ID   B4DGD0_HUMAN            Unreviewed;       714 AA.
AC   B4DGD0;
DT   23-SEP-2008, integrated into UniProtKB/TrEMBL.
DT   23-SEP-2008, sequence version 1.
DT   02-SEP-2026, entry version 102.
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:BAG57741.1};
RN   [1] {ECO:0000313|EMBL:BAG57741.1}
RP   NUCLEOTIDE SEQUENCE.
RC   TISSUE=Amygdala {ECO:0000313|EMBL:BAG57741.1};
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.
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   -!- FUNCTION: The gamma-CTF peptides as well as the caspase-cleaved
CC       peptides, including C31, are potent enhancers of neuronal apoptosis.
CC       {ECO:0000256|ARBA:ARBA00002651}.
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}. Endoplasmic reticulum
CC       {ECO:0000256|ARBA:ARBA00004240}. Golgi apparatus
CC       {ECO:0000256|ARBA:ARBA00004555}. Membrane, clathrin-coated pit
CC       {ECO:0000256|ARBA:ARBA00004600}. Nucleus
CC       {ECO:0000256|ARBA:ARBA00004123}. Perikaryon
CC       {ECO:0000256|ARBA:ARBA00004484}. Secreted
CC       {ECO:0000256|ARBA:ARBA00004613}.
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}.
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DR   EMBL; AK294534; BAG57741.1; -; mRNA.
DR   RefSeq; NP_001129602.1; NM_001136130.3.
DR   RefSeq; NP_001191230.1; NM_001204301.2.
DR   AlphaFoldDB; B4DGD0; -.
DR   SMR; B4DGD0; -.
DR   MEROPS; I02.015; -.
DR   PeptideAtlas; B4DGD0; -.
DR   DNASU; 351; -.
DR   GeneID; 351; -.
DR   ClinPGx; PA24910; -.
DR   CTD; 351; -.
DR   DisGeNET; 351; -.
DR   OrthoDB; 6147836at2759; -.
DR   BioGRID-ORCS; 351; 12 hits in 1170 CRISPR screens.
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:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005794; C:Golgi apparatus; 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:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0031091; C:platelet alpha granule; IEA:UniProtKB-ARBA.
DR   GO; GO:0008201; F:heparin binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:InterPro.
DR   GO; GO:0046914; F:transition metal ion binding; IEA:InterPro.
DR   CDD; cd22607; Kunitz_ABPP-like; 1.
DR   FunFam; 3.30.1490.140:FF:000001; Amyloid beta (A4) protein b; 1.
DR   FunFam; 4.10.230.10:FF:000001; Amyloid beta A4 protein; 1.
DR   FunFam; 4.10.410.10:FF:000001; Amyloid beta A4 protein; 1.
DR   FunFam; 1.20.120.770:FF:000001; Amyloid beta A4 protein-like isoform 1; 1.
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; 3.30.1490.140; Amyloidogenic glycoprotein, copper-binding domain; 1.
DR   Gene3D; 3.90.570.10; Amyloidogenic glycoprotein, heparin-binding domain; 1.
DR   Gene3D; 4.10.410.10; Pancreatic trypsin inhibitor Kunitz domain; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR   InterPro; IPR036669; Amyloid_Cu-bd_sf.
DR   InterPro; IPR008155; Amyloid_glyco.
DR   InterPro; IPR013803; Amyloid_glyco_Abeta.
DR   InterPro; IPR037071; Amyloid_glyco_Abeta_sf.
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; 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   InterPro; IPR020901; Prtase_inh_Kunz-CS.
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; 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; SSF56491; A heparin-binding domain; 1.
DR   SUPFAM; SSF89811; Amyloid beta a4 protein copper binding domain (domain 2); 1.
DR   SUPFAM; SSF57362; BPTI-like; 1.
DR   SUPFAM; SSF109843; CAPPD, an extracellular domain of amyloid beta A4 protein; 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; PS00280; BPTI_KUNITZ_1; 1.
DR   PROSITE; PS50279; BPTI_KUNITZ_2; 1.
PE   2: Evidence at transcript level;
KW   Amyloid {ECO:0000256|ARBA:ARBA00023087, ECO:0000256|RuleBase:RU367156};
KW   Apoptosis {ECO:0000256|ARBA:ARBA00022703};
KW   Cell adhesion {ECO:0000256|ARBA:ARBA00022889};
KW   Cell membrane {ECO:0000256|ARBA:ARBA00022475,
KW   ECO:0000256|RuleBase:RU367156};
KW   Cell projection {ECO:0000256|ARBA:ARBA00023273};
KW   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|ARBA:ARBA00023157, ECO:0000256|PROSITE-
KW   ProRule:PRU00031}; Endocytosis {ECO:0000256|ARBA:ARBA00022583};
KW   Endoplasmic reticulum {ECO:0000256|ARBA:ARBA00022824};
KW   Endosome {ECO:0000256|ARBA:ARBA00022753};
KW   Glycoprotein {ECO:0000256|ARBA:ARBA00023180};
KW   Golgi apparatus {ECO:0000256|ARBA:ARBA00023034};
KW   Heparin-binding {ECO:0000256|ARBA:ARBA00022674};
KW   Hydrolase {ECO:0000313|EMBL:BAG57741.1};
KW   Iron {ECO:0000256|ARBA:ARBA00023004};
KW   Isopeptide bond {ECO:0000256|ARBA:ARBA00022499};
KW   Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|RuleBase:RU367156};
KW   Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW   Notch signaling pathway {ECO:0000256|ARBA:ARBA00022976};
KW   Nucleus {ECO:0000256|ARBA:ARBA00023242};
KW   Phosphoprotein {ECO:0000256|ARBA:ARBA00022553};
KW   Protease {ECO:0000313|EMBL:BAG57741.1};
KW   Protease inhibitor {ECO:0000256|ARBA:ARBA00022690, ECO:0000256|PROSITE-
KW   ProRule:PRU00031}; Proteoglycan {ECO:0000256|ARBA:ARBA00022974};
KW   Secreted {ECO:0000256|ARBA:ARBA00022525};
KW   Serine protease inhibitor {ECO:0000256|ARBA:ARBA00022900,
KW   ECO:0000256|PROSITE-ProRule:PRU00031};
KW   Signal {ECO:0000256|ARBA:ARBA00022729, ECO:0000256|SAM:SignalP};
KW   Sulfation {ECO:0000256|ARBA:ARBA00022641};
KW   Transmembrane {ECO:0000256|ARBA:ARBA00022692,
KW   ECO:0000256|RuleBase:RU367156};
KW   Transmembrane helix {ECO:0000256|ARBA:ARBA00022989,
KW   ECO:0000256|RuleBase:RU367156};
KW   Ubl conjugation {ECO:0000256|ARBA:ARBA00022843};
KW   Zinc {ECO:0000256|ARBA:ARBA00022833}.
FT   SIGNAL          1..17
FT                   /evidence="ECO:0000256|SAM:SignalP"
FT   CHAIN           18..714
FT                   /note="Amyloid-beta A4 protein"
FT                   /evidence="ECO:0000256|SAM:SignalP"
FT                   /id="PRO_5002803541"
FT   TRANSMEM        645..667
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|RuleBase:RU367156"
FT   DOMAIN          1..133
FT                   /note="E1"
FT                   /evidence="ECO:0000259|PROSITE:PS51869"
FT   DOMAIN          235..285
FT                   /note="BPTI/Kunitz inhibitor"
FT                   /evidence="ECO:0000259|PROSITE:PS50279"
FT   DOMAIN          318..509
FT                   /note="E2"
FT                   /evidence="ECO:0000259|PROSITE:PS51870"
FT   REGION          1..67
FT                   /note="GFLD subdomain"
FT                   /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT   REGION          75..133
FT                   /note="CuBD subdomain"
FT                   /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT   REGION          138..228
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          343..403
FT                   /evidence="ECO:0000256|SAM:Coils"
FT   COMPBIAS        138..151
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        172..208
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        212..225
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   DISULFID        42..49
FT                   /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT   DISULFID        77..131
FT                   /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT   DISULFID        88..118
FT                   /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT   DISULFID        102..130
FT                   /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT   DISULFID        235..285
FT                   /evidence="ECO:0000256|PROSITE-ProRule:PRU00031"
FT   DISULFID        244..268
FT                   /evidence="ECO:0000256|PROSITE-ProRule:PRU00031"
FT   DISULFID        260..281
FT                   /evidence="ECO:0000256|PROSITE-ProRule:PRU00031"
SQ   SEQUENCE   714 AA;  80806 MW;  471EA43FF6B14888 CRC64;
     MLPGLALLLL AAWTARALEV YPELQITNVV EANQPVTIQN WCKRGRKQCK THPHFVIPYR
     CLVGEFVSDA LLVPDKCKFL HQERMDVCET HLHWHTVAKE TCSEKSTNLH DYGMLLPCGI
     DKFRGVEFVC CPLAEESDNV DSADAEEDDS DVWWGGADTD YADGSEDKVV EVAEEEEVAE
     VEEEEADDDE DDEDGDEVEE EAEEPYEEAT ERTTSIATTT TTTTESVEEV VREVCSEQAE
     TGPCRAMISR WYFDVTEGKC APFFYGGCGG NRNNFDTEEY CMAVCGSAMS QSLLKTTQEP
     LARDPVKLPT TAASTPDAVD KYLETPGDES EHAHFQKAKE RLEAKHRERM SQVMREWEEA
     ERQAKNLPKA DKKAVIQHFQ EKVESLEQEA ANERQQLVET HMARVEAMLN DRRRLALENY
     ITALQAVPPR PRHVFNMLKK YVRAEQKDRQ HTLKHFEHVR MVDPKKAAQI RSQVMTHLRV
     IYERMNQSLS LLYNVPAVAE EIQDEVDELL QKEQNYSDDV LANMISEPRI SYGNDALMPS
     LTETKTTVEL LPVNGEFSLD DLQPWHSFGA DSVPANTENE VEPVDARPAA DRGLTTRPGS
     GLTNIKTEEI SEVKMDAEFR HDSGYEVHHQ KLVFFAEDVG SNKGAIIGLM VGGVVIATVI
     VITLVMLKKK QYTSIHHGVV EVDAAVTPEE RHLSKMQQNG YENPTYKFFE QMQN
//