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Q9H013

- ADA19_HUMAN

UniProt

Q9H013 - ADA19_HUMAN

Protein

Disintegrin and metalloproteinase domain-containing protein 19

Gene

ADAM19

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 139 (01 Oct 2014)
      Sequence version 3 (10 Aug 2010)
      Previous versions | rss
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    Functioni

    Participates in the proteolytic processing of beta-type neuregulin isoforms which are involved in neurogenesis and synaptogenesis, suggesting a regulatory role in glial cell. Also cleaves alpha-2 macroglobulin. May be involved in osteoblast differentiation and/or osteoblast activity in bone By similarity.By similarity

    Cofactori

    Binds 1 zinc ion per subunit.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi132 – 1321Zinc; in inhibited formBy similarity
    Metal bindingi345 – 3451Zinc; catalyticBy similarity
    Active sitei346 – 3461PROSITE-ProRule annotation
    Metal bindingi349 – 3491Zinc; catalyticBy similarity
    Metal bindingi355 – 3551Zinc; catalyticBy similarity

    GO - Molecular functioni

    1. metalloendopeptidase activity Source: InterPro
    2. zinc ion binding Source: InterPro

    GO - Biological processi

    1. heart development Source: Ensembl
    2. membrane protein ectodomain proteolysis Source: Ensembl

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    SABIO-RKQ9H013.

    Protein family/group databases

    MEROPSiM12.214.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Disintegrin and metalloproteinase domain-containing protein 19 (EC:3.4.24.-)
    Short name:
    ADAM 19
    Alternative name(s):
    Meltrin-beta
    Metalloprotease and disintegrin dendritic antigen marker
    Short name:
    MADDAM
    Gene namesi
    Name:ADAM19
    Synonyms:MLTNB
    ORF Names:FKSG34
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:197. ADAM19.

    Subcellular locationi

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB-KW

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA24514.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2525Sequence AnalysisAdd
    BLAST
    Propeptidei26 – 202177By similarityPRO_0000029102Add
    BLAST
    Chaini203 – 955753Disintegrin and metalloproteinase domain-containing protein 19PRO_0000029103Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi144 – 1441N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi320 ↔ 403By similarity
    Disulfide bondi360 ↔ 387By similarity
    Disulfide bondi361 ↔ 370By similarity
    Glycosylationi444 – 4441N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi447 – 4471N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi474 ↔ 494By similarity
    Glycosylationi645 – 6451N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi654 ↔ 664By similarity
    Disulfide bondi658 ↔ 670By similarity
    Disulfide bondi672 ↔ 681By similarity

    Post-translational modificationi

    The precursor is cleaved by a furin endopeptidase.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Zymogen

    Proteomic databases

    MaxQBiQ9H013.
    PaxDbiQ9H013.
    PRIDEiQ9H013.

    PTM databases

    PhosphoSiteiQ9H013.

    Expressioni

    Tissue specificityi

    Expressed in many normal organ tissues and several cancer cell lines.

    Inductioni

    By 1,25(OH)2VD3 in monocytes.

    Gene expression databases

    ArrayExpressiQ9H013.
    BgeeiQ9H013.
    CleanExiHS_ADAM19.
    GenevestigatoriQ9H013.

    Organism-specific databases

    HPAiHPA055537.

    Interactioni

    Subunit structurei

    Interacts with SH3PXD2A.1 Publication

    Protein-protein interaction databases

    BioGridi114267. 4 interactions.
    IntActiQ9H013. 3 interactions.
    MINTiMINT-246384.
    STRINGi9606.ENSP00000257527.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9H013.
    SMRiQ9H013. Positions 206-685.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini203 – 699497ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini721 – 955235CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei700 – 72021HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini210 – 408199Peptidase M12BPROSITE-ProRule annotationAdd
    BLAST
    Domaini416 – 50287DisintegrinPROSITE-ProRule annotationAdd
    BLAST
    Domaini650 – 68233EGF-likePROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi130 – 1378Cysteine switchBy similarity
    Motifi833 – 84412SH3-bindingSequence AnalysisAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi434 – 4374Poly-Glu
    Compositional biasi502 – 649148Cys-richAdd
    BLAST

    Domaini

    The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

    Sequence similaritiesi

    Contains 1 disintegrin domain.PROSITE-ProRule annotation
    Contains 1 EGF-like domain.PROSITE-ProRule annotation
    Contains 1 peptidase M12B domain.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, SH3-binding, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG294463.
    HOGENOMiHOG000230883.
    HOVERGENiHBG006978.
    InParanoidiQ9H013.
    KOiK08608.
    OMAiFQKNRRD.
    OrthoDBiEOG7F7W89.
    PhylomeDBiQ9H013.
    TreeFamiTF314733.

    Family and domain databases

    Gene3Di3.40.390.10. 1 hit.
    4.10.70.10. 1 hit.
    InterProiIPR006586. ADAM_Cys-rich.
    IPR001762. Blood-coag_inhib_Disintegrin.
    IPR018358. Disintegrin_CS.
    IPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    IPR024079. MetalloPept_cat_dom.
    IPR001590. Peptidase_M12B.
    IPR002870. Peptidase_M12B_N.
    [Graphical view]
    PfamiPF08516. ADAM_CR. 1 hit.
    PF00200. Disintegrin. 1 hit.
    PF01562. Pep_M12B_propep. 1 hit.
    PF01421. Reprolysin. 1 hit.
    [Graphical view]
    PRINTSiPR00289. DISINTEGRIN.
    SMARTiSM00608. ACR. 1 hit.
    SM00050. DISIN. 1 hit.
    [Graphical view]
    SUPFAMiSSF57552. SSF57552. 1 hit.
    PROSITEiPS50215. ADAM_MEPRO. 1 hit.
    PS00427. DISINTEGRIN_1. 1 hit.
    PS50214. DISINTEGRIN_2. 1 hit.
    PS01186. EGF_2. 1 hit.
    PS50026. EGF_3. 1 hit.
    PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform A (identifier: Q9H013-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MPGGAGAARL CLLAFALQPL RPRAAREPGW TRGSEEGSPK LQHELIIPQW    50
    KTSESPVREK HPLKAELRVM AEGRELILDL EKNEQLFAPS YTETHYTSSG 100
    NPQTTTRKLE DHCFYHGTVR ETELSSVTLS TCRGIRGLIT VSSNLSYVIE 150
    PLPDSKGQHL IYRSEHLKPP PGNCGFEHSK PTTRDWALQF TQQTKKRPRR 200
    MKREDLNSMK YVELYLVADY LEFQKNRRDQ DATKHKLIEI ANYVDKFYRS 250
    LNIRIALVGL EVWTHGNMCE VSENPYSTLW SFLSWRRKLL AQKYHDNAQL 300
    ITGMSFHGTT IGLAPLMAMC SVYQSGGVNM DHSENAIGVA ATMAHEMGHN 350
    FGMTHDSADC CSASAADGGC IMAAATGHPF PKVFNGCNRR ELDRYLQSGG 400
    GMCLSNMPDT RMLYGGRRCG NGYLEDGEEC DCGEEEECNN PCCNASNCTL 450
    RPGAECAHGS CCHQCKLLAP GTLCREQARQ CDLPEFCTGK SPHCPTNFYQ 500
    MDGTPCEGGQ AYCYNGMCLT YQEQCQQLWG PGARPAPDLC FEKVNVAGDT 550
    FGNCGKDMNG EHRKCNMRDA KCGKIQCQSS EARPLESNAV PIDTTIIMNG 600
    RQIQCRGTHV YRGPEEEGDM LDPGLVMTGT KCGYNHICFE GQCRNTSFFE 650
    TEGCGKKCNG HGVCNNNQNC HCLPGWAPPF CNTPGHGGSI DSGPMPPESV 700
    GPVVAGVLVA ILVLAVLMLM YYCCRQNNKL GQLKPSALPS KLRQQFSCPF 750
    RVSQNSGTGH ANPTFKLQTP QGKRKVINTP EILRKPSQPP PRPPPDYLRG 800
    GSPPAPLPAH LSRAARNSPG PGSQIERTES SRRPPPSRPI PPAPNCIVSQ 850
    DFSRPRPPQK ALPANPVPGR RSLPRPGGAS PLRPPGAGPQ QSRPLAALAP 900
    KVSPREALKV KAGTRGLQGG RCRVEKTKQF MLLVVWTELP EQKPRAKHSC 950
    FLVPA 955
    Length:955
    Mass (Da):104,997
    Last modified:August 10, 2010 - v3
    Checksum:i9C9D42BED18BF7F9
    GO
    Isoform B (identifier: Q9H013-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         902-955: VSPREALKVKAGTRGLQGGRCRVEKTKQFMLLVVWTELPEQKPRAKHSCFLVPA → FPEYRSQRAGGMISSKI

    Show »
    Length:918
    Mass (Da):100,848
    Checksum:i048EA0189D3D126A
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti32 – 321R → SK in AAG50282. 1 PublicationCurated
    Sequence conflicti557 – 5571D → V in AAG50282. 1 PublicationCurated
    Sequence conflicti557 – 5571D → V in AAF22162. 1 PublicationCurated
    Sequence conflicti622 – 6221D → N in AAG50282. 1 PublicationCurated
    Sequence conflicti622 – 6221D → N in AAF22162. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti4 – 41G → S.1 Publication
    Corresponds to variant rs11465228 [ dbSNP | Ensembl ].
    VAR_057066
    Natural varianti133 – 1331R → Q in a colorectal cancer sample; somatic mutation. 1 Publication
    VAR_036146
    Natural varianti298 – 2981A → T in a colorectal cancer sample; somatic mutation. 1 Publication
    VAR_036147
    Natural varianti609 – 6091H → Q in a pancreatic ductal adenocarcinoma sample; somatic mutation. 1 Publication
    VAR_062670

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei902 – 95554VSPRE…FLVPA → FPEYRSQRAGGMISSKI in isoform B. 2 PublicationsVSP_005481Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF326918 mRNA. Translation: AAG50282.1.
    Y13786 mRNA. Translation: CAC20585.1.
    AF311317 mRNA. Translation: AAK07852.1.
    AC008676 Genomic DNA. No translation available.
    AC008694 Genomic DNA. No translation available.
    AC106801 Genomic DNA. No translation available.
    AF134707 mRNA. Translation: AAF22162.1.
    CCDSiCCDS4338.1. [Q9H013-2]
    RefSeqiNP_150377.1. NM_033274.4. [Q9H013-2]
    XP_005266060.1. XM_005266003.1. [Q9H013-1]
    UniGeneiHs.483944.

    Genome annotation databases

    EnsembliENST00000257527; ENSP00000257527; ENSG00000135074. [Q9H013-2]
    ENST00000517905; ENSP00000428654; ENSG00000135074. [Q9H013-1]
    GeneIDi8728.
    KEGGihsa:8728.
    UCSCiuc003lwy.3. human. [Q9H013-1]
    uc003lwz.4. human. [Q9H013-2]

    Polymorphism databases

    DMDMi302393821.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF326918 mRNA. Translation: AAG50282.1 .
    Y13786 mRNA. Translation: CAC20585.1 .
    AF311317 mRNA. Translation: AAK07852.1 .
    AC008676 Genomic DNA. No translation available.
    AC008694 Genomic DNA. No translation available.
    AC106801 Genomic DNA. No translation available.
    AF134707 mRNA. Translation: AAF22162.1 .
    CCDSi CCDS4338.1. [Q9H013-2 ]
    RefSeqi NP_150377.1. NM_033274.4. [Q9H013-2 ]
    XP_005266060.1. XM_005266003.1. [Q9H013-1 ]
    UniGenei Hs.483944.

    3D structure databases

    ProteinModelPortali Q9H013.
    SMRi Q9H013. Positions 206-685.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114267. 4 interactions.
    IntActi Q9H013. 3 interactions.
    MINTi MINT-246384.
    STRINGi 9606.ENSP00000257527.

    Protein family/group databases

    MEROPSi M12.214.

    PTM databases

    PhosphoSitei Q9H013.

    Polymorphism databases

    DMDMi 302393821.

    Proteomic databases

    MaxQBi Q9H013.
    PaxDbi Q9H013.
    PRIDEi Q9H013.

    Protocols and materials databases

    DNASUi 8728.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000257527 ; ENSP00000257527 ; ENSG00000135074 . [Q9H013-2 ]
    ENST00000517905 ; ENSP00000428654 ; ENSG00000135074 . [Q9H013-1 ]
    GeneIDi 8728.
    KEGGi hsa:8728.
    UCSCi uc003lwy.3. human. [Q9H013-1 ]
    uc003lwz.4. human. [Q9H013-2 ]

    Organism-specific databases

    CTDi 8728.
    GeneCardsi GC05M156836.
    HGNCi HGNC:197. ADAM19.
    HPAi HPA055537.
    MIMi 603640. gene.
    neXtProti NX_Q9H013.
    PharmGKBi PA24514.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG294463.
    HOGENOMi HOG000230883.
    HOVERGENi HBG006978.
    InParanoidi Q9H013.
    KOi K08608.
    OMAi FQKNRRD.
    OrthoDBi EOG7F7W89.
    PhylomeDBi Q9H013.
    TreeFami TF314733.

    Enzyme and pathway databases

    SABIO-RK Q9H013.

    Miscellaneous databases

    GeneWikii ADAM19.
    GenomeRNAii 8728.
    NextBioi 32743.
    PROi Q9H013.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9H013.
    Bgeei Q9H013.
    CleanExi HS_ADAM19.
    Genevestigatori Q9H013.

    Family and domain databases

    Gene3Di 3.40.390.10. 1 hit.
    4.10.70.10. 1 hit.
    InterProi IPR006586. ADAM_Cys-rich.
    IPR001762. Blood-coag_inhib_Disintegrin.
    IPR018358. Disintegrin_CS.
    IPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    IPR024079. MetalloPept_cat_dom.
    IPR001590. Peptidase_M12B.
    IPR002870. Peptidase_M12B_N.
    [Graphical view ]
    Pfami PF08516. ADAM_CR. 1 hit.
    PF00200. Disintegrin. 1 hit.
    PF01562. Pep_M12B_propep. 1 hit.
    PF01421. Reprolysin. 1 hit.
    [Graphical view ]
    PRINTSi PR00289. DISINTEGRIN.
    SMARTi SM00608. ACR. 1 hit.
    SM00050. DISIN. 1 hit.
    [Graphical view ]
    SUPFAMi SSF57552. SSF57552. 1 hit.
    PROSITEi PS50215. ADAM_MEPRO. 1 hit.
    PS00427. DISINTEGRIN_1. 1 hit.
    PS50214. DISINTEGRIN_2. 1 hit.
    PS01186. EGF_2. 1 hit.
    PS50026. EGF_3. 1 hit.
    PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Identification of FKSG34, a novel human gene encoding for metalloprotease-disintegrin meltrin beta."
      Wang Y.-G., Gong L.
      Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
    2. "Molecular cloning and characterization of a human metalloprotease disintegrin a novel marker for dendritic cell differentiation."
      Fritsche J., Moser M., Faust S., Peuker A., Buettner R., Andreesen R., Kreutz M.
      Blood 96:732-739(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), VARIANT SER-4.
      Tissue: Lymph node.
    3. "Expression and enzymatic activity of human disintegrin and metalloproteinase ADAM19/meltrin beta."
      Wei P., Zhao Y.-G., Zhuang L., Ruben S., Sang Q.-X.A.
      Biochem. Biophys. Res. Commun. 280:744-755(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
      Tissue: Dendritic cell.
    4. "The DNA sequence and comparative analysis of human chromosome 5."
      Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
      , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
      Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "Partial sequence of Homo sapiens ADAM19."
      Xu R., Cai J., Ying B., Wang F., Xu T., Zhao S., Li C.
      Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 99-955 (ISOFORM A).
    6. "The adaptor protein fish associates with members of the ADAMs family and localizes to podosomes of Src-transformed cells."
      Abram C.L., Seals D.F., Pass I., Salinsky D., Maurer L., Roth T.M., Courtneidge S.A.
      J. Biol. Chem. 278:16844-16851(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SH3PXD2A.
    7. Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-133 AND THR-298.
    8. Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-609.

    Entry informationi

    Entry nameiADA19_HUMAN
    AccessioniPrimary (citable) accession number: Q9H013
    Secondary accession number(s): Q9BZL5, Q9UHP2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 31, 2002
    Last sequence update: August 10, 2010
    Last modified: October 1, 2014
    This is version 139 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. Peptidase families
      Classification of peptidase families and list of entries
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3