APLP2_HUMAN
ID APLP2_HUMAN Reviewed; 763 AA.
AC Q06481; B3KXX9; H7BXI4; Q13861; Q14594; Q14662; Q71U10; Q7M4L3; Q9BT36;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Amyloid beta precursor like protein 2 {ECO:0000312|HGNC:HGNC:598};
DE AltName: Full=APPH;
DE AltName: Full=Amyloid beta (A4) precursor-like protein 2 {ECO:0000250|UniProtKB:Q06335};
DE AltName: Full=Amyloid protein homolog {ECO:0000305};
DE AltName: Full=Amyloid-like protein 2 {ECO:0000250|UniProtKB:P15943};
DE Short=APLP-2;
DE AltName: Full=CDEI box-binding protein;
DE Short=CDEBP;
DE AltName: Full=Sperm membrane protein YWK-II {ECO:0000250|UniProtKB:P15943};
DE Flags: Precursor;
GN Name=APLP2 {ECO:0000312|HGNC:HGNC:598};
GN Synonyms=APPL2 {ECO:0000312|HGNC:HGNC:598};
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=8485127; DOI=10.1021/bi00068a002;
RA Sprecher C.A., Grant F.J., Grimm G., O'Hara P.J., Norris F., Norris K.,
RA Foster D.C.;
RT "Molecular cloning of the cDNA for a human amyloid precursor protein
RT homolog: evidence for a multigene family.";
RL Biochemistry 32:4481-4486(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=8220435; DOI=10.1038/ng0993-95;
RA Wasco W., Gurubhagavatula S., Paradis M., Romano D.M., Sisodia S.S.,
RA Hyman B.T., Neve R.L., Tanzi R.E.;
RT "Isolation and characterization of APLP2 encoding a homologue of the
RT Alzheimer's associated amyloid beta protein precursor.";
RL Nat. Genet. 5:95-99(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Ovary;
RX PubMed=7702756; DOI=10.1089/dna.1994.13.1137;
RA von der Kammer H., Hanes J., Klaudiny J., Scheit K.H.;
RT "A human amyloid precursor-like protein is highly homologous to a mouse
RT sequence-specific DNA-binding protein.";
RL DNA Cell Biol. 13:1137-1143(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 39-763 (ISOFORM 2), AND NUCLEOTIDE SEQUENCE [MRNA] OF 229-763 (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=7651835; DOI=10.1093/nar/23.14.2734;
RA Vostrov A.A., Quitschke W.W., Vidal F., Schwarzman A.L., Goldgaber D.;
RT "USF binds to the APB alpha sequence in the promoter of the amyloid beta-
RT protein precursor gene.";
RL Nucleic Acids Res. 23:2734-2741(1995).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=11101689; DOI=10.1093/molehr/6.12.1069;
RA Huang P., Miao S., Fan H., Sheng Q., Yan Y., Wang L., Koide S.S.;
RT "Expression and characterization of the human YWK-II gene, encoding a sperm
RT membrane protein related to the alzheimer betaA4-amyloid precursor
RT protein.";
RL Mol. Hum. Reprod. 6:1069-1078(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 5).
RC TISSUE=Lung, and Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 305-362 (ISOFORMS 1/3), FUNCTION, AND
RP GLYCOSYLATION.
RX PubMed=8307156; DOI=10.1016/0014-5793(94)80115-0;
RA Petersen L.C., Bjorn S.E., Norris F., Norris K., Sprecher C., Foster D.C.;
RT "Expression, purification and characterization of a Kunitz-type protease
RT inhibitor domain from human amyloid precursor protein homolog.";
RL FEBS Lett. 338:53-57(1994).
RN [10]
RP INTERACTION WITH APBB2.
RX PubMed=8855266; DOI=10.1073/pnas.93.20.10832;
RA Guenette S.Y., Chen J., Jondro P.D., Tanzi R.E.;
RT "Association of a novel human FE65-like protein with the cytoplasmic domain
RT of the amyloid-beta precursor protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:10832-10837(1996).
RN [11]
RP INTERACTION WITH APBB3.
RX PubMed=10081969; DOI=10.1016/s0304-3940(98)00995-1;
RA Tanahashi H.;
RT "Molecular cloning of human Fe65L2 and its interaction with the Alzheimer's
RT beta-amyloid precursor protein.";
RL Neurosci. Lett. 261:143-146(1999).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP PHOSPHORYLATION AT SER-590.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: May play a role in the regulation of hemostasis. The soluble
CC form may have inhibitory properties towards coagulation factors. May
CC interact with cellular G-protein signaling pathways. May bind to the
CC DNA 5'-GTCACATG-3'(CDEI box). Inhibits trypsin, chymotrypsin, plasmin,
CC factor XIA and plasma and glandular kallikrein. Modulates the Cu/Zn
CC nitric oxide-catalyzed autodegradation of GPC1 heparan sulfate side
CC chains in fibroblasts (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:8307156}.
CC -!- SUBUNIT: Interacts with CPEB1. Interacts (via NPXY motif) with DAB2
CC (via PID domain); the interaction is impaired by tyrosine
CC phosphorylation of the NPXY motif (By similarity). Interacts (via
CC cytoplasmic domain) with APBB2/FE65L (PubMed:8855266). Interacts (via
CC intracellular domain) with APBB3/FE65L2 (PubMed:10081969).
CC {ECO:0000250, ECO:0000269|PubMed:10081969, ECO:0000269|PubMed:8855266}.
CC -!- INTERACTION:
CC Q06481; P51693: APLP1; NbExp=2; IntAct=EBI-79306, EBI-74648;
CC Q06481; Q06481: APLP2; NbExp=3; IntAct=EBI-79306, EBI-79306;
CC Q06481; P05067-4: APP; NbExp=2; IntAct=EBI-79306, EBI-302641;
CC Q06481; O75618: DEDD; NbExp=3; IntAct=EBI-79306, EBI-1043164;
CC Q06481; P14921: ETS1; NbExp=2; IntAct=EBI-79306, EBI-913209;
CC Q06481; P05412: JUN; NbExp=3; IntAct=EBI-79306, EBI-852823;
CC Q06481; Q93074: MED12; NbExp=2; IntAct=EBI-79306, EBI-394357;
CC Q06481-5; P02649: APOE; NbExp=3; IntAct=EBI-25646567, EBI-1222467;
CC Q06481-5; P05067: APP; NbExp=3; IntAct=EBI-25646567, EBI-77613;
CC Q06481-5; Q96GW7: BCAN; NbExp=3; IntAct=EBI-25646567, EBI-2690445;
CC Q06481-5; Q13867: BLMH; NbExp=3; IntAct=EBI-25646567, EBI-718504;
CC Q06481-5; Q9BS26: ERP44; NbExp=3; IntAct=EBI-25646567, EBI-541644;
CC Q06481-5; Q06787-7: FMR1; NbExp=3; IntAct=EBI-25646567, EBI-25856644;
CC Q06481-5; P06241: FYN; NbExp=3; IntAct=EBI-25646567, EBI-515315;
CC Q06481-5; P14136: GFAP; NbExp=3; IntAct=EBI-25646567, EBI-744302;
CC Q06481-5; Q14114-3: LRP8; NbExp=3; IntAct=EBI-25646567, EBI-25832196;
CC Q06481-5; Q96L34: MARK4; NbExp=3; IntAct=EBI-25646567, EBI-302319;
CC Q06481-5; P17252: PRKCA; NbExp=3; IntAct=EBI-25646567, EBI-1383528;
CC Q06481-5; P23443: RPS6KB1; NbExp=3; IntAct=EBI-25646567, EBI-1775921;
CC Q06481-5; P04271: S100B; NbExp=3; IntAct=EBI-25646567, EBI-458391;
CC Q06481-5; Q8IUQ4-2: SIAH1; NbExp=3; IntAct=EBI-25646567, EBI-11522811;
CC Q06481-5; P84022: SMAD3; NbExp=3; IntAct=EBI-25646567, EBI-347161;
CC Q06481-5; Q13190: STX5; NbExp=3; IntAct=EBI-25646567, EBI-714206;
CC Q06481-5; P43405-2: SYK; NbExp=3; IntAct=EBI-25646567, EBI-25892332;
CC Q06481-5; Q13428-5: TCOF1; NbExp=3; IntAct=EBI-25646567, EBI-25832010;
CC Q06481-5; Q9BX74: TM2D1; NbExp=3; IntAct=EBI-25646567, EBI-25832057;
CC Q06481-5; Q9BVJ6: UTP14A; NbExp=3; IntAct=EBI-25646567, EBI-473284;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=Q06481-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q06481-2; Sequence=VSP_000018;
CC Name=3;
CC IsoId=Q06481-3; Sequence=VSP_000019;
CC Name=4;
CC IsoId=Q06481-4; Sequence=VSP_000018, VSP_046882, VSP_000019;
CC Name=5;
CC IsoId=Q06481-5; Sequence=VSP_030921, VSP_000019;
CC Name=6;
CC IsoId=Q06481-6; Sequence=VSP_046881, VSP_000019;
CC -!- TISSUE SPECIFICITY: Expressed in placenta, brain, heart, lung, liver,
CC kidney and endothelial tissues.
CC -!- PTM: The BPTI/Kunitz inhibitor domain is O-glycosylated.
CC {ECO:0000269|PubMed:8307156}.
CC -!- SIMILARITY: Belongs to the APP family. {ECO:0000255|PROSITE-
CC ProRule:PRU01217}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAG54641.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; S60099; AAC60589.1; -; mRNA.
DR EMBL; L09209; AAA35526.1; -; mRNA.
DR EMBL; L27631; AAC41701.1; -; mRNA.
DR EMBL; Z22572; CAA80295.1; -; mRNA.
DR EMBL; AK128162; BAG54641.1; ALT_FRAME; mRNA.
DR EMBL; L19597; AAA35601.1; -; mRNA.
DR EMBL; L23113; AAA36032.1; -; mRNA.
DR EMBL; L23114; AAA36130.1; -; mRNA.
DR EMBL; AF168956; AAD47291.1; -; mRNA.
DR EMBL; AP001183; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP003041; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000373; AAH00373.1; -; mRNA.
DR EMBL; BC004371; AAH04371.1; -; mRNA.
DR CCDS; CCDS44773.1; -. [Q06481-3]
DR CCDS; CCDS44774.1; -. [Q06481-4]
DR CCDS; CCDS44775.1; -. [Q06481-5]
DR CCDS; CCDS58196.1; -. [Q06481-6]
DR CCDS; CCDS8486.1; -. [Q06481-1]
DR PIR; A49321; A49321.
DR PIR; S41082; S41082.
DR RefSeq; NP_001135748.1; NM_001142276.1. [Q06481-3]
DR RefSeq; NP_001135749.1; NM_001142277.1. [Q06481-4]
DR RefSeq; NP_001135750.1; NM_001142278.1. [Q06481-5]
DR RefSeq; NP_001230228.1; NM_001243299.1. [Q06481-6]
DR RefSeq; NP_001633.1; NM_001642.2. [Q06481-1]
DR PDB; 5JBT; X-ray; 1.40 A; X=307-320, Y=323-360.
DR PDB; 5TPT; X-ray; 2.42 A; A/B=373-569.
DR PDBsum; 5JBT; -.
DR PDBsum; 5TPT; -.
DR AlphaFoldDB; Q06481; -.
DR SMR; Q06481; -.
DR BioGRID; 106831; 122.
DR DIP; DIP-31047N; -.
DR ELM; Q06481; -.
DR IntAct; Q06481; 56.
DR MINT; Q06481; -.
DR STRING; 9606.ENSP00000263574; -.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR MEROPS; I02.016; -.
DR GlyConnect; 1008; 4 N-Linked glycans (1 site).
DR GlyGen; Q06481; 4 sites, 4 N-linked glycans (1 site), 1 O-linked glycan (3 sites).
DR iPTMnet; Q06481; -.
DR PhosphoSitePlus; Q06481; -.
DR BioMuta; APLP2; -.
DR DMDM; 1703344; -.
DR EPD; Q06481; -.
DR jPOST; Q06481; -.
DR MassIVE; Q06481; -.
DR MaxQB; Q06481; -.
DR PaxDb; Q06481; -.
DR PeptideAtlas; Q06481; -.
DR PRIDE; Q06481; -.
DR ProteomicsDB; 43292; -.
DR ProteomicsDB; 58449; -. [Q06481-1]
DR ProteomicsDB; 58450; -. [Q06481-2]
DR ProteomicsDB; 58451; -. [Q06481-3]
DR ProteomicsDB; 58452; -. [Q06481-4]
DR ProteomicsDB; 58453; -. [Q06481-5]
DR TopDownProteomics; Q06481-5; -. [Q06481-5]
DR Antibodypedia; 33074; 384 antibodies from 35 providers.
DR DNASU; 334; -.
DR Ensembl; ENST00000263574.9; ENSP00000263574.5; ENSG00000084234.18. [Q06481-1]
DR Ensembl; ENST00000278756.7; ENSP00000278756.7; ENSG00000084234.18. [Q06481-6]
DR Ensembl; ENST00000338167.10; ENSP00000345444.5; ENSG00000084234.18. [Q06481-3]
DR Ensembl; ENST00000345598.9; ENSP00000263575.6; ENSG00000084234.18. [Q06481-5]
DR Ensembl; ENST00000528499.5; ENSP00000435914.1; ENSG00000084234.18. [Q06481-4]
DR Ensembl; ENST00000650012.1; ENSP00000497691.1; ENSG00000084234.18. [Q06481-1]
DR GeneID; 334; -.
DR KEGG; hsa:334; -.
DR MANE-Select; ENST00000338167.10; ENSP00000345444.5; NM_001142276.2; NP_001135748.1. [Q06481-3]
DR UCSC; uc001qfp.4; human. [Q06481-1]
DR CTD; 334; -.
DR DisGeNET; 334; -.
DR GeneCards; APLP2; -.
DR HGNC; HGNC:598; APLP2.
DR HPA; ENSG00000084234; Low tissue specificity.
DR MIM; 104776; gene.
DR neXtProt; NX_Q06481; -.
DR OpenTargets; ENSG00000084234; -.
DR PharmGKB; PA24885; -.
DR VEuPathDB; HostDB:ENSG00000084234; -.
DR eggNOG; KOG3540; Eukaryota.
DR GeneTree; ENSGT00530000063252; -.
DR HOGENOM; CLU_014607_2_1_1; -.
DR InParanoid; Q06481; -.
DR OMA; QCRSHIV; -.
DR OrthoDB; 953529at2759; -.
DR PhylomeDB; Q06481; -.
DR TreeFam; TF317274; -.
DR PathwayCommons; Q06481; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR SignaLink; Q06481; -.
DR SIGNOR; Q06481; -.
DR BioGRID-ORCS; 334; 14 hits in 1082 CRISPR screens.
DR ChiTaRS; APLP2; human.
DR GeneWiki; APLP2; -.
DR GenomeRNAi; 334; -.
DR Pharos; Q06481; Tbio.
DR PRO; PR:Q06481; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q06481; protein.
DR Bgee; ENSG00000084234; Expressed in renal medulla and 221 other tissues.
DR ExpressionAtlas; Q06481; baseline and differential.
DR Genevisible; Q06481; HS.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0031092; C:platelet alpha granule membrane; TAS:Reactome.
DR GO; GO:0003677; F:DNA binding; NAS:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0046914; F:transition metal ion binding; IEA:InterPro.
DR GO; GO:0007409; P:axonogenesis; IBA:GO_Central.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; NAS:UniProtKB.
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; 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; PTHR23103; 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; PF00014; Kunitz_BPTI; 1.
DR PRINTS; PR00203; AMYLOIDA4.
DR PRINTS; PR00759; BASICPTASE.
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; PS00280; BPTI_KUNITZ_1; 1.
DR PROSITE; PS50279; BPTI_KUNITZ_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Copper; Disulfide bond;
KW DNA-binding; Glycoprotein; Membrane; Metal-binding; Nucleus;
KW Phosphoprotein; Protease inhibitor; Reference proteome;
KW Serine protease inhibitor; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..763
FT /note="Amyloid beta precursor like protein 2"
FT /id="PRO_0000000207"
FT TOPO_DOM 32..692
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 693..716
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 717..763
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 46..205
FT /note="E1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT DOMAIN 306..364
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DOMAIN 373..564
FT /note="E2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01218"
FT REGION 46..139
FT /note="GFLD subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT REGION 147..205
FT /note="CuBD subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT REGION 211..299
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 749..763
FT /note="Interaction with DAB2"
FT /evidence="ECO:0000250"
FT MOTIF 750..755
FT /note="NPXY motif"
FT COMPBIAS 215..236
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 245..270
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..286
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 163
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT BINDING 167
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT BINDING 184
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT SITE 186
FT /note="Required for Cu(2+) reduction"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT SITE 320..321
FT /note="Reactive bond"
FT /evidence="ECO:0000250"
FT MOD_RES 590
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT DISULFID 56..80
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT DISULFID 91..133
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT DISULFID 116..123
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT DISULFID 149..203
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT DISULFID 160..190
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT DISULFID 174..202
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT DISULFID 310..360
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DISULFID 319..343
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DISULFID 335..356
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT VAR_SEQ 1..35
FT /note="MAATGTAAAAATGRLLLLLLVGLTAPALALAGYIE -> MLRAPGELPRQAA
FT RCSLCRLGPGRGRAFFKWRCLPASVDRGNPLW (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_046881"
FT VAR_SEQ 136..364
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030921"
FT VAR_SEQ 308..363
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:7651835"
FT /id="VSP_000018"
FT VAR_SEQ 364
FT /note="I -> V (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:7651835"
FT /id="VSP_046882"
FT VAR_SEQ 613..624
FT /note="Missing (in isoform 3, isoform 4, isoform 5 and
FT isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:7651835"
FT /id="VSP_000019"
FT VARIANT 632
FT /note="D -> N (in dbSNP:rs3740881)"
FT /id="VAR_022039"
FT CONFLICT 224
FT /note="E -> D (in Ref. 5; AAD47291)"
FT /evidence="ECO:0000305"
FT CONFLICT 226..227
FT /note="Missing (in Ref. 4; BAG54641)"
FT /evidence="ECO:0000305"
FT CONFLICT 543
FT /note="S -> I (in Ref. 1; AAA35526)"
FT /evidence="ECO:0000305"
FT CONFLICT 543
FT /note="S -> T (in Ref. 8; AAH04371)"
FT /evidence="ECO:0000305"
FT STRAND 325..329
FT /evidence="ECO:0007829|PDB:5JBT"
FT TURN 330..333
FT /evidence="ECO:0007829|PDB:5JBT"
FT STRAND 334..338
FT /evidence="ECO:0007829|PDB:5JBT"
FT HELIX 345..347
FT /evidence="ECO:0007829|PDB:5JBT"
FT HELIX 353..359
FT /evidence="ECO:0007829|PDB:5JBT"
FT HELIX 374..377
FT /evidence="ECO:0007829|PDB:5TPT"
FT HELIX 386..417
FT /evidence="ECO:0007829|PDB:5TPT"
FT TURN 418..421
FT /evidence="ECO:0007829|PDB:5TPT"
FT HELIX 424..480
FT /evidence="ECO:0007829|PDB:5TPT"
FT STRAND 481..483
FT /evidence="ECO:0007829|PDB:5TPT"
FT HELIX 486..517
FT /evidence="ECO:0007829|PDB:5TPT"
FT HELIX 519..545
FT /evidence="ECO:0007829|PDB:5TPT"
FT HELIX 546..549
FT /evidence="ECO:0007829|PDB:5TPT"
FT HELIX 551..556
FT /evidence="ECO:0007829|PDB:5TPT"
FT HELIX 558..566
FT /evidence="ECO:0007829|PDB:5TPT"
SQ SEQUENCE 763 AA; 86956 MW; CA3A7D6DDB8A28D0 CRC64;
MAATGTAAAA ATGRLLLLLL VGLTAPALAL AGYIEALAAN AGTGFAVAEP QIAMFCGKLN
MHVNIQTGKW EPDPTGTKSC FETKEEVLQY CQEMYPELQI TNVMEANQRV SIDNWCRRDK
KQCKSRFVTP FKCLVGEFVS DVLLVPEKCQ FFHKERMEVC ENHQHWHTVV KEACLTQGMT
LYSYGMLLPC GVDQFHGTEY VCCPQTKIIG SVSKEEEEED EEEEEEEDEE EDYDVYKSEF
PTEADLEDFT EAAVDEDDED EEEGEEVVED RDYYYDTFKG DDYNEENPTE PGSDGTMSDK
EITHDVKAVC SQEAMTGPCR AVMPRWYFDL SKGKCVRFIY GGCGGNRNNF ESEDYCMAVC
KAMIPPTPLP TNDVDVYFET SADDNEHARF QKAKEQLEIR HRNRMDRVKK EWEEAELQAK
NLPKAERQTL IQHFQAMVKA LEKEAASEKQ QLVETHLARV EAMLNDRRRM ALENYLAALQ
SDPPRPHRIL QALRRYVRAE NKDRLHTIRH YQHVLAVDPE KAAQMKSQVM THLHVIEERR
NQSLSLLYKV PYVAQEIQEE IDELLQEQRA DMDQFTASIS ETPVDVRVSS EESEEIPPFH
PFHPFPALPE NEDTQPELYH PMKKGSGVGE QDGGLIGAEE KVINSKNKVD ENMVIDETLD
VKEMIFNAER VGGLEEERES VGPLREDFSL SSSALIGLLV IAVAIATVIV ISLVMLRKRQ
YGTISHGIVE VDPMLTPEER HLNKMQNHGY ENPTYKYLEQ MQI
