQQSPSMPLSHLP----GMPDTHLGISHLNVAAKPEMAALAGGSRLAFEPPPPRLSH 2265
Cdd:PHA03247 2706 PTPEPaPHALVSATPLPPGPAAARQASPALPAAPAPpavpAGPATPGGPARPARPPTTAGPPAPAPPAAPAAGPPRRLTR 2785

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065 2266 LPVASSAStvlSTNGTGAMNFTVGAPASLNGQCEWLPRLQNgmvPSqynplrPGVTPGTLSTQAAGLQHSmmGPLHSSLS 2345
Cdd:PHA03247 2786 PAVASLSE---SRESLPSPWDPADPPAAVLAPAAALPPAAS---PA------GPLPPPTSAQPTAPPPPP--GPPPPSLP 2851

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224967065 2346 T-NTLSPiiyqGLPNTRLATqphlvqtqqvqpqnlqLQPQNLQPPSQPHLSVSSAANGHLGRSFLSGEPSQADVQPLGPS 2424
Cdd:PHA03247 2852 LgGSVAP----GGDVRRRPP----------------SRSPAAKPAAPARPPVRRLARPAVSRSTESFALPPDQPERPPQP 2911

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 224967065 2425 SLPVHTILPQESQALPTSLPSSMVPPMTTTQfLTPPSQHSYSSSPVDNTPSHQL------QVPEHPFLTPSPESP 2493
Cdd:PHA03247 2912 QAPPPPQPQPQPPPPPQPQPPPPPPPRPQPP-LAPTTDPAGAGEPSGAVPQPWLgalvpgRVAVPRFRVPQPAPS 2985

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 224967065    791 NINECAS-NPCLNQGTCIDDVAGYKCNCPLPYT-GATCE 827
Cdd:smart00179    1 DIDECASgNPCQNGGTCVNTVGSYRCECPPGYTdGRNCE 39

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 224967065  566 DIDECD-PDPCHY-GSCKDGVATFTCLCQPGYTGHHCE 601
Cdd:cd00054     1 DIDECAsGNPCQNgGTCVNTVGSYRCSCPPGYTGRNCE 38