ID ADA10_BOVIN Reviewed; 748 AA.
AC Q10741; A8E663;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 27-MAR-2024, entry version 192.
DE RecName: Full=Disintegrin and metalloproteinase domain-containing protein 10;
DE Short=ADAM 10;
DE EC=3.4.24.81 {ECO:0000250|UniProtKB:O14672};
DE AltName: Full=Kuzbanian protein homolog;
DE AltName: Full=Mammalian disintegrin-metalloprotease;
DE AltName: Full=Myelin-associated metalloproteinase;
DE AltName: CD_antigen=CD156c;
DE Flags: Precursor;
GN Name=ADAM10; Synonyms=MADM;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=8694785; DOI=10.1042/bj3170045;
RA Howard L., Mitchell S., Lu X., Griffiths S., Glynn P.;
RT "Molecular cloning of MADM: a catalytically active mammalian disintegrin-
RT metalloprotease expressed in various cell types.";
RL Biochem. J. 317:45-50(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 214-233, FUNCTION,
RP SUBCELLULAR LOCATION, ACTIVE SITE, AND MUTAGENESIS OF GLU-384.
RX PubMed=10097139; DOI=10.1073/pnas.96.7.3922;
RA Lammich S., Kojro E., Postina R., Gilbert S., Pfeiffer R., Jasionowski M.,
RA Haass C., Fahrenholz F.;
RT "Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid
RT precursor protein by a disintegrin metalloprotease.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:3922-3927(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Basal ganglia;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP MUTAGENESIS OF 210-ARG--ARG-213, SUBCELLULAR LOCATION, AND CLEAVAGE.
RX PubMed=11481247; DOI=10.1096/fj.01-0007fje;
RA Anders A., Gilbert S., Garten W., Postina R., Fahrenholz F.;
RT "Regulation of the alpha-secretase ADAM10 by its prodomain and proprotein
RT convertases.";
RL FASEB J. 15:1837-1839(2001).
RN [5]
RP INTERACTION WITH TSPAN5; TSPAN10; TSPAN14; TSPAN15; TSPAN17 AND TSPAN33.
RX PubMed=23035126; DOI=10.1074/jbc.m112.416503;
RA Haining E.J., Yang J., Bailey R.L., Khan K., Collier R., Tsai S.,
RA Watson S.P., Frampton J., Garcia P., Tomlinson M.G.;
RT "The TspanC8 subgroup of tetraspanins interacts with A disintegrin and
RT metalloprotease 10 (ADAM10) and regulates its maturation and cell surface
RT expression.";
RL J. Biol. Chem. 287:39753-39765(2012).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 455-646, DISULFIDE BONDS, SUBUNIT,
RP AND MUTAGENESIS OF GLU-573; GLU-578 AND GLU-579.
RX PubMed=16239146; DOI=10.1016/j.cell.2005.08.014;
RA Janes P.W., Saha N., Barton W.A., Kolev M.V., Wimmer-Kleikamp S.H.,
RA Nievergall E., Blobel C.P., Himanen J.P., Lackmann M., Nikolov D.B.;
RT "Adam meets Eph: an ADAM substrate recognition module acts as a molecular
RT switch for ephrin cleavage in trans.";
RL Cell 123:291-304(2005).
RN [7] {ECO:0007744|PDB:5L0Q}
RP X-RAY CRYSTALLOGRAPHY (2.76 ANGSTROMS) OF 455-646, GLYCOSYLATION AT
RP ASN-551, AND DISULFIDE BONDS.
RX PubMed=27503072; DOI=10.1084/jem.20151095;
RA Atapattu L., Saha N., Chheang C., Eissman M.F., Xu K., Vail M.E., Hii L.,
RA Llerena C., Liu Z., Horvay K., Abud H.E., Kusebauch U., Moritz R.L.,
RA Ding B.S., Cao Z., Rafii S., Ernst M., Scott A.M., Nikolov D.B.,
RA Lackmann M., Janes P.W.;
RT "An activated form of ADAM10 is tumor selective and regulates cancer stem-
RT like cells and tumor growth.";
RL J. Exp. Med. 213:1741-1757(2016).
CC -!- FUNCTION: Transmembrane metalloprotease which mediates the ectodomain
CC shedding of a myriad of transmembrane proteins, including adhesion
CC proteins, growth factor precursors and cytokines being essential for
CC development and tissue homeostasis. Associates with six members of the
CC tetraspanin superfamily TspanC8 which regulate its exit from the
CC endoplasmic reticulum and its substrate selectivity (By similarity).
CC Cleaves the membrane-bound precursor of TNF-alpha at '76-Ala-|-Val-77'
CC to its mature soluble form. Responsible for the proteolytical release
CC of soluble JAM3 from endothelial cells surface (By similarity).
CC Responsible for the proteolytic release of several other cell-surface
CC proteins, including heparin-binding epidermal growth-like factor,
CC ephrin-A2, CD44, CDH2 and for constitutive and regulated alpha-
CC secretase cleavage of amyloid precursor protein (APP)
CC (PubMed:10097139). Contributes to the normal cleavage of the cellular
CC prion protein. Involved in the cleavage of the adhesion molecule L1 at
CC the cell surface and in released membrane vesicles, suggesting a
CC vesicle-based protease activity (By similarity). Controls also the
CC proteolytic processing of Notch and mediates lateral inhibition during
CC neurogenesis (By similarity). Responsible for the FasL ectodomain
CC shedding and for the generation of the remnant ADAM10-processed FasL
CC (FasL APL) transmembrane form. Also cleaves the ectodomain of the
CC integral membrane proteins CORIN and ITM2B (By similarity). Mediates
CC the proteolytic cleavage of LAG3, leading to release the secreted form
CC of LAG3 (By similarity). Mediates the proteolytic cleavage of IL6R and
CC IL11RA, leading to the release of secreted forms of IL6R and IL11RA (By
CC similarity). Enhances the cleavage of CHL1 by BACE1 (By similarity).
CC Cleaves NRCAM (By similarity). Cleaves TREM2, resulting in shedding of
CC the TREM2 ectodomain (By similarity). Involved in the development and
CC maturation of glomerular and coronary vasculature (By similarity).
CC During development of the cochlear organ of Corti, promotes pillar cell
CC separation by forming a ternary complex with CADH1 and EPHA4 and
CC cleaving CADH1 at adherens junctions (By similarity). May regulate the
CC EFNA5-EPHA3 signaling (By similarity). Regulates leukocyte
CC transmigration as a sheddase for the adherens junction protein VE-
CC cadherin/CDH5 in endothelial cells (By similarity).
CC {ECO:0000250|UniProtKB:O14672, ECO:0000250|UniProtKB:O35598,
CC ECO:0000269|PubMed:10097139}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endopeptidase of broad specificity.; EC=3.4.24.81;
CC Evidence={ECO:0000250|UniProtKB:O14672};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:O14672};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:O14672};
CC -!- ACTIVITY REGULATION: Catalytically inactive when the propeptide is
CC intact and associated with the mature enzyme (PubMed:11481247). The
CC disintegrin and cysteine-rich regions modulate access of substrates to
CC exerts an inhibitory effect on the cleavage of ADAM10 substrates (By
CC similarity). {ECO:0000250|UniProtKB:O14672,
CC ECO:0000269|PubMed:11481247}.
CC -!- SUBUNIT: Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5
CC extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3
CC complex internalization and function, the cleavage occurs in trans,
CC with ADAM10 and its substrate being on the membranes of opposing cells
CC (PubMed:16239146). Interacts with the clathrin adapter AP2 complex
CC subunits AP2A1, AP2A2, AP2B1, and AP2M1; this interaction facilitates
CC ADAM10 endocytosis from the plasma membrane during long-term
CC potentiation in hippocampal neurons (By similarity). Forms a ternary
CC complex composed of ADAM10, EPHA4 and CADH1; within the complex, ADAM10
CC cleaves CADH1 which disrupts adherens junctions (By similarity).
CC Interacts with EPHA2 (By similarity). Interacts with NGF in a divalent
CC cation-dependent manner. Interacts with TSPAN14; the interaction
CC promotes ADAM10 maturation and cell surface expression. Interacts with
CC TSPAN5, TSPAN10, TSPAN14, TSPAN15, TSPAN17 and TSPAN33; these
CC interactions regulate ADAM10 substrate specificity, endocytosis and
CC turnover (PubMed:23035126). Interacts (via extracellular domain) with
CC TSPAN33 (via extracellular domain) and (via cytoplasmic domain) with
CC AFDN; interaction with TSPAN33 allows the docking of ADAM10 to zonula
CC adherens through a PDZ11-dependent interaction between TSPAN33 and
CC PLEKHA7 while interaction with AFDN locks ADAM10 at zonula adherens (By
CC similarity). Interacts with DLG1; this interaction recruits ADAM10 to
CC the cell membrane during long-term depression in hippocampal neurons
CC (By similarity). Interacts (via extracellular domain) with BACE1 (via
CC extracellular domain) (By similarity). Interacts with FAM171A1 (By
CC similarity). {ECO:0000250|UniProtKB:O14672,
CC ECO:0000250|UniProtKB:O35598, ECO:0000269|PubMed:16239146,
CC ECO:0000269|PubMed:23035126}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:10097139}; Single-pass type I membrane protein
CC {ECO:0000305}. Cell membrane {ECO:0000269|PubMed:10097139,
CC ECO:0000269|PubMed:11481247}; Single-pass type I membrane protein
CC {ECO:0000305}. Cytoplasmic vesicle, clathrin-coated vesicle
CC {ECO:0000250|UniProtKB:O14672}. Cell projection, axon
CC {ECO:0000250|UniProtKB:O35598}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:O35598}. Cell junction, adherens junction
CC {ECO:0000250|UniProtKB:O14672}. Cytoplasm
CC {ECO:0000250|UniProtKB:O14672}. Note=Is localized in the plasma
CC membrane but is also expressed in the Golgi apparatus and in clathrin-
CC coated vesicles derived likely from the Golgi (By similarity). During
CC long term depression, it is recruited to the cell membrane by DLG1 (By
CC similarity). The immature form is mainly located near cytoplasmic
CC fibrillar structures, while the mature form is predominantly located at
CC zonula adherens and the cell membrane (By similarity). The localization
CC and clustering of mature ADAM10 to zonula adherens is regulated by
CC AFDN, TSPAN33, PLEKHA7 and PDZD11 (By similarity).
CC {ECO:0000250|UniProtKB:O14672, ECO:0000250|UniProtKB:O35598}.
CC -!- TISSUE SPECIFICITY: Expressed at low level in kidney, spleen, lung,
CC adrenal, heart and peripheral nerve.
CC -!- INDUCTION: By interleukin-1 alpha in nasal cartilage.
CC -!- DOMAIN: The Cys-rich region C-terminal to the disintegrin domain
CC functions as a substrate-recognition module, it recognizes the EFNA5-
CC EPHA3 Complex but not the individual proteins PubMed:16239146. Both
CC Cys-rich and stalk region are necessary for interaction with TSPAN5,
CC TSPAN10, TSPAN14, TSPAN17, TSPAN33 (By similarity). Stalk region is
CC sufficient for interaction with TSPAN15 (By similarity).
CC {ECO:0000250|UniProtKB:O35598, ECO:0000269|PubMed:16239146}.
CC -!- DOMAIN: The propeptide keeps the metalloprotease in a latent form via a
CC cysteine switch mechanism. This mechanism may be mediated by a highly
CC conserved cysteine (Cys-173) in the propeptide, which interacts and
CC neutralizes the zinc-coordinating HEXGHXXGXXHD catalytic core of the
CC metalloprotease domain. The dissociation of the cysteine from the zinc
CC ion upon the activation-peptide release activates the enzyme.
CC {ECO:0000250|UniProtKB:P03956}.
CC -!- PTM: The precursor is cleaved by furin and PCSK7.
CC {ECO:0000269|PubMed:11481247}.
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DR EMBL; Z21961; CAA79973.1; -; mRNA.
DR EMBL; BC153863; AAI53864.1; -; mRNA.
DR PIR; S66129; S66129.
DR RefSeq; NP_776921.1; NM_174496.2.
DR PDB; 2AO7; X-ray; 2.90 A; A=455-646.
DR PDB; 5L0Q; X-ray; 2.76 A; A/D=455-646.
DR PDB; 8GH4; X-ray; 3.80 A; E=455-646.
DR PDBsum; 2AO7; -.
DR PDBsum; 5L0Q; -.
DR PDBsum; 8GH4; -.
DR AlphaFoldDB; Q10741; -.
DR SMR; Q10741; -.
DR DIP; DIP-48422N; -.
DR IntAct; Q10741; 5.
DR STRING; 9913.ENSBTAP00000056919; -.
DR MEROPS; M12.210; -.
DR GlyCosmos; Q10741; 4 sites, No reported glycans.
DR PaxDb; 9913-ENSBTAP00000042110; -.
DR PeptideAtlas; Q10741; -.
DR ABCD; Q10741; 1 sequenced antibody.
DR Ensembl; ENSBTAT00000075105.1; ENSBTAP00000056919.1; ENSBTAG00000005481.6.
DR GeneID; 282132; -.
DR KEGG; bta:282132; -.
DR CTD; 102; -.
DR VEuPathDB; HostDB:ENSBTAG00000005481; -.
DR VGNC; VGNC:25604; ADAM10.
DR eggNOG; KOG3658; Eukaryota.
DR GeneTree; ENSGT00940000160579; -.
DR HOGENOM; CLU_004602_0_0_1; -.
DR InParanoid; Q10741; -.
DR OMA; CRKVDAD; -.
DR OrthoDB; 5395001at2759; -.
DR TreeFam; TF352021; -.
DR Reactome; R-BTA-1474228; Degradation of the extracellular matrix.
DR Reactome; R-BTA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-BTA-6798695; Neutrophil degranulation.
DR Reactome; R-BTA-8957275; Post-translational protein phosphorylation.
DR EvolutionaryTrace; Q10741; -.
DR Proteomes; UP000009136; Chromosome 10.
DR Bgee; ENSBTAG00000005481; Expressed in conceptus and 111 other cell types or tissues.
DR ExpressionAtlas; Q10741; baseline and differential.
DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005798; C:Golgi-associated vesicle; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0046930; C:pore complex; IEA:Ensembl.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0097060; C:synaptic membrane; IBA:GO_Central.
DR GO; GO:0097197; C:tetraspanin-enriched microdomain; IEA:Ensembl.
DR GO; GO:0004175; F:endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070573; F:metallodipeptidase activity; IEA:Ensembl.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:ARUK-UCL.
DR GO; GO:1902945; F:metalloendopeptidase activity involved in amyloid precursor protein catabolic process; IDA:ARUK-UCL.
DR GO; GO:0008237; F:metallopeptidase activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0034332; P:adherens junction organization; IEA:Ensembl.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; IDA:ARUK-UCL.
DR GO; GO:0090102; P:cochlea development; IEA:Ensembl.
DR GO; GO:0051089; P:constitutive protein ectodomain proteolysis; IEA:Ensembl.
DR GO; GO:0038004; P:epidermal growth factor receptor ligand maturation; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; ISS:UniProtKB.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; ISS:UniProtKB.
DR GO; GO:0042117; P:monocyte activation; IEA:Ensembl.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0046931; P:pore complex assembly; IEA:Ensembl.
DR GO; GO:0030307; P:positive regulation of cell growth; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; IEA:Ensembl.
DR GO; GO:0099173; P:postsynapse organization; IEA:Ensembl.
DR GO; GO:0140249; P:protein catabolic process at postsynapse; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0016485; P:protein processing; IDA:ARUK-UCL.
DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; IEA:Ensembl.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0099175; P:regulation of postsynapse organization; IEA:Ensembl.
DR GO; GO:1901342; P:regulation of vasculature development; IEA:Ensembl.
DR GO; GO:0034612; P:response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:1901998; P:toxin transport; IEA:Ensembl.
DR CDD; cd04270; ZnMc_TACE_like; 1.
DR Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1.
DR Gene3D; 4.10.70.10; Disintegrin domain; 1.
DR InterPro; IPR034025; ADAM10_ADAM17.
DR InterPro; IPR049038; ADAM10_Cys-rich.
DR InterPro; IPR001762; Disintegrin_dom.
DR InterPro; IPR036436; Disintegrin_dom_sf.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001590; Peptidase_M12B.
DR PANTHER; PTHR45702; ADAM10/ADAM17 METALLOPEPTIDASE FAMILY MEMBER; 1.
DR PANTHER; PTHR45702:SF4; DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 10; 1.
DR Pfam; PF21299; ADAM10_Cys-rich; 1.
DR Pfam; PF00200; Disintegrin; 1.
DR Pfam; PF13574; Reprolysin_2; 1.
DR SMART; SM00050; DISIN; 1.
DR SUPFAM; SSF57552; Blood coagulation inhibitor (disintegrin); 1.
DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS50214; DISINTEGRIN_2; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell junction; Cell membrane; Cell projection;
KW Cleavage on pair of basic residues; Cytoplasm; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Golgi apparatus;
KW Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Notch signaling pathway; Phosphoprotein; Protease; Reference proteome;
KW SH3-binding; Signal; Transmembrane; Transmembrane helix; Zinc; Zymogen.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..213
FT /evidence="ECO:0000269|PubMed:10097139,
FT ECO:0000269|PubMed:11481247"
FT /id="PRO_0000029064"
FT CHAIN 214..748
FT /note="Disintegrin and metalloproteinase domain-containing
FT protein 10"
FT /id="PRO_0000029065"
FT TOPO_DOM 20..672
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 673..696
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 697..748
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 220..456
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 457..551
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT REGION 704..748
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 734..748
FT /note="Interaction with AP2A1, AP2A2 and AP2M1"
FT /evidence="ECO:0000250|UniProtKB:O35598"
FT MOTIF 171..178
FT /note="Cysteine switch"
FT MOTIF 708..715
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT MOTIF 722..728
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 706..722
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 384
FT /evidence="ECO:0000269|PubMed:10097139"
FT BINDING 173
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /note="in inhibited form"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 383
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT BINDING 387
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT BINDING 393
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT SITE 213..214
FT /note="Cleavage; by furin and PCSK7"
FT /evidence="ECO:0000269|PubMed:11481247"
FT MOD_RES 719
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT CARBOHYD 267
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 278
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 439
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 551
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PDB:5L0Q"
FT DISULFID 344..451
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 399..435
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 460..495
FT /evidence="ECO:0000269|PubMed:27503072,
FT ECO:0007744|PDB:5L0Q"
FT DISULFID 471..484
FT /evidence="ECO:0000269|PubMed:27503072,
FT ECO:0007744|PDB:5L0Q"
FT DISULFID 473..479
FT /evidence="ECO:0000269|PubMed:27503072,
FT ECO:0007744|PDB:5L0Q"
FT DISULFID 483..515
FT /evidence="ECO:0000269|PubMed:27503072,
FT ECO:0007744|PDB:5L0Q"
FT DISULFID 503..511
FT /evidence="ECO:0000269|PubMed:16239146,
FT ECO:0000269|PubMed:27503072, ECO:0007744|PDB:2AO7,
FT ECO:0007744|PDB:5L0Q"
FT DISULFID 510..536
FT /evidence="ECO:0000269|PubMed:16239146,
FT ECO:0000269|PubMed:27503072, ECO:0007744|PDB:2AO7,
FT ECO:0007744|PDB:5L0Q"
FT DISULFID 524..543
FT /evidence="ECO:0000269|PubMed:16239146,
FT ECO:0000269|PubMed:27503072, ECO:0007744|PDB:2AO7,
FT ECO:0007744|PDB:5L0Q"
FT DISULFID 530..562
FT /evidence="ECO:0000269|PubMed:16239146,
FT ECO:0000269|PubMed:27503072, ECO:0007744|PDB:2AO7,
FT ECO:0007744|PDB:5L0Q"
FT DISULFID 555..567
FT /evidence="ECO:0000269|PubMed:16239146,
FT ECO:0000269|PubMed:27503072, ECO:0007744|PDB:2AO7,
FT ECO:0007744|PDB:5L0Q"
FT DISULFID 572..598
FT /evidence="ECO:0000269|PubMed:16239146,
FT ECO:0000269|PubMed:27503072, ECO:0007744|PDB:2AO7,
FT ECO:0007744|PDB:5L0Q"
FT DISULFID 580..607
FT /evidence="ECO:0000269|PubMed:16239146,
FT ECO:0000269|PubMed:27503072, ECO:0007744|PDB:2AO7,
FT ECO:0007744|PDB:5L0Q"
FT DISULFID 582..597
FT /evidence="ECO:0000269|PubMed:16239146,
FT ECO:0000269|PubMed:27503072, ECO:0007744|PDB:2AO7,
FT ECO:0007744|PDB:5L0Q"
FT DISULFID 594..639
FT /evidence="ECO:0000269|PubMed:16239146,
FT ECO:0000269|PubMed:27503072, ECO:0007744|PDB:2AO7,
FT ECO:0007744|PDB:5L0Q"
FT DISULFID 632..645
FT /evidence="ECO:0000269|PubMed:16239146,
FT ECO:0000269|PubMed:27503072, ECO:0007744|PDB:2AO7,
FT ECO:0007744|PDB:5L0Q"
FT MUTAGEN 210..213
FT /note="RKKR->NAQA: Abolishes furin cleavage site, leading
FT to defects in pro."
FT /evidence="ECO:0000269|PubMed:11481247"
FT MUTAGEN 384
FT /note="E->A: Decreased stimulated and constitutive
FT secretion of APP."
FT /evidence="ECO:0000269|PubMed:10097139"
FT MUTAGEN 573
FT /note="E->A: Abrogates EFNA5 cleavage; when associated with
FT Ala-578 and 579."
FT /evidence="ECO:0000269|PubMed:16239146"
FT MUTAGEN 578
FT /note="E->A: Abrogates EFNA5 cleavage; when associated with
FT Ala-573 and 579."
FT /evidence="ECO:0000269|PubMed:16239146"
FT MUTAGEN 579
FT /note="E->A: Abrogates EFNA5 cleavage; when associated with
FT Ala-573 and 578."
FT /evidence="ECO:0000269|PubMed:16239146"
FT TURN 476..478
FT /evidence="ECO:0007829|PDB:5L0Q"
FT STRAND 482..484
FT /evidence="ECO:0007829|PDB:5L0Q"
FT STRAND 487..489
FT /evidence="ECO:0007829|PDB:5L0Q"
FT TURN 505..507
FT /evidence="ECO:0007829|PDB:5L0Q"
FT STRAND 523..525
FT /evidence="ECO:0007829|PDB:5L0Q"
FT STRAND 529..531
FT /evidence="ECO:0007829|PDB:5L0Q"
FT TURN 556..559
FT /evidence="ECO:0007829|PDB:5L0Q"
FT STRAND 563..566
FT /evidence="ECO:0007829|PDB:5L0Q"
FT HELIX 571..574
FT /evidence="ECO:0007829|PDB:5L0Q"
FT STRAND 578..580
FT /evidence="ECO:0007829|PDB:5L0Q"
FT HELIX 591..594
FT /evidence="ECO:0007829|PDB:5L0Q"
FT STRAND 597..600
FT /evidence="ECO:0007829|PDB:5L0Q"
FT HELIX 604..606
FT /evidence="ECO:0007829|PDB:5L0Q"
FT HELIX 616..619
FT /evidence="ECO:0007829|PDB:5L0Q"
FT TURN 633..636
FT /evidence="ECO:0007829|PDB:5L0Q"
FT STRAND 637..639
FT /evidence="ECO:0007829|PDB:5L0Q"
SQ SEQUENCE 748 AA; 84188 MW; 202E29830611F9E1 CRC64;
MVLLRVLILL LSWVAGLGGQ YGNPLNKYIR HYEGLSYDVD SLHQKHQRAK RAVSHEDQFL
RLDFHAHGRH FNLRMKRDTS LFSEEFRVET SNAVLDYDTS HIYTGHIYGE EGSFSHGSVI
DGRFEGFIQT HGGTFYVEPA ERYIKDRTLP FHSVIYHEDD IKYPHKYGPQ GGCADHSVFE
RMRKYQMTGV EEVTQTPQEK HAINGPELLR KKRTTVAEKN TCQLYIQTDH LFFKYYGTRE
AVIAQISSHV KAIDTIYQTT DFSGIRNISF MVKRIRINTT ADEKDPTNPF RFPNIGVEKF
LELNSEQNHD DYCLAYVFTD RDFDDGVLGL AWVGAPSGSS GGICEKSKLY SDGKKKSLNT
GIITVQNYGS HVPPKVSHIT FAHEVGHNFG SPHDSGTECT PGESKNLGQK ENGNYIMYAR
ATSGDKLNNN KFSLCSIRNI SQVLEKKRNN CFVESGQPIC GNGMVEQGEE CDCGYSDQCK
DECCYDANQP EGKKCKLKPG KQCSPSQGPC CTAHCAFKSK TEKCRDDSDC AKEGICNGIT
ALCPASDPKP NFTDCNRHTQ VCINGQCAGS ICEKHGLEEC TCASSDGKDD KELCHVCCMK
KMEPSTCAST GSVQWNKYFL GRTITLQPGS PCNDFRGYCD VFMRCRLVDA DGPLARLKKA
IFSPELYENI AEWIVAYWWA VLLMGIALIM LMAGFIKICS VHTPSSNPKL PPPKPLPGTL
KRRRPPQPIQ QPQRQRPRES YQMGHMRR
//
