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Reviewed, UniProtKB/Swiss-Prot Q9Z1K9 (ADA17_RAT)

Last modified November 4, 2008. Version 67. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    ADAM 17
    EC=3.4.24.86
Alternative name(s):
    A disintegrin and metalloproteinase domain 17
    TNF-alpha-converting enzyme
    TNF-alpha convertase
    CD_antigen=CD156b
Gene names
Name: Adam17
Synonyms: Tace
OrganismRattus norvegicus (Rat)
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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Protein attributes

Sequence length827 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level.

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General annotation (Comments)

Function

Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. 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. Also involved in the activation of Notch pathway By similarity.

Catalytic activity

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.

Cofactor

Binds 1 zinc ion per subunit By similarity.

Subunit structure

Interacts with MAD2L1 and MUC1 By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein.

Domain

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.

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.

Post-translational modification

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 By similarity.

Sequence similarities

Contains 1 disintegrin domain.

Contains 1 peptidase M12B domain.

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Ontologies

Keywords

   Biological processNotch signaling pathway
   Cellular componentMembrane
   DomainSH3-binding
Signal
Transmembrane
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMCleavage on pair of basic residues
Glycoprotein
Phosphoprotein
Zymogen

Gene Ontology (GO)

   Biological processNotch signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentintegral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular functionSH3 domain binding

Inferred from electronic annotation. Source: UniProtKB-KW

zinc ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Potential
Propeptide18 – 214197 By similarity
PRO_0000029092
Chain215 – 827613ADAM 17
PRO_0000029093

Regions

Topological domain215 – 671457Extracellular Potential
Transmembrane672 – 69221 Potential
Topological domain693 – 827135Cytoplasmic Potential
Domain223 – 474252Peptidase M12B
Domain475 – 56389Disintegrin
Region603 – 67169Crambin-like
Motif182 – 1898Cysteine switch By similarity
Motif731 – 7388SH3-binding Potential
Compositional bias96 – 994Poly-Val
Compositional bias564 – 60239Cys-rich

Sites

Active site4061 By similarity
Metal binding1841Zinc; in inhibited form By similarity
Metal binding4051Zinc; catalytic By similarity
Metal binding4091Zinc; catalytic By similarity
Metal binding4151Zinc; catalytic By similarity

Amino acid modifications

Modified residue3791Phosphotyrosine By similarity
Modified residue3821Phosphoserine By similarity
Modified residue7351Phosphothreonine; by MAPK By similarity
Modified residue7941Phosphoserine By similarity
Modified residue8221Phosphoserine By similarity
Glycosylation1571N-linked (GlcNAc...) Potential
Glycosylation2641N-linked (GlcNAc...) Potential
Glycosylation4521N-linked (GlcNAc...) Potential
Glycosylation4981N-linked (GlcNAc...) Potential
Glycosylation5391N-linked (GlcNAc...) Potential
Glycosylation5511N-linked (GlcNAc...) Potential
Glycosylation6061N-linked (GlcNAc...) Potential
Disulfide bond225 ↔ 333 By similarity
Disulfide bond365 ↔ 469 By similarity
Disulfide bond423 ↔ 453 By similarity
Disulfide bond534 ↔ 555 By similarity
Disulfide bond573 ↔ 582 By similarity
Disulfide bond578 ↔ 591 By similarity
Disulfide bond593 ↔ 600 By similarity

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Sequences

Sequence LengthMass (Da)Tools
Q9Z1K9-1 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: EF82239C067F2AFF

FASTA82793,017
        10         20         30         40         50         60 
MRQRLLFLTT LVPFVLAPRP PEEPGSGSHL RLEKLDSLLS DYDILSLSNI QQHSIRKRDL 

        70         80         90        100        110        120 
QSATHLETLL TFSALKRHFK LYLTSSTERF SQNLRVVVVD GKEESEYSVK WQDFFSGHVV 

       130        140        150        160        170        180 
GEPDSRVLAH IGDDDVTVRI NTDGAEYNIE PLWRFVNDTK DKRMLVYKSE DIKDFSRLQS 

       190        200        210        220        230        240 
PKVCGYLNAD SEELLPKGLI DREPSEEFVR RVKRRAEPNP LKNTCKLLVV ADHRFYKYMG 

       250        260        270        280        290        300 
RGEESTTTNY LIELIDRVDD IYRNTSWDNA GFKGYGVQIE QIRILKSPQE VKPGERHFNM 

       310        320        330        340        350        360 
AKSFPNEEKD AWDVKMLLEQ FSLDIAEEAS KVCLAHLFTY QDFDMGTLGL AYVGSPRANS 

       370        380        390        400        410        420 
HGGVCPKAYY NPGVKKNIYL NSGLTSTKNY GKTILTKEAD LVTTHELGHN FGAEHDPDGL 

       430        440        450        460        470        480 
AECAPNEDQG GKYVMYPIAV SGDHENNKMF SNCSKQSIYK TIESKAQECF QERSNKVCGN 

       490        500        510        520        530        540 
SRVDEGEECD PGIMYLNNDT CCNSDCTLKP GVQCSDRNSP CCKNCQFETA QKKCQEAINA 

       550        560        570        580        590        600 
TCKGVSYCTG NSSECPPPGD AEDDTVCLDL GKCKAGKCIP FCKREQELES CACADTDNSC 

       610        620        630        640        650        660 
KVCCRNLSGP CVPYVDAEQK NLFLRKGKPC TVGFCDMNGK CEKRVQDVIE RFWDFIDQLS 

       670        680        690        700        710        720 
INTFGKFLAD NIVGSVLVFS LIFWIPFSIL VHCVDKKLDK QYESLSLFHH SNIEMLSSMD 

       730        740        750        760        770        780 
SASVRIIKPF PAPQTPGRLQ ALQPAAMMPP VSAAPKLDHQ RMDTIQEDPS TDSHVDDDGF 

       790        800        810        820 
EKDPFPNSSA AAKSFEDLTD HPVTRSEKAA SFKLQRQSRV DSKETEC

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References

[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.

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Cross-references

Sequence databases

AJ012603 mRNA. Translation: CAA10072.1.
RefSeqNP_064702.1.
UniGeneRn.144585

3D structure databases

HSSPHSSP built from PDB template 1BKC based on UniProtKB P78536.
SMRQ9Z1K9. Positions 216-475.
ModBaseSearch...

Protein family/group databases

MEROPSM12.217.

PTM databases

PhosphoSiteQ9Z1K9.

Genome annotation databases

EnsemblENSRNOG00000007503. Rattus norvegicus. [Contig view]
GeneID57027.
KEGGrno:57027.

Organism-specific databases

RGD620404. Adam17.

Phylogenomic databases

HOVERGENQ9Z1K9.

Gene expression databases

ArrayExpressQ9Z1K9.
GermOnlineENSRNOG00000007503. Rattus norvegicus.

Family and domain databases

InterProIPR001762. Blood-coag_inhib_Disintegrin.
IPR013032. EGF_like_reg_CS.
IPR001818. Pept_M10A_M12B.
IPR006025. Pept_M_Zn_BS.
IPR001590. Peptidase_M12B.
[Graphical view]
PfamPF00200. Disintegrin. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view]
ProDomPD000664. Disintegrin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00050. DISIN. 1 hit.
[Graphical view]
PROSITEPS50215. ADAM_MEPRO. 1 hit.
PS00546. CYSTEINE_SWITCH. False negative.
PS00427. DISINTEGRIN_1. False negative.
PS50214. DISINTEGRIN_2. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
BLOCKSSearch...
ProtoNetSearch...

Other Resources

NextBio611284.

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Entry information

Entry nameADA17_RAT
AccessionPrimary (citable) accession number: Q9Z1K9
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: May 1, 1999
Last modified: November 4, 2008
This is version 67 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents