ID ADA19_HUMAN Reviewed; 955 AA. AC Q9H013; Q9BZL5; Q9UHP2; DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 10-AUG-2010, sequence version 3. DT 24-JUL-2024, entry version 205. 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 AltName: Full=Metalloprotease and disintegrin dendritic antigen marker; DE Short=MADDAM; DE Flags: Precursor; GN Name=ADAM19; Synonyms=MLTNB; ORFNames=FKSG34; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). RA Wang Y.-G., Gong L.; RT "Identification of FKSG34, a novel human gene encoding for metalloprotease- RT disintegrin meltrin beta."; RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), AND VARIANT SER-4. RC TISSUE=Lymph node; RX PubMed=10887142; RA Fritsche J., Moser M., Faust S., Peuker A., Buettner R., Andreesen R., RA Kreutz M.; RT "Molecular cloning and characterization of a human metalloprotease RT disintegrin a novel marker for dendritic cell differentiation."; RL Blood 96:732-739(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B). RC TISSUE=Dendritic cell; RX PubMed=11162584; DOI=10.1006/bbrc.2000.4200; RA Wei P., Zhao Y.-G., Zhuang L., Ruben S., Sang Q.-X.A.; RT "Expression and enzymatic activity of human disintegrin and RT metalloproteinase ADAM19/meltrin beta."; RL Biochem. Biophys. Res. Commun. 280:744-755(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 99-955 (ISOFORM A). RA Xu R., Cai J., Ying B., Wang F., Xu T., Zhao S., Li C.; RT "Partial sequence of Homo sapiens ADAM19."; RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases. RN [6] RP INTERACTION WITH SH3PXD2A. RX PubMed=12615925; DOI=10.1074/jbc.m300267200; RA Abram C.L., Seals D.F., Pass I., Salinsky D., Maurer L., Roth T.M., RA Courtneidge S.A.; RT "The adaptor protein fish associates with members of the ADAMs family and RT localizes to podosomes of Src-transformed cells."; RL J. Biol. Chem. 278:16844-16851(2003). RN [7] RP VARIANTS [LARGE SCALE ANALYSIS] GLN-133 AND THR-298. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [8] RP VARIANT [LARGE SCALE ANALYSIS] GLN-609. RX PubMed=18772397; DOI=10.1126/science.1164368; RA Jones S., Zhang X., Parsons D.W., Lin J.C., Leary R.J., Angenendt P., RA Mankoo P., Carter H., Kamiyama H., Jimeno A., Hong S.M., Fu B., Lin M.T., RA Calhoun E.S., Kamiyama M., Walter K., Nikolskaya T., Nikolsky Y., RA Hartigan J., Smith D.R., Hidalgo M., Leach S.D., Klein A.P., Jaffee E.M., RA Goggins M., Maitra A., Iacobuzio-Donahue C., Eshleman J.R., Kern S.E., RA Hruban R.H., Karchin R., Papadopoulos N., Parmigiani G., Vogelstein B., RA Velculescu V.E., Kinzler K.W.; RT "Core signaling pathways in human pancreatic cancers revealed by global RT genomic analyses."; RL Science 321:1801-1806(2008). 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}. 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:0000269|PubMed:12615925}. CC -!- INTERACTION: CC Q9H013; Q8TE68: EPS8L1; NbExp=2; IntAct=EBI-8567699, EBI-7487998; CC Q9H013; O95153: TSPOAP1; NbExp=2; IntAct=EBI-8567699, EBI-5915931; CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=A; CC IsoId=Q9H013-1; Sequence=Displayed; CC Name=B; CC IsoId=Q9H013-2; Sequence=VSP_005481; CC -!- TISSUE SPECIFICITY: Expressed in many normal organ tissues and several CC cancer cell lines. CC -!- INDUCTION: By 1,25(OH)2VD3 in monocytes. 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; AF326918; AAG50282.1; -; mRNA. DR EMBL; Y13786; CAC20585.1; -; mRNA. DR EMBL; AF311317; AAK07852.1; -; mRNA. DR EMBL; AC008676; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC008694; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC106801; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AF134707; AAF22162.1; -; mRNA. DR CCDS; CCDS4338.1; -. [Q9H013-2] DR RefSeq; NP_150377.1; NM_033274.4. [Q9H013-2] DR RefSeq; XP_005266060.1; XM_005266003.2. DR AlphaFoldDB; Q9H013; -. DR SMR; Q9H013; -. DR BioGRID; 114267; 51. DR IntAct; Q9H013; 18. DR MINT; Q9H013; -. DR STRING; 9606.ENSP00000257527; -. DR MEROPS; M12.214; -. DR GlyCosmos; Q9H013; 4 sites, No reported glycans. DR GlyGen; Q9H013; 8 sites, 1 O-linked glycan (4 sites). DR iPTMnet; Q9H013; -. DR PhosphoSitePlus; Q9H013; -. DR SwissPalm; Q9H013; -. DR BioMuta; ADAM19; -. DR DMDM; 302393821; -. DR jPOST; Q9H013; -. DR MassIVE; Q9H013; -. DR PaxDb; 9606-ENSP00000257527; -. DR PeptideAtlas; Q9H013; -. DR ProteomicsDB; 80195; -. [Q9H013-1] DR ProteomicsDB; 80196; -. [Q9H013-2] DR Antibodypedia; 16547; 262 antibodies from 37 providers. DR DNASU; 8728; -. DR Ensembl; ENST00000257527.9; ENSP00000257527.5; ENSG00000135074.16. [Q9H013-2] DR Ensembl; ENST00000517905.1; ENSP00000428654.1; ENSG00000135074.16. [Q9H013-1] DR GeneID; 8728; -. DR KEGG; hsa:8728; -. DR MANE-Select; ENST00000257527.9; ENSP00000257527.5; NM_033274.5; NP_150377.1. [Q9H013-2] DR UCSC; uc003lwz.5; human. [Q9H013-1] DR AGR; HGNC:197; -. DR CTD; 8728; -. DR DisGeNET; 8728; -. DR GeneCards; ADAM19; -. DR HGNC; HGNC:197; ADAM19. DR HPA; ENSG00000135074; Low tissue specificity. DR MIM; 603640; gene. DR neXtProt; NX_Q9H013; -. DR OpenTargets; ENSG00000135074; -. DR PharmGKB; PA24514; -. DR VEuPathDB; HostDB:ENSG00000135074; -. DR eggNOG; KOG3607; Eukaryota. DR GeneTree; ENSGT00940000159624; -. DR HOGENOM; CLU_012714_7_0_1; -. DR InParanoid; Q9H013; -. DR OMA; HGMMSPR; -. DR OrthoDB; 5406290at2759; -. DR PhylomeDB; Q9H013; -. DR TreeFam; TF314733; -. DR PathwayCommons; Q9H013; -. DR Reactome; R-HSA-8941237; Invadopodia formation. DR Reactome; R-HSA-9762292; Regulation of CDH11 function. DR SABIO-RK; Q9H013; -. DR SignaLink; Q9H013; -. DR SIGNOR; Q9H013; -. DR BioGRID-ORCS; 8728; 9 hits in 1148 CRISPR screens. DR ChiTaRS; ADAM19; human. DR GeneWiki; ADAM19; -. DR GenomeRNAi; 8728; -. DR Pharos; Q9H013; Tbio. DR PRO; PR:Q9H013; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q9H013; Protein. DR Bgee; ENSG00000135074; Expressed in oocyte and 180 other cell types or tissues. DR ExpressionAtlas; Q9H013; baseline and differential. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004222; F:metalloendopeptidase activity; IMP:UniProtKB. DR GO; GO:1902945; F:metalloendopeptidase activity involved in amyloid precursor protein catabolic process; IMP:ARUK-UCL. DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW. DR GO; GO:0042987; P:amyloid precursor protein catabolic process; IMP:ARUK-UCL. DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IBA:GO_Central. DR GO; GO:0001890; P:placenta development; IEP:UniProtKB. DR GO; GO:2000049; P:positive regulation of cell-cell adhesion mediated by cadherin; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB. DR GO; GO:0016485; P:protein processing; IMP:ARUK-UCL. 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 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 1: Evidence at protein level; KW Alternative splicing; Disulfide bond; EGF-like domain; Glycoprotein; KW Hydrolase; Membrane; Metal-binding; Metalloprotease; Protease; KW Reference proteome; SH3-binding; Signal; Transmembrane; KW Transmembrane helix; Zinc; Zymogen. FT SIGNAL 1..25 FT /evidence="ECO:0000255" FT PROPEP 26..202 FT /evidence="ECO:0000250" FT /id="PRO_0000029102" FT CHAIN 203..955 FT /note="Disintegrin and metalloproteinase domain-containing FT protein 19" FT /id="PRO_0000029103" FT TOPO_DOM 203..699 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 700..720 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 721..955 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 210..408 FT /note="Peptidase M12B" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276" FT DOMAIN 416..502 FT /note="Disintegrin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068" FT DOMAIN 650..682 FT /note="EGF-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REGION 753..917 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 130..137 FT /note="Cysteine switch" FT /evidence="ECO:0000250" FT MOTIF 833..844 FT /note="SH3-binding" FT /evidence="ECO:0000255" FT COMPBIAS 753..775 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 784..802 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 346 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276, FT ECO:0000255|PROSITE-ProRule:PRU10095" FT BINDING 132 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 345 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 349 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 355 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT CARBOHYD 144 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 444 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 447 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 645 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 320..403 FT /evidence="ECO:0000250" FT DISULFID 360..387 FT /evidence="ECO:0000250" FT DISULFID 361..370 FT /evidence="ECO:0000250" FT DISULFID 474..494 FT /evidence="ECO:0000250" FT DISULFID 654..664 FT /evidence="ECO:0000250" FT DISULFID 658..670 FT /evidence="ECO:0000250" FT DISULFID 672..681 FT /evidence="ECO:0000250" FT VAR_SEQ 902..955 FT /note="VSPREALKVKAGTRGLQGGRCRVEKTKQFMLLVVWTELPEQKPRAKHSCFLV FT PA -> FPEYRSQRAGGMISSKI (in isoform B)" FT /evidence="ECO:0000303|PubMed:10887142, FT ECO:0000303|PubMed:11162584" FT /id="VSP_005481" FT VARIANT 4 FT /note="G -> S (in dbSNP:rs11465228)" FT /evidence="ECO:0000269|PubMed:10887142" FT /id="VAR_057066" FT VARIANT 133 FT /note="R -> Q (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs200894535)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036146" FT VARIANT 298 FT /note="A -> T (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs1178207005)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036147" FT VARIANT 609 FT /note="H -> Q (in a pancreatic ductal adenocarcinoma FT sample; somatic mutation)" FT /evidence="ECO:0000269|PubMed:18772397" FT /id="VAR_062670" FT CONFLICT 32 FT /note="R -> SK (in Ref. 1; AAG50282)" FT /evidence="ECO:0000305" FT CONFLICT 557 FT /note="D -> V (in Ref. 1; AAG50282 and 5; AAF22162)" FT /evidence="ECO:0000305" FT CONFLICT 622 FT /note="D -> N (in Ref. 1; AAG50282 and 5; AAF22162)" FT /evidence="ECO:0000305" SQ SEQUENCE 955 AA; 104997 MW; 9C9D42BED18BF7F9 CRC64; MPGGAGAARL CLLAFALQPL RPRAAREPGW TRGSEEGSPK LQHELIIPQW KTSESPVREK HPLKAELRVM AEGRELILDL EKNEQLFAPS YTETHYTSSG NPQTTTRKLE DHCFYHGTVR ETELSSVTLS TCRGIRGLIT VSSNLSYVIE PLPDSKGQHL IYRSEHLKPP PGNCGFEHSK PTTRDWALQF TQQTKKRPRR MKREDLNSMK YVELYLVADY LEFQKNRRDQ DATKHKLIEI ANYVDKFYRS LNIRIALVGL EVWTHGNMCE VSENPYSTLW SFLSWRRKLL AQKYHDNAQL ITGMSFHGTT IGLAPLMAMC SVYQSGGVNM DHSENAIGVA ATMAHEMGHN FGMTHDSADC CSASAADGGC IMAAATGHPF PKVFNGCNRR ELDRYLQSGG GMCLSNMPDT RMLYGGRRCG NGYLEDGEEC DCGEEEECNN PCCNASNCTL RPGAECAHGS CCHQCKLLAP GTLCREQARQ CDLPEFCTGK SPHCPTNFYQ MDGTPCEGGQ AYCYNGMCLT YQEQCQQLWG PGARPAPDLC FEKVNVAGDT FGNCGKDMNG EHRKCNMRDA KCGKIQCQSS EARPLESNAV PIDTTIIMNG RQIQCRGTHV YRGPEEEGDM LDPGLVMTGT KCGYNHICFE GQCRNTSFFE TEGCGKKCNG HGVCNNNQNC HCLPGWAPPF CNTPGHGGSI DSGPMPPESV GPVVAGVLVA ILVLAVLMLM YYCCRQNNKL GQLKPSALPS KLRQQFSCPF RVSQNSGTGH ANPTFKLQTP QGKRKVINTP EILRKPSQPP PRPPPDYLRG GSPPAPLPAH LSRAARNSPG PGSQIERTES SRRPPPSRPI PPAPNCIVSQ DFSRPRPPQK ALPANPVPGR RSLPRPGGAS PLRPPGAGPQ QSRPLAALAP KVSPREALKV KAGTRGLQGG RCRVEKTKQF MLLVVWTELP EQKPRAKHSC FLVPA //