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Protein

Disintegrin and metalloproteinase domain-containing protein 17

Gene

Adam17

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 (By similarity). 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 (By similarity).By similarity

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

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi184 – 1841Zinc; in inhibited formBy similarity
Metal bindingi405 – 4051Zinc; catalyticBy similarity
Active sitei406 – 4061PROSITE-ProRule annotation
Metal bindingi409 – 4091Zinc; catalyticBy similarity
Metal bindingi415 – 4151Zinc; catalyticBy similarity

GO - Molecular functioni

  • metalloendopeptidase activity Source: RGD
  • metallopeptidase activity Source: RGD
  • Notch binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • membrane protein ectodomain proteolysis Source: RGD
  • negative regulation of apoptotic process Source: RGD
  • Notch receptor processing Source: UniProtKB
  • Notch signaling pathway Source: UniProtKB-KW
  • proteolysis Source: UniProtKB
Complete GO annotation...

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. 5301.

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):
TNF-alpha convertase
TNF-alpha-converting enzyme
CD_antigen: CD156b
Gene namesi
Name:Adam17
Synonyms:Tace
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620404. Adam17.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini215 – 671457ExtracellularSequence analysisAdd
BLAST
Transmembranei672 – 69221HelicalSequence analysisAdd
BLAST
Topological domaini693 – 827135CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cell surface Source: RGD
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL2523.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1717Sequence analysisAdd
BLAST
Propeptidei18 – 214197By similarityPRO_0000029092Add
BLAST
Chaini215 – 827613Disintegrin and metalloproteinase domain-containing protein 17PRO_0000029093Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi157 – 1571N-linked (GlcNAc...)Sequence analysis
Disulfide bondi225 ↔ 333By similarity
Glycosylationi264 – 2641N-linked (GlcNAc...)Sequence analysis
Disulfide bondi365 ↔ 469By similarity
Disulfide bondi423 ↔ 453By similarity
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
Glycosylationi606 – 6061N-linked (GlcNAc...)Sequence analysis
Modified residuei735 – 7351Phosphothreonine; by MAPK14By similarity
Modified residuei770 – 7701PhosphoserineCombined sources
Modified residuei794 – 7941PhosphoserineCombined sources
Modified residuei822 – 8221PhosphoserineBy similarity

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-822 but decreases phosphorylation of Ser-794. Phosphorylation at THR-735 by MAPK14 is required for ADAM17-mediated ectodomain shedding (By similarity).By similarity

Keywords - PTMi

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

Proteomic databases

PaxDbiQ9Z1K9.

PTM databases

iPTMnetiQ9Z1K9.
PhosphoSiteiQ9Z1K9.

Interactioni

Subunit structurei

Interacts with MAD2L1, MAPK14 and MUC1.By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ9Z1K9. 1 interaction.
STRINGi10116.ENSRNOP00000010648.

Chemistry

BindingDBiQ9Z1K9.

Structurei

3D structure databases

ProteinModelPortaliQ9Z1K9.
SMRiQ9Z1K9. Positions 216-477.
ModBaseiSearch...
MobiDBiSearch...

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

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

eggNOGiKOG3658. Eukaryota.
ENOG410XQWB. LUCA.
HOGENOMiHOG000033797.
HOVERGENiHBG050457.
InParanoidiQ9Z1K9.
KOiK06059.
PhylomeDBiQ9Z1K9.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR032029. ADAM17_MPD.
IPR001762. Disintegrin_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PfamiPF16698. ADAM17_MPD. 1 hit.
PF00200. 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]

Sequencei

Sequence statusi: Complete.

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

Q9Z1K9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRQRLLFLTT LVPFVLAPRP PEEPGSGSHL RLEKLDSLLS DYDILSLSNI
60 70 80 90 100
QQHSIRKRDL QSATHLETLL TFSALKRHFK LYLTSSTERF SQNLRVVVVD
110 120 130 140 150
GKEESEYSVK WQDFFSGHVV GEPDSRVLAH IGDDDVTVRI NTDGAEYNIE
160 170 180 190 200
PLWRFVNDTK DKRMLVYKSE DIKDFSRLQS PKVCGYLNAD SEELLPKGLI
210 220 230 240 250
DREPSEEFVR RVKRRAEPNP LKNTCKLLVV ADHRFYKYMG RGEESTTTNY
260 270 280 290 300
LIELIDRVDD IYRNTSWDNA GFKGYGVQIE QIRILKSPQE VKPGERHFNM
310 320 330 340 350
AKSFPNEEKD AWDVKMLLEQ FSLDIAEEAS KVCLAHLFTY QDFDMGTLGL
360 370 380 390 400
AYVGSPRANS HGGVCPKAYY NPGVKKNIYL NSGLTSTKNY GKTILTKEAD
410 420 430 440 450
LVTTHELGHN FGAEHDPDGL AECAPNEDQG GKYVMYPIAV SGDHENNKMF
460 470 480 490 500
SNCSKQSIYK TIESKAQECF QERSNKVCGN SRVDEGEECD PGIMYLNNDT
510 520 530 540 550
CCNSDCTLKP GVQCSDRNSP CCKNCQFETA QKKCQEAINA TCKGVSYCTG
560 570 580 590 600
NSSECPPPGD AEDDTVCLDL GKCKAGKCIP FCKREQELES CACADTDNSC
610 620 630 640 650
KVCCRNLSGP CVPYVDAEQK NLFLRKGKPC TVGFCDMNGK CEKRVQDVIE
660 670 680 690 700
RFWDFIDQLS INTFGKFLAD NIVGSVLVFS LIFWIPFSIL VHCVDKKLDK
710 720 730 740 750
QYESLSLFHH SNIEMLSSMD SASVRIIKPF PAPQTPGRLQ ALQPAAMMPP
760 770 780 790 800
VSAAPKLDHQ RMDTIQEDPS TDSHVDDDGF EKDPFPNSSA AAKSFEDLTD
810 820
HPVTRSEKAA SFKLQRQSRV DSKETEC
Length:827
Mass (Da):93,017
Last modified:May 1, 1999 - v1
Checksum:iEF82239C067F2AFF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ012603 mRNA. Translation: CAA10072.1.
RefSeqiNP_064702.1. NM_020306.2.
UniGeneiRn.144585.

Genome annotation databases

GeneIDi57027.
KEGGirno:57027.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ012603 mRNA. Translation: CAA10072.1.
RefSeqiNP_064702.1. NM_020306.2.
UniGeneiRn.144585.

3D structure databases

ProteinModelPortaliQ9Z1K9.
SMRiQ9Z1K9. Positions 216-477.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9Z1K9. 1 interaction.
STRINGi10116.ENSRNOP00000010648.

Chemistry

BindingDBiQ9Z1K9.
ChEMBLiCHEMBL2523.

Protein family/group databases

MEROPSiM12.217.

PTM databases

iPTMnetiQ9Z1K9.
PhosphoSiteiQ9Z1K9.

Proteomic databases

PaxDbiQ9Z1K9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi57027.
KEGGirno:57027.

Organism-specific databases

CTDi6868.
RGDi620404. Adam17.

Phylogenomic databases

eggNOGiKOG3658. Eukaryota.
ENOG410XQWB. LUCA.
HOGENOMiHOG000033797.
HOVERGENiHBG050457.
InParanoidiQ9Z1K9.
KOiK06059.
PhylomeDBiQ9Z1K9.

Enzyme and pathway databases

BRENDAi3.4.24.86. 5301.

Miscellaneous databases

NextBioi611284.
PROiQ9Z1K9.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR032029. ADAM17_MPD.
IPR001762. Disintegrin_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PfamiPF16698. ADAM17_MPD. 1 hit.
PF00200. 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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Sequence analysis of rat TNF-alpha converting enzyme (TACE) cDNA."
    Hall L., Beaumont A.J., Jury J.A., Frayne J.
    Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Testis.
  2. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-770 AND SER-794, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiADA17_RAT
AccessioniPrimary (citable) accession number: Q9Z1K9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: May 1, 1999
Last modified: January 20, 2016
This is version 125 of the entry and version 1 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. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.