juxtamembrane and transmembrane (JMTM) domain found in neurogenic locus notch homolog protein 1 (Notch1) and similar proteins; Neurogenic locus notch homolog protein 1 (Notch1), also called translocation-associated notch protein TAN-1, functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. It affects the implementation of differentiation, proliferation and apoptotic programs. It is also involved in angiogenesis, and also negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. This model corresponds to the juxtamembrane and transmembrane (JMTM) domain of Notch1, which comprises an extended coil, a transmembrane helix (TM), and a beta-strand.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726074330 1672 AVKSETAEPTKNSQLYPMYVVGAVLVLLAFFGVGVLVSRKRRREHGQLWFPEGFKVTESSKKKRREPLGEDSVGLKPLKN 1751
Cdd:cd21702      1 AVKSETVEPPPPSQLYPMYVVLAALVLLAFVGVGVLVSRKRRREHGQLWFPEGFKVSEPSKKKRREPVGEDSVGLKPLKN 80

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. Role of NOD domain remains to be elucidated.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1726074330 1519 PEKLADGTLVVVVLITPENLKNNSFNFLRELSRVLHTNVVFKKNPKGEYMIFPYYG 1574
Cdd:pfam06816    1 PEKLAEGVLVIVVLMDPEELLNNSVQFLRELSTVLRTNVRFKKDENGNPMIYPWYG 56

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 1726074330 1441 WKNCSQSlQCWKYFNDGKCDSQCNNAGCLYDGFDCQ 1476
Cdd:pfam00066    1 WPNCPYP-YCWDKFGNGVCDEECNNAECLWDGGDCS 35

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 1726074330  528 DIDECAST-PCKNGAKCVDGPNTYSCECTEGFSGAHCE 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 1726074330  412 DVDECSLGaNPCEHAGKCINTQGSFECQCLQGYSGPRCE 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 1726074330 1021 NINECDSK-PCLNGGTCQDSYGTYKCTCPQGYTGLNCQ 1057
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 1726074330  869 DINECV-KSPCRNGATCQNINGSYRCACRTGFTGRNC 904
Cdd:cd00054      1 DIDECAsGNPCQNGGTCVNTVGSYRCSCPPGYTGRNC 37

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 1726074330 1479 EGQCNPlydQYCKDHFSDGHCDQGCNNFECEWDGLDC 1515
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 1726074330  452 DVNECLS-NPCQNDATCLDQIGEFQCICMPGYEGVYCE 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 1726074330  178 DVNECNiSPPLCKNGGSCTNEVGTYQCSCKPAYTGQNCE 216
Cdd:cd00054      1 DIDECA-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 1726074330  603 NINECQSQ-PCKNGGTCQDRNNAYHCLCPKGTTGPNCE 639
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 1726074330  257 NINDC-PGNNCKNGGTCVDGVNTYNCQCPPEWTGQYCT 293
Cdd:cd00054      1 DIDECaSGNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

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 1726074330 2392 SQPEMQPVSssTMAVHTILPQDSQMLPTSLPS--TLAQPMT--------TTQFLTPPSQHSYSSP----LDNTPSH-QLQ 2456
Cdd:pfam03154  215 SQPPNQTQS--TAAPHTLIQQTPTLHPQRLPSphPPLQPMTqppppsqvSPQPLPQPSLHGQMPPmphsLQTGPSHmQHP 292

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1726074330 2457 VPDHPFLTPSPESPDQWSSSSPHSNVSDWSEGMSSPPTSMQSQMGHIP 2504
Cdd:pfam03154  293 VPPQPFPLTPQSSQSQVPPGPSPAAPGQSQQRIHTPPSQSQLQSQQPP 340

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 1726074330 1221 DVNECLS-NPCDARGTqnCVQRVNDYKCECRPGYAGRRC 1258
Cdd:cd00054      1 DIDECASgNPCQNGGT--CVNTVGSYRCSCPPGYTGRNC 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 1726074330  490 NTDECAS-SPCLHNGNCLDKINEFHCECPTGFNGHLCQ 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 1726074330  142 DPCAS-NPCANGGQCVPFEAHYICRCTAGFHGANCK 176
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 1726074330  335 NIDDCAMAA-CFHGATCHDRVASFYCECPHGRTGLLC 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        30
                   ....*....|....*....|....*....|..
gi 1726074330  224 PSPCQNGGTCRQiGDTTYDCTCLPGFTGQNCE 255
Cdd:cd00054      8 GNPCQNGGTCVN-TVGSYRCSCPPGYTGRNCE 38

juxtamembrane and transmembrane (JMTM) domain found in neurogenic locus notch homolog protein 1 (Notch1) and similar proteins; Neurogenic locus notch homolog protein 1 (Notch1), also called translocation-associated notch protein TAN-1, functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. It affects the implementation of differentiation, proliferation and apoptotic programs. It is also involved in angiogenesis, and also negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. This model corresponds to the juxtamembrane and transmembrane (JMTM) domain of Notch1, which comprises an extended coil, a transmembrane helix (TM), and a beta-strand.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726074330 1672 AVKSETAEPTKNSQLYPMYVVGAVLVLLAFFGVGVLVSRKRRREHGQLWFPEGFKVTESSKKKRREPLGEDSVGLKPLKN 1751
Cdd:cd21702      1 AVKSETVEPPPPSQLYPMYVVLAALVLLAFVGVGVLVSRKRRREHGQLWFPEGFKVSEPSKKKRREPVGEDSVGLKPLKN 80

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. Role of NOD domain remains to be elucidated.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1726074330 1519 PEKLADGTLVVVVLITPENLKNNSFNFLRELSRVLHTNVVFKKNPKGEYMIFPYYG 1574
Cdd:pfam06816    1 PEKLAEGVLVIVVLMDPEELLNNSVQFLRELSTVLRTNVRFKKDENGNPMIYPWYG 56

Ankyrin repeats (3 copies);

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726074330 1885 LHLAARYSRSDAAKRLLEASADANIQDNMGRTPLHAAVSADAQGVFQILIRNRATDLDarmHDGTTPLILAARLAVEGML 1964
Cdd:pfam12796    1 LHLAAKNGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHLEIVKLLLEHADVNLK---DNGRTALHYAARSGHLEIV 77

                           90
                   ....*....|....
gi 1726074330 1965 DDLINCHADVNAVD 1978
Cdd:pfam12796   78 KLLLEKGADINVKD 91

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 1726074330 1441 WKNCSQSlQCWKYFNDGKCDSQCNNAGCLYDGFDCQ 1476
Cdd:pfam00066    1 WPNCPYP-YCWDKFGNGVCDEECNNAECLWDGGDCS 35

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 1726074330 1881 GETALHLAARYSRSDAAKRLLEASADAnIQDNM------GRTPLHAAVSADAQGVFQILIRNRATDLDAR---------- 1944
Cdd:cd22192     51 GETALHVAALYDNLEAAVVLMEAAPEL-VNEPMtsdlyqGETALHIAVVNQNLNLVRELIARGADVVSPRatgtffrpgp 129

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726074330 1945 ---MHDGTTPLILAARLAVEGMLDDLINCHADVNAVDDLGKSALHWAAAVNNVEAAVV----LLKNGANKD------MQN 2011
Cdd:cd22192    130 knlIYYGEHPLSFAACVGNEEIVRLLIEHGADIRAQDSLGNTVLHILVLQPNKTFACQmydlILSYDKEDDlqpldlVPN 209

                          170
                   ....*....|....
gi 1726074330 2012 NKEETPLFLAAREG 2025
Cdd:cd22192    210 NQGLTPFKLAAKEG 223

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 1726074330  528 DIDECAST-PCKNGAKCVDGPNTYSCECTEGFSGAHCE 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 1726074330  412 DVDECSLGaNPCEHAGKCINTQGSFECQCLQGYSGPRCE 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 1726074330 1021 NINECDSK-PCLNGGTCQDSYGTYKCTCPQGYTGLNCQ 1057
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 1726074330  869 DINECV-KSPCRNGATCQNINGSYRCACRTGFTGRNC 904
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 1726074330  678 NIDECSS-NPCHNGGTCKDGINGFTCLCPEGFHDPKC 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 1726074330 1146 VDEC-SPNPCQNGATCTDYLGGYSCECVAGYHGVNC 1180
Cdd:cd00054      2 IDECaSGNPCQNGGTCVNTVGSYRCSCPPGYTGRNC 37

Calcium-binding EGF-like domain;

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|
gi 1726074330   412 DVDECSLGaNPCEHAGKCINTQGSFECQCLQGYS-GPRCE 450
Cdd:smart00179    1 DIDECASG-NPCQNGGTCVNTVGSYRCECPPGYTdGRNCE 39

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 1726074330  1183 EINECLS-HPCQNGGTCIDLINTYKCSCPRG-TQGERCE 1219
Cdd:smart00179    1 DIDECASgNPCQNGGTCVNTVGSYRCECPPGyTDGRNCE 39

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
                    ....*....|....*....|....*....
gi 1726074330  1487 DQYCKDHFSDGHCDQGCNNFECEWDGLDC 1515
Cdd:smart00004   10 DAQCWDKFGDGVCDEECNNAECLWDGGDC 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 1726074330  295 DVDECQlMPNACQNGGTCHNNHGGYNCVCVNGWTGEDC 332
Cdd:cd00054      1 DIDECA-SGNPCQNGGTCVNTVGSYRCSCPPGYTGRNC 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 1726074330  907 DIDDCK-PNPCHNGGSCSDGIGTFFCECLAGFRGPKCE 943
Cdd:cd00054      1 DIDECAsGNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 1726074330   528 DIDECAST-PCKNGAKCVDGPNTYSCECTEGFS-GAHCE 564
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 1726074330  791 NINECAS-NPCLNQGTCIDDVAGYTCNCLLPYTGATCE 827
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 1726074330  257 NINDC-PGNNCKNGGTCVDGVNTYNCQCPPEWTGQYCT 293
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 1726074330  755 NECES-NPCMNGGTCKDMTSGYICTCREGFSGPNCQ 789
Cdd:cd00054      3 DECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

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 1726074330 2392 SQPEMQPVSssTMAVHTILPQDSQMLPTSLPS--TLAQPMT--------TTQFLTPPSQHSYSSP----LDNTPSH-QLQ 2456
Cdd:pfam03154  215 SQPPNQTQS--TAAPHTLIQQTPTLHPQRLPSphPPLQPMTqppppsqvSPQPLPQPSLHGQMPPmphsLQTGPSHmQHP 292

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1726074330 2457 VPDHPFLTPSPESPDQWSSSSPHSNVSDWSEGMSSPPTSMQSQMGHIP 2504
Cdd:pfam03154  293 VPPQPFPLTPQSSQSQVPPGPSPAAPGQSQQRIHTPPSQSQLQSQQPP 340

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 1726074330   295 DVDECQlMPNACQNGGTCHNNHGGYNCVCVNGWT-GEDC 332
Cdd:smart00179    1 DIDECA-SGNPCQNGGTCVNTVGSYRCECPPGYTdGRNC 38

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 1726074330   603 NINECQS-QPCKNGGTCQDRNNAYHCLCPKG-TTGPNCE 639
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 1726074330 1221 DVNECLS-NPCDARGTqnCVQRVNDYKCECRPGYAGRRC 1258
Cdd:cd00054      1 DIDECASgNPCQNGGT--CVNTVGSYRCSCPPGYTGRNC 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 1726074330  717 VNECNS-NPC-IHGKCHDGLNGYRCDCDPGWSGTNC 750
Cdd:cd00054      2 IDECASgNPCqNGGTCVNTVGSYRCSCPPGYTGRNC 37

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.

                           10        20        30
                   ....*....|....*....|....*....|.
gi 1726074330  532 CASTPCKNGAKCVDGPNTYSCECTEGFSGAH 562
Cdd:pfam00008    1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGKR 31

Calcium-binding EGF domain;

                           10        20        30
                   ....*....|....*....|....*....|..
gi 1726074330  295 DVDECQLMPNACQNGGTCHNNHGGYNCVCVNG 326
Cdd:pfam07645    1 DVDECATGTHNCPANTVCVNTIGSFECRCPDG 32