ID ADA19_HUMAN Reviewed; 956 AA. AC Q9H013; Q9BZL5; Q9UHP2; DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 31-JAN-2002, sequence version 2. DT 22-JUL-2008, entry version 78. DE RecName: Full=ADAM 19; DE EC=3.4.24.-; DE AltName: Full=A disintegrin and metalloproteinase domain 19; 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT metalloprotease-disintegrin meltrin beta."; RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B). RC TISSUE=Lymph node; RX MEDLINE=20346928; 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 MEDLINE=21092672; 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 [MRNA] OF 100-956 (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 [5] 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 RT and localizes to podosomes of Src-transformed cells."; RL J. Biol. Chem. 278:16844-16851(2003). RN [6] RP VARIANTS [LARGE SCALE ANALYSIS] GLN-134 AND THR-299. 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., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). 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 CC similarity). CC -!- COFACTOR: Binds 1 zinc ion per subunit (By similarity). CC -!- SUBUNIT: Interacts with SH3PXD2A. CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane CC 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 CC several cancer cell lines. CC -!- INDUCTION: By 1,25(OH)2VD3 in monocytes. CC -!- DOMAIN: The conserved cysteine present in the cysteine-switch CC motif binds the catalytic zinc ion, thus inhibiting the enzyme. CC The dissociation of the cysteine from the zinc ion upon the CC activation-peptide release activates the enzyme. CC -!- PTM: The precursor is cleaved by a furin endopeptidase (By CC similarity). CC -!- SIMILARITY: Contains 1 disintegrin domain. CC -!- SIMILARITY: Contains 1 EGF-like domain. CC -!- SIMILARITY: Contains 1 peptidase M12B domain. 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; AF134707; AAF22162.1; -; mRNA. DR RefSeq; NP_075525.2; -. DR RefSeq; NP_150377.1; -. DR UniGene; Hs.483944; -. DR HSSP; P18619; 1FVL. DR MEROPS; M12.214; -. DR Ensembl; ENSG00000135074; Homo sapiens. DR GeneID; 8728; -. DR KEGG; hsa:8728; -. DR HGNC; HGNC:197; ADAM19. DR MIM; 603640; gene. DR PharmGKB; PA24514; -. DR HOGENOM; Q9H013; -. DR HOVERGEN; Q9H013; -. DR ArrayExpress; Q9H013; -. DR CleanEx; HS_ADAM19; -. DR GermOnline; ENSG00000135074; Homo sapiens. DR InterPro; IPR006586; ADAM_cysteine. DR InterPro; IPR001762; Blood-coag_inhib_Disintegrin. DR InterPro; IPR000742; EGF_3. DR InterPro; IPR013111; EGF_extracell. DR InterPro; IPR013032; EGF_like_reg_CS. DR InterPro; IPR001818; Pept_M10A_M12B. DR InterPro; IPR006025; Pept_M_Zn_BS. DR InterPro; IPR001590; Peptidase_M12B. DR InterPro; IPR002870; Peptidase_M12B_N. DR Gene3D; G3DSA:4.10.70.10; Blood-coag_inhib_Disintegrin; 1. DR Pfam; PF08516; ADAM_CR; 1. DR Pfam; PF00200; Disintegrin; 1. DR Pfam; PF07974; EGF_2; 1. DR Pfam; PF01562; Pep_M12B_propep; 1. DR Pfam; PF01421; Reprolysin; 1. DR PRINTS; PR00289; DISINTEGRIN. DR ProDom; PD000664; Disintegrin; 1. DR SMART; SM00608; ACR; 1. DR SMART; SM00050; DISIN; 1. DR PROSITE; PS50215; ADAM_MEPRO; 1. DR PROSITE; PS00546; CYSTEINE_SWITCH; FALSE_NEG. DR PROSITE; PS00427; DISINTEGRIN_1; 1. DR PROSITE; PS50214; DISINTEGRIN_2; 1. DR PROSITE; PS00022; EGF_1; FALSE_NEG. 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; EGF-like domain; Glycoprotein; Hydrolase; KW Membrane; Metal-binding; Metalloprotease; Polymorphism; Protease; KW SH3-binding; Signal; Transmembrane; Zinc; Zymogen. FT SIGNAL 1 25 Potential. FT PROPEP 26 203 By similarity. FT /FTId=PRO_0000029102. FT CHAIN 204 956 ADAM 19. FT /FTId=PRO_0000029103. FT TOPO_DOM 204 700 Extracellular (Potential). FT TRANSMEM 701 721 Potential. FT TOPO_DOM 722 956 Cytoplasmic (Potential). FT DOMAIN 211 409 Peptidase M12B. FT DOMAIN 417 503 Disintegrin. FT DOMAIN 651 683 EGF-like. FT MOTIF 131 138 Cysteine switch (By similarity). FT MOTIF 834 840 SH3-binding (Potential). FT MOTIF 839 845 SH3-binding (Potential). FT COMPBIAS 435 438 Poly-Glu. FT COMPBIAS 503 650 Cys-rich. FT ACT_SITE 347 347 By similarity. FT METAL 133 133 Zinc (in inhibited form) (By similarity). FT METAL 346 346 Zinc (catalytic) (By similarity). FT METAL 350 350 Zinc (catalytic) (By similarity). FT METAL 356 356 Zinc (catalytic) (By similarity). FT CARBOHYD 145 145 N-linked (GlcNAc...) (Potential). FT CARBOHYD 445 445 N-linked (GlcNAc...) (Potential). FT CARBOHYD 448 448 N-linked (GlcNAc...) (Potential). FT CARBOHYD 646 646 N-linked (GlcNAc...) (Potential). FT DISULFID 321 404 By similarity. FT DISULFID 361 388 By similarity. FT DISULFID 362 371 By similarity. FT DISULFID 475 495 By similarity. FT DISULFID 655 665 By similarity. FT DISULFID 659 671 By similarity. FT DISULFID 673 682 By similarity. FT VAR_SEQ 903 956 VSPREALKVKAGTRGLQGGRCRVEKTKQFMLLVVWTELPEQ FT KPRAKHSCFLVPA -> FPEYRSQRAGGMISSKI (in FT isoform B). FT /FTId=VSP_005481. FT VARIANT 134 134 R -> Q (in a colorectal cancer sample; FT somatic mutation). FT /FTId=VAR_036146. FT VARIANT 299 299 A -> T (in a colorectal cancer sample; FT somatic mutation). FT /FTId=VAR_036147. FT CONFLICT 4 4 G -> S (in Ref. 2; CAC20585). FT CONFLICT 32 33 SK -> R (in Ref. 2 and 3). FT CONFLICT 558 558 V -> D (in Ref. 2 and 3). FT CONFLICT 623 623 N -> D (in Ref. 2 and 3). SQ SEQUENCE 956 AA; 105039 MW; 8373F10FA0418B12 CRC64; MPGGAGAARL CLLAFALQPL RPRAAREPGW TSKGSEEGSP KLQHELIIPQ WKTSESPVRE KHPLKAELRV MAEGRELILD LEKNEQLFAP SYTETHYTSS GNPQTTTRKL EDHCFYHGTV RETELSSVTL STCRGIRGLI TVSSNLSYVI EPLPDSKGQH LIYRSEHLKP PPGNCGFEHS KPTTRDWALQ FTQQTKKRPR RMKREDLNSM KYVELYLVAD YLEFQKNRRD QDATKHKLIE IANYVDKFYR SLNIRIALVG LEVWTHGNMC EVSENPYSTL WSFLSWRRKL LAQKYHDNAQ LITGMSFHGT TIGLAPLMAM CSVYQSGGVN MDHSENAIGV AATMAHEMGH NFGMTHDSAD CCSASAADGG CIMAAATGHP FPKVFNGCNR RELDRYLQSG GGMCLSNMPD TRMLYGGRRC GNGYLEDGEE CDCGEEEECN NPCCNASNCT LRPGAECAHG SCCHQCKLLA PGTLCREQAR QCDLPEFCTG KSPHCPTNFY QMDGTPCEGG QAYCYNGMCL TYQEQCQQLW GPGARPAPDL CFEKVNVAGD TFGNCGKVMN GEHRKCNMRD AKCGKIQCQS SEARPLESNA VPIDTTIIMN GRQIQCRGTH VYRGPEEEGD MLNPGLVMTG TKCGYNHICF EGQCRNTSFF ETEGCGKKCN GHGVCNNNQN CHCLPGWAPP FCNTPGHGGS IDSGPMPPES VGPVVAGVLV AILVLAVLML MYYCCRQNNK LGQLKPSALP SKLRQQFSCP FRVSQNSGTG HANPTFKLQT PQGKRKVINT PEILRKPSQP PPRPPPDYLR GGSPPAPLPA HLSRAARNSP GPGSQIERTE SSRRPPPSRP IPPAPNCIVS QDFSRPRPPQ KALPANPVPG RRSLPRPGGA SPLRPPGAGP QQSRPLAALA PKVSPREALK VKAGTRGLQG GRCRVEKTKQ FMLLVVWTEL PEQKPRAKHS CFLVPA //