E2 domain of amyloid precursor protein; The E2 domain is the largest of the conserved domains of the amyloid precursor protein. The structure of E2 consists of two coiled-coil sub-structures connected through a continuous helix, and bears an unexpected resemblance to the spectrin family of protein structures.E 2 can reversibly dimerize in solution, and the dimerization occurs along the longest dimension of the molecule in an antiparallel orientation, which enables the N-terminal substructure of one monomer to pack against the C-terminal substructure of a second monomer. The high degree of conservation of residues at the putative dimer interface suggests that the E2 dimer observed in the crystal could be physiologically relevant. Heparin sulfate proteoglycans, the putative ligands for the precursor present in extracellular matrix, bind to E2 at a conserved and positively charged site near the dimer interface.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1841445386 213 PPTPLPTNDVDVYFETSADDNEHARFQKAKEQLEIRHRNRMDRVKKEWEEAELQAKNLPKAE-------RQTLIQHFQAM 285
Cdd:pfam12925   1 TTTPPPTDAVDPYFEHPDPRNEHESFKKAKKRLEEKHRERMTKVMKEWEEAEERYQNLPKADpkaaekfKKAMTARFQET 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1841445386 286 VKALEKEAASEKQQLVETHLARVEAMLNDRRRMALENYLAALQSDPPRPHRILQALRRYVRAENKDRLHTIRHYQHVLAV 365
Cdd:pfam12925  81 VEALEEEAAAERQQLVETHQQRVEAHLNDRRRDALECYLQALQENPPNPHRILKALKKLLRAEQKDRRHTLRHYRHLLAS 160

                         170       180       190
                  ....*....|....*....|....*....|
gi 1841445386 366 DPEKAAQMKSQVMTHLHVIEERRNQSLSLL 395
Cdd:pfam12925 161 DPEKAEQMKPQVLTHLRVIDRRMNQSLTLL 190

Amyloid A4 N-terminal heparin-binding; This N-terminal domain of APP, amyloid precursor protein, is the heparin-binding domain of the protein. this region is also responsible for stimulation of neurite outgrowth. The structure reveals both a highly charged basic surface that may interact with glycosaminoglycans in the brain and an abutting hydrophobic surface that is proposed to play an important functional role such as in dimerization or ligand-binding. Structural similarities with cysteine-rich growth factors, taken together with its known growth-promoting properties, suggest the APP N-terminal domain could function as a growth factor in vivo.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1841445386  49 EPQIAMFCGKLNMHVNIQTGKWEPDPTGTKSCFETKEEVLQYCQEMYPELQITNVMEANQRTKI 112
Cdd:pfam02177   1 EPQVAMFCGKLNQHMDLETGRWEPDPSGKATCFKDKEEILDYCQKVYPELDITNIVEASQPVTI 64

E2 domain of amyloid precursor protein; The E2 domain is the largest of the conserved domains of the amyloid precursor protein. The structure of E2 consists of two coiled-coil sub-structures connected through a continuous helix, and bears an unexpected resemblance to the spectrin family of protein structures.E 2 can reversibly dimerize in solution, and the dimerization occurs along the longest dimension of the molecule in an antiparallel orientation, which enables the N-terminal substructure of one monomer to pack against the C-terminal substructure of a second monomer. The high degree of conservation of residues at the putative dimer interface suggests that the E2 dimer observed in the crystal could be physiologically relevant. Heparin sulfate proteoglycans, the putative ligands for the precursor present in extracellular matrix, bind to E2 at a conserved and positively charged site near the dimer interface.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1841445386 213 PPTPLPTNDVDVYFETSADDNEHARFQKAKEQLEIRHRNRMDRVKKEWEEAELQAKNLPKAE-------RQTLIQHFQAM 285
Cdd:pfam12925   1 TTTPPPTDAVDPYFEHPDPRNEHESFKKAKKRLEEKHRERMTKVMKEWEEAEERYQNLPKADpkaaekfKKAMTARFQET 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1841445386 286 VKALEKEAASEKQQLVETHLARVEAMLNDRRRMALENYLAALQSDPPRPHRILQALRRYVRAENKDRLHTIRHYQHVLAV 365
Cdd:pfam12925  81 VEALEEEAAAERQQLVETHQQRVEAHLNDRRRDALECYLQALQENPPNPHRILKALKKLLRAEQKDRRHTLRHYRHLLAS 160

                         170       180       190
                  ....*....|....*....|....*....|
gi 1841445386 366 DPEKAAQMKSQVMTHLHVIEERRNQSLSLL 395
Cdd:pfam12925 161 DPEKAEQMKPQVLTHLRVIDRRMNQSLTLL 190

Amyloid A4 N-terminal heparin-binding; This N-terminal domain of APP, amyloid precursor protein, is the heparin-binding domain of the protein. this region is also responsible for stimulation of neurite outgrowth. The structure reveals both a highly charged basic surface that may interact with glycosaminoglycans in the brain and an abutting hydrophobic surface that is proposed to play an important functional role such as in dimerization or ligand-binding. Structural similarities with cysteine-rich growth factors, taken together with its known growth-promoting properties, suggest the APP N-terminal domain could function as a growth factor in vivo.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1841445386  49 EPQIAMFCGKLNMHVNIQTGKWEPDPTGTKSCFETKEEVLQYCQEMYPELQITNVMEANQRTKI 112
Cdd:pfam02177   1 EPQVAMFCGKLNQHMDLETGRWEPDPSGKATCFKDKEEILDYCQKVYPELDITNIVEASQPVTI 64

Beta-amyloid precursor protein C-terminus; This is the amyloid, C-terminal, protein of the beta-Amyloid precursor protein (APP) which is a conserved and ubiquitous transmembrane glycoprotein strongly implicated in the pathogenesis of Alzheimer's disease but whose normal biological function is unknown. The C-terminal 100 residues are released and aggregate into amyloid deposits which are strongly implicated in the pathology of Alzheimer's disease plaque-formation. The domain is associated with family A4_EXTRA, pfam02177, further towards the N-terminus.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1841445386 557 IVISLVMLRKR-QYGTISHGIVEVDPMLTPEERHLNKMQNHGYENPTYKYLE 607
Cdd:pfam10515   1 IVVGMALLRRRaARSPSAHGFVEVDPNVTPEERHVANMQVNGYENPTYKYFE 52

E2 domain of amyloid precursor protein; The E2 domain is the largest of the conserved domains of the amyloid precursor protein. The structure of E2 consists of two coiled-coil sub-structures connected through a continuous helix, and bears an unexpected resemblance to the spectrin family of protein structures.E 2 can reversibly dimerize in solution, and the dimerization occurs along the longest dimension of the molecule in an antiparallel orientation, which enables the N-terminal substructure of one monomer to pack against the C-terminal substructure of a second monomer. The high degree of conservation of residues at the putative dimer interface suggests that the E2 dimer observed in the crystal could be physiologically relevant. Heparin sulfate proteoglycans, the putative ligands for the precursor present in extracellular matrix, bind to E2 at a conserved and positively charged site near the dimer interface.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1841445386 213 PPTPLPTNDVDVYFETSADDNEHARFQKAKEQLEIRHRNRMDRVKKEWEEAELQAKNLPKAE-------RQTLIQHFQAM 285
Cdd:pfam12925   1 TTTPPPTDAVDPYFEHPDPRNEHESFKKAKKRLEEKHRERMTKVMKEWEEAEERYQNLPKADpkaaekfKKAMTARFQET 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1841445386 286 VKALEKEAASEKQQLVETHLARVEAMLNDRRRMALENYLAALQSDPPRPHRILQALRRYVRAENKDRLHTIRHYQHVLAV 365
Cdd:pfam12925  81 VEALEEEAAAERQQLVETHQQRVEAHLNDRRRDALECYLQALQENPPNPHRILKALKKLLRAEQKDRRHTLRHYRHLLAS 160

                         170       180       190
                  ....*....|....*....|....*....|
gi 1841445386 366 DPEKAAQMKSQVMTHLHVIEERRNQSLSLL 395
Cdd:pfam12925 161 DPEKAEQMKPQVLTHLRVIDRRMNQSLTLL 190

Amyloid A4 N-terminal heparin-binding; This N-terminal domain of APP, amyloid precursor protein, is the heparin-binding domain of the protein. this region is also responsible for stimulation of neurite outgrowth. The structure reveals both a highly charged basic surface that may interact with glycosaminoglycans in the brain and an abutting hydrophobic surface that is proposed to play an important functional role such as in dimerization or ligand-binding. Structural similarities with cysteine-rich growth factors, taken together with its known growth-promoting properties, suggest the APP N-terminal domain could function as a growth factor in vivo.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1841445386  49 EPQIAMFCGKLNMHVNIQTGKWEPDPTGTKSCFETKEEVLQYCQEMYPELQITNVMEANQRTKI 112
Cdd:pfam02177   1 EPQVAMFCGKLNQHMDLETGRWEPDPSGKATCFKDKEEILDYCQKVYPELDITNIVEASQPVTI 64

juxtamembrane and transmembrane (JMTM) domain found in amyloid-like protein 1 (APLP-1) and similar proteins; Amyloid-like protein 1 (APLP-1), also called APLP, may play a role in postsynaptic function. It couples to JIP signal transduction through C-terminal binding. APLP-1 may interact with cellular G-protein signaling pathways. It can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I. This model corresponds to the juxtamembrane and transmembrane (JMTM) domain of APLP-1, which consists of the intact transmembrane (TM) domain with adjacent N-terminal juxtamembrane (JM) region.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1841445386 537 SLSSSALIGLLVIAVAIATVIVISLVMLRKRQYGTISHGIVEVDPMLTPEERHLNKMQNHGYENPTYKYLEQ 608
Cdd:cd21708    14 TFNRGALIGLLVVAVAVAMVIVISLLLVRRKPYGTISHGIVEVDPMLTPEERQLSKMQNHGYENPTYRFLEE 85

juxtamembrane and transmembrane (JMTM) domain found in the amyloid-beta precursor protein (APP) family; The amyloid-beta precursor protein (APP) family includes amyloid-like proteins APLP-1 and APLP-2. APP (also called ABPP, APPI, Alzheimer disease (AD) amyloid protein, amyloid precursor protein, amyloid-beta A4 protein, cerebral vascular amyloid peptide (CVAP), PreA4, or protease nexin-II (PN-II)) functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity; they bind transient metals such as copper, zinc and iron. APLP-1, also called APLP, may play a role in postsynaptic function. It couples to JIP signal transduction through C-terminal binding. APLP-1 may interact with cellular G-protein signaling pathways. It can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I. APLP-2 (also called amyloid protein homolog (APPH), or CDEI box-binding protein (CDEBP)) may play a role in the regulation of hemostasis. Its soluble form may have inhibitory properties towards coagulation factors. APLP-2 may bind to the DNA 5'-GTCACATG-3'(CDEI box). It inhibits trypsin, chymotrypsin, plasmin, factor XIA, and plasma and glandular kallikrein. This model corresponds to juxtamembrane and transmembrane (JMTM) domain of APP, which consists of the intact transmembrane (TM) domain with adjacent N-terminal juxtamembrane (JM) region. More than half of all familial APP mutations of Alzheimer's disease are seen in its JMTM domain region.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1841445386 528 SVGPLREDFS-LSSSALIGLLVIAVAIATVIVISLVMLRKR 567
Cdd:cd21699     1 ERVFLAEDSSnSSFGAVIGLAVGGVAVAIVIVVAVVMLRRR 41

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1841445386 237 RFQKAKEQLEIRHRN----RMDRVKKEWEEAELQAknlpkAERQTLIQHFQAMVKALEKEAASEKQQLVETHLaRVEAML 312
Cdd:COG1196   214 RYRELKEELKELEAEllllKLRELEAELEELEAEL-----EELEAELEELEAELAELEAELEELRLELEELEL-ELEEAQ 287

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1841445386 313 NDRRRmaLENYLAALQSDpprpHRILQALRRYVRAENKDRLHTIRHYQHVLAVDPEKAAQMKSQVMTHLHVIEERRNQSL 392
Cdd:COG1196   288 AEEYE--LLAELARLEQD----IARLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELA 361

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 1841445386 393 SLLYKVPYVAQEIQEEIDELLQEQRADMDQFTASISE 429
Cdd:COG1196   362 EAEEALLEAEAELAEAEEELEELAEELLEALRAAAEL 398