ID ADA19_MOUSE Reviewed; 920 AA. AC O35674; DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 2. DT 29-MAY-2024, entry version 182. DE RecName: Full=Disintegrin and metalloproteinase domain-containing protein 19; DE Short=ADAM 19; DE EC=3.4.24.-; DE AltName: Full=Meltrin-beta; DE Flags: Precursor; GN Name=Adam19; Synonyms=Mltnb; 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]. RC TISSUE=Myoblast; RX PubMed=9461614; DOI=10.1074/jbc.273.7.4180; RA Inoue D., Reid M.S., Lum L., Kraetzschmar J., Weskamp G., Myung Y.M., RA Baron R., Blobel C.P.; RT "Cloning and initial characterization of mouse meltrin beta and analysis of RT the expression of four metalloprotease-disintegrins in bone cells."; RL J. Biol. Chem. 273:4180-4187(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE. RC TISSUE=Myoblast; RX PubMed=9622634; DOI=10.1016/s0925-4773(98)00043-4; RA Kurisaki T., Masuda A., Osumi N., Nabeshima Y., Fujisawa-Sehara A.; RT "Spatially- and temporally-restricted expression of meltrin alpha (ADAM12) RT and beta (ADAM19) in mouse embryo."; RL Mech. Dev. 73:211-215(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 429-578. RC TISSUE=Embryonic fibroblast; RX PubMed=7566181; DOI=10.1038/377652a0; RA Yagami-Hiromasa T., Sato T., Kurisaki T., Kamijo K., Nabeshima Y., RA Fujisawa-Sehara A.; RT "A metalloprotease-disintegrin participating in myoblast fusion."; RL Nature 377:652-656(1995). RN [4] RP FUNCTION. RX PubMed=11116142; DOI=10.1074/jbc.m007913200; RA Shirakabe K., Wakatsuki S., Kurisaki T., Fujisawa-Sehara A.; RT "Roles of Meltrin beta /ADAM19 in the processing of neuregulin."; RL J. Biol. Chem. 276:9352-9358(2001). CC -!- FUNCTION: Participates in the proteolytic processing of beta-type CC neuregulin isoforms which are involved in neurogenesis and CC synaptogenesis, suggesting a regulatory role in glial cell. Also CC cleaves alpha-2 macroglobulin. May be involved in osteoblast CC differentiation and/or osteoblast activity in bone (By similarity). CC {ECO:0000250, ECO:0000269|PubMed:11116142}. CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000250}; CC -!- SUBUNIT: Interacts with SH3PXD2A. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. CC -!- TISSUE SPECIFICITY: Widely expressed, with the highest expression in CC bone, heart and lung, followed by brain and spleen and relatively low CC expression in liver, skeletal muscle, kidney and testis. In bone, CC primarily expressed in cell of the osteoblast lineage and not detected CC in mature osteoclasts. CC -!- DEVELOPMENTAL STAGE: Expressed in the heart and in the tail bud at 8.0 CC dpc, and then in the cranial and dorsal root ganglia. Also expressed CC weakly and transiently in the intestine, lung and in bone marrow. CC {ECO:0000269|PubMed:9622634}. CC -!- INDUCTION: By calcitriol and during osteoblast differentiation. CC -!- DOMAIN: The conserved cysteine present in the cysteine-switch motif CC binds the catalytic zinc ion, thus inhibiting the enzyme. The CC dissociation of the cysteine from the zinc ion upon the activation- CC peptide release activates the enzyme. CC -!- PTM: The precursor is cleaved by a furin endopeptidase. {ECO:0000250}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF019887; AAC40037.1; -; mRNA. DR EMBL; D50410; BAA18923.2; -; mRNA. DR CCDS; CCDS24571.1; -. DR PIR; PC7067; PC7067. DR RefSeq; NP_033746.1; NM_009616.4. DR AlphaFoldDB; O35674; -. DR SMR; O35674; -. DR BioGRID; 197965; 13. DR STRING; 10090.ENSMUSP00000011400; -. DR MEROPS; M12.214; -. DR GlyCosmos; O35674; 4 sites, No reported glycans. DR GlyGen; O35674; 4 sites. DR iPTMnet; O35674; -. DR PhosphoSitePlus; O35674; -. DR SwissPalm; O35674; -. DR EPD; O35674; -. DR PaxDb; 10090-ENSMUSP00000011400; -. DR PeptideAtlas; O35674; -. DR ProteomicsDB; 285548; -. DR DNASU; 11492; -. DR Ensembl; ENSMUST00000011400.8; ENSMUSP00000011400.8; ENSMUSG00000011256.17. DR GeneID; 11492; -. DR KEGG; mmu:11492; -. DR UCSC; uc007iny.2; mouse. DR AGR; MGI:105377; -. DR CTD; 8728; -. DR MGI; MGI:105377; Adam19. DR VEuPathDB; HostDB:ENSMUSG00000011256; -. DR eggNOG; KOG3607; Eukaryota. DR GeneTree; ENSGT00940000158971; -. DR HOGENOM; CLU_012714_7_0_1; -. DR InParanoid; O35674; -. DR OMA; HGMMSPR; -. DR OrthoDB; 5406290at2759; -. DR PhylomeDB; O35674; -. DR TreeFam; TF314733; -. DR BRENDA; 3.4.24.B27; 3474. DR Reactome; R-MMU-8941237; Invadopodia formation. DR Reactome; R-MMU-9762292; Regulation of CDH11 function. DR BioGRID-ORCS; 11492; 1 hit in 79 CRISPR screens. DR ChiTaRS; Adam19; mouse. DR PRO; PR:O35674; -. DR Proteomes; UP000000589; Chromosome 11. DR RNAct; O35674; Protein. DR Bgee; ENSMUSG00000011256; Expressed in gastrula and 241 other cell types or tissues. DR ExpressionAtlas; O35674; baseline and differential. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB. DR GO; GO:0017124; F:SH3 domain binding; IMP:UniProtKB. DR GO; GO:0007507; P:heart development; IMP:MGI. DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:MGI. DR GO; GO:0001890; P:placenta development; ISS:UniProtKB. DR GO; GO:2000049; P:positive regulation of cell-cell adhesion mediated by cadherin; ISS:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB. DR CDD; cd04269; ZnMc_adamalysin_II_like; 1. DR Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1. DR Gene3D; 4.10.70.10; Disintegrin domain; 1. DR Gene3D; 2.60.120.260; Galactose-binding domain-like; 1. DR InterPro; IPR006586; ADAM_Cys-rich. DR InterPro; IPR018358; Disintegrin_CS. DR InterPro; IPR001762; Disintegrin_dom. DR InterPro; IPR036436; Disintegrin_dom_sf. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR024079; MetalloPept_cat_dom_sf. DR InterPro; IPR001590; Peptidase_M12B. DR InterPro; IPR002870; Peptidase_M12B_N. DR InterPro; IPR034027; Reprolysin_adamalysin. DR PANTHER; PTHR11905; ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN; 1. DR PANTHER; PTHR11905:SF19; DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 19; 1. DR Pfam; PF08516; ADAM_CR; 1. DR Pfam; PF00200; Disintegrin; 1. DR Pfam; PF01562; Pep_M12B_propep; 1. DR Pfam; PF01421; Reprolysin; 1. DR PRINTS; PR00289; DISINTEGRIN. DR SMART; SM00608; ACR; 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; PS00427; DISINTEGRIN_1; 1. DR PROSITE; PS50214; DISINTEGRIN_2; 1. DR PROSITE; PS01186; EGF_2; 1. DR PROSITE; PS50026; EGF_3; 1. DR PROSITE; PS00142; ZINC_PROTEASE; 1. PE 2: Evidence at transcript level; KW Cleavage on pair of basic residues; Disulfide bond; EGF-like domain; KW Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease; KW Protease; Reference proteome; SH3-binding; Signal; Transmembrane; KW Transmembrane helix; Zinc; Zymogen. FT SIGNAL 1..26 FT /evidence="ECO:0000255" FT PROPEP 27..204 FT /evidence="ECO:0000250" FT /id="PRO_0000029104" FT CHAIN 205..920 FT /note="Disintegrin and metalloproteinase domain-containing FT protein 19" FT /id="PRO_0000029105" FT TOPO_DOM 27..703 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 704..724 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 725..920 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 211..409 FT /note="Peptidase M12B" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276" FT DOMAIN 417..503 FT /note="Disintegrin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068" FT DOMAIN 654..686 FT /note="EGF-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REGION 755..920 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 131..138 FT /note="Cysteine switch" FT /evidence="ECO:0000250" FT MOTIF 835..846 FT /note="SH3-binding" FT /evidence="ECO:0000255" FT COMPBIAS 755..779 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 786..804 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 887..903 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 347 FT BINDING 133 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /note="in inhibited form" FT /evidence="ECO:0000250" FT BINDING 346 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT BINDING 350 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT BINDING 356 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT CARBOHYD 145 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 445 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 448 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 649 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 321..404 FT /evidence="ECO:0000250" FT DISULFID 361..388 FT /evidence="ECO:0000250" FT DISULFID 362..371 FT /evidence="ECO:0000250" FT DISULFID 475..495 FT /evidence="ECO:0000250" FT DISULFID 658..668 FT /evidence="ECO:0000250" FT DISULFID 662..674 FT /evidence="ECO:0000250" FT DISULFID 676..685 FT /evidence="ECO:0000250" SQ SEQUENCE 920 AA; 100860 MW; 7094FDD4EE547382 CRC64; MPGRAGVARF CLLALALQLH WPLAACEPGW TTRGSQEGSP PLQHELIIPQ WRTSESPGRG KHPLRAELRV MAEGRELILD LEKNEHLFAP AYTETCYTAS GNPQTSTLKS EDHCFYHGTV RDVDESSVTL STCRGIRGLI IVRSNLSYII EPVPNSDSQH RIYRSEHLTL PPGNCGFEHS GPTSKDWALQ FTHQTKKQPR RMKREDLHSM KYVELYLVAD YAEFQKNRHD QDATKRKLME IANYVDKFYR SLNIRIALVG LEVWTHGDKC EVSENPYSTL WSFLSWRRKL LAQKSHDNAQ LITGRSFQGT TIGLAPLMAM CSVYQSGGVS MDHSENAIGV ASTVAHEIGH NFGMSHDSAH CCSASAADGG CIMAAATGHP FPKVFSWCNR KELDRYLQTG GGMCLSNMPD TRTLYGGRRC GNGYLEDGEE CDCGEEEECK NPCCNASNCT LKEGAECAHG SCCHQCKLVA PGTQCREQVR QCDLPEFCTG KSPHCPTNYY QMDGTPCEGG QAYCYNGMCL TYQEQCQQLW GPGARPALDL CFERVNAAGD TYGNCGKGLN GQYRKCSPRD AKCGKIQCQS TQARPLESNA VSIDTTITLN GRRIHCRGTH VYRGPEEEEG EGDMLDPGLV MTGTKCGHNH ICFEGQCRNT SFFETEGCGK KCNGHGVCNN NKNCHCFPGW SPPFCNTPGD GGSVDSGPLP PKSVGPVIAG VFSALFVLAV LVLLCHCYRQ SHKLGKPSAL PFKLRHQFSC PFRVSQSGGT GHANPTFKLQ TPQGKRKVTN TPESLRKPSH PPPRPPPDYL RVESPPAPLP AHLNRAAGSS PEAGARIERK ESARRPPPSR PMPPAPNCLL SQDFSRPRPP QKALPANPVP GQRTGPRSGG TSLLQPPTSG PQPPRPPAVP VPKLPEYRSQ RVGAIISSKI //