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   27-MAR-2024, entry version 224.
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).
RN   [15]
RP   GLYCOSYLATION AT SER-626.
RX   PubMed=32337544; DOI=10.1093/glycob/cwaa039;
RA   Toledo A.G., Pihl J., Spliid C.B., Persson A., Nilsson J., Pereira M.A.,
RA   Gustavsson T., Choudhary S., Oo H.Z., Black P.C., Daugaard M., Esko J.D.,
RA   Larson G., Salanti A., Clausen T.M.;
RT   "An affinity chromatography and glycoproteomics workflow to profile the
RT   chondroitin sulfate proteoglycans that interact with malarial VAR2CSA in
RT   the placenta and in cancer.";
RL   Glycobiology 30:989-1002(2020).
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; 134.
DR   DIP; DIP-31047N; -.
DR   ELM; Q06481; -.
DR   IntAct; Q06481; 57.
DR   MINT; Q06481; -.
DR   STRING; 9606.ENSP00000497691; -.
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   GlyCosmos; Q06481; 4 sites, 5 glycans.
DR   GlyGen; Q06481; 10 sites, 4 N-linked glycans (1 site), 2 O-linked glycans (8 sites).
DR   iPTMnet; Q06481; -.
DR   PhosphoSitePlus; Q06481; -.
DR   SwissPalm; Q06481; -.
DR   BioMuta; APLP2; -.
DR   DMDM; 1703344; -.
DR   EPD; Q06481; -.
DR   jPOST; Q06481; -.
DR   MassIVE; Q06481; -.
DR   MaxQB; Q06481; -.
DR   PaxDb; 9606-ENSP00000263574; -.
DR   PeptideAtlas; 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   Pumba; Q06481; -.
DR   TopDownProteomics; Q06481-5; -. [Q06481-5]
DR   Antibodypedia; 33074; 420 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   AGR; HGNC:598; -.
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; THRVQKC; -.
DR   OrthoDB; 2907766at2759; -.
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 1162 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 223 other cell types or tissues.
DR   ExpressionAtlas; Q06481; baseline and differential.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; HDA: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   CDD; cd21709; JMTM_APLP2; 1.
DR   CDD; cd22607; Kunitz_ABPP-like; 1.
DR   Gene3D; 6.10.250.1670; -; 1.
DR   Gene3D; 1.20.120.770; Amyloid precursor protein, E2 domain; 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; 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:SF14; AMYLOID BETA PRECURSOR LIKE PROTEIN 2; 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; 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.
DR   Genevisible; Q06481; HS.
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; Proteoglycan; 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   CARBOHYD        626
FT                   /note="O-linked (Xyl...) (chondroitin sulfate) serine"
FT                   /evidence="ECO:0000269|PubMed:32337544"
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
//