ID   APLP1_HUMAN             Reviewed;         650 AA.
AC   P51693; O00113; Q96A92;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   22-FEB-2003, sequence version 3.
DT   27-MAR-2024, entry version 204.
DE   RecName: Full=Amyloid beta precursor like protein 1 {ECO:0000312|HGNC:HGNC:597};
DE   AltName: Full=Amyloid beta (A4) precursor-like protein 1 {ECO:0000250|UniProtKB:Q03157};
DE   AltName: Full=Amyloid-like protein 1 {ECO:0000312|HGNC:HGNC:597};
DE            Short=APLP {ECO:0000312|HGNC:HGNC:597};
DE            Short=APLP-1;
DE   Contains:
DE     RecName: Full=C30;
DE   Flags: Precursor;
GN   Name=APLP1;
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).
RX   PubMed=9428684; DOI=10.1111/j.1432-1033.1997.0354a.x;
RA   Paliga K., Peraus G., Kreger S., Duwrrwang U., Hesse L., Multhaup G.,
RA   Masters C.L., Beyreuther K., Weidemann A.;
RT   "Human amyloid precursor-like protein 1 -- cDNA cloning, ectopic expression
RT   in COS-7 cells and identification of soluble forms in the cerebrospinal
RT   fluid.";
RL   Eur. J. Biochem. 250:354-363(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX   PubMed=9521588; DOI=10.1007/s004390050676;
RA   Lenkkeri U., Kestila M., Lamerdin J.E., McCready P., Adamson A., Olsen A.,
RA   Tryggvason K.;
RT   "Structure of the human amyloid-precursor-like protein gene APLP1 at
RT   19q13.1.";
RL   Hum. Genet. 102:192-196(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057824; DOI=10.1038/nature02399;
RA   Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA   Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA   Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA   Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA   Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA   Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA   Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA   Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA   Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA   McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA   Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA   Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA   She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA   Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA   Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA   Rubin E.M., Lucas S.M.;
RT   "The DNA sequence and biology of human chromosome 19.";
RL   Nature 428:529-535(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Brain, and Ovary;
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   [5]
RP   POSSIBLE FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=7494461; DOI=10.1016/0169-328x(95)00328-p;
RA   Kim T.-W., Wu K., Xu J.-L., McAuliffe G., Tanzi R.E., Wasco W., Black I.B.;
RT   "Selective localization of amyloid precursor-like protein 1 in the cerebral
RT   cortex postsynaptic density.";
RL   Brain Res. Mol. Brain Res. 32:36-44(1995).
RN   [6]
RP   HEPARIN AND ZINC-BINDING.
RX   PubMed=7929392; DOI=10.1016/s0021-9258(18)47062-7;
RA   Bush A.I., Pettingell W.H. Jr., de Paradis M., Tanzi R.E., Wasco W.;
RT   "The amyloid beta-protein precursor and its mammalian homologues. Evidence
RT   for a zinc-modulated heparin-binding superfamily.";
RL   J. Biol. Chem. 269:26618-26621(1994).
RN   [7]
RP   INTERACTION WITH APBA2.
RX   PubMed=9890987; DOI=10.1074/jbc.274.4.2243;
RA   Tomita S., Ozaki T., Taru H., Oguchi S., Takeda S., Yagi Y., Sakiyama S.,
RA   Kirino Y., Suzuki T.;
RT   "Interaction of a neuron-specific protein containing PDZ domains with
RT   Alzheimer's amyloid precursor protein.";
RL   J. Biol. Chem. 274:2243-2254(1999).
RN   [8]
RP   EXTRACELLULAR COPPER-BINDING.
RX   PubMed=12135352; DOI=10.1021/bi0258647;
RA   Simons A., Ruppert T., Schmidt C., Schlicksupp A., Pipkorn R., Reed J.,
RA   Masters C.L., White A.R., Cappai R., Beyreuther K., Bayer T.A.,
RA   Multhaup G.;
RT   "Evidence for a copper-binding superfamily of the amyloid precursor
RT   protein.";
RL   Biochemistry 41:9310-9320(2002).
RN   [9]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT THR-215; SER-227 AND THR-228, AND
RP   STRUCTURE OF CARBOHYDRATES.
RC   TISSUE=Cerebrospinal fluid;
RX   PubMed=19838169; DOI=10.1038/nmeth.1392;
RA   Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G.,
RA   Larson G.;
RT   "Enrichment of glycopeptides for glycan structure and attachment site
RT   identification.";
RL   Nat. Methods 6:809-811(2009).
RN   [10]
RP   GLYCOSYLATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=23234360; DOI=10.1021/pr300963h;
RA   Halim A., Ruetschi U., Larson G., Nilsson J.;
RT   "LC-MS/MS characterization of O-glycosylation sites and glycan structures
RT   of human cerebrospinal fluid glycoproteins.";
RL   J. Proteome Res. 12:573-584(2013).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (2.11 ANGSTROMS) OF 285-499, HEPARIN-BINDING,
RP   MUTAGENESIS OF HIS-426; ARG-429 AND HIS-433, AND SUBUNIT.
RX   PubMed=21574595; DOI=10.1021/bi101846x;
RA   Lee S., Xue Y., Hu J., Wang Y., Liu X., Demeler B., Ha Y.;
RT   "The E2 Domains of APP and APLP1 Share a Conserved Mode of Dimerization.";
RL   Biochemistry 50:5453-5464(2011).
CC   -!- FUNCTION: May play a role in postsynaptic function. The C-terminal
CC       gamma-secretase processed fragment, ALID1, activates transcription
CC       activation through APBB1 (Fe65) binding (By similarity). Couples to JIP
CC       signal transduction through C-terminal binding. May interact with
CC       cellular G-protein signaling pathways. Can regulate neurite outgrowth
CC       through binding to components of the extracellular matrix such as
CC       heparin and collagen I. {ECO:0000250}.
CC   -!- FUNCTION: The gamma-CTF peptide, C30, is a potent enhancer of neuronal
CC       apoptosis. {ECO:0000250}.
CC   -!- SUBUNIT: Monomer and homodimer. Heparin binding promotes
CC       homodimerization. Binds, via its C-terminus, to the PID domain of
CC       several cytoplasmic proteins, including APBB and APBA family members,
CC       MAPK8IP1 and DAB1 (By similarity). Binding to Dab1 inhibits its serine
CC       phosphorylation (By similarity). Interacts with CPEB1. Interacts (via
CC       NPXY motif) with DAB2 (via PID domain); the interaction is impaired by
CC       tyrosine phosphorylation of the NPXY motif. Interacts (via NPXY motif)
CC       with DAB1 (By similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       P51693; P51693: APLP1; NbExp=4; IntAct=EBI-74648, EBI-74648;
CC       P51693; Q06481: APLP2; NbExp=2; IntAct=EBI-74648, EBI-79306;
CC       P51693; P05067-4: APP; NbExp=2; IntAct=EBI-74648, EBI-302641;
CC       P51693; Q93074: MED12; NbExp=2; IntAct=EBI-74648, EBI-394357;
CC       P51693; Q9UBQ0-2: VPS29; NbExp=3; IntAct=EBI-74648, EBI-11141397;
CC       P51693; P17028: ZNF24; NbExp=2; IntAct=EBI-74648, EBI-707773;
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC       protein.
CC   -!- SUBCELLULAR LOCATION: [C30]: Cytoplasm. Note=C-terminally processed in
CC       the Golgi complex.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P51693-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P51693-2; Sequence=VSP_039100;
CC   -!- TISSUE SPECIFICITY: Expressed in the cerebral cortex where it is
CC       localized to the postsynaptic density (PSD).
CC       {ECO:0000269|PubMed:7494461}.
CC   -!- DOMAIN: The NPXY sequence motif found in many tyrosine-phosphorylated
CC       proteins is required for the specific binding of the PID domain.
CC       However, additional amino acids either N- or C-terminal to the NPXY
CC       motif are often required for complete interaction. The NPXY site is
CC       also involved in clathrin-mediated endocytosis.
CC   -!- PTM: Proteolytically cleaved by caspases during neuronal apoptosis.
CC       Cleaved, in vitro, at Asp-620 by caspase-3 (By similarity).
CC       {ECO:0000250}.
CC   -!- PTM: N- and O-glycosylated. O-glycosylation with core 1 or possibly
CC       core 8 glycans. Glycosylation on Ser-227 is the preferred site to Thr-
CC       228. {ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:23234360}.
CC   -!- MISCELLANEOUS: Binds zinc and copper in the extracellular domain. Zinc-
CC       binding increases heparin binding. No Cu(2+) reducing activity with
CC       copper-binding.
CC   -!- SIMILARITY: Belongs to the APP family. {ECO:0000255|PROSITE-
CC       ProRule:PRU01217}.
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DR   EMBL; U48437; AAB96331.1; -; mRNA.
DR   EMBL; AD000864; AAB50173.1; -; Genomic_DNA.
DR   EMBL; BC012889; AAH12889.1; -; mRNA.
DR   EMBL; BC013850; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS32997.1; -. [P51693-2]
DR   CCDS; CCDS92600.1; -. [P51693-1]
DR   RefSeq; NP_001019978.1; NM_001024807.2. [P51693-2]
DR   RefSeq; NP_005157.1; NM_005166.4. [P51693-1]
DR   PDB; 3PMR; X-ray; 2.11 A; A/B=285-499.
DR   PDB; 3Q7G; X-ray; 2.30 A; A/B=285-494.
DR   PDB; 3Q7L; X-ray; 2.20 A; A/B=285-494.
DR   PDB; 3QMK; X-ray; 2.21 A; A/B=285-494.
DR   PDB; 4RD9; X-ray; 2.60 A; A/B=292-494.
DR   PDB; 4RDA; X-ray; 2.50 A; A/B=290-495.
DR   PDBsum; 3PMR; -.
DR   PDBsum; 3Q7G; -.
DR   PDBsum; 3Q7L; -.
DR   PDBsum; 3QMK; -.
DR   PDBsum; 4RD9; -.
DR   PDBsum; 4RDA; -.
DR   AlphaFoldDB; P51693; -.
DR   SMR; P51693; -.
DR   BioGRID; 106830; 52.
DR   DIP; DIP-30846N; -.
DR   IntAct; P51693; 48.
DR   MINT; P51693; -.
DR   STRING; 9606.ENSP00000221891; -.
DR   DrugBank; DB09130; Copper.
DR   DrugBank; DB01593; Zinc.
DR   DrugBank; DB14487; Zinc acetate.
DR   DrugBank; DB14533; Zinc chloride.
DR   DrugBank; DB14548; Zinc sulfate, unspecified form.
DR   GlyConnect; 716; 1 O-Linked glycan (1 site).
DR   GlyCosmos; P51693; 7 sites, 2 glycans.
DR   GlyGen; P51693; 7 sites, 2 O-linked glycans (2 sites).
DR   iPTMnet; P51693; -.
DR   PhosphoSitePlus; P51693; -.
DR   BioMuta; APLP1; -.
DR   DMDM; 28558769; -.
DR   MassIVE; P51693; -.
DR   PaxDb; 9606-ENSP00000221891; -.
DR   PeptideAtlas; P51693; -.
DR   ProteomicsDB; 56379; -. [P51693-1]
DR   ProteomicsDB; 56380; -. [P51693-2]
DR   Pumba; P51693; -.
DR   TopDownProteomics; P51693-2; -. [P51693-2]
DR   Antibodypedia; 16162; 296 antibodies from 28 providers.
DR   DNASU; 333; -.
DR   Ensembl; ENST00000221891.9; ENSP00000221891.4; ENSG00000105290.13. [P51693-2]
DR   Ensembl; ENST00000652533.1; ENSP00000498366.1; ENSG00000105290.13. [P51693-1]
DR   GeneID; 333; -.
DR   KEGG; hsa:333; -.
DR   MANE-Select; ENST00000221891.9; ENSP00000221891.4; NM_001024807.3; NP_001019978.1. [P51693-2]
DR   UCSC; uc002ocf.4; human. [P51693-1]
DR   AGR; HGNC:597; -.
DR   CTD; 333; -.
DR   DisGeNET; 333; -.
DR   GeneCards; APLP1; -.
DR   HGNC; HGNC:597; APLP1.
DR   HPA; ENSG00000105290; Tissue enriched (brain).
DR   MIM; 104775; gene.
DR   neXtProt; NX_P51693; -.
DR   OpenTargets; ENSG00000105290; -.
DR   PharmGKB; PA24884; -.
DR   VEuPathDB; HostDB:ENSG00000105290; -.
DR   eggNOG; KOG3540; Eukaryota.
DR   GeneTree; ENSGT00530000063252; -.
DR   InParanoid; P51693; -.
DR   OMA; CLRDPQH; -.
DR   OrthoDB; 2907766at2759; -.
DR   PhylomeDB; P51693; -.
DR   TreeFam; TF317274; -.
DR   PathwayCommons; P51693; -.
DR   SignaLink; P51693; -.
DR   BioGRID-ORCS; 333; 11 hits in 1157 CRISPR screens.
DR   ChiTaRS; APLP1; human.
DR   EvolutionaryTrace; P51693; -.
DR   GeneWiki; APLP1; -.
DR   GenomeRNAi; 333; -.
DR   Pharos; P51693; Tbio.
DR   PRO; PR:P51693; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; P51693; Protein.
DR   Bgee; ENSG00000105290; Expressed in C1 segment of cervical spinal cord and 139 other cell types or tissues.
DR   ExpressionAtlas; P51693; baseline and differential.
DR   GO; GO:0005604; C:basement membrane; TAS:ProtInc.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR   GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR   GO; GO:0031694; F:alpha-2A adrenergic receptor binding; IPI:BHF-UCL.
DR   GO; GO:0031695; F:alpha-2B adrenergic receptor binding; IPI:BHF-UCL.
DR   GO; GO:0031696; F:alpha-2C adrenergic receptor binding; IPI:BHF-UCL.
DR   GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0046914; F:transition metal ion binding; IEA:InterPro.
DR   GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0007409; P:axonogenesis; IBA:GO_Central.
DR   GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR   GO; GO:0071874; P:cellular response to norepinephrine stimulus; IDA:BHF-UCL.
DR   GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR   GO; GO:0180011; P:cytoplasmic polyadenylation; IEA:Ensembl.
DR   GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR   GO; GO:0030198; P:extracellular matrix organization; ISS:ARUK-UCL.
DR   GO; GO:0030900; P:forebrain development; ISS:ARUK-UCL.
DR   GO; GO:0106072; P:negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR   GO; GO:0006417; P:regulation of translation; IEA:Ensembl.
DR   CDD; cd21708; JMTM_APLP1; 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   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   PANTHER; PTHR23103; ALZHEIMER'S DISEASE BETA-AMYLOID RELATED; 1.
DR   PANTHER; PTHR23103:SF13; AMYLOID BETA PRECURSOR LIKE PROTEIN 1; 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   PRINTS; PR00203; AMYLOIDA4.
DR   SMART; SM00006; A4_EXTRA; 1.
DR   SUPFAM; SSF56491; A heparin-binding domain; 1.
DR   SUPFAM; SSF89811; Amyloid beta a4 protein copper binding domain (domain 2); 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   Genevisible; P51693; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Apoptosis; Cell adhesion;
KW   Cell membrane; Copper; Cytoplasm; Disulfide bond; Endocytosis;
KW   Glycoprotein; Heparin-binding; Membrane; Metal-binding; Neurodegeneration;
KW   Reference proteome; Signal; Transmembrane; Transmembrane helix; Zinc.
FT   SIGNAL          1..38
FT                   /evidence="ECO:0000255"
FT   CHAIN           39..650
FT                   /note="Amyloid beta precursor like protein 1"
FT                   /id="PRO_0000000203"
FT   PEPTIDE         621..650
FT                   /note="C30"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000000204"
FT   TOPO_DOM        39..580
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        581..603
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        604..650
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          50..212
FT                   /note="E1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   DOMAIN          293..484
FT                   /note="E2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01218"
FT   REGION          50..146
FT                   /note="GFLD subdomain"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   REGION          154..212
FT                   /note="CuBD subdomain"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   REGION          214..287
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          285..305
FT                   /note="O-glycosylated at three sites"
FT   REGION          310..342
FT                   /note="Heparin-binding"
FT                   /evidence="ECO:0000250"
FT   REGION          410..441
FT                   /note="Heparin-binding"
FT                   /evidence="ECO:0000250"
FT   REGION          442..459
FT                   /note="Collagen-binding"
FT                   /evidence="ECO:0000250"
FT   REGION          492..546
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          632..649
FT                   /note="Interaction with DAB1"
FT                   /evidence="ECO:0000250"
FT   REGION          636..650
FT                   /note="Interaction with DAB2"
FT                   /evidence="ECO:0000250"
FT   MOTIF           604..615
FT                   /note="Basolateral sorting signal"
FT                   /evidence="ECO:0000250"
FT   MOTIF           640..643
FT                   /note="Clathrin-binding"
FT                   /evidence="ECO:0000255"
FT   MOTIF           640..643
FT                   /note="NPXY motif; contains endocytosis signal"
FT   COMPBIAS        531..545
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         174
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P05067"
FT   BINDING         206
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P05067"
FT   BINDING         209
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P05067"
FT   BINDING         210
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P05067"
FT   BINDING         561
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P05067"
FT   BINDING         561
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P05067"
FT   SITE            620..621
FT                   /note="Cleavage; by caspase-3"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        215
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:19838169"
FT   CARBOHYD        227
FT                   /note="O-linked (GalNAc...) serine"
FT                   /evidence="ECO:0000305|PubMed:19838169"
FT   CARBOHYD        228
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000305|PubMed:19838169"
FT   CARBOHYD        337
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        461
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        551
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        60..84
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   DISULFID        95..140
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   DISULFID        120..128
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   DISULFID        156..210
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   DISULFID        167..197
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   DISULFID        181..209
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT   VAR_SEQ         517
FT                   /note="D -> DA (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_039100"
FT   MUTAGEN         426
FT                   /note="H->A: Reduced affinity for heparin. Reduces
FT                   homodimerization."
FT                   /evidence="ECO:0000269|PubMed:21574595"
FT   MUTAGEN         429
FT                   /note="R->A: Strongly reduced affinity for heparin.
FT                   Strongly reduced homodimerization."
FT                   /evidence="ECO:0000269|PubMed:21574595"
FT   MUTAGEN         433
FT                   /note="H->A: Reduced affinity for heparin. Reduces
FT                   homodimerization."
FT                   /evidence="ECO:0000269|PubMed:21574595"
FT   CONFLICT        48
FT                   /note="A -> P (in Ref. 1; AAB96331)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        78
FT                   /note="P -> S (in Ref. 4; BC013850)"
FT                   /evidence="ECO:0000305"
FT   HELIX           293..298
FT                   /evidence="ECO:0007829|PDB:3PMR"
FT   STRAND          302..304
FT                   /evidence="ECO:0007829|PDB:4RDA"
FT   HELIX           306..337
FT                   /evidence="ECO:0007829|PDB:3PMR"
FT   TURN            338..341
FT                   /evidence="ECO:0007829|PDB:3PMR"
FT   HELIX           344..399
FT                   /evidence="ECO:0007829|PDB:3PMR"
FT   STRAND          401..403
FT                   /evidence="ECO:0007829|PDB:3PMR"
FT   HELIX           406..437
FT                   /evidence="ECO:0007829|PDB:3PMR"
FT   HELIX           439..442
FT                   /evidence="ECO:0007829|PDB:3PMR"
FT   TURN            443..445
FT                   /evidence="ECO:0007829|PDB:3PMR"
FT   HELIX           446..467
FT                   /evidence="ECO:0007829|PDB:3PMR"
FT   HELIX           471..485
FT                   /evidence="ECO:0007829|PDB:3PMR"
SQ   SEQUENCE   650 AA;  72176 MW;  B95F0F4D1C5CBAC7 CRC64;
     MGPASPAARG LSRRPGQPPL PLLLPLLLLL LRAQPAIGSL AGGSPGAAEA PGSAQVAGLC
     GRLTLHRDLR TGRWEPDPQR SRRCLRDPQR VLEYCRQMYP ELQIARVEQA TQAIPMERWC
     GGSRSGSCAH PHHQVVPFRC LPGEFVSEAL LVPEGCRFLH QERMDQCESS TRRHQEAQEA
     CSSQGLILHG SGMLLPCGSD RFRGVEYVCC PPPGTPDPSG TAVGDPSTRS WPPGSRVEGA
     EDEEEEESFP QPVDDYFVEP PQAEEEEETV PPPSSHTLAV VGKVTPTPRP TDGVDIYFGM
     PGEISEHEGF LRAKMDLEER RMRQINEVMR EWAMADNQSK NLPKADRQAL NEHFQSILQT
     LEEQVSGERQ RLVETHATRV IALINDQRRA ALEGFLAALQ ADPPQAERVL LALRRYLRAE
     QKEQRHTLRH YQHVAAVDPE KAQQMRFQVH THLQVIEERV NQSLGLLDQN PHLAQELRPQ
     IQELLHSEHL GPSELEAPAP GGSSEDKGGL QPPDSKDDTP MTLPKGSTEQ DAASPEKEKM
     NPLEQYERKV NASVPRGFPF HSSEIQRDEL APAGTGVSRE AVSGLLIMGA GGGSLIVLSM
     LLLRRKKPYG AISHGVVEVD PMLTLEEQQL RELQRHGYEN PTYRFLEERP
//