 | |||
| Home | Search | Reports | Help |
| Gene Model: App |
| Nomenclature | Genomic Location | ||
| Symbol | App | Chromosome | 1 |
| Name | Amyloid precursor protein | Linkage map | unknown |
| Species | Dracomimus familiaris | Genome Coordinates | Chr1: 92 Mbp |
| Molecular Function |
|
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity. Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu2+-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu2+ and Fe3+ to Cu+ and Fe2+, respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain. The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis. N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6). Molecular Function Terms: binding
enzyme regulator activity
|
| Human Disease Association |
|
Defects in APP are the cause of Alzheimer disease type 1 (AD1) [MIM:104300]. AD1 is a familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death. Defects in APP are the cause of cerebral amyloid angiopathy APP-related (CAA-APP) [MIM:605714]. A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications. |
| Predicted Transcript |
1 GTAACTCCATTGTTGGTTAAAAGAGATCTTTGCTTCTTCCACTTGCCCACCTTTGAGGTG
61 CCTACTGATGGAAATGCTGGCTTGTTGGCAGAGCCCCAAGTGGCCATGTTTTGTGGCAAA
121 CTGAATATGCATATGAATGTTCAGAATGGGAAATGGGAATCAGATCCTTCTGGAACCAAG
181 AGCTGCATTGGAACAAAAGAAGGCATTTTGCAGTACTGTCAGCAAGTTTACCCTGAACTG
241 CAAATTACCAATGTTGTTGAAGCCAACCAGCCTGTAACAATACAAAATTGGTGCAAACGT
301 GGATGGAAACAATGCAGGAGTCACCCCCACATTGTAGTTCCCTATAGGTGCTTAGTTGGA
361 GAATTCGTGAGTGATGCTCTTCTAGTGCCAGATAAATGCAAGTTCCTTCACCAAGAAAGA
421 ATGGATGTATGTGAGACCCACCTGCATTGGCACACAGCTGCTAAGGAGTCCTGTAGTGAA
481 AAAGGTATGAATCTACATGACTATGGGATGCTGCTACCCTGTGGAATTGACAAGTTTCGT
541 GGTGTGGAGTTCGTTTGCTGCCCTGTAGCAGATGAGAGTGACAATGTTGATTCTGCTGAA
601 GCCGAAGAAGATGACTCTGATGTTTGGTGGGGCGGTGCAGATGCAGACTATGCAGATGGC
661 AGGGAAGAAGAAATCATTCTTATTTGTATGTTGTTAATGGAAGCTGCCACTCATGCCTCC
721 ATGGCTTTTAAAAACTTGCTAAGCACACAGGGAGTAGAAGGTCCCTCAAAATGCCGGGAG
781 AAAGCGCTTTCAAACTGCCAAAAAATCACGAGTTTTTCAAGTGCAACAGCACCTTTTTGT
841 TCCATGGCCAGGCAGCAAGGTCAAATAATGATGACAAAGCTTTGTTCCTGTTACAAACAA
901 GATAGGTTCTGTAGATTTCTTCTTAAGAGATTTTACCGTGCAAATGACTGTGACACTCGT
961 TGTTTAACCTTTTGCACAGTTGGTTGCAGAAAAAACAGAAGGGGTACAGCAGTGCCAGTT
1021 TACTCTCCCACAGTCTGCTCCCCTCTTTGTGACAGCTTCCCCCCCCCCCTCAACCAGTTT
1081 GATACCAGAATTCCCACCACAGCTGCTAGCACTCCTGATGCTGTTGACAAGTACTTGGAG
1141 ACCCCGGGAGATGAGAATGAACATTCCCATTTCCAGAAAGCAAAAGAGAGACTTGAAGCT
1201 AAGCACCGTGAAAGAATGTCTCAGGTCATGAGGGAATGGGAAGAAGCAGAACATCAAGCA
1261 AAGAATTTGCCAAAGGCTGACAAAAAGGCTGTTATCCAGCACTTCCAAGAGAAGGTAGAA
1321 TCACTAGAACAAGAAGCTGCAAATGAGAGACAACAGCTCGTAGAGACTCACATGGCACGA
1381 GTGGAAGCCATGCTTAATGACCGTCGCCGTGTGGCCCTAGAAAATTACATTACAGCTCTG
1441 CAGGCTGTTCCACCCAAAGTTCCTCATCAATTCAATACTCTTATGTATATTTCTGCCAAA
1501 GCTGTCAAAGATGTCACAACAACTTGGCAACAAAATGAAGAAATATGTATGTGTGATTTA
1561 TATGAATGCAACAAGATAAAGAGATTACCTCTTCTGCGACTACGGTCATGTTGTGCCTTC
1621 CTGGCACAGACAGTTAAAATTCTTTCCCATGGACCTACTGTCTCCACTACAGATCAGCAC
1681 AATGAAGAAGAAGAACTGCTTCAAAAAGAGCAAAACTACTCTGACGATGTCTTGGCAAAC
1741 ATGATCAGTGAGCCCAGGATCAGTTATGGAAATGATGCCCTCATGCCTTCATTGACAGAG
1801 ACAAAAACAACAGTTGAACTCCTTCCAGTCGATGGGGAGGTCAGCCTAGATAACTTTCAA
1861 CCTTGGCATCCCTTTGCAGTTGATTCAGTCCCAGCAAATACTGAAAATGAAGGCTGTGCA
1921 TACCCAGTTGAGCCTGTTGATGCCCGTCCAGCTGCAGACAGAGGACTCACCACACGACCA
1981 GGTTCTGGATTAACCAATGTGAAAACAGAAGAGACCTCAGAACTAAAAATGGATGCAGAG
2041 TATAGACATGACTCGGGATATGAAGTACATCATCAGAAACTGGTATTCTTTGCTGAAGAT
2101 GTAGGCTCGAACAAAGGCGCCATCATTGGACTAATGGTGGGCGGTGTTGTAATTGCAACT
2161 GTGATTGTCATTACTTTGGTGATGCTAAAGAAGAAACAGTATACATCCATCCATCATGGT
2221 GTAGTGGAGGTGGATGCTGCAGTGACACCAGAGGAACGCCACCTTTCTAAGATGCAACAA
2281 AATGGCTATGAAAACCCAACCTACAAGTTCTTTGAACAGATGCAGAATTAG
| Predicted Protein Product |
VTPLLVKRDLCFFHLPTFEVPTDGNAGLLAEPQVAMFCGKLNMHMNVQNGKWESDPSGTK SCIGTKEGILQYCQQVYPELQITNVVEANQPVTIQNWCKRGWKQCRSHPHIVVPYRCLVG EFVSDALLVPDKCKFLHQERMDVCETHLHWHTAAKESCSEKGMNLHDYGMLLPCGIDKFR GVEFVCCPVADESDNVDSAEAEEDDSDVWWGGADADYADGREEEIILICMLLMEAATHAS MAFKNLLSTQGVEGPSKCREKALSNCQKITSFSSATAPFCSMARQQGQIMMTKLCSCYKQ DRFCRFLLKRFYRANDCDTRCLTFCTVGCRKNRRGTAVPVYSPTVCSPLCDSFPPPLNQF DTRIPTTAASTPDAVDKYLETPGDENEHSHFQKAKERLEAKHRERMSQVMREWEEAEHQA KNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRVALENYITAL QAVPPKVPHQFNTLMYISAKAVKDVTTTWQQNEEICMCDLYECNKIKRLPLLRLRSCCAF LAQTVKILSHGPTVSTTDQHNEEEELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTE TKTTVELLPVDGEVSLDNFQPWHPFAVDSVPANTENEGCAYPVEPVDARPAADRGLTTRP GSGLTNVKTEETSELKMDAEYRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIAT VIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN
| Protein Alignment to Mouse |
sp|P12023|A4_MOUSE Amyloid beta A4 protein OS=Mus musculus GN=App PE=1 SV=3
MGI:88059 App amyloid beta (A4) precursor protein (Chr 16)
Length = 770
Score = 2531 (896.0 bits), Expect = 9.1e-264, P = 9.1e-264
Identities = 508/780 (65%), Positives = 574/780 (73%)
Query: 3 PLLVKRDLCFFHLPTFEVPTDGNAGLLAEPQVAMFCGKLNMHMNVQNGKWESDPSGTKSC 62
P L L + + EVPTDGNAGLLAEPQ+AMFCGKLNMHMNVQNGKWESDPSGTK+C
Sbjct: 3 PSLALLLLAAWTVRALEVPTDGNAGLLAEPQIAMFCGKLNMHMNVQNGKWESDPSGTKTC 62
Query: 63 IGTKEGILQYCQQVYPELQITNVVEANQPVTIQNWCKRGWKQCRSHPHIVVPYRCLVGEF 122
IGTKEGILQYCQ+VYPELQITNVVEANQPVTIQNWCKRG KQC++H HIV+PYRCLVGEF
Sbjct: 63 IGTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHTHIVIPYRCLVGEF 122
Query: 123 VSDALLVPDKCKFLHQERMDVCETHLHWHTAAKESCSEKGMNLHDYGMLLPCGIDKFRGV 182
VSDALLVPDKCKFLHQERMDVCETHLHWHT AKE+CSEK NLHDYGMLLPCGIDKFRGV
Sbjct: 123 VSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGV 182
Query: 183 EFVCCPVXXXXXXXXXXXXXXXXXXXWWGGADADYADGREEEIILICMLLMEAATHASMA 242
EFVCCP+ WWGGAD DYADG E++++ + E A +
Sbjct: 183 EFVCCPLAEESDSVDSADAEEDDSDVWWGGADTDYADGGEDKVVEVA----EEEEVADVE 238
Query: 243 FKNLLSTQGVEGPSKCREKALSNCQKITSFSSATAPFCSMARQQGQIMMTKLCSCYKQDR 302
+ + VE + E+A ++ T +++TA + + + ++ ++CS +
Sbjct: 239 EEEADDDEDVEDGDEVEEEAEEPYEEATERTTSTATTTTTTTESVEEVVREVCSEQAETG 298
Query: 303 FCRFLLKRFYRANDCDTRCLTFCTVGCRKNRRGTAVPVYSPTVCSP-----LCDSFPPPL 357
CR ++ R+Y + + +C+ F GC NR Y VC L + PL
Sbjct: 299 PCRAMISRWY-FDVTEGKCVPFFYGGCGGNRNNFDTEEYCMAVCGSVSTQSLLKTTSEPL 357
Query: 358 NQFDTRIPTTAASTPDAVDKYLETPGDENEHSHFQKAKERLEAKHRERMSQVMREWEEAE 417
Q ++PTTAASTPDAVDKYLETPGDENEH+HFQKAKERLEAKHRERMSQVMREWEEAE
Sbjct: 358 PQDPDKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAE 417
Query: 418 HQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRVALENYI 477
QAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRR+ALENYI
Sbjct: 418 RQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYI 477
Query: 478 TALQAVPPKVPHQFNTLM-YISAKAVKDVTTTWQQNEEICMCDLYECNKIKRLPLLRLRS 536
TALQAVPP+ H FN L Y+ A+ KD T + E + M D + +I+ + LR
Sbjct: 478 TALQAVPPRPHHVFNMLKKYVRAEQ-KDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRV 536
Query: 537 CCAFLAQTVKILSHGPTVSTTDQHXXXXXXXXXXXXYSDDVLANMISEPRISYGNDALMP 596
+ Q++ +L + P V+ Q YSDDVLANMISEPRISYGNDALMP
Sbjct: 537 IYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQN-YSDDVLANMISEPRISYGNDALMP 595
Query: 597 SLTETKTTVELLPVDGEVSLDNFQPWHPFAVDSVPANTENEGCAYPVEPVDARPAADRGL 656
SLTETKTTVELLPV+GE SLD+ QPWHPF VDSVPANTENE VEPVDARPAADRGL
Sbjct: 596 SLTETKTTVELLPVNGEFSLDDLQPWHPFGVDSVPANTENE-----VEPVDARPAADRGL 650
Query: 657 TTRPGSGLTNVKTEETSELKMDAEYRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLXXXXX 716
TTRPGSGLTN+KTEE SE+KMDAE+ HDSG+EV HQKLVFFAEDVGSNKGAIIGL
Sbjct: 651 TTRPGSGLTNIKTEEISEVKMDAEFGHDSGFEVRHQKLVFFAEDVGSNKGAIIGLMVGGV 710
Query: 717 XXXXXXXXXXXXXKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN 776
KKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN
Sbjct: 711 VIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN 770