APLP2_MOUSE
ID APLP2_MOUSE Reviewed; 707 AA.
AC Q06335; Q80US7;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 4.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Amyloid beta precursor like protein 2 {ECO:0000250|UniProtKB:Q06481};
DE AltName: Full=Amyloid beta (A4) precursor-like protein 2 {ECO:0000312|MGI:MGI:88047};
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|MGI:MGI:88047}; Synonyms=APPL2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Fetal brain;
RA von der Kammer H.;
RL Submitted (JUL-1994) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-246 (ISOFORMS 1/2).
RX PubMed=8218408; DOI=10.1016/0167-4781(93)90055-i;
RA Hanes J., von der Kammer H., Kristjansson G.I., Scheit K.H.;
RT "The complete cDNA coding sequence for the mouse CDEI binding protein.";
RL Biochim. Biophys. Acta 1216:154-156(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 185-707 (ISOFORM 2).
RC STRAIN=BALB/cJ; TISSUE=Heart;
RX PubMed=1482349; DOI=10.1016/0006-291x(92)90220-f;
RA Vidal F., Blangy A., Rassoulzadegan M., Cuzin F.;
RT "A murine sequence-specific DNA binding protein shows extensive local
RT similarities to the amyloid precursor protein.";
RL Biochem. Biophys. Res. Commun. 189:1336-1341(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35.
RC STRAIN=129/Sv;
RX PubMed=7592716; DOI=10.1074/jbc.270.43.25475;
RA von Koch C.S., Lahiri D.K., Mammen A.L., Copeland N.G., Gilbert D.J.,
RA Jenkins N.A., Sisodia S.S.;
RT "The mouse APLP2 gene. Chromosomal localization and promoter
RT characterization.";
RL J. Biol. Chem. 270:25475-25480(1995).
RN [6]
RP INTERACTION WITH DAB2.
RX PubMed=11247302; DOI=10.1034/j.1600-0854.2001.020206.x;
RA Morris S.M., Cooper J.A.;
RT "Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts
RT with AP-2.";
RL Traffic 2:111-123(2001).
RN [7]
RP FUNCTION.
RX PubMed=15677459; DOI=10.1074/jbc.m409179200;
RA Cappai R., Cheng F., Ciccotosto G.D., Needham B.E., Masters C.L.,
RA Multhaup G., Fransson L.A., Mani K.;
RT "The amyloid precursor protein (APP) of Alzheimer disease and its paralog,
RT APLP2, modulate the Cu/Zn-nitric oxide-catalyzed degradation of glypican-1
RT heparan sulfate in vivo.";
RL J. Biol. Chem. 280:13913-13920(2005).
RN [8]
RP INTERACTION WITH CPEB1.
RX PubMed=16314516; DOI=10.1128/mcb.25.24.10930-10939.2005;
RA Cao Q., Huang Y.-S., Kan M.-C., Richter J.D.;
RT "Amyloid precursor proteins anchor CPEB to membranes and promote
RT polyadenylation-induced translation.";
RL Mol. Cell. Biol. 25:10930-10939(2005).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (By similarity).
CC Modulates the Cu/Zn nitric oxide-catalyzed autodegradation of GPC1
CC heparan sulfate side chains in fibroblasts. {ECO:0000250,
CC ECO:0000269|PubMed:15677459}.
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. Interacts (via cytoplasmic domain)
CC with APBB2/FE65L (By similarity). Interacts (via intracellular domain)
CC with APBB3/FE65L2 (By similarity). {ECO:0000250|UniProtKB:Q06481,
CC ECO:0000269|PubMed:11247302, ECO:0000269|PubMed:16314516}.
CC -!- INTERACTION:
CC Q06335; P12023: App; NbExp=3; IntAct=EBI-446708, EBI-78814;
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=2;
CC Name=1;
CC IsoId=Q06335-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q06335-2; Sequence=VSP_041386;
CC -!- SIMILARITY: Belongs to the APP family. {ECO:0000255|PROSITE-
CC ProRule:PRU01217}.
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DR EMBL; Z22592; CAA80306.1; -; mRNA.
DR EMBL; BC051999; AAH51999.1; -; mRNA.
DR EMBL; M97216; AAA20039.1; -; mRNA.
DR EMBL; U34291; AAC52318.1; -; Genomic_DNA.
DR CCDS; CCDS52748.1; -. [Q06335-1]
DR CCDS; CCDS90528.1; -. [Q06335-2]
DR PIR; JC1404; JC1404.
DR PIR; S38344; S38344.
DR RefSeq; NP_001095926.1; NM_001102456.1. [Q06335-1]
DR AlphaFoldDB; Q06335; -.
DR SMR; Q06335; -.
DR BioGRID; 198154; 15.
DR IntAct; Q06335; 11.
DR MINT; Q06335; -.
DR STRING; 10090.ENSMUSP00000072428; -.
DR GlyGen; Q06335; 1 site.
DR iPTMnet; Q06335; -.
DR PhosphoSitePlus; Q06335; -.
DR jPOST; Q06335; -.
DR MaxQB; Q06335; -.
DR PaxDb; Q06335; -.
DR PeptideAtlas; Q06335; -.
DR PRIDE; Q06335; -.
DR ProteomicsDB; 296378; -. [Q06335-1]
DR ProteomicsDB; 296379; -. [Q06335-2]
DR Antibodypedia; 33074; 384 antibodies from 35 providers.
DR DNASU; 11804; -.
DR Ensembl; ENSMUST00000079758; ENSMUSP00000078694; ENSMUSG00000031996. [Q06335-1]
DR Ensembl; ENSMUST00000217641; ENSMUSP00000149023; ENSMUSG00000031996. [Q06335-2]
DR GeneID; 11804; -.
DR KEGG; mmu:11804; -.
DR UCSC; uc009orl.1; mouse. [Q06335-1]
DR CTD; 334; -.
DR MGI; MGI:88047; Aplp2.
DR VEuPathDB; HostDB:ENSMUSG00000031996; -.
DR eggNOG; KOG3540; Eukaryota.
DR GeneTree; ENSGT00530000063252; -.
DR InParanoid; Q06335; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR BioGRID-ORCS; 11804; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Aplp2; mouse.
DR PRO; PR:Q06335; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q06335; protein.
DR Bgee; ENSMUSG00000031996; Expressed in retinal neural layer and 260 other tissues.
DR ExpressionAtlas; Q06335; baseline and differential.
DR Genevisible; Q06335; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0008201; F:heparin binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; ISO:MGI.
DR GO; GO:0046914; F:transition metal ion binding; IEA:InterPro.
DR GO; GO:0007409; P:axonogenesis; IBA:GO_Central.
DR GO; GO:0006878; P:cellular copper ion homeostasis; IMP:MGI.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0008203; P:cholesterol metabolic process; IGI:MGI.
DR GO; GO:0030198; P:extracellular matrix organization; IGI:MGI.
DR GO; GO:0030900; P:forebrain development; IGI:MGI.
DR GO; GO:0007626; P:locomotory behavior; IGI:MGI.
DR GO; GO:0007617; P:mating behavior; IGI:MGI.
DR GO; GO:0030901; P:midbrain development; IGI:MGI.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IGI:MGI.
DR GO; GO:0032268; P:regulation of cellular protein metabolic process; IEA:UniProt.
DR GO; GO:0007176; P:regulation of epidermal growth factor-activated receptor activity; IGI:MGI.
DR GO; GO:0043393; P:regulation of protein binding; IGI:MGI.
DR GO; GO:0001967; P:suckling behavior; IGI:MGI.
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 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; IPR011993; PH-like_dom_sf.
DR PANTHER; PTHR23103; PTHR23103; 2.
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 PRINTS; PR00203; AMYLOIDA4.
DR SMART; SM00006; A4_EXTRA; 1.
DR SUPFAM; SSF109843; SSF109843; 1.
DR SUPFAM; SSF56491; SSF56491; 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.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Copper; Disulfide bond; DNA-binding;
KW Glycoprotein; Membrane; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..707
FT /note="Amyloid beta precursor like protein 2"
FT /id="PRO_0000000208"
FT TOPO_DOM 32..636
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 637..660
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 661..707
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 46..205
FT /note="E1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT DOMAIN 317..508
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 208..298
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 539..575
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 693..707
FT /note="Interaction with DAB2"
FT /evidence="ECO:0000269|PubMed:11247302"
FT MOTIF 694..699
FT /note="NPXY motif"
FT COMPBIAS 215..238
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 MOD_RES 216
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15943"
FT MOD_RES 534
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06481"
FT CARBOHYD 485
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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 VAR_SEQ 557..568
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1482349, ECO:0000303|Ref.1"
FT /id="VSP_041386"
FT CONFLICT 55
FT /note="F -> L (in Ref. 1; CAA80306)"
FT /evidence="ECO:0000305"
FT CONFLICT 185..189
FT /note="GMLLP -> MACCC (in Ref. 4; AAA20039)"
FT /evidence="ECO:0000305"
FT CONFLICT 322
FT /note="F -> L (in Ref. 1; CAA80306 and 4; AAA20039)"
FT /evidence="ECO:0000305"
FT CONFLICT 489
FT /note="S -> T (in Ref. 1; CAA80306 and 4; AAA20039)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 707 AA; 80467 MW; BBB8C3E25A6CC503 CRC64;
MAATGTAAAA ATGKLLVLLL LGLTAPAAAL AGYIEALAAN AGTGFAVAEP QIAMFCGKLN
MHVNIQTGKW EPDPTGTKSC LGTKEEVLQY CQEIYPELQI TNVMEANQPV NIDSWCRRDK
RQCKSHIVIP FKCLVGEFVS DVLLVPDNCQ FFHQERMEVC EKHQRWHTLV KEACLTEGLT
LYSYGMLLPC GVDQFHGTEY VCCPQTKTVD SDSTMSKEEE EEEEDEEDEE EDYDLDKSEF
PTEADLEDFT EAAADEEEED EEEGEEVVED RDYYYDPFKG DDYNEENPTE PSSEGTISDK
EIVHDVKVPP TPLPTNDVDV YFETSADDNE HARFQKAKEQ LEIRHRNRMD RVKKEWEEAE
LQAKNLPKTE RQTLIQHFQA MVKALEKEAA SEKQQLVETH LARVEAMLND RRRIALENYL
AALQSDPPRP HRILQALRRY VRAENKDRLH TIRHYQHVLA VDPEKAAQMK SQVMTHLHVI
EERRNQSLSL LYKVPYVAQE IQEEIDELLQ EQRADMDQFT SSISENPVDV RVSSEESEEI
PPFHPLHPFP SLSENEDTQP ELYHPMKKGS GMAEQDGGLI GAEEKVINSK NKMDENMVID
ETLDVKEMIF NAERVGGLEE EPESVGPLRE DFSLSSNALI GLLVIAVAIA TVIVISLVML
RKRQYGTISH GIVEVDPMLT PEERHLNKMQ NHGYENPTYK YLEQMQI
