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P78536 (ADA17_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 164. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Disintegrin and metalloproteinase domain-containing protein 17

Short name=ADAM 17
EC=3.4.24.86
Alternative name(s):
Snake venom-like protease
TNF-alpha convertase
TNF-alpha-converting enzyme
CD_antigen=CD156b
Gene names
Name:ADAM17
Synonyms:CSVP, TACE
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length824 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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). Ref.5 Ref.9 Ref.14

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.

Subunit structure

Interacts with MAD2L1, MAPK14 and MUC1. Ref.5 Ref.10

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

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.

Induction

In arthritis-affected cartilage.

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-819 but decreases phosphorylation of Ser-791. Phosphorylation at THR-735 by MAPK14 is required for ADAM17-mediated ectodomain shedding. Ref.4 Ref.6 Ref.10

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12

Sequence similarities

Contains 1 disintegrin domain.

Contains 1 peptidase M12B domain.

Ontologies

Keywords
   Biological processNotch signaling pathway
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSH3-binding
Signal
Transmembrane
Transmembrane helix
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Phosphoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processB cell differentiation

Inferred from sequence or structural similarity PubMed 10433800. Source: BHF-UCL

JAK-STAT cascade involved in growth hormone signaling pathway

Traceable author statement. Source: Reactome

Notch receptor processing

Inferred from direct assay Ref.14. Source: UniProtKB

Notch signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

PMA-inducible membrane protein ectodomain proteolysis

Inferred from direct assay PubMed 14625290PubMed 15691827PubMed 17010968. Source: BHF-UCL

T cell differentiation in thymus

Inferred from sequence or structural similarity PubMed 10433800. Source: BHF-UCL

apoptotic process

Traceable author statement. Source: Reactome

apoptotic signaling pathway

Traceable author statement. Source: Reactome

cell adhesion

Inferred from direct assay PubMed 14970227. Source: BHF-UCL

cell adhesion mediated by integrin

Inferred from direct assay PubMed 14970227. Source: BHF-UCL

cell motility

Inferred from sequence or structural similarity PubMed 10433800. Source: BHF-UCL

collagen catabolic process

Traceable author statement. Source: Reactome

epidermal growth factor receptor signaling pathway

Inferred from direct assay PubMed 12743035. Source: BHF-UCL

epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway

Inferred from mutant phenotype PubMed 17655843. Source: BHF-UCL

extracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

germinal center formation

Inferred from sequence or structural similarity PubMed 10433800. Source: BHF-UCL

membrane protein ectodomain proteolysis

Inferred from direct assay PubMed 17786981PubMed 18676862Ref.2Ref.3. Source: BHF-UCL

membrane protein intracellular domain proteolysis

Traceable author statement. Source: Reactome

negative regulation of interleukin-8 production

Inferred from mutant phenotype PubMed 16034137. Source: BHF-UCL

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

neutrophil mediated immunity

Inferred by curator PubMed 16034137. Source: BHF-UCL

positive regulation of T cell chemotaxis

Inferred from mutant phenotype PubMed 18373975. Source: BHF-UCL

positive regulation of cell growth

Inferred from mutant phenotype PubMed 18373975. Source: BHF-UCL

positive regulation of cell migration

Inferred from mutant phenotype PubMed 18373975. Source: BHF-UCL

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 18373975. Source: BHF-UCL

positive regulation of cellular component movement

Inferred from sequence or structural similarity PubMed 10433800. Source: BHF-UCL

positive regulation of chemokine production

Inferred from mutant phenotype PubMed 16034137. Source: BHF-UCL

positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle

Inferred from direct assay PubMed 18483258. Source: BHF-UCL

positive regulation of epidermal growth factor-activated receptor activity

Inferred from direct assay PubMed 18483258. Source: BHF-UCL

positive regulation of leukocyte chemotaxis

Inferred by curator PubMed 16034137. Source: BHF-UCL

positive regulation of protein phosphorylation

Inferred from mutant phenotype PubMed 18625725. Source: BHF-UCL

positive regulation of transforming growth factor beta receptor signaling pathway

Inferred from sequence or structural similarity PubMed 10433800. Source: BHF-UCL

regulation of mast cell apoptotic process

Inferred from sequence or structural similarity PubMed 10433800. Source: BHF-UCL

response to drug

Inferred from sequence or structural similarity PubMed 10433800. Source: BHF-UCL

response to high density lipoprotein particle

Inferred from direct assay PubMed 17786981. Source: BHF-UCL

response to hypoxia

Inferred from direct assay PubMed 18276953. Source: BHF-UCL

response to lipopolysaccharide

Inferred from direct assay PubMed 18383040. Source: BHF-UCL

spleen development

Inferred from sequence or structural similarity PubMed 10433800. Source: BHF-UCL

wound healing, spreading of epidermal cells

Inferred from expression pattern PubMed 14970227. Source: BHF-UCL

   Cellular_componentactin cytoskeleton

Inferred from direct assay PubMed 17010968. Source: BHF-UCL

apical plasma membrane

Inferred from direct assay PubMed 16034137. Source: BHF-UCL

cell surface

Inferred from direct assay PubMed 18383040PubMed 18625725Ref.2. Source: BHF-UCL

cytoplasm

Inferred from direct assay. Source: HPA

integral component of plasma membrane

Inferred from direct assay PubMed 17786981. Source: BHF-UCL

membrane raft

Inferred from direct assay PubMed 17010968PubMed 17786981. Source: BHF-UCL

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionNotch binding

Inferred from direct assay Ref.14. Source: UniProtKB

PDZ domain binding

Inferred from physical interaction PubMed 12207026. Source: BHF-UCL

integrin binding

Inferred from physical interaction PubMed 14970227. Source: BHF-UCL

interleukin-6 receptor binding

Inferred from physical interaction PubMed 16034137. Source: BHF-UCL

metalloendopeptidase activity

Inferred from direct assay Ref.14. Source: UniProtKB

metallopeptidase activity

Inferred from direct assay PubMed 12777399. Source: BHF-UCL

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DLG1Q129597EBI-78188,EBI-357481
MAD2L1Q132573EBI-78188,EBI-78203

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: P78536-1)

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.
Isoform B (identifier: P78536-2)

The sequence of this isoform differs from the canonical sequence as follows:
     695-824: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Potential
Propeptide18 – 214197
PRO_0000029088
Chain215 – 824610Disintegrin and metalloproteinase domain-containing protein 17
PRO_0000029089

Regions

Topological domain215 – 671457Extracellular Potential
Transmembrane672 – 69221Helical; Potential
Topological domain693 – 824132Cytoplasmic Potential
Domain223 – 474252Peptidase M12B
Domain475 – 56389Disintegrin
Region603 – 67169Crambin-like
Motif182 – 1898Cysteine switch By similarity
Motif731 – 7388SH3-binding Potential
Motif741 – 7488SH3-binding Potential
Compositional bias96 – 994Poly-Val
Compositional bias564 – 60239Cys-rich

Sites

Active site4061 Ref.15
Metal binding1841Zinc; in inhibited form By similarity
Metal binding4051Zinc; catalytic
Metal binding4091Zinc; catalytic
Metal binding4151Zinc; catalytic

Amino acid modifications

Modified residue7351Phosphothreonine; by MAPK14 Ref.4 Ref.10
Modified residue7911Phosphoserine Ref.7 Ref.8 Ref.11 Ref.13
Modified residue8191Phosphoserine Ref.6
Glycosylation1031N-linked (GlcNAc...) Potential
Glycosylation1571N-linked (GlcNAc...) Potential
Glycosylation1741N-linked (GlcNAc...) Potential
Glycosylation2641N-linked (GlcNAc...) Potential
Glycosylation4521N-linked (GlcNAc...) Potential
Glycosylation4981N-linked (GlcNAc...) Potential
Glycosylation5391N-linked (GlcNAc...) Potential
Glycosylation5511N-linked (GlcNAc...) Potential
Glycosylation5941N-linked (GlcNAc...) Potential
Disulfide bond225 ↔ 333
Disulfide bond365 ↔ 469
Disulfide bond423 ↔ 453
Disulfide bond534 ↔ 555 By similarity
Disulfide bond573 ↔ 582 By similarity
Disulfide bond578 ↔ 591 By similarity
Disulfide bond593 ↔ 600 By similarity

Natural variations

Alternative sequence695 – 824130Missing in isoform B.
VSP_005478
Natural variant1621K → E.
Corresponds to variant rs34431503 [ dbSNP | Ensembl ].
VAR_051586
Natural variant2021R → G.
Corresponds to variant rs2230818 [ dbSNP | Ensembl ].
VAR_051587

Experimental info

Sequence conflict1091V → A in AAC39721. Ref.3
Sequence conflict5631D → N in AAC39721. Ref.3
Sequence conflict8011T → A in AAC39721. Ref.3
Sequence conflict8181D → N in AAC39721. Ref.3

Secondary structure

................................................................. 824
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform A [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 5B1032F6B88A837F

FASTA82493,021
        10         20         30         40         50         60 
MRQSLLFLTS VVPFVLAPRP PDDPGFGPHQ RLEKLDSLLS DYDILSLSNI QQHSVRKRDL 

        70         80         90        100        110        120 
QTSTHVETLL TFSALKRHFK LYLTSSTERF SQNFKVVVVD GKNESEYTVK WQDFFTGHVV 

       130        140        150        160        170        180 
GEPDSRVLAH IRDDDVIIRI NTDGAEYNIE PLWRFVNDTK DKRMLVYKSE DIKNVSRLQS 

       190        200        210        220        230        240 
PKVCGYLKVD NEELLPKGLV DREPPEELVH RVKRRADPDP MKNTCKLLVV ADHRFYRYMG 

       250        260        270        280        290        300 
RGEESTTTNY LIELIDRVDD IYRNTSWDNA GFKGYGIQIE QIRILKSPQE VKPGEKHYNM 

       310        320        330        340        350        360 
AKSYPNEEKD AWDVKMLLEQ FSFDIAEEAS KVCLAHLFTY QDFDMGTLGL AYVGSPRANS 

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

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

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

       550        560        570        580        590        600 
TCKGVSYCTG NSSECPPPGN AEDDTVCLDL GKCKDGKCIP FCEREQQLES CACNETDNSC 

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

       670        680        690        700        710        720 
INTFGKFLAD NIVGSVLVFS LIFWIPFSIL VHCVDKKLDK QYESLSLFHP SNVEMLSSMD 

       730        740        750        760        770        780 
SASVRIIKPF PAPQTPGRLQ PAPVIPSAPA APKLDHQRMD TIQEDPSTDS HMDEDGFEKD 

       790        800        810        820 
PFPNSSTAAK SFEDLTDHPV TRSEKAASFK LQRQNRVDSK ETEC 

« Hide

Isoform B [UniParc].

Checksum: 9DD63A5B13490AA1
Show »

FASTA69478,543

References

« Hide 'large scale' references
[1]"Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha."
Moss M.L., Jin S.-L.C., Milla M.E., Burkhart W., Carter H.L., Chen W.-J., Clay W.C., Didsbury J.R., Hassler D., Hoffman C.R., Kost T.A., Lambert M.H., Leesnitzer M.A., McCauley P., McGeehan G., Mitchell J., Moyer M., Pahel G. expand/collapse author list , Rocque W., Overton L.K., Schoenen F., Seaton T., Su J.-L., Warner J., Willard D., Becherer J.D.
Nature 385:733-736(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), PARTIAL PROTEIN SEQUENCE.
Tissue: Leukocyte and Monocyte.
[2]"A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells."
Black R.A., Rauch C.T., Kozlosky C.J., Peschon J.J., Slack J.L., Wolfson M.F., Castner B.J., Stocking K.L., Reddy P., Srinivasan S., Nelson N., Bioani N., Schooley K.A., Gerhart M., Davis R., Fitzner J.N., Johnson R.S., Paxton R.J., March C.J., Cerretti D.P.
Nature 385:729-733(1997) [PubMed] [Europe PMC] [Abstract]
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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Junctional adhesion molecule-C is a soluble mediator of angiogenesis."
Rabquer B.J., Amin M.A., Teegala N., Shaheen M.K., Tsou P.S., Ruth J.H., Lesch C.A., Imhof B.A., Koch A.E.
J. Immunol. 185:1777-1785(2010) [PubMed] [Europe PMC] [Abstract]
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]"Inflammatory skin and bowel disease linked to ADAM17 deletion."
Blaydon D.C., Biancheri P., Di W.L., Plagnol V., Cabral R.M., Brooke M.A., van Heel D.A., Ruschendorf F., Toynbee M., Walne A., O'Toole E.A., Martin J.E., Lindley K., Vulliamy T., Abrams D.J., MacDonald T.T., Harper J.I., Kelsell D.P.
N. Engl. J. Med. 365:1502-1508(2011) [PubMed] [Europe PMC] [Abstract]
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]"Crystal structure of the catalytic domain of human tumor necrosis factor-alpha-converting enzyme."
Maskos K., Fernandez-Catalan C., Huber R., Bourenkov G.P., Bartunik H., Ellestad G.A., Reddy P., Wolfson M.F., Rauch C.T., Castner B.J., Davis R., Clarke H.R.G., Petersen M., Fitzner J.N., Cerretti D.P., March C.J., Paxton R.J., Black R.A., Bode W.
Proc. Natl. Acad. Sci. U.S.A. 95:3408-3412(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 219-473, ACTIVE SITE.
+Additional computationally mapped references.

Web resources

Wikipedia

Tumor necrosis factor alpha-converting enzyme entry

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U86755 mRNA. Translation: AAB51586.1.
U69611 mRNA. Translation: AAB51514.1.
U69612 mRNA. Translation: AAB53014.1.
U92649 mRNA. Translation: AAC39721.1.
RefSeqNP_003174.3. NM_003183.4.
UniGeneHs.404914.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP78536.
SMRP78536. Positions 216-642.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112731. 9 interactions.
IntActP78536. 7 interactions.
MINTMINT-108290.
STRING9606.ENSP00000309968.

Chemistry

BindingDBP78536.
ChEMBLCHEMBL3706.
GuidetoPHARMACOLOGY1662.

Protein family/group databases

MEROPSM12.217.

PTM databases

PhosphoSiteP78536.

Polymorphism databases

DMDM14423632.

Proteomic databases

PaxDbP78536.
PRIDEP78536.

Protocols and materials databases

DNASU6868.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000310823; ENSP00000309968; ENSG00000151694. [P78536-1]
GeneID6868.
KEGGhsa:6868.
UCSCuc002qzu.3. human. [P78536-1]

Organism-specific databases

CTD6868.
GeneCardsGC02M009580.
HGNCHGNC:195. ADAM17.
HPACAB025906.
HPA010738.
HPA051575.
MIM603639. gene.
614328. phenotype.
neXtProtNX_P78536.
Orphanet294023. Neonatal inflammatory skin and bowel disease.
PharmGKBPA24512.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG269976.
HOGENOMHOG000033797.
HOVERGENHBG050457.
InParanoidP78536.
KOK06059.
OMAKVCCRDE.
OrthoDBEOG7S4X58.
PhylomeDBP78536.
TreeFamTF314733.

Enzyme and pathway databases

BRENDA3.4.24.86. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_118779. Extracellular matrix organization.
REACT_2001. Receptor-ligand binding initiates the second proteolytic cleavage of Notch receptor.
REACT_578. Apoptosis.
REACT_6900. Immune System.
SignaLinkP78536.

Gene expression databases

ArrayExpressP78536.
BgeeP78536.
CleanExHS_ADAM17.
GenevestigatorP78536.

Family and domain databases

Gene3D3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProIPR001762. Blood-coag_inhib_Disintegrin.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PfamPF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
[Graphical view]
SMARTSM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMSSF57552. SSF57552. 1 hit.
PROSITEPS50215. ADAM_MEPRO. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSADAM17. human.
EvolutionaryTraceP78536.
GeneWikiADAM17.
GenomeRNAi6868.
NextBio26807.
PROP78536.
SOURCESearch...

Entry information

Entry nameADA17_HUMAN
AccessionPrimary (citable) accession number: P78536
Secondary accession number(s): O60226
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: May 1, 1997
Last modified: April 16, 2014
This is version 164 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries