ADA19_HUMAN
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 03-AUG-2022, entry version 194.
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}.
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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; 47.
DR IntAct; Q9H013; 17.
DR MINT; Q9H013; -.
DR STRING; 9606.ENSP00000257527; -.
DR MEROPS; M12.214; -.
DR GlyGen; Q9H013; 4 sites.
DR iPTMnet; Q9H013; -.
DR PhosphoSitePlus; Q9H013; -.
DR BioMuta; ADAM19; -.
DR DMDM; 302393821; -.
DR EPD; Q9H013; -.
DR jPOST; Q9H013; -.
DR MassIVE; Q9H013; -.
DR MaxQB; Q9H013; -.
DR PaxDb; Q9H013; -.
DR PeptideAtlas; Q9H013; -.
DR PRIDE; Q9H013; -.
DR ProteomicsDB; 80195; -. [Q9H013-1]
DR ProteomicsDB; 80196; -. [Q9H013-2]
DR Antibodypedia; 16547; 256 antibodies from 36 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 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; DSYGNCG; -.
DR OrthoDB; 162519at2759; -.
DR PhylomeDB; Q9H013; -.
DR TreeFam; TF314733; -.
DR PathwayCommons; Q9H013; -.
DR Reactome; R-HSA-8941237; Invadopodia formation.
DR SABIO-RK; Q9H013; -.
DR SignaLink; Q9H013; -.
DR SIGNOR; Q9H013; -.
DR BioGRID-ORCS; 8728; 8 hits in 1067 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 178 other tissues.
DR ExpressionAtlas; Q9H013; baseline and differential.
DR Genevisible; Q9H013; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IEA:InterPro.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; -; 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 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
