ADA10_RAT
ID ADA10_RAT Reviewed; 749 AA.
AC Q10743; A0A0G2K562;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2018, sequence version 2.
DT 03-AUG-2022, entry version 166.
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: CD_antigen=CD156c;
DE Flags: Precursor;
GN Name=Adam10; Synonyms=Madm;
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].
RC STRAIN=Sprague-Dawley; 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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-279 AND ASN-440, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24090084; DOI=10.1021/pr400783j;
RA Parker B.L., Thaysen-Andersen M., Solis N., Scott N.E., Larsen M.R.,
RA Graham M.E., Packer N.H., Cordwell S.J.;
RT "Site-specific glycan-peptide analysis for determination of N-glycoproteome
RT heterogeneity.";
RL J. Proteome Res. 12:5791-5800(2013).
CC -!- FUNCTION: Cleaves the membrane-bound precursor of TNF-alpha to its
CC mature soluble form. Responsible for the proteolytical release of
CC soluble JAM3 from endothelial cells surface. Responsible for the
CC proteolytic release of several other cell-surface proteins, including
CC heparin-binding epidermal growth-like factor, ephrin-A2, CD44, CDH2 and
CC for constitutive and regulated alpha-secretase cleavage of amyloid
CC precursor protein (APP). Contributes to the normal cleavage of the
CC cellular prion protein. Involved in the cleavage of the adhesion
CC molecule L1 at the cell surface and in released membrane vesicles,
CC suggesting a vesicle-based protease activity. Controls also the
CC proteolytic processing of Notch and mediates lateral inhibition during
CC neurogenesis. Responsible for the FasL ectodomain shedding and for the
CC generation of the remnant ADAM10-processed FasL (FasL APL)
CC transmembrane form. Also cleaves the ectodomain of the integral
CC membrane proteins CORIN and ITM2B. Mediates the proteolytic cleavage of
CC LAG3, leading to release the secreted form of LAG3 (By similarity).
CC Mediates the proteolytic cleavage of IL6R and IL11RA, leading to the
CC release of secreted forms of IL6R and IL11RA (By similarity). Enhances
CC the cleavage of CHL1 by BACE1 (By similarity). Cleaves NRCAM (By
CC similarity). Cleaves TREM2, resulting in shedding of the TREM2
CC ectodomain (By similarity). Involved in the development and maturation
CC of glomerular and coronary vasculature (By similarity). During
CC 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). {ECO:0000250|UniProtKB:O14672,
CC ECO:0000250|UniProtKB:O35598}.
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 (By similarity). 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:0000250|UniProtKB:Q10741}.
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 (By similarity). Interacts with
CC the clathrin adapter AP2 complex subunits AP2A1, AP2A2, AP2B1, and
CC AP2M1; this interaction facilitates ADAM10 endocytosis from the plasma
CC membrane during long-term potentiation in hippocampal neurons (By
CC similarity). Interacts with EPHA2 (By similarity). Interacts (via
CC extracellular domain) with TSPAN33 (via extracellular domain) and (via
CC cytoplasmic domain) with AFDN; interaction with TSPAN33 allows the
CC docking of ADAM10 to zonula adherens through a PDZ11-dependent
CC interaction between TSPAN33 and PLEKHA7 while interaction with AFDN
CC locks ADAM10 at zonula adherens (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 NGF in a divalent cation-dependent manner (By
CC similarity). Interacts with TSPAN14; the interaction promotes ADAM10
CC maturation and cell surface expression (By similarity). Interacts with
CC TSPAN5, TSPAN10, TSPAN15, TSPAN17 and TSPAN33; these interactions
CC regulate ADAM10 substrate specificity (By similarity). Interacts with
CC DLG1; this interaction recruits ADAM10 to the cell membrane during
CC long-term depression in hippocampal neurons (By similarity). Interacts
CC (via extracellular domain) with BACE1 (via extracellular domain) (By
CC similarity). Interacts with FAM171A1 (By similarity).
CC {ECO:0000250|UniProtKB:O14672, ECO:0000250|UniProtKB:O35598,
CC ECO:0000250|UniProtKB:Q10741}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O14672};
CC Single-pass type I membrane protein {ECO:0000305}. Golgi apparatus
CC membrane {ECO:0000250|UniProtKB:O14672}; Single-pass type I membrane
CC protein {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 in brain, kidney, lung, spleen, ovary and
CC testis.
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. Both Cys-rich and stalk
CC region are necessary for interaction with TSPAN5, TSPAN10, TSPAN14,
CC TSPAN17, TSPAN33. Stalk region is sufficient for interaction with
CC TSPAN15. {ECO:0000250|UniProtKB:P62080, ECO:0000250|UniProtKB:Q10741}.
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:0000250|UniProtKB:Q10741}.
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DR EMBL; Z48444; CAA88359.1; -; mRNA.
DR EMBL; AABR07070609; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH474041; EDL84174.1; -; Genomic_DNA.
DR EMBL; AABR07070614; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07070613; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07070612; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07070611; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07070610; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; S52477; S52477.
DR RefSeq; NP_062127.1; NM_019254.1.
DR AlphaFoldDB; Q10743; -.
DR SMR; Q10743; -.
DR STRING; 10116.ENSRNOP00000021066; -.
DR MEROPS; M12.210; -.
DR GlyGen; Q10743; 4 sites.
DR iPTMnet; Q10743; -.
DR PhosphoSitePlus; Q10743; -.
DR SwissPalm; Q10743; -.
DR PaxDb; Q10743; -.
DR Ensembl; ENSRNOT00000083255; ENSRNOP00000073306; ENSRNOG00000054257.
DR GeneID; 29650; -.
DR KEGG; rno:29650; -.
DR UCSC; RGD:2032; rat.
DR CTD; 102; -.
DR RGD; 2032; Adam10.
DR eggNOG; KOG3658; Eukaryota.
DR GeneTree; ENSGT00940000160579; -.
DR InParanoid; Q10743; -.
DR OMA; GICERYK; -.
DR OrthoDB; 162519at2759; -.
DR PhylomeDB; Q10743; -.
DR BRENDA; 3.4.24.81; 5301.
DR Reactome; R-RNO-1474228; Degradation of the extracellular matrix.
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-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR Reactome; R-RNO-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus.
DR PRO; PR:Q10743; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Proteomes; UP000234681; Chromosome 8.
DR Bgee; ENSRNOG00000054257; Expressed in ileum and 19 other tissues.
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; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:SynGO-UCL.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
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:0016020; C:membrane; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0046930; C:pore complex; ISO:RGD.
DR GO; GO:0098794; C:postsynapse; IDA:RGD.
DR GO; GO:0014069; C:postsynaptic density; ISO:RGD.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:SynGO-UCL.
DR GO; GO:0097060; C:synaptic membrane; ISO:RGD.
DR GO; GO:0008021; C:synaptic vesicle; IDA:RGD.
DR GO; GO:0097197; C:tetraspanin-enriched microdomain; ISO:RGD.
DR GO; GO:0005802; C:trans-Golgi network; IDA:RGD.
DR GO; GO:0004175; F:endopeptidase activity; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070573; F:metallodipeptidase activity; ISO:RGD.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:RGD.
DR GO; GO:1902945; F:metalloendopeptidase activity involved in amyloid precursor protein catabolic process; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; ISO:RGD.
DR GO; GO:0034205; P:amyloid-beta formation; IMP:SynGO-UCL.
DR GO; GO:0090102; P:cochlea development; ISO:RGD.
DR GO; GO:0051089; P:constitutive protein ectodomain proteolysis; ISO:RGD.
DR GO; GO:0038004; P:epidermal growth factor receptor ligand maturation; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0007219; P:Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0046931; P:pore complex assembly; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:0030307; P:positive regulation of cell growth; ISO:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; ISO:RGD.
DR GO; GO:0099173; P:postsynapse organization; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0016485; P:protein processing; ISO:RGD.
DR GO; GO:0061001; P:regulation of dendritic spine morphogenesis; IMP:RGD.
DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; ISO:RGD.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; ISO:RGD.
DR GO; GO:0045670; P:regulation of osteoclast differentiation; NAS:RGD.
DR GO; GO:1901342; P:regulation of vasculature development; ISO:RGD.
DR GO; GO:0097327; P:response to antineoplastic agent; IEP:RGD.
DR GO; GO:0034612; P:response to tumor necrosis factor; ISO:RGD.
DR GO; GO:0140448; P:signaling receptor ligand precursor processing; ISO:RGD.
DR GO; GO:0007283; P:spermatogenesis; IEP:RGD.
DR GO; GO:1901998; P:toxin transport; ISO:RGD.
DR CDD; cd04270; ZnMc_TACE_like; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR Gene3D; 4.10.70.10; -; 1.
DR InterPro; IPR034025; ADAM10_ADAM17.
DR InterPro; IPR027053; ADAM_10.
DR InterPro; IPR001762; Disintegrin_dom.
DR InterPro; IPR036436; Disintegrin_dom_sf.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001590; Peptidase_M12B.
DR InterPro; IPR002870; Peptidase_M12B_N.
DR PANTHER; PTHR45702:SF4; PTHR45702:SF4; 1.
DR Pfam; PF00200; Disintegrin; 1.
DR Pfam; PF01562; Pep_M12B_propep; 1.
DR SMART; SM00050; DISIN; 1.
DR SUPFAM; SSF57552; SSF57552; 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 Cell junction; Cell membrane; Cell projection;
KW Cleavage on pair of basic residues; Cytoplasm; Cytoplasmic vesicle;
KW Disulfide bond; Glycoprotein; Golgi apparatus; Hydrolase; Membrane;
KW Metal-binding; Metalloprotease; Notch signaling pathway; Phosphoprotein;
KW Protease; Reference proteome; SH3-binding; Signal; Transmembrane;
KW Transmembrane helix; Zinc; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..214
FT /evidence="ECO:0000250|UniProtKB:Q10741"
FT /id="PRO_0000029070"
FT CHAIN 215..749
FT /note="Disintegrin and metalloproteinase domain-containing
FT protein 10"
FT /id="PRO_0000029071"
FT TOPO_DOM 215..673
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 674..697
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 698..749
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 221..457
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 458..552
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT REGION 705..749
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 735..749
FT /note="Interaction with AP2A1, AP2A2 and AP2M1"
FT /evidence="ECO:0000250|UniProtKB:O35598"
FT MOTIF 171..178
FT /note="Cysteine switch"
FT MOTIF 709..716
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT MOTIF 723..729
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 707..734
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 385
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
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 384
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT BINDING 388
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT BINDING 394
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT SITE 214..215
FT /note="Cleavage; by furin and PCSK7"
FT /evidence="ECO:0000250|UniProtKB:Q10741"
FT MOD_RES 720
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT CARBOHYD 268
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 279
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PubMed:24090084"
FT CARBOHYD 440
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PubMed:24090084"
FT CARBOHYD 552
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 223..314
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 345..452
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 400..436
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 461..496
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 472..485
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 474..480
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 484..516
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 504..512
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 511..537
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 525..544
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 531..563
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 556..568
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 573..599
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 581..608
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 583..598
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 595..640
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 633..646
FT /evidence="ECO:0000250|UniProtKB:O14672"
SQ SEQUENCE 749 AA; 84087 MW; 7E506394D93A3095 CRC64;
MVLPTVLILL LSWAAGLGGQ YGNPLNKYIR HYEGLSYNVD SLHQKHQRAK RAVSHEDQFL
LLDFHAHGRQ FNLRMKRDTS LFSDEFKVET SNKVLDYDTS HIYTGHIYGE EGSFSHGSVV
DGRFEGFIQT RGGTFYIEPA ERYIKDRILP FHSVIYHEDD INYPHKYGPQ GGCADHSVFE
RMRKYQMTGV EEGTRAHSEE HAASMGPELL RKKRTTLAER NTCQLYIQTD HLFFKYYGTR
EAVIAQISSH VKAIDTIYQT TDFSGIRNIS FMVKRIRINT TSDEKDPTNP FRFPNIGVEK
FLELNSEQNH DDYCLAYVFT DRDFDDGVLG LAWVGAPSGS SGGICEKSKL YSDGKKKSLN
TGIITVQNYG SHVPPKVSHI TFAHEVGHNF GSPHDSGTEC TPGESKNLGQ KENGNYIMYA
RATSGDKLNN NKFSLCSIRN ISQVLEKKRN NCFVESGQPI CGNGMVEQGE ECDCGYSDQC
KDECCFDANQ PEGKKCKLKP GKQCSPSQGP CCTAQCAFKS KSEKCRDDSD CAKEGICNGF
TALCPASDPK PNFTDCNRHT QVCINGQCAG SICEKYDLEE CTCASSDGKD DKELCHVCCM
KKMAPSTCAS TGSLQWNKQF NGRTITLQPG SPCNDFRGYC DVFMRCRLVD ADGPLARLKK
AIFSPQLYEN IAEWIVAHWW AVLLMGIALI MLMAGFIKIC SVHTPSSNPK LPPPKPLPGT
LKRRRPPQPI QQPPRQRPRE SYQMGHMRR
