ID Q6NRR1_XENLA Unreviewed; 749 AA.
AC Q6NRR1;
DT 05-JUL-2004, integrated into UniProtKB/TrEMBL.
DT 05-JUL-2004, sequence version 1.
DT 27-MAR-2024, entry version 113.
DE RecName: Full=Amyloid-beta A4 protein {ECO:0000256|RuleBase:RU367156};
GN Name=app.L {ECO:0000313|RefSeq:NP_001082098.1,
GN ECO:0000313|Xenbase:XB-GENE-479158};
GN Synonyms=app {ECO:0000313|EMBL:AAH70668.1,
GN ECO:0000313|RefSeq:NP_001082098.1};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355 {ECO:0000313|EMBL:AAH70668.1};
RN [1] {ECO:0000313|RefSeq:NP_001082098.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=11744158; DOI=10.1016/S0169-328X(01)00279-0;
RA van den Hurk W.H., Bloemen M., Martens G.J.;
RT "Expression of the gene encoding the beta-amyloid precursor protein APP in
RT Xenopus laevis.";
RL Brain Res. Mol. Brain Res. 97:13-20(2001).
RN [2] {ECO:0000313|RefSeq:NP_001082098.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=12454917; DOI=10.1002/dvdy.10174;
RA Klein S.L., Strausberg R.L., Wagner L., Pontius J., Clifton S.W.,
RA Richardson P.;
RT "Genetic and genomic tools for Xenopus research: The NIH Xenopus
RT initiative.";
RL Dev. Dyn. 225:384-391(2002).
RN [3] {ECO:0000313|RefSeq:NP_001082098.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=15208260;
RA Maloney B., Ge Y.W., Greig N., Lahiri D.K.;
RT "Presence of a 'CAGA box' in the APP gene unique to amyloid plaque-forming
RT species and absent in all APLP-1/2 genes: implications in Alzheimer's
RT disease.";
RL FASEB J. 18:1288-1290(2004).
RN [4] {ECO:0000313|EMBL:AAH70668.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney {ECO:0000313|EMBL:AAH70668.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000313|RefSeq:NP_001082098.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=16092943;
RA Collin R.W., van den Hurk W.H., Martens G.J.;
RT "Biosynthesis and differential processing of two pools of amyloid-beta
RT precursor protein in a physiologically inducible neuroendocrine cell.";
RL J. Neurochem. 94:1015-1024(2005).
RN [6] {ECO:0000313|RefSeq:NP_001082098.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=17270477;
RA Clamagirand C., El Abida B., Der Garabedian P.A., Hanquez C., Dubost L.,
RA Marie A., Rholam M., Friguet B., Cohen P.;
RT "Endogenous C-terminal fragments of beta-amyloid precursor protein from
RT Xenopus laevis skin exudate.";
RL Comp. Biochem. Physiol. B, Biochem. Mol. Biol. 146:530-539(2007).
RN [7] {ECO:0000313|RefSeq:NP_001082098.1}
RP IDENTIFICATION.
RG RefSeq;
RL Submitted (NOV-2023) to UniProtKB.
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 -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|RuleBase:RU367156};
CC Single-pass type I membrane protein {ECO:0000256|RuleBase:RU367156}.
CC Membrane {ECO:0000256|ARBA:ARBA00004479}; Single-pass type I membrane
CC protein {ECO:0000256|ARBA:ARBA00004479}.
CC -!- SIMILARITY: Belongs to the APP family. {ECO:0000256|PROSITE-
CC 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; BC070668; AAH70668.1; -; mRNA.
DR RefSeq; NP_001082098.1; NM_001088629.1.
DR MEROPS; I02.015; -.
DR DNASU; 398223; -.
DR GeneID; 398223; -.
DR KEGG; xla:398223; -.
DR AGR; Xenbase:XB-GENE-479158; -.
DR CTD; 398223; -.
DR Xenbase; XB-GENE-479158; app.L.
DR OrthoDB; 2907766at2759; -.
DR Proteomes; UP000186698; Chromosome 2L.
DR Bgee; 398223; Expressed in brain and 20 other cell types or tissues.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005798; C:Golgi-associated vesicle; IEA:UniProtKB-UniRule.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0046914; F:transition metal ion binding; IEA:InterPro.
DR GO; GO:0008344; P:adult locomotory behavior; ISS:UniProtKB.
DR GO; GO:0008088; P:axo-dendritic transport; ISS:UniProtKB.
DR GO; GO:0016199; P:axon midline choice point recognition; ISS:UniProtKB.
DR GO; GO:0007409; P:axonogenesis; ISS:UniProtKB.
DR GO; GO:0048669; P:collateral sprouting in absence of injury; ISS:UniProtKB.
DR GO; GO:0016358; P:dendrite development; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; ISS:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; ISS:UniProtKB.
DR GO; GO:0006878; P:intracellular copper ion homeostasis; ISS:UniProtKB.
DR GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007626; P:locomotory behavior; ISS:UniProtKB.
DR GO; GO:0007617; P:mating behavior; ISS:UniProtKB.
DR GO; GO:0006378; P:mRNA polyadenylation; ISS:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0016322; P:neuron remodeling; ISS:UniProtKB.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0007176; P:regulation of epidermal growth factor-activated receptor activity; ISS:UniProtKB.
DR GO; GO:0040014; P:regulation of multicellular organism growth; ISS:UniProtKB.
DR GO; GO:0050803; P:regulation of synapse structure or activity; ISS:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; ISS:UniProtKB.
DR GO; GO:0008542; P:visual learning; ISS:UniProtKB.
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; IPR013803; Amyloid_glyco_Abeta.
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 Cell membrane {ECO:0000256|RuleBase:RU367156};
KW Coiled coil {ECO:0000256|SAM:Coils};
KW Copper {ECO:0000256|ARBA:ARBA00023008};
KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157, ECO:0000256|PROSITE-
KW ProRule:PRU01217}; Glycoprotein {ECO:0000256|ARBA:ARBA00023180};
KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|RuleBase:RU367156};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW Protease inhibitor {ECO:0000256|ARBA:ARBA00022690};
KW Reference proteome {ECO:0000313|Proteomes:UP000186698};
KW Serine protease inhibitor {ECO:0000256|ARBA:ARBA00022900};
KW Signal {ECO:0000256|ARBA:ARBA00022729, ECO:0000256|SAM:SignalP};
KW Transmembrane {ECO:0000256|ARBA:ARBA00022692,
KW ECO:0000256|RuleBase:RU367156};
KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989,
KW ECO:0000256|RuleBase:RU367156}.
FT SIGNAL 1..16
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 17..749
FT /note="Amyloid-beta A4 protein"
FT /evidence="ECO:0000256|SAM:SignalP,
FT ECO:0000313|RefSeq:NP_001082098.1"
FT /id="PRO_5033206658"
FT TRANSMEM 680..702
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU367156"
FT DOMAIN 27..188
FT /note="E1"
FT /evidence="ECO:0000259|PROSITE:PS51869"
FT DOMAIN 289..339
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000259|PROSITE:PS50279"
FT DOMAIN 353..544
FT /note="E2"
FT /evidence="ECO:0000259|PROSITE:PS51870"
FT REGION 27..122
FT /note="GFLD subdomain"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT REGION 130..188
FT /note="CuBD subdomain"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT REGION 192..281
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 382..438
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 194..208
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 226..261
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 265..281
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 72..116
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT DISULFID 97..104
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT DISULFID 132..186
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT DISULFID 143..173
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT DISULFID 157..185
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
SQ SEQUENCE 749 AA; 84767 MW; 33478C6B6A8C295D CRC64;
MLPHITLLVL TAGALALEVP ADGNGGLLAE PQIAMFCGKL NMHMNVQNGK WETDVSGTKG
CIGTKEGILQ YCQEVYPELQ ITNVVEANQP VTIQNWCKKG RKQCKSRTHI VVPYRCLVGE
FVSDALLVPD KCKFLHQERM DICETHLHWH TVAKESCSEK SMSLHEYGML LPCGIDKFRG
VEFVCCPSAE ESESFDSADA EDDSDVWWGG ADADYVDRSD DKAVEAQPDE EEEVVEVEEE
ETDDDEDDGD EAEEEPEEPY EEATERTTSI ATTTTTTTES VEEVVREVCS EQAETGPCRA
MISRWYYDVT ESKCAQFIYG GCGGNRNNFE SDDYCMAVCG SVIPATAAST PDAVDKYLEN
PNDENEHDRF LKAKERLEGK HREKMSEVMK EWEEAERQAK NLPKADKKAV IQHFQEKVES
LEQEAANERQ QLVETHMARV EAMLNDRRRI ALENYITALQ ADPPRPRHVF NMLKKYVRAE
QKDRQHTLKH FEHVRMVDPK KAAQIRSQVM THLRVINERM NQSFSLLYKV PAVAEEIQDE
VDELFQKEQN YSDDMVSNMV SDHRVSYGND ALMPSLSETK TTVELLPVDG EFNIEDLQPW
HSFGVDSVPA NTENEVEPVD ARPAADRGLT TRPGSGLTNI KTEEISEVKM DSEYRHDTAY
EVHHQKLVFF AEEVGSNKGA IIGLMVGGVV IATVIVITLV MLKKKQYTTI HHGVVEVDAA
VTPEERHLTK MQQNGYENPT YKFFEQMQN
//
