ID   A4_TETFL                Reviewed;         780 AA.
AC   O73683;
DT   19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1998, sequence version 1.
DT   03-AUG-2022, entry version 106.
DE   RecName: Full=Amyloid-beta A4 protein;
DE   AltName: Full=ABPP;
DE            Short=APP;
DE   AltName: Full=Alzheimer disease amyloid A4 protein homolog;
DE   AltName: Full=Amyloid precursor protein {ECO:0000305};
DE   AltName: Full=Amyloid-beta precursor protein {ECO:0000305};
DE   Contains:
DE     RecName: Full=Amyloid-beta protein;
DE     AltName: Full=A-beta;
DE     AltName: Full=APP-beta;
DE   Flags: Precursor;
GN   Name=app;
OS   Tetraodon fluviatilis (Green pufferfish) (Chelonodon fluviatilis).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Neoteleostei; Acanthomorphata;
OC   Eupercaria; Tetraodontiformes; Tetradontoidea; Tetraodontidae; Tetraodon.
OX   NCBI_TaxID=47145;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=9599080; DOI=10.1016/s0378-1119(98)00032-8;
RA   Villard L., Tassone F., Crnogorac-Jurcevic T., Clancy K., Gardiner K.;
RT   "Analysis of pufferfish homologues of the AT-rich human APP gene.";
RL   Gene 210:17-24(1998).
CC   -!- FUNCTION: Functional neuronal receptor which couples to intracellular
CC       signaling pathway through the GTP-binding protein G(O). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC   -!- SIMILARITY: Belongs to the APP family. {ECO:0000255|PROSITE-
CC       ProRule:PRU01217}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AF018165; AAC41275.1; -; mRNA.
DR   AlphaFoldDB; O73683; -.
DR   BMRB; O73683; -.
DR   SMR; O73683; -.
DR   GO; GO:0005798; C:Golgi-associated vesicle; ISS:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0055037; C:recycling endosome; ISS:UniProtKB.
DR   GO; GO:0008201; F:heparin binding; IEA:InterPro.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR   GO; GO:0046914; F:transition metal ion binding; IEA:InterPro.
DR   GO; GO:0007399; P:nervous system development; IEA:InterPro.
DR   GO; GO:0032268; P:regulation of cellular protein metabolic process; IEA:UniProt.
DR   CDD; cd00109; KU; 1.
DR   Gene3D; 1.20.120.770; -; 1.
DR   Gene3D; 2.30.29.30; -; 1.
DR   Gene3D; 3.30.1490.140; -; 1.
DR   Gene3D; 3.90.570.10; -; 1.
DR   Gene3D; 4.10.410.10; -; 1.
DR   InterPro; IPR036669; Amyloid_Cu-bd_sf.
DR   InterPro; IPR008155; Amyloid_glyco.
DR   InterPro; IPR013803; Amyloid_glyco_Abeta.
DR   InterPro; IPR011178; Amyloid_glyco_Cu-bd.
DR   InterPro; IPR024329; Amyloid_glyco_E2_domain.
DR   InterPro; IPR008154; Amyloid_glyco_extra.
DR   InterPro; IPR015849; Amyloid_glyco_heparin-bd.
DR   InterPro; IPR036454; Amyloid_glyco_heparin-bd_sf.
DR   InterPro; IPR019745; Amyloid_glyco_intracell_CS.
DR   InterPro; IPR028866; APP.
DR   InterPro; IPR019543; APP_amyloid_C.
DR   InterPro; IPR019744; APP_CUBD_CS.
DR   InterPro; IPR036176; E2_sf.
DR   InterPro; IPR002223; Kunitz_BPTI.
DR   InterPro; IPR036880; Kunitz_BPTI_sf.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   PANTHER; PTHR23103; PTHR23103; 1.
DR   PANTHER; PTHR23103:SF7; PTHR23103:SF7; 1.
DR   Pfam; PF10515; APP_amyloid; 1.
DR   Pfam; PF12924; APP_Cu_bd; 1.
DR   Pfam; PF12925; APP_E2; 1.
DR   Pfam; PF02177; APP_N; 1.
DR   Pfam; PF03494; Beta-APP; 1.
DR   Pfam; PF00014; Kunitz_BPTI; 1.
DR   PRINTS; PR00203; AMYLOIDA4.
DR   PRINTS; PR00759; BASICPTASE.
DR   PRINTS; PR00204; BETAAMYLOID.
DR   SMART; SM00006; A4_EXTRA; 1.
DR   SMART; SM00131; KU; 1.
DR   SUPFAM; SSF109843; SSF109843; 1.
DR   SUPFAM; SSF56491; SSF56491; 1.
DR   SUPFAM; SSF57362; SSF57362; 1.
DR   SUPFAM; SSF89811; SSF89811; 1.
DR   PROSITE; PS00319; APP_CUBD; 1.
DR   PROSITE; PS51869; APP_E1; 1.
DR   PROSITE; PS51870; APP_E2; 1.
DR   PROSITE; PS00320; APP_INTRA; 1.
DR   PROSITE; PS50279; BPTI_KUNITZ_2; 1.
PE   2: Evidence at transcript level;
KW   Amyloid; Copper; Disulfide bond; Glycoprotein; Membrane; Metal-binding;
KW   Protease inhibitor; Serine protease inhibitor; Signal; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   CHAIN           19..780
FT                   /note="Amyloid-beta A4 protein"
FT                   /id="PRO_0000000199"
FT   CHAIN           682..724
FT                   /note="Amyloid-beta protein"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000000200"
FT   TOPO_DOM        19..711
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        712..732
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        733..780
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          29..190
FT                   /note="E1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   DOMAIN          323..382
FT                   /note="BPTI/Kunitz inhibitor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT   DOMAIN          392..583
FT                   /note="E2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01218"
FT   REGION          29..124
FT                   /note="GFLD subdomain"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   REGION          132..190
FT                   /note="CuBD subdomain"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   REGION          194..316
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          648..669
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          769..772
FT                   /note="Clathrin-binding"
FT                   /evidence="ECO:0000250"
FT   MOTIF           767..772
FT                   /note="YENPXY motif"
FT                   /evidence="ECO:0000250|UniProtKB:P05067"
FT   COMPBIAS        194..208
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        220..236
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        237..299
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        302..316
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         148
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   BINDING         152
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   BINDING         169
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   SITE            171
FT                   /note="Required for Cu(2+) reduction"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   CARBOHYD        560
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        39..63
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   DISULFID        74..118
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   DISULFID        99..106
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   DISULFID        134..188
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   DISULFID        145..175
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   DISULFID        159..187
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   DISULFID        327..378
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT   DISULFID        336..361
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
SQ   SEQUENCE   780 AA;  88238 MW;  60071BE94520191D CRC64;
     MGHSVAWLLL VAAASTLAAE VPTDVSMGLL AEPQVAMFCG KINMHINVQS GKWEPDPSGT
     KSCIGTKEGI LQYCQEVYPE LQITNVVEAN QPVSIQNWCK KGRKQCRSHM HIVVPYRCLV
     GEFVSDALLV PDKCKFLHQE RMNQCESHLH WHTVAKESCG DRAMNLHDYG MLLPCGIDRF
     RGVEFVCCPA EAERDMDSTE KDADDSDVWW GGADNDYSDN SMVREPEPAE QQEETRPSVV
     EEEEEGEVAQ EDDEEEEEVL DTDQDGDGEE DHEAADDEEE EEDVDEIDAF GESDDVDADE
     PTTNVAMTTT TTTTTTESVE EVVRMFCWAH ADTGPCTASM PSWYFDAVDG RTMYELMYGG
     CGGNMNNFES EEYCLSVCSS VVPTDMPSSP DAVDHYLETP ADENEHAHFQ KAKESLEAKH
     RERMSQVMRE WEEAERQAKN LPRADKKIVI QRFQEKVEAL EQEAASERQQ LVETHMARVE
     ALLNDRRRLA LENYLTALQQ DPPRPRHVFS LLKKYVRAEQ KDRQHTLKHF EHVRMVDPKK
     AAQIRPQVLT HLRVIEERMN QSLGLLYKVP GVADDIQDQV ELLQREQAEM AQQLANLQTD
     VRVSYGNDAL MPDQELGDGQ ADLLPQEDTL GGVGFVHPES FNQLNTENQV EPVDSRPTFE
     RGVPTRPVTG KSMEAVPELR METEDRQSTE YEVHHQKLVF FAEDVGSNKG AIIGLMVGGV
     VIATVIVITL VMLRKKQYTS IHHGIIEVDA AVTPEERHLS KMQQNGYENP TYKFFEQMQN