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P78536

- ADA17_HUMAN

UniProt

P78536 - ADA17_HUMAN

Protein

Disintegrin and metalloproteinase domain-containing protein 17

Gene

ADAM17

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 169 (01 Oct 2014)
      Sequence version 1 (01 May 1997)
      Previous versions | rss
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    Functioni

    Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein. Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT). Plays a role in the proteolytic processing of ACE2.4 Publications

    Catalytic activityi

    Narrow endopeptidase specificity. Cleaves Pro-Leu-Ala-Gln-Ala-|-Val-Arg-Ser-Ser-Ser in the membrane-bound, 26-kDa form of tumor necrosis factor alpha (TNF-alpha). Similarly cleaves other membrane-anchored, cell-surface proteins to 'shed' the extracellular domains.

    Cofactori

    Binds 1 zinc ion per subunit.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi184 – 1841Zinc; in inhibited formBy similarity
    Metal bindingi405 – 4051Zinc; catalytic
    Active sitei406 – 40611 PublicationPROSITE-ProRule annotation
    Metal bindingi409 – 4091Zinc; catalytic
    Metal bindingi415 – 4151Zinc; catalytic

    GO - Molecular functioni

    1. integrin binding Source: BHF-UCL
    2. interleukin-6 receptor binding Source: BHF-UCL
    3. metalloendopeptidase activity Source: UniProtKB
    4. metallopeptidase activity Source: BHF-UCL
    5. Notch binding Source: UniProtKB
    6. PDZ domain binding Source: BHF-UCL
    7. protein binding Source: IntAct
    8. zinc ion binding Source: InterPro

    GO - Biological processi

    1. apoptotic process Source: Reactome
    2. apoptotic signaling pathway Source: Reactome
    3. B cell differentiation Source: BHF-UCL
    4. cell adhesion Source: BHF-UCL
    5. cell adhesion mediated by integrin Source: BHF-UCL
    6. cell motility Source: BHF-UCL
    7. collagen catabolic process Source: Reactome
    8. epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway Source: BHF-UCL
    9. epidermal growth factor receptor signaling pathway Source: BHF-UCL
    10. extracellular matrix disassembly Source: Reactome
    11. extracellular matrix organization Source: Reactome
    12. germinal center formation Source: BHF-UCL
    13. JAK-STAT cascade involved in growth hormone signaling pathway Source: Reactome
    14. membrane protein ectodomain proteolysis Source: BHF-UCL
    15. membrane protein intracellular domain proteolysis Source: Reactome
    16. negative regulation of interleukin-8 production Source: BHF-UCL
    17. negative regulation of transforming growth factor beta receptor signaling pathway Source: UniProt
    18. neurotrophin TRK receptor signaling pathway Source: Reactome
    19. neutrophil mediated immunity Source: BHF-UCL
    20. Notch receptor processing Source: UniProtKB
    21. Notch signaling pathway Source: UniProtKB-KW
    22. PMA-inducible membrane protein ectodomain proteolysis Source: BHF-UCL
    23. positive regulation of cell growth Source: BHF-UCL
    24. positive regulation of cell migration Source: BHF-UCL
    25. positive regulation of cell proliferation Source: BHF-UCL
    26. positive regulation of cellular component movement Source: BHF-UCL
    27. positive regulation of chemokine production Source: BHF-UCL
    28. positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle Source: BHF-UCL
    29. positive regulation of epidermal growth factor-activated receptor activity Source: BHF-UCL
    30. positive regulation of leukocyte chemotaxis Source: BHF-UCL
    31. positive regulation of protein phosphorylation Source: BHF-UCL
    32. positive regulation of T cell chemotaxis Source: BHF-UCL
    33. positive regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
    34. proteolysis Source: UniProtKB
    35. regulation of mast cell apoptotic process Source: BHF-UCL
    36. response to drug Source: BHF-UCL
    37. response to high density lipoprotein particle Source: BHF-UCL
    38. response to hypoxia Source: BHF-UCL
    39. response to lipopolysaccharide Source: BHF-UCL
    40. spleen development Source: BHF-UCL
    41. T cell differentiation in thymus Source: BHF-UCL
    42. wound healing, spreading of epidermal cells Source: BHF-UCL

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Biological processi

    Notch signaling pathway

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    BRENDAi3.4.24.86. 2681.
    ReactomeiREACT_111133. Growth hormone receptor signaling.
    REACT_116022. Nuclear signaling by ERBB4.
    REACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_13443. Regulated proteolysis of p75NTR.
    REACT_1432. TNF signaling.
    REACT_150401. Collagen degradation.
    REACT_160089. Constitutive Signaling by NOTCH1 HD Domain Mutants.
    REACT_160106. Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant.
    REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
    REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
    REACT_9417. Signaling by EGFR.
    SignaLinkiP78536.

    Protein family/group databases

    MEROPSiM12.217.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Disintegrin and metalloproteinase domain-containing protein 17 (EC:3.4.24.86)
    Short name:
    ADAM 17
    Alternative name(s):
    Snake venom-like protease
    TNF-alpha convertase
    TNF-alpha-converting enzyme
    CD_antigen: CD156b
    Gene namesi
    Name:ADAM17
    Synonyms:CSVP, TACE
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:195. ADAM17.

    Subcellular locationi

    GO - Cellular componenti

    1. actin cytoskeleton Source: BHF-UCL
    2. apical plasma membrane Source: BHF-UCL
    3. cell surface Source: BHF-UCL
    4. cytoplasm Source: HPA
    5. integral component of plasma membrane Source: BHF-UCL
    6. membrane Source: UniProtKB
    7. membrane raft Source: BHF-UCL
    8. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Neonatal inflammatory skin and bowel disease (NISBD) [MIM:614328]: A disorder characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut. The skin lesions involve perioral and perianal erythema, psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules. Gastrointestinal symptoms include malabsorptive diarrhea that is exacerbated by intercurrent gastrointestinal infections. The hair is short or broken, and the eyelashes and eyebrows are wiry and disorganized.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    Organism-specific databases

    MIMi614328. phenotype.
    Orphaneti294023. Neonatal inflammatory skin and bowel disease.
    PharmGKBiPA24512.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1717Sequence AnalysisAdd
    BLAST
    Propeptidei18 – 214197PRO_0000029088Add
    BLAST
    Chaini215 – 824610Disintegrin and metalloproteinase domain-containing protein 17PRO_0000029089Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi103 – 1031N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi157 – 1571N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi174 – 1741N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi225 ↔ 333
    Glycosylationi264 – 2641N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi365 ↔ 469
    Disulfide bondi423 ↔ 453
    Glycosylationi452 – 4521N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi498 – 4981N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi534 ↔ 555By similarity
    Glycosylationi539 – 5391N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi551 – 5511N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi573 ↔ 582By similarity
    Disulfide bondi578 ↔ 591By similarity
    Disulfide bondi593 ↔ 600By similarity
    Glycosylationi594 – 5941N-linked (GlcNAc...)Sequence Analysis
    Modified residuei735 – 7351Phosphothreonine; by MAPK142 Publications
    Modified residuei791 – 7911Phosphoserine4 Publications
    Modified residuei819 – 8191Phosphoserine1 Publication

    Post-translational modificationi

    The precursor is cleaved by a furin endopeptidase.By similarity
    Phosphorylated. Stimulation by growth factor or phorbol 12-myristate 13-acetate induces phosphorylation of Ser-819 but decreases phosphorylation of Ser-791. Phosphorylation at THR-735 by MAPK14 is required for ADAM17-mediated ectodomain shedding.7 Publications

    Keywords - PTMi

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

    Proteomic databases

    MaxQBiP78536.
    PaxDbiP78536.
    PRIDEiP78536.

    PTM databases

    PhosphoSiteiP78536.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed. Expressed at highest levels in adult heart, placenta, skeletal muscle, pancreas, spleen, thymus, prostate, testes, ovary and small intestine, and in fetal brain, lung, liver and kidney.

    Inductioni

    In arthritis-affected cartilage.

    Gene expression databases

    ArrayExpressiP78536.
    BgeeiP78536.
    CleanExiHS_ADAM17.
    GenevestigatoriP78536.

    Organism-specific databases

    HPAiCAB025906.
    HPA010738.
    HPA051575.

    Interactioni

    Subunit structurei

    Interacts with MAD2L1, MAPK14 and MUC1.2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    DLG1Q129597EBI-78188,EBI-357481
    MAD2L1Q132573EBI-78188,EBI-78203

    Protein-protein interaction databases

    BioGridi112731. 9 interactions.
    IntActiP78536. 8 interactions.
    MINTiMINT-108290.
    STRINGi9606.ENSP00000309968.

    Structurei

    Secondary structure

    1
    824
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi220 – 2223
    Beta strandi224 – 2318
    Helixi233 – 2386
    Turni239 – 2424
    Helixi244 – 26320
    Beta strandi269 – 2713
    Beta strandi276 – 2849
    Beta strandi300 – 3023
    Beta strandi309 – 3113
    Helixi314 – 32411
    Helixi326 – 3294
    Beta strandi332 – 3398
    Helixi344 – 3463
    Beta strandi349 – 3546
    Beta strandi356 – 3594
    Beta strandi363 – 3653
    Beta strandi368 – 3714
    Turni372 – 3754
    Beta strandi376 – 3794
    Beta strandi382 – 3898
    Helixi396 – 41015
    Beta strandi418 – 4203
    Turni421 – 4233
    Helixi427 – 4293
    Beta strandi436 – 4383
    Beta strandi442 – 4443
    Turni445 – 4484
    Helixi452 – 46918
    Helixi583 – 5864
    Beta strandi589 – 5913
    Helixi597 – 6004
    Beta strandi603 – 6053
    Beta strandi611 – 6133
    Beta strandi631 – 6366
    Turni637 – 6393

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1BKCX-ray2.00A/C/E/I219-474[»]
    1ZXCX-ray2.28A/B215-477[»]
    2A8HX-ray2.30A/B215-477[»]
    2DDFX-ray1.70A/B218-474[»]
    2FV5X-ray2.10A/B216-475[»]
    2FV9X-ray2.02A/B218-475[»]
    2I47X-ray1.90A/B/C/D212-492[»]
    2M2FNMR-A581-642[»]
    2OI0X-ray2.00A216-477[»]
    3B92X-ray2.00A216-474[»]
    3CKIX-ray2.30A219-474[»]
    3E8RX-ray1.90A/B215-477[»]
    3EDZX-ray1.90A/B215-477[»]
    3EWJX-ray1.80A/B215-477[»]
    3G42X-ray2.10A/B/C/D212-492[»]
    3KMCX-ray1.80A/B215-476[»]
    3KMEX-ray1.85A/B215-476[»]
    3L0TX-ray1.92A/B215-476[»]
    3L0VX-ray1.75A/B215-476[»]
    3LE9X-ray1.85A/B215-476[»]
    3LEAX-ray2.00A/B215-476[»]
    3LGPX-ray1.90A/B215-476[»]
    3O64X-ray1.88A/B215-476[»]
    ProteinModelPortaliP78536.
    SMRiP78536. Positions 216-642.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP78536.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini215 – 671457ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini693 – 824132CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei672 – 69221HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini223 – 474252Peptidase M12BPROSITE-ProRule annotationAdd
    BLAST
    Domaini475 – 56389DisintegrinPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni603 – 67169Crambin-likeAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi182 – 1898Cysteine switchBy similarity
    Motifi731 – 7388SH3-bindingSequence Analysis
    Motifi741 – 7488SH3-bindingSequence Analysis

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi96 – 994Poly-Val
    Compositional biasi564 – 60239Cys-richAdd
    BLAST

    Domaini

    Must be membrane anchored to cleave the different substrates. The cytoplasmic domain is not required for the this activity. Only the catalytic domain is essential to shed TNF and p75 TNFR By similarity.By similarity
    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 peptidase M12B domain.PROSITE-ProRule annotation

    Keywords - Domaini

    SH3-binding, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG269976.
    HOGENOMiHOG000033797.
    HOVERGENiHBG050457.
    InParanoidiP78536.
    KOiK06059.
    OMAiKVCCRDE.
    OrthoDBiEOG7S4X58.
    PhylomeDBiP78536.
    TreeFamiTF314733.

    Family and domain databases

    Gene3Di3.40.390.10. 1 hit.
    4.10.70.10. 1 hit.
    InterProiIPR001762. Blood-coag_inhib_Disintegrin.
    IPR024079. MetalloPept_cat_dom.
    IPR001590. Peptidase_M12B.
    IPR002870. Peptidase_M12B_N.
    [Graphical view]
    PfamiPF00200. Disintegrin. 1 hit.
    PF01562. Pep_M12B_propep. 1 hit.
    [Graphical view]
    SMARTiSM00050. DISIN. 1 hit.
    [Graphical view]
    SUPFAMiSSF57552. SSF57552. 1 hit.
    PROSITEiPS50215. ADAM_MEPRO. 1 hit.
    PS50214. DISINTEGRIN_2. 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: P78536-1) [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

    MRQSLLFLTS VVPFVLAPRP PDDPGFGPHQ RLEKLDSLLS DYDILSLSNI    50
    QQHSVRKRDL QTSTHVETLL TFSALKRHFK LYLTSSTERF SQNFKVVVVD 100
    GKNESEYTVK WQDFFTGHVV GEPDSRVLAH IRDDDVIIRI NTDGAEYNIE 150
    PLWRFVNDTK DKRMLVYKSE DIKNVSRLQS PKVCGYLKVD NEELLPKGLV 200
    DREPPEELVH RVKRRADPDP MKNTCKLLVV ADHRFYRYMG RGEESTTTNY 250
    LIELIDRVDD IYRNTSWDNA GFKGYGIQIE QIRILKSPQE VKPGEKHYNM 300
    AKSYPNEEKD AWDVKMLLEQ FSFDIAEEAS KVCLAHLFTY QDFDMGTLGL 350
    AYVGSPRANS HGGVCPKAYY SPVGKKNIYL NSGLTSTKNY GKTILTKEAD 400
    LVTTHELGHN FGAEHDPDGL AECAPNEDQG GKYVMYPIAV SGDHENNKMF 450
    SNCSKQSIYK TIESKAQECF QERSNKVCGN SRVDEGEECD PGIMYLNNDT 500
    CCNSDCTLKE GVQCSDRNSP CCKNCQFETA QKKCQEAINA TCKGVSYCTG 550
    NSSECPPPGN AEDDTVCLDL GKCKDGKCIP FCEREQQLES CACNETDNSC 600
    KVCCRDLSGR CVPYVDAEQK NLFLRKGKPC TVGFCDMNGK CEKRVQDVIE 650
    RFWDFIDQLS INTFGKFLAD NIVGSVLVFS LIFWIPFSIL VHCVDKKLDK 700
    QYESLSLFHP SNVEMLSSMD SASVRIIKPF PAPQTPGRLQ PAPVIPSAPA 750
    APKLDHQRMD TIQEDPSTDS HMDEDGFEKD PFPNSSTAAK SFEDLTDHPV 800
    TRSEKAASFK LQRQNRVDSK ETEC 824
    Length:824
    Mass (Da):93,021
    Last modified:May 1, 1997 - v1
    Checksum:i5B1032F6B88A837F
    GO
    Isoform B (identifier: P78536-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         695-824: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:694
    Mass (Da):78,543
    Checksum:i9DD63A5B13490AA1
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti109 – 1091V → A in AAC39721. (PubMed:9574564)Curated
    Sequence conflicti563 – 5631D → N in AAC39721. (PubMed:9574564)Curated
    Sequence conflicti801 – 8011T → A in AAC39721. (PubMed:9574564)Curated
    Sequence conflicti818 – 8181D → N in AAC39721. (PubMed:9574564)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti162 – 1621K → E.
    Corresponds to variant rs34431503 [ dbSNP | Ensembl ].
    VAR_051586
    Natural varianti202 – 2021R → G.
    Corresponds to variant rs2230818 [ dbSNP | Ensembl ].
    VAR_051587

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei695 – 824130Missing in isoform B. 1 PublicationVSP_005478Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U86755 mRNA. Translation: AAB51586.1.
    U69611 mRNA. Translation: AAB51514.1.
    U69612 mRNA. Translation: AAB53014.1.
    U92649 mRNA. Translation: AAC39721.1.
    CCDSiCCDS1665.1. [P78536-1]
    RefSeqiNP_003174.3. NM_003183.4. [P78536-1]
    UniGeneiHs.404914.

    Genome annotation databases

    EnsembliENST00000310823; ENSP00000309968; ENSG00000151694. [P78536-1]
    GeneIDi6868.
    KEGGihsa:6868.
    UCSCiuc002qzu.3. human. [P78536-1]

    Polymorphism databases

    DMDMi14423632.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Wikipedia

    Tumor necrosis factor alpha-converting enzyme entry

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U86755 mRNA. Translation: AAB51586.1 .
    U69611 mRNA. Translation: AAB51514.1 .
    U69612 mRNA. Translation: AAB53014.1 .
    U92649 mRNA. Translation: AAC39721.1 .
    CCDSi CCDS1665.1. [P78536-1 ]
    RefSeqi NP_003174.3. NM_003183.4. [P78536-1 ]
    UniGenei Hs.404914.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1BKC X-ray 2.00 A/C/E/I 219-474 [» ]
    1ZXC X-ray 2.28 A/B 215-477 [» ]
    2A8H X-ray 2.30 A/B 215-477 [» ]
    2DDF X-ray 1.70 A/B 218-474 [» ]
    2FV5 X-ray 2.10 A/B 216-475 [» ]
    2FV9 X-ray 2.02 A/B 218-475 [» ]
    2I47 X-ray 1.90 A/B/C/D 212-492 [» ]
    2M2F NMR - A 581-642 [» ]
    2OI0 X-ray 2.00 A 216-477 [» ]
    3B92 X-ray 2.00 A 216-474 [» ]
    3CKI X-ray 2.30 A 219-474 [» ]
    3E8R X-ray 1.90 A/B 215-477 [» ]
    3EDZ X-ray 1.90 A/B 215-477 [» ]
    3EWJ X-ray 1.80 A/B 215-477 [» ]
    3G42 X-ray 2.10 A/B/C/D 212-492 [» ]
    3KMC X-ray 1.80 A/B 215-476 [» ]
    3KME X-ray 1.85 A/B 215-476 [» ]
    3L0T X-ray 1.92 A/B 215-476 [» ]
    3L0V X-ray 1.75 A/B 215-476 [» ]
    3LE9 X-ray 1.85 A/B 215-476 [» ]
    3LEA X-ray 2.00 A/B 215-476 [» ]
    3LGP X-ray 1.90 A/B 215-476 [» ]
    3O64 X-ray 1.88 A/B 215-476 [» ]
    ProteinModelPortali P78536.
    SMRi P78536. Positions 216-642.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112731. 9 interactions.
    IntActi P78536. 8 interactions.
    MINTi MINT-108290.
    STRINGi 9606.ENSP00000309968.

    Chemistry

    BindingDBi P78536.
    ChEMBLi CHEMBL3706.
    GuidetoPHARMACOLOGYi 1662.

    Protein family/group databases

    MEROPSi M12.217.

    PTM databases

    PhosphoSitei P78536.

    Polymorphism databases

    DMDMi 14423632.

    Proteomic databases

    MaxQBi P78536.
    PaxDbi P78536.
    PRIDEi P78536.

    Protocols and materials databases

    DNASUi 6868.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000310823 ; ENSP00000309968 ; ENSG00000151694 . [P78536-1 ]
    GeneIDi 6868.
    KEGGi hsa:6868.
    UCSCi uc002qzu.3. human. [P78536-1 ]

    Organism-specific databases

    CTDi 6868.
    GeneCardsi GC02M009580.
    HGNCi HGNC:195. ADAM17.
    HPAi CAB025906.
    HPA010738.
    HPA051575.
    MIMi 603639. gene.
    614328. phenotype.
    neXtProti NX_P78536.
    Orphaneti 294023. Neonatal inflammatory skin and bowel disease.
    PharmGKBi PA24512.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG269976.
    HOGENOMi HOG000033797.
    HOVERGENi HBG050457.
    InParanoidi P78536.
    KOi K06059.
    OMAi KVCCRDE.
    OrthoDBi EOG7S4X58.
    PhylomeDBi P78536.
    TreeFami TF314733.

    Enzyme and pathway databases

    BRENDAi 3.4.24.86. 2681.
    Reactomei REACT_111133. Growth hormone receptor signaling.
    REACT_116022. Nuclear signaling by ERBB4.
    REACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_13443. Regulated proteolysis of p75NTR.
    REACT_1432. TNF signaling.
    REACT_150401. Collagen degradation.
    REACT_160089. Constitutive Signaling by NOTCH1 HD Domain Mutants.
    REACT_160106. Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant.
    REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
    REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
    REACT_9417. Signaling by EGFR.
    SignaLinki P78536.

    Miscellaneous databases

    ChiTaRSi ADAM17. human.
    EvolutionaryTracei P78536.
    GeneWikii ADAM17.
    GenomeRNAii 6868.
    NextBioi 26807.
    PROi P78536.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P78536.
    Bgeei P78536.
    CleanExi HS_ADAM17.
    Genevestigatori P78536.

    Family and domain databases

    Gene3Di 3.40.390.10. 1 hit.
    4.10.70.10. 1 hit.
    InterProi IPR001762. Blood-coag_inhib_Disintegrin.
    IPR024079. MetalloPept_cat_dom.
    IPR001590. Peptidase_M12B.
    IPR002870. Peptidase_M12B_N.
    [Graphical view ]
    Pfami PF00200. Disintegrin. 1 hit.
    PF01562. Pep_M12B_propep. 1 hit.
    [Graphical view ]
    SMARTi SM00050. DISIN. 1 hit.
    [Graphical view ]
    SUPFAMi SSF57552. SSF57552. 1 hit.
    PROSITEi PS50215. ADAM_MEPRO. 1 hit.
    PS50214. DISINTEGRIN_2. 1 hit.
    PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), PARTIAL PROTEIN SEQUENCE.
      Tissue: Leukocyte and Monocyte.
    2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
    3. "TNF-alpha convertase enzyme from human arthritis-affected cartilage: isolation of cDNA by differential display, expression of the active enzyme, and regulation of TNF-alpha."
      Patel I.R., Attur M.G., Patel R.N., Stuchin S.A., Abagyan R.A., Abramson S.B., Amin A.R.
      J. Immunol. 160:4570-4579(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
      Tissue: Cartilage.
    4. "Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a potential role in regulated shedding."
      Diaz-Rodriguez E., Montero J.C., Esparis-Ogando A., Yuste L., Pandiella A.
      Mol. Biol. Cell 13:2031-2044(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-735.
    5. "Tumor necrosis factor-alpha converting enzyme/ADAM 17 mediates MUC1 shedding."
      Thathiah A., Blobel C.P., Carson D.D.
      J. Biol. Chem. 278:3386-3394(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MUC1, FUNCTION.
    6. "Characterization of growth factor-induced serine phosphorylation of tumor necrosis factor-alpha converting enzyme and of an alternatively translated polypeptide."
      Fan H., Turck C.W., Derynck R.
      J. Biol. Chem. 278:18617-18627(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-819.
    7. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
      Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
      Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    8. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    9. Cited for: ROLE IN PROTEOLYTICAL RELEASE OF JAM3.
    10. "Direct activation of TACE-mediated ectodomain shedding by p38 MAP kinase regulates EGF receptor-dependent cell proliferation."
      Xu P., Derynck R.
      Mol. Cell 37:551-566(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-735, INTERACTION WITH MAPK14.
    11. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    12. Cited for: INVOLVEMENT IN NISBD.
    13. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
      Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
      Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    14. "The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality."
      Boskovski M.T., Yuan S., Pedersen N.B., Goth C.K., Makova S., Clausen H., Brueckner M., Khokha M.K.
      Nature 504:456-459(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    15. "TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein."
      Heurich A., Hofmann-Winkler H., Gierer S., Liepold T., Jahn O., Poehlmann S.
      J. Virol. 88:1293-1307(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    16. Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 219-473, ACTIVE SITE.

    Entry informationi

    Entry nameiADA17_HUMAN
    AccessioniPrimary (citable) accession number: P78536
    Secondary accession number(s): O60226
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 20, 2001
    Last sequence update: May 1, 1997
    Last modified: October 1, 2014
    This is version 169 of the entry and version 1 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

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. Peptidase families
      Classification of peptidase families and list of entries
    8. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3