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O35674

- ADA19_MOUSE

UniProt

O35674 - ADA19_MOUSE

Protein

Disintegrin and metalloproteinase domain-containing protein 19

Gene

Adam19

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 129 (01 Oct 2014)
      Sequence version 2 (01 Nov 1998)
      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 bindingi133 – 1331Zinc; in inhibited formBy similarity
    Metal bindingi346 – 3461Zinc; catalytic
    Active sitei347 – 3471
    Metal bindingi350 – 3501Zinc; catalytic
    Metal bindingi356 – 3561Zinc; catalytic

    GO - Molecular functioni

    1. metalloendopeptidase activity Source: InterPro
    2. protein binding Source: BHF-UCL
    3. zinc ion binding Source: InterPro

    GO - Biological processi

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

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    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
    Gene namesi
    Name:Adam19
    Synonyms:Mltnb
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 11

    Organism-specific databases

    MGIiMGI:105377. Adam19.

    Subcellular locationi

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB-KW

    Keywords - Cellular componenti

    Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2626Sequence AnalysisAdd
    BLAST
    Propeptidei27 – 204178By similarityPRO_0000029104Add
    BLAST
    Chaini205 – 920716Disintegrin and metalloproteinase domain-containing protein 19PRO_0000029105Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi145 – 1451N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi321 ↔ 404By similarity
    Disulfide bondi361 ↔ 388By similarity
    Disulfide bondi362 ↔ 371By similarity
    Glycosylationi445 – 4451N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi448 – 4481N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi475 ↔ 495By similarity
    Glycosylationi649 – 6491N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi658 ↔ 668By similarity
    Disulfide bondi662 ↔ 674By similarity
    Disulfide bondi676 ↔ 685By similarity

    Post-translational modificationi

    The precursor is cleaved by a furin endopeptidase.By similarity

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Zymogen

    Proteomic databases

    PRIDEiO35674.

    PTM databases

    PhosphoSiteiO35674.

    Expressioni

    Tissue specificityi

    Widely expressed, with the highest expression in bone, heart and lung, followed by brain and spleen and relatively low expression in liver, skeletal muscle, kidney and testis. In bone, primarily expressed in cell of the osteoblast lineage and not detected in mature osteoclasts.

    Developmental stagei

    Expressed in the heart and in the tail bud at 8.0 dpc, and then in the cranial and dorsal root ganglia. Also expressed weakly and transiently in the intestine, lung and in bone marrow.1 Publication

    Inductioni

    By calcitriol and during osteoblast differentiation.

    Gene expression databases

    ArrayExpressiO35674.
    BgeeiO35674.
    GenevestigatoriO35674.

    Interactioni

    Subunit structurei

    Interacts with SH3PXD2A.By similarity

    Protein-protein interaction databases

    MINTiMINT-4996200.

    Structurei

    3D structure databases

    ProteinModelPortaliO35674.
    SMRiO35674. Positions 207-651, 660-687.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini27 – 703677ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini725 – 920196CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei704 – 72421HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini211 – 409199Peptidase M12BPROSITE-ProRule annotationAdd
    BLAST
    Domaini417 – 50387DisintegrinPROSITE-ProRule annotationAdd
    BLAST
    Domaini654 – 68633EGF-likePROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi131 – 1388Cysteine switchBy similarity
    Motifi835 – 84612SH3-bindingSequence AnalysisAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi435 – 4384Poly-Glu
    Compositional biasi504 – 653150Cys-richAdd
    BLAST
    Compositional biasi616 – 6216Poly-Glu

    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.
    InParanoidiO35674.
    KOiK08608.
    OMAiFQKNRRD.
    OrthoDBiEOG7F7W89.
    PhylomeDBiO35674.
    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]

    Sequencei

    Sequence statusi: Complete.

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

    O35674-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPGRAGVARF CLLALALQLH WPLAACEPGW TTRGSQEGSP PLQHELIIPQ    50
    WRTSESPGRG KHPLRAELRV MAEGRELILD LEKNEHLFAP AYTETCYTAS 100
    GNPQTSTLKS EDHCFYHGTV RDVDESSVTL STCRGIRGLI IVRSNLSYII 150
    EPVPNSDSQH RIYRSEHLTL PPGNCGFEHS GPTSKDWALQ FTHQTKKQPR 200
    RMKREDLHSM KYVELYLVAD YAEFQKNRHD QDATKRKLME IANYVDKFYR 250
    SLNIRIALVG LEVWTHGDKC EVSENPYSTL WSFLSWRRKL LAQKSHDNAQ 300
    LITGRSFQGT TIGLAPLMAM CSVYQSGGVS MDHSENAIGV ASTVAHEIGH 350
    NFGMSHDSAH CCSASAADGG CIMAAATGHP FPKVFSWCNR KELDRYLQTG 400
    GGMCLSNMPD TRTLYGGRRC GNGYLEDGEE CDCGEEEECK NPCCNASNCT 450
    LKEGAECAHG SCCHQCKLVA PGTQCREQVR QCDLPEFCTG KSPHCPTNYY 500
    QMDGTPCEGG QAYCYNGMCL TYQEQCQQLW GPGARPALDL CFERVNAAGD 550
    TYGNCGKGLN GQYRKCSPRD AKCGKIQCQS TQARPLESNA VSIDTTITLN 600
    GRRIHCRGTH VYRGPEEEEG EGDMLDPGLV MTGTKCGHNH ICFEGQCRNT 650
    SFFETEGCGK KCNGHGVCNN NKNCHCFPGW SPPFCNTPGD GGSVDSGPLP 700
    PKSVGPVIAG VFSALFVLAV LVLLCHCYRQ SHKLGKPSAL PFKLRHQFSC 750
    PFRVSQSGGT GHANPTFKLQ TPQGKRKVTN TPESLRKPSH PPPRPPPDYL 800
    RVESPPAPLP AHLNRAAGSS PEAGARIERK ESARRPPPSR PMPPAPNCLL 850
    SQDFSRPRPP QKALPANPVP GQRTGPRSGG TSLLQPPTSG PQPPRPPAVP 900
    VPKLPEYRSQ RVGAIISSKI 920
    Length:920
    Mass (Da):100,860
    Last modified:November 1, 1998 - v2
    Checksum:i7094FDD4EE547382
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF019887 mRNA. Translation: AAC40037.1.
    D50410 mRNA. Translation: BAA18923.2.
    CCDSiCCDS24571.1.
    PIRiPC7067.
    RefSeqiNP_033746.1. NM_009616.4.
    UniGeneiMm.89940.

    Genome annotation databases

    EnsembliENSMUST00000011400; ENSMUSP00000011400; ENSMUSG00000011256.
    GeneIDi11492.
    KEGGimmu:11492.
    UCSCiuc007iny.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF019887 mRNA. Translation: AAC40037.1 .
    D50410 mRNA. Translation: BAA18923.2 .
    CCDSi CCDS24571.1.
    PIRi PC7067.
    RefSeqi NP_033746.1. NM_009616.4.
    UniGenei Mm.89940.

    3D structure databases

    ProteinModelPortali O35674.
    SMRi O35674. Positions 207-651, 660-687.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    MINTi MINT-4996200.

    Protein family/group databases

    MEROPSi M12.214.

    PTM databases

    PhosphoSitei O35674.

    Proteomic databases

    PRIDEi O35674.

    Protocols and materials databases

    DNASUi 11492.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000011400 ; ENSMUSP00000011400 ; ENSMUSG00000011256 .
    GeneIDi 11492.
    KEGGi mmu:11492.
    UCSCi uc007iny.1. mouse.

    Organism-specific databases

    CTDi 8728.
    MGIi MGI:105377. Adam19.

    Phylogenomic databases

    eggNOGi NOG294463.
    HOGENOMi HOG000230883.
    HOVERGENi HBG006978.
    InParanoidi O35674.
    KOi K08608.
    OMAi FQKNRRD.
    OrthoDBi EOG7F7W89.
    PhylomeDBi O35674.
    TreeFami TF314733.

    Miscellaneous databases

    NextBioi 278870.
    PROi O35674.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O35674.
    Bgeei O35674.
    Genevestigatori O35674.

    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. "Cloning and initial characterization of mouse meltrin beta and analysis of the expression of four metalloprotease-disintegrins in bone cells."
      Inoue D., Reid M.S., Lum L., Kraetzschmar J., Weskamp G., Myung Y.M., Baron R., Blobel C.P.
      J. Biol. Chem. 273:4180-4187(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Myoblast.
    2. "Spatially- and temporally-restricted expression of meltrin alpha (ADAM12) and beta (ADAM19) in mouse embryo."
      Kurisaki T., Masuda A., Osumi N., Nabeshima Y., Fujisawa-Sehara A.
      Mech. Dev. 73:211-215(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE.
      Tissue: Myoblast.
    3. "A metalloprotease-disintegrin participating in myoblast fusion."
      Yagami-Hiromasa T., Sato T., Kurisaki T., Kamijo K., Nabeshima Y., Fujisawa-Sehara A.
      Nature 377:652-656(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 429-578.
      Tissue: Embryonic fibroblast.
    4. "Roles of Meltrin beta /ADAM19 in the processing of neuregulin."
      Shirakabe K., Wakatsuki S., Kurisaki T., Fujisawa-Sehara A.
      J. Biol. Chem. 276:9352-9358(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiADA19_MOUSE
    AccessioniPrimary (citable) accession number: O35674
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 31, 2002
    Last sequence update: November 1, 1998
    Last modified: October 1, 2014
    This is version 129 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3