APLP2_RAT
ID APLP2_RAT Reviewed; 765 AA.
AC P15943;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Amyloid beta precursor like protein 2 {ECO:0000312|RGD:2128};
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:0000312|RGD:2128};
DE Short=APLP-2;
DE AltName: Full=CDEI box-binding protein;
DE Short=CDEBP;
DE AltName: Full=Sperm membrane protein YWK-II {ECO:0000312|RGD:2128};
DE Flags: Precursor;
GN Name=Aplp2 {ECO:0000312|RGD:2128}; Synonyms=APPL2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-627.
RC STRAIN=Wistar; TISSUE=Brain, and Heart;
RX PubMed=8086458; DOI=10.1016/0167-4781(94)90263-1;
RA Sandbrink R., Masters C.L., Beyreuther K.;
RT "Complete nucleotide and deduced amino acid sequence of rat amyloid protein
RT precursor-like protein 2 (APLP2/APPH): two amino acids length difference to
RT human and murine homologues.";
RL Biochim. Biophys. Acta 1219:167-170(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 575-765.
RC TISSUE=Testis;
RX PubMed=1690887; DOI=10.1073/pnas.87.7.2405;
RA Yan Y.C., Bai Y., Wang L.F., Miao S.Y., Koide S.S.;
RT "Characterization of cDNA encoding a human sperm membrane protein related
RT to A4 amyloid protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:2405-2408(1990).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 -!- 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 (By similarity). Interacts (via
CC intracellular domain) with APBB3/FE65L2 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q06481}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=A;
CC IsoId=P15943-1; Sequence=Displayed;
CC Name=B;
CC IsoId=P15943-2; Sequence=VSP_000021;
CC Name=C;
CC IsoId=P15943-3; Sequence=VSP_000020;
CC Name=D;
CC IsoId=P15943-4; Sequence=VSP_000020, VSP_000021;
CC -!- SIMILARITY: Belongs to the APP family. {ECO:0000255|PROSITE-
CC ProRule:PRU01217}.
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DR EMBL; X77934; CAA54906.1; -; mRNA.
DR EMBL; M31322; AAA42352.1; -; mRNA.
DR PIR; A35981; A35981.
DR PIR; S42880; S42880.
DR AlphaFoldDB; P15943; -.
DR SMR; P15943; -.
DR IntAct; P15943; 1.
DR STRING; 10116.ENSRNOP00000067835; -.
DR MEROPS; I02.016; -.
DR GlyGen; P15943; 1 site.
DR iPTMnet; P15943; -.
DR PhosphoSitePlus; P15943; -.
DR jPOST; P15943; -.
DR PaxDb; P15943; -.
DR PRIDE; P15943; -.
DR RGD; 2128; Aplp2.
DR eggNOG; KOG3540; Eukaryota.
DR InParanoid; P15943; -.
DR PhylomeDB; P15943; -.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR PRO; PR:P15943; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0008201; F:heparin binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0008203; P:cholesterol metabolic process; ISO:RGD.
DR GO; GO:0030198; P:extracellular matrix organization; ISO:RGD.
DR GO; GO:0030900; P:forebrain development; ISO:RGD.
DR GO; GO:0007626; P:locomotory behavior; ISO:RGD.
DR GO; GO:0007617; P:mating behavior; ISO:RGD.
DR GO; GO:0030901; P:midbrain development; ISO:RGD.
DR GO; GO:0050885; P:neuromuscular process controlling balance; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0043393; P:regulation of protein binding; ISO:RGD.
DR GO; GO:0001967; P:suckling behavior; ISO:RGD.
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 Alternative splicing; Copper; Disulfide bond; Glycoprotein; Membrane;
KW Metal-binding; Phosphoprotein; Protease inhibitor; Proteoglycan;
KW Reference proteome; Serine protease inhibitor; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..765
FT /note="Amyloid beta precursor like protein 2"
FT /id="PRO_0000000209"
FT TOPO_DOM 32..695
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 696..718
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 719..765
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 46..205
FT /note="E1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT DOMAIN 308..366
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DOMAIN 375..566
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..301
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 597..616
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 751..765
FT /note="Interaction with DAB2"
FT /evidence="ECO:0000250"
FT MOTIF 752..757
FT /note="NPXY motif"
FT COMPBIAS 215..234
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 243..272
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 273..288
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 322..323
FT /note="Reactive bond"
FT /evidence="ECO:0000250"
FT MOD_RES 216
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 592
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06481"
FT CARBOHYD 628
FT /note="O-linked (Xyl...) (glycosaminoglycan) serine"
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 DISULFID 312..362
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DISULFID 321..345
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DISULFID 337..358
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT VAR_SEQ 311..365
FT /note="Missing (in isoform C and isoform D)"
FT /evidence="ECO:0000305"
FT /id="VSP_000020"
FT VAR_SEQ 616..627
FT /note="Missing (in isoform B and isoform D)"
FT /evidence="ECO:0000305"
FT /id="VSP_000021"
FT CONFLICT 575..577
FT /note="DQF -> EFV (in Ref. 2; AAA42352)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 765 AA; 86883 MW; CF51FCCCE305A0CF CRC64;
MAATGTAAAA ATGKLLVLLL LGLTAPAAAL AGYIEALAAN AGTGFAVAEP QIAMFCGKLN
MHVNIQTGKW EPDPTGTKSC LGTKEEVLQY CQEIYPELQI TNVMEANQPV NIDSWCRRDK
KQCRSHIVIP FKCLVGEFVS DVLLVPENCQ FFHQERMEVC EKHQRWHTVV KEACLTEGMT
LYSYGMLLPC GVDQFHGTEY VCCPQTKVVD SDSTMSKEEE EEEEEDEEED YALDKSEFPT
EADLEDFTEA AADEDEDEEE EEEEEGEEVV EDRDYYYDSF KGDDYNEENP TEPSSDGTIS
DKEIAHDVKA VCSQEAMTGP CRAVMPRWYF DLSKGKCVRF IYGGCGGNRN NFESEDYCMA
VCKTMIPPTP LPTNDVDVYF ETSADDNEHA RFQKAKEQLE IRHRSRMDRV KKEWEEAELQ
AKNLPKAERQ TLIQHFQAMV KALEKEAASE KQQLVETHLA RVEAMLNDRR RIALENYLAA
LQSDPPRPHR ILQALRRYVR AENKDRLHTI RHYQHVLAVD PEKAAQMKSQ VMTHLHVIEE
RRNQSLSLLY KVPYVAQEIQ EEIDELLQEQ RADMDQFTSS ISENPVDVRV SSEESEEIPP
FHPFHPFPSL SENEDTQPEL YHPMKKGSGM AEQDGGLIGA EEKVINSKNK MDENMVIDET
LDVKEMIFNA ERVGGLEEEP DSVGPLREDF SLSSSALIGL LVIAVAIATV IVISLVMLRK
RQYGTISHGI VEVHPMLTPE ERHLNKMQNH GYENPTYKYL EQMQI
