ID B4DM00_HUMAN Unreviewed; 528 AA. AC B4DM00; DT 23-SEP-2008, integrated into UniProtKB/TrEMBL. DT 23-SEP-2008, sequence version 1. DT 03-MAY-2023, entry version 58. DE RecName: Full=Amyloid-beta A4 protein {ECO:0000256|RuleBase:RU367156}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606 {ECO:0000313|EMBL:BAG59712.1}; RN [1] {ECO:0000313|EMBL:BAG59712.1} RP NUCLEOTIDE SEQUENCE. RC TISSUE=Brain {ECO:0000313|EMBL:BAG59712.1}; RA Wakamatsu A., Yamamoto J., Kimura K., Ishii S., Watanabe K., Sugiyama A., RA Murakawa K., Kaida T., Tsuchiya K., Fukuzumi Y., Kumagai A., Oishi Y., RA Yamamoto S., Ono Y., Komori Y., Yamazaki M., Kisu Y., Nishikawa T., RA Sugano S., Nomura N., Isogai T.; RT "NEDO human cDNA sequencing project focused on splicing variants."; RL Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases. RN [2] {ECO:0007829|PDB:7F29} RP STRUCTURE BY ELECTRON MICROSCOPY (3.10 ANGSTROMS) OF 435-471. RX DOI=10.1021/jacs.1c08607; RA Liu D., Wei Q., Xia W., He C., Zhang Q., Huang L., Wang X., Sun Y., Ma Y., RA Zhang X., Wang Y., Shi X., Liu C., Dong S.; RT "O-Glycosylation Induces Amyloid-beta To Form New Fibril Polymorphs RT Vulnerable for Degradation."; RL J. Am. Chem. Soc. 143:20216-20223(2021). CC -!- FUNCTION: Functions as a cell surface receptor and performs CC physiological functions on the surface of neurons relevant to neurite CC growth, neuronal adhesion and axonogenesis. CC {ECO:0000256|RuleBase:RU367156}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|ARBA:ARBA00004251, CC ECO:0000256|RuleBase:RU367156}; Single-pass type I membrane protein CC {ECO:0000256|ARBA:ARBA00004251, ECO:0000256|RuleBase:RU367156}. Cell CC projection, growth cone {ECO:0000256|ARBA:ARBA00004624}. Cell surface CC {ECO:0000256|ARBA:ARBA00004241}. Cytoplasmic vesicle CC {ECO:0000256|ARBA:ARBA00004541}. Early endosome CC {ECO:0000256|ARBA:ARBA00004412}. Endosome CC {ECO:0000256|ARBA:ARBA00004177}. Golgi apparatus CC {ECO:0000256|ARBA:ARBA00004555}. Membrane, clathrin-coated pit CC {ECO:0000256|ARBA:ARBA00004600}. Membrane CC {ECO:0000256|ARBA:ARBA00004479}; Single-pass type I membrane protein CC {ECO:0000256|ARBA:ARBA00004479}. Nucleus CC {ECO:0000256|ARBA:ARBA00004123}. Perikaryon CC {ECO:0000256|ARBA:ARBA00004484}. Secreted CC {ECO:0000256|ARBA:ARBA00004613}. Vesicle CC {ECO:0000256|ARBA:ARBA00004373}. CC -!- SIMILARITY: Belongs to the APP family. {ECO:0000256|ARBA:ARBA00009449, CC ECO:0000256|PROSITE-ProRule:PRU01217, ECO:0000256|RuleBase:RU367156}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of CC feature annotation. {ECO:0000256|PROSITE-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; AK297229; BAG59712.1; -; mRNA. DR PDB; 7F29; EM; 3.10 A; A/B/C/D/E/F=435-471. DR AlphaFoldDB; B4DM00; -. DR SMR; B4DM00; -. DR PeptideAtlas; B4DM00; -. DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell. DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell. DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0005798; C:Golgi-associated vesicle; IEA:UniProtKB-UniRule. DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell. DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-UniRule. DR Gene3D; 1.20.120.770; Amyloid precursor protein, E2 domain; 1. DR Gene3D; 4.10.230.10; Amyloidogenic glycoprotein, amyloid-beta peptide; 1. DR Gene3D; 3.90.570.10; Amyloidogenic glycoprotein, heparin-binding domain; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR InterPro; IPR008155; Amyloid_glyco. DR InterPro; IPR013803; Amyloid_glyco_Abeta. DR InterPro; IPR037071; Amyloid_glyco_Abeta_sf. 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; IPR019543; APP_amyloid_C. DR InterPro; IPR036176; E2_sf. DR InterPro; IPR011993; PH-like_dom_sf. DR PANTHER; PTHR23103; ALZHEIMER'S DISEASE BETA-AMYLOID RELATED; 1. DR PANTHER; PTHR23103:SF7; AMYLOID-BETA PRECURSOR PROTEIN; 1. DR Pfam; PF10515; APP_amyloid; 1. DR Pfam; PF12925; APP_E2; 1. DR Pfam; PF02177; APP_N; 1. DR Pfam; PF03494; Beta-APP; 1. DR PRINTS; PR00203; AMYLOIDA4. DR PRINTS; PR00204; BETAAMYLOID. DR SMART; SM00006; A4_EXTRA; 1. DR SUPFAM; SSF56491; A heparin-binding domain; 1. DR SUPFAM; SSF109843; CAPPD, an extracellular domain of amyloid beta A4 protein; 1. DR PROSITE; PS51869; APP_E1; 1. DR PROSITE; PS51870; APP_E2; 1. DR PROSITE; PS00320; APP_INTRA; 1. PE 1: Evidence at protein level; KW 3D-structure {ECO:0007829|PDB:7F29}; KW Amyloid {ECO:0000256|RuleBase:RU367156}; KW Cell membrane {ECO:0000256|ARBA:ARBA00022475, KW ECO:0000256|RuleBase:RU367156}; Coated pit {ECO:0000256|ARBA:ARBA00023176}; KW Coiled coil {ECO:0000256|SAM:Coils}; KW Copper {ECO:0000256|ARBA:ARBA00023008}; KW Cytoplasm {ECO:0000256|ARBA:ARBA00022490}; KW Cytoplasmic vesicle {ECO:0000256|ARBA:ARBA00023329}; KW Disulfide bond {ECO:0000256|PROSITE-ProRule:PRU01217}; KW Endosome {ECO:0000256|ARBA:ARBA00022753}; KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|RuleBase:RU367156}; KW Nucleus {ECO:0000256|ARBA:ARBA00023242}; KW Secreted {ECO:0000256|ARBA:ARBA00022525}; Signal {ECO:0000256|SAM:SignalP}; KW Transmembrane {ECO:0000256|ARBA:ARBA00022692, KW ECO:0000256|RuleBase:RU367156}; KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989, KW ECO:0000256|RuleBase:RU367156}. FT SIGNAL 1..17 FT /evidence="ECO:0000256|SAM:SignalP" FT CHAIN 18..528 FT /note="Amyloid-beta A4 protein" FT /evidence="ECO:0000256|SAM:SignalP" FT /id="PRO_5002803142" FT TRANSMEM 459..481 FT /note="Helical" FT /evidence="ECO:0000256|RuleBase:RU367156" FT DOMAIN 28..141 FT /note="E1" FT /evidence="ECO:0000259|PROSITE:PS51869" FT DOMAIN 132..323 FT /note="E2" FT /evidence="ECO:0000259|PROSITE:PS51870" FT REGION 28..123 FT /note="GFLD subdomain" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" FT REGION 131..141 FT /note="CuBD subdomain" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" FT COILED 157..217 FT /evidence="ECO:0000256|SAM:Coils" FT DISULFID 73..117 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" FT DISULFID 98..105 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" SQ SEQUENCE 528 AA; 60074 MW; BDBBEAA72994D7D6 CRC64; MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHPH FVIPYRCLVG EFVSDALLVP DAVDKYLETP GDENEHAHFQ KAKERLEAKH RERMSQVMRE WEEAERQAKN LPKADKKAVI QHFQEKVESL EQEAANERQQ LVETHMARVE AMLNDRRRLA LENYITALQA VPPRPRHVFN MLKKYVRAEQ KDRQHTLKHF EHVRMVDPKK AAQIRSQVMT HLRVIYERMN QSLSLLYNVP AVAEEIQDEV DELLQKEQNY SDDVLANMIS EPRISYGNDA LMPSLTETKT TVELLPVNGE FSLDDLQPWH SFGADSVPAN TENEVEPVDA RPAADRGLTT RPGSGLTNIK TEEISEVKMD AEFRHDSGYE VHHQKLVFFA EDVGSNKGAI IGLMVGGVVI ATVIVITLVM LKKKQYTSIH HGVVEVDAAV TPEERHLSKM QQNGYENPTY KFFEQMQN //