ADA10_MOUSE
ID ADA10_MOUSE Reviewed; 749 AA.
AC O35598; B8JJJ0;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Disintegrin and metalloproteinase domain-containing protein 10;
DE Short=ADAM 10;
DE EC=3.4.24.81 {ECO:0000269|PubMed:17245433, ECO:0000269|PubMed:29325091, ECO:0000269|PubMed:29430990, ECO:0000269|PubMed:30639848};
DE AltName: Full=Kuzbanian protein homolog;
DE AltName: Full=Mammalian disintegrin-metalloprotease;
DE AltName: CD_antigen=CD156c;
DE Flags: Precursor;
GN Name=Adam10; Synonyms=Kuz, Madm;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=9244301; DOI=10.1016/s0092-8674(00)80335-9;
RA Pan D., Rubin G.M.;
RT "Kuzbanian controls proteolytic processing of Notch and mediates lateral
RT inhibition during Drosophila and vertebrate neurogenesis.";
RL Cell 90:271-280(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 252-749.
RC STRAIN=C57BL/6J; TISSUE=Bone, and Vagina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP INTERACTION WITH EPHA2.
RX PubMed=10958785; DOI=10.1126/science.289.5483.1360;
RA Hattori M., Osterfield M., Flanagan J.G.;
RT "Regulated cleavage of a contact-mediated axon repellent.";
RL Science 289:1360-1365(2000).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=17245433; DOI=10.1038/sj.emboj.7601520;
RA Li N., Wang Y., Forbes K., Vignali K.M., Heale B.S., Saftig P.,
RA Hartmann D., Black R.A., Rossi J.J., Blobel C.P., Dempsey P.J.,
RA Workman C.J., Vignali D.A.;
RT "Metalloproteases regulate T-cell proliferation and effector function via
RT LAG-3.";
RL EMBO J. 26:494-504(2007).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-279.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-720, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP INTERACTION WITH TSPAN5; TSPAN10; TSPAN15; TSPAN14; 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 [10]
RP INTERACTION WITH AP2A1; AP2A2; AP2B1; AP2M1 AND DLG1, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND MUTAGENESIS OF 735-ARG--ARG-737 AND GLN-736.
RX PubMed=23676497; DOI=10.1172/jci65401;
RA Marcello E., Saraceno C., Musardo S., Vara H., de la Fuente A.G.,
RA Pelucchi S., Di Marino D., Borroni B., Tramontano A., Perez-Otano I.,
RA Padovani A., Giustetto M., Gardoni F., Di Luca M.;
RT "Endocytosis of synaptic ADAM10 in neuronal plasticity and Alzheimer's
RT disease.";
RL J. Clin. Invest. 123:2523-2538(2013).
RN [11]
RP FUNCTION.
RX PubMed=26876177; DOI=10.1016/j.celrep.2016.01.053;
RA Lokau J., Nitz R., Agthe M., Monhasery N., Aparicio-Siegmund S.,
RA Schumacher N., Wolf J., Moeller-Hackbarth K., Waetzig G.H., Groetzinger J.,
RA Mueller-Newen G., Rose-John S., Scheller J., Garbers C.;
RT "Proteolytic Cleavage Governs Interleukin-11 Trans-signaling.";
RL Cell Rep. 14:1761-1773(2016).
RN [12]
RP INTERACTION WITH TSPAN5; TSPAN10; TSPAN15; TSPAN14; TSPAN17 AND TSPAN33,
RP SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=26668317; DOI=10.1074/jbc.m115.703058;
RA Noy P.J., Yang J., Reyat J.S., Matthews A.L., Charlton A.E., Furmston J.,
RA Rogers D.A., Rainger G.E., Tomlinson M.G.;
RT "TspanC8 tetraspanins and A disintegrin and metalloprotease 10 (ADAM10)
RT interact via their extracellular regions: evidence for distinct binding
RT mechanisms for different TspanC8 proteins.";
RL J. Biol. Chem. 291:3145-3157(2016).
RN [13]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29397483; DOI=10.1007/s10456-018-9599-4;
RA Farber G., Hurtado R., Loh S., Monette S., Mtui J., Kopan R., Quaggin S.,
RA Meyer-Schwesinger C., Herzlinger D., Scott R.P., Blobel C.P.;
RT "Glomerular endothelial cell maturation depends on ADAM10, a key regulator
RT of Notch signaling.";
RL Angiogenesis 21:335-347(2018).
RN [14]
RP INTERACTION WITH TSPAN33 AND AFDN, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=30463011; DOI=10.1016/j.celrep.2018.10.088;
RA Shah J., Rouaud F., Guerrera D., Vasileva E., Popov L.M., Kelley W.L.,
RA Rubinstein E., Carette J.E., Amieva M.R., Citi S.;
RT "A Dock-and-Lock Mechanism Clusters ADAM10 at Cell-Cell Junctions to
RT Promote alpha-Toxin Cytotoxicity.";
RL Cell Rep. 25:2132-2147(2018).
RN [15]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=29430990; DOI=10.1096/fj.201700823rr;
RA Brummer T., Pigoni M., Rossello A., Wang H., Noy P.J., Tomlinson M.G.,
RA Blobel C.P., Lichtenthaler S.F.;
RT "The metalloprotease ADAM10 (a disintegrin and metalloprotease 10)
RT undergoes rapid, postlysis autocatalytic degradation.";
RL FASEB J. 32:3560-3573(2018).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH BACE1, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, ACTIVE SITE, AND MUTAGENESIS OF GLU-385.
RX PubMed=29325091; DOI=10.1093/jmcb/mjy001;
RA Wang X., Wang C., Pei G.;
RT "alpha-secretase ADAM10 physically interacts with beta-secretase BACE1 in
RT neurons and regulates CHL1 proteolysis.";
RL J. Mol. Cell Biol. 10:411-422(2018).
RN [17]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30446855; DOI=10.1007/s10456-018-9653-2;
RA Farber G., Parks M.M., Lustgarten Guahmich N., Zhang Y., Monette S.,
RA Blanchard S.C., Di Lorenzo A., Blobel C.P.;
RT "ADAM10 controls the differentiation of the coronary arterial
RT endothelium.";
RL Angiogenesis 22:237-250(2019).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION IN COMPLEX WITH EPHA4 AND
RP CADH1, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=30639848; DOI=10.1016/j.isci.2018.12.017;
RA Defourny J., Peuckert C., Kullander K., Malgrange B.;
RT "EphA4-ADAM10 Interplay Patterns the Cochlear Sensory Epithelium through
RT Local Disruption of Adherens Junctions.";
RL IScience 11:246-257(2019).
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 (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) at '687-Lys-|-
CC Leu-688' (By similarity). Contributes to the normal cleavage of the
CC cellular prion protein (By similarity). Involved in the cleavage of the
CC adhesion molecule L1 at the cell surface and in released membrane
CC vesicles, suggesting a vesicle-based protease activity (By similarity).
CC Controls also the proteolytic processing of Notch and mediates lateral
CC inhibition during neurogenesis (PubMed:9244301). Responsible for the
CC FasL ectodomain shedding and for the generation of the remnant ADAM10-
CC processed FasL (FasL APL) transmembrane form (By similarity). Also
CC cleaves the ectodomain of the integral membrane proteins CORIN and
CC ITM2B (By similarity). Mediates the proteolytic cleavage of LAG3,
CC leading to release the secreted form of LAG3 (PubMed:17245433).
CC Mediates the proteolytic cleavage of IL6R and IL11RA, leading to the
CC release of secreted forms of IL6R and IL11RA (PubMed:26876177).
CC Enhances the cleavage of CHL1 by BACE1 (PubMed:29325091). Cleaves NRCAM
CC (PubMed:29430990). Cleaves TREM2, resulting in shedding of the TREM2
CC ectodomain (By similarity). Involved in the development and maturation
CC of glomerular and coronary vasculature (PubMed:30446855,
CC PubMed:29397483). During development of the cochlear organ of Corti,
CC promotes pillar cell separation by forming a ternary complex with CADH1
CC and EPHA4 and cleaving CADH1 at adherens junctions (PubMed:30639848).
CC May regulate the EFNA5-EPHA3 signaling (By similarity).
CC {ECO:0000250|UniProtKB:O14672, ECO:0000269|PubMed:17245433,
CC ECO:0000269|PubMed:29325091, ECO:0000269|PubMed:29397483,
CC ECO:0000269|PubMed:29430990, ECO:0000269|PubMed:30446855,
CC ECO:0000269|PubMed:30639848, ECO:0000269|PubMed:9244301}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endopeptidase of broad specificity.; EC=3.4.24.81;
CC Evidence={ECO:0000269|PubMed:17245433, ECO:0000269|PubMed:29325091,
CC ECO:0000269|PubMed:29430990, ECO:0000269|PubMed:30639848};
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, the cleavage occurs in trans,
CC with ADAM10 and its substrate being on the membranes of opposing cells
CC (By similarity). 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 (PubMed:23676497). 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 (PubMed:30463011). Forms a ternary
CC complex composed of ADAM10, EPHA4 and CADH1; within the complex, ADAM10
CC cleaves CADH1 which disrupts adherens junctions (PubMed:30639848).
CC Interacts with EPHA2 (PubMed:10958785). Interacts with NGF in a
CC divalent cation-dependent manner (By similarity). Interacts with
CC TSPAN14; the interaction promotes ADAM10 maturation and cell surface
CC expression (PubMed:23035126, PubMed:26668317). Interacts with TSPAN5,
CC TSPAN10, TSPAN15, TSPAN17 and TSPAN33; these interactions regulate
CC ADAM10 substrate specificity (PubMed:23035126, PubMed:26668317).
CC Interacts with DLG1; this interaction recruits ADAM10 to the cell
CC membrane during long-term depression in hippocampal neurons
CC (PubMed:23676497). Interacts (via extracellular domain) with BACE1 (via
CC extracellular domain) (PubMed:29325091). Interacts with FAM171A1 (By
CC similarity). {ECO:0000250|UniProtKB:O14672,
CC ECO:0000269|PubMed:10958785, ECO:0000269|PubMed:23035126,
CC ECO:0000269|PubMed:23676497, ECO:0000269|PubMed:26668317,
CC ECO:0000269|PubMed:29325091, ECO:0000269|PubMed:30463011,
CC ECO:0000269|PubMed:30639848}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23676497,
CC ECO:0000269|PubMed:26668317, ECO:0000269|PubMed:30463011}; Single-pass
CC type I membrane protein {ECO:0000305}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:O14672}; Single-pass type I membrane protein
CC {ECO:0000305}. Cytoplasmic vesicle, clathrin-coated vesicle
CC {ECO:0000250|UniProtKB:O14672}. Cell projection, axon
CC {ECO:0000269|PubMed:29325091}. Cell projection, dendrite
CC {ECO:0000269|PubMed:29325091}. Cell junction, adherens junction
CC {ECO:0000269|PubMed:30463011, ECO:0000269|PubMed:30639848}. Cytoplasm
CC {ECO:0000269|PubMed:30463011}. Note=Is localized in the plasma membrane
CC but is also expressed in the Golgi apparatus and in clathrin-coated
CC vesicles derived likely from the Golgi (By similarity). During long
CC term depression, it is recruited to the cell membrane by DLG1
CC (PubMed:23676497). 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 (PubMed:30463011). The
CC localization and clustering of mature ADAM10 to zonula adherens is
CC regulated by AFDN, TSPAN33, PLEKHA7 and PDZD11 (PubMed:30463011).
CC {ECO:0000250|UniProtKB:O14672, ECO:0000269|PubMed:23676497,
CC ECO:0000269|PubMed:30463011}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain, specifically in neurons and
CC astrocytes (at protein level) (PubMed:23676497, PubMed:29325091).
CC Expressed in inner and outer pillar cells of the organ of Corti (at
CC protein level) (PubMed:30639848). Expressed in kidney and lung
CC (PubMed:30463011). {ECO:0000269|PubMed:23676497,
CC ECO:0000269|PubMed:29325091, ECO:0000269|PubMed:30463011,
CC ECO:0000269|PubMed:30639848}.
CC -!- DEVELOPMENTAL STAGE: Widely expressed in the nervous system at 18 dpc,
CC with high expression in the posterior midbrain, which diminished toward
CC the anterior midbrain.
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 (By similarity). Both
CC Cys-rich and stalk region are necessary for interaction with TSPAN5,
CC TSPAN10, TSPAN14, TSPAN17, TSPAN33 (PubMed:26668317). Stalk region is
CC sufficient for interaction with TSPAN15 (PubMed:26668317).
CC {ECO:0000250|UniProtKB:Q10741, ECO:0000269|PubMed:26668317}.
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}.
CC -!- DISRUPTION PHENOTYPE: Conditional knockout in endothelial cells results
CC in abnormal myocardial compaction, insufficient systolic contraction,
CC and enlarged hearts relative to body weight (PubMed:30446855).
CC Conditional knockout in endothelial cells also results in dilated
CC glomerular vessels and maturation defects in glomerular endothelial
CC cells but kidney function is not impacted (PubMed:29397483).
CC {ECO:0000269|PubMed:29397483, ECO:0000269|PubMed:30446855}.
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DR EMBL; AF011379; AAC53303.1; -; mRNA.
DR EMBL; AC091263; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC160636; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CT025701; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466522; EDL26211.1; -; Genomic_DNA.
DR EMBL; AK036883; BAC29620.1; -; mRNA.
DR EMBL; AK036599; BAC29502.1; -; mRNA.
DR CCDS; CCDS23323.1; -.
DR RefSeq; NP_031425.2; NM_007399.4.
DR AlphaFoldDB; O35598; -.
DR SMR; O35598; -.
DR BioGRID; 197960; 8.
DR IntAct; O35598; 1.
DR STRING; 10090.ENSMUSP00000063839; -.
DR MEROPS; M12.210; -.
DR GlyConnect; 2257; 6 N-Linked glycans (4 sites).
DR GlyGen; O35598; 4 sites, 6 N-linked glycans (4 sites).
DR iPTMnet; O35598; -.
DR PhosphoSitePlus; O35598; -.
DR SwissPalm; O35598; -.
DR EPD; O35598; -.
DR jPOST; O35598; -.
DR MaxQB; O35598; -.
DR PaxDb; O35598; -.
DR PeptideAtlas; O35598; -.
DR PRIDE; O35598; -.
DR ProteomicsDB; 285601; -.
DR ABCD; O35598; 1 sequenced antibody.
DR Antibodypedia; 3441; 581 antibodies from 42 providers.
DR DNASU; 11487; -.
DR Ensembl; ENSMUST00000067880; ENSMUSP00000063839; ENSMUSG00000054693.
DR GeneID; 11487; -.
DR KEGG; mmu:11487; -.
DR UCSC; uc009qor.1; mouse.
DR CTD; 102; -.
DR MGI; MGI:109548; Adam10.
DR VEuPathDB; HostDB:ENSMUSG00000054693; -.
DR eggNOG; KOG3658; Eukaryota.
DR GeneTree; ENSGT00940000160579; -.
DR HOGENOM; CLU_004602_0_0_1; -.
DR InParanoid; O35598; -.
DR OMA; GICERYK; -.
DR OrthoDB; 162519at2759; -.
DR PhylomeDB; O35598; -.
DR TreeFam; TF352021; -.
DR BRENDA; 3.4.24.81; 3474.
DR Reactome; R-MMU-1474228; Degradation of the extracellular matrix.
DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR Reactome; R-MMU-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus.
DR BioGRID-ORCS; 11487; 8 hits in 74 CRISPR screens.
DR ChiTaRS; Adam10; mouse.
DR PRO; PR:O35598; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; O35598; protein.
DR Bgee; ENSMUSG00000054693; Expressed in brain blood vessel and 265 other tissues.
DR ExpressionAtlas; O35598; baseline and differential.
DR Genevisible; O35598; MM.
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:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
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:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0046930; C:pore complex; IMP:UniProtKB.
DR GO; GO:0098794; C:postsynapse; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0045211; C:postsynaptic membrane; ISO:MGI.
DR GO; GO:0097060; C:synaptic membrane; IDA:UniProtKB.
DR GO; GO:0008021; C:synaptic vesicle; ISO:MGI.
DR GO; GO:0097197; C:tetraspanin-enriched microdomain; ISO:MGI.
DR GO; GO:0005802; C:trans-Golgi network; ISO:MGI.
DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070573; F:metallodipeptidase activity; IMP:MGI.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR GO; GO:1902945; F:metalloendopeptidase activity involved in amyloid precursor protein catabolic process; ISO:MGI.
DR GO; GO:0008237; F:metallopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IDA:UniProtKB.
DR GO; GO:0042169; F:SH2 domain binding; NAS:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0034332; P:adherens junction organization; IMP:ARUK-UCL.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; ISO:MGI.
DR GO; GO:0034205; P:amyloid-beta formation; ISO:MGI.
DR GO; GO:0090102; P:cochlea development; IMP:UniProtKB.
DR GO; GO:0051089; P:constitutive protein ectodomain proteolysis; ISO:MGI.
DR GO; GO:0038004; P:epidermal growth factor receptor ligand maturation; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:UniProtKB.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:UniProtKB.
DR GO; GO:0042117; P:monocyte activation; ISO:MGI.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0007220; P:Notch receptor processing; NAS:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IMP:UniProtKB.
DR GO; GO:0006913; P:nucleocytoplasmic transport; NAS:UniProtKB.
DR GO; GO:0046931; P:pore complex assembly; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0030307; P:positive regulation of cell growth; ISO:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; ISO:MGI.
DR GO; GO:0099173; P:postsynapse organization; IDA:SynGO.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0016485; P:protein processing; IDA:MGI.
DR GO; GO:0061001; P:regulation of dendritic spine morphogenesis; ISO:MGI.
DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; IDA:SynGO.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; IMP:UniProtKB.
DR GO; GO:1901342; P:regulation of vasculature development; IMP:UniProtKB.
DR GO; GO:0034612; P:response to tumor necrosis factor; ISO:MGI.
DR GO; GO:0140448; P:signaling receptor ligand precursor processing; IMP:MGI.
DR GO; GO:1901998; P:toxin transport; ISO:MGI.
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..19
FT /evidence="ECO:0000255"
FT PROPEP 20..214
FT /evidence="ECO:0000250|UniProtKB:Q10741"
FT /id="PRO_0000029068"
FT CHAIN 215..749
FT /note="Disintegrin and metalloproteinase domain-containing
FT protein 10"
FT /id="PRO_0000029069"
FT TOPO_DOM 20..673
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 674..694
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 695..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:0000269|PubMed:23676497"
FT MOTIF 171..178
FT /note="Cysteine switch"
FT /evidence="ECO:0000305"
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 ECO:0000269|PubMed:29325091"
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:0007744|PubMed:21183079"
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:0000269|PubMed:19349973"
FT CARBOHYD 440
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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"
FT MUTAGEN 385
FT /note="E->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:29325091"
FT MUTAGEN 735..737
FT /note="RQR->AQA: Loss of binding to AP2A1 and AP2A2.
FT Decreased localization to the plasma membrane."
FT /evidence="ECO:0000269|PubMed:23676497"
FT MUTAGEN 736
FT /note="Q->A: No loss of binding to AP2A1 and AP2A2."
FT /evidence="ECO:0000269|PubMed:23676497"
FT CONFLICT 591
FT /note="D -> N (in Ref. 1; AAC53303)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 749 AA; 83968 MW; 6AA2230B2251ABDA CRC64;
MVLPTVLILL LSWAAGLGGQ YGNPLNKYIR HYEGLSYNVD SLHQKHQRAK RAVSHEDQFL
LLDFHAHGRQ FNLRMKRDTS LFSDEFKVET SNKVLDYDTS HIYTGHIYGE EGSFSHGSVI
DGRFEGFIKT RGGTFYIEPA ERYIKDRILP FHSVIYHEDD INYPHKYGPQ GGCADHSVFE
RMRKYQMTGV EEGARAHPEK HAASSGPELL 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
KDDCCFDANQ PEGKKCKLKP GKQCSPSQGP CCTAQCAFKS KSEKCRDDSD CAKEGICNGF
TALCPASDPK PNFTDCNRHT QVCINGQCAG SICEKYDLEE CTCASSDGKD DKELCHVCCM
KKMAPSTCAS TGSLQWSKQF SGRTITLQPG SPCNDFRGYC DVFMRCRLVD ADGPLARLKK
AIFSPQLYEN IAEWIVAHWW AVLLMGIALI MLMAGFIKIC SVHTPSSNPK LPPPKPLPGT
LKRRRPPQPI QQPPRQRPRE SYQMGHMRR
