ADA19_MOUSE
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 03-AUG-2022, entry version 174.
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}.
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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 GlyGen; O35674; 4 sites.
DR iPTMnet; O35674; -.
DR PhosphoSitePlus; O35674; -.
DR EPD; O35674; -.
DR PaxDb; O35674; -.
DR PeptideAtlas; O35674; -.
DR PRIDE; O35674; -.
DR ProteomicsDB; 285548; -.
DR DNASU; 11492; -.
DR Ensembl; ENSMUST00000011400; ENSMUSP00000011400; ENSMUSG00000011256.
DR GeneID; 11492; -.
DR KEGG; mmu:11492; -.
DR UCSC; uc007iny.2; mouse.
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; DSYGNCG; -.
DR OrthoDB; 162519at2759; -.
DR PhylomeDB; O35674; -.
DR TreeFam; TF314733; -.
DR BRENDA; 3.4.24.B27; 3474.
DR Reactome; R-MMU-8941237; Invadopodia formation.
DR BioGRID-ORCS; 11492; 1 hit in 74 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 238 other tissues.
DR ExpressionAtlas; O35674; baseline and differential.
DR Genevisible; O35674; MM.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:1902945; F:metalloendopeptidase activity involved in amyloid precursor protein catabolic process; ISO:MGI.
DR GO; GO:0017124; F:SH3 domain binding; IMP:UniProtKB.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; ISO:MGI.
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 GO; GO:0016485; P:protein processing; ISO:MGI.
DR CDD; cd04269; ZnMc_adamalysin_II_like; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR Gene3D; 4.10.70.10; -; 1.
DR InterPro; IPR033596; ADAM19.
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:SF19; PTHR11905:SF19; 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; SSF57552; 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
