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Protein

Disintegrin and metalloproteinase domain-containing protein 17

Gene

ADAM17

Organism
Homo sapiens (Human)
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. 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

Zn2+1 PublicationNote: Binds 1 zinc ion per subunit.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi184Zinc; in inhibited formBy similarity1
Metal bindingi405Zinc; catalytic1 Publication1
Active sitei406PROSITE-ProRule annotation1 Publication1
Metal bindingi409Zinc; catalytic1 Publication1
Metal bindingi415Zinc; catalytic1 Publication1

GO - Molecular functioni

  • integrin binding Source: BHF-UCL
  • interleukin-6 receptor binding Source: BHF-UCL
  • metal ion binding Source: UniProtKB-KW
  • metalloendopeptidase activity Source: UniProtKB
  • metallopeptidase activity Source: BHF-UCL
  • Notch binding Source: UniProtKB
  • PDZ domain binding Source: BHF-UCL

GO - Biological processi

  • B cell differentiation Source: BHF-UCL
  • cell adhesion Source: BHF-UCL
  • cell adhesion mediated by integrin Source: BHF-UCL
  • cell motility Source: BHF-UCL
  • defense response to Gram-positive bacterium Source: BHF-UCL
  • epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway Source: BHF-UCL
  • epidermal growth factor receptor signaling pathway Source: BHF-UCL
  • germinal center formation Source: BHF-UCL
  • membrane protein ectodomain proteolysis Source: UniProtKB
  • membrane protein intracellular domain proteolysis Source: Reactome
  • negative regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
  • neutrophil mediated immunity Source: BHF-UCL
  • Notch receptor processing Source: UniProtKB
  • Notch signaling pathway Source: UniProtKB-KW
  • PMA-inducible membrane protein ectodomain proteolysis Source: BHF-UCL
  • positive regulation of cell growth Source: BHF-UCL
  • positive regulation of cell migration Source: BHF-UCL
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of cellular component movement Source: BHF-UCL
  • positive regulation of chemokine production Source: BHF-UCL
  • positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle Source: BHF-UCL
  • positive regulation of epidermal growth factor-activated receptor activity Source: BHF-UCL
  • positive regulation of leukocyte chemotaxis Source: BHF-UCL
  • positive regulation of protein phosphorylation Source: BHF-UCL
  • positive regulation of T cell chemotaxis Source: BHF-UCL
  • positive regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
  • proteolysis Source: UniProtKB
  • regulation of mast cell apoptotic process Source: BHF-UCL
  • response to drug Source: BHF-UCL
  • response to high density lipoprotein particle Source: BHF-UCL
  • response to hypoxia Source: BHF-UCL
  • response to lipopolysaccharide Source: BHF-UCL
  • spleen development Source: BHF-UCL
  • T cell differentiation in thymus Source: BHF-UCL
  • tumor necrosis factor-mediated signaling pathway Source: Reactome
  • wound healing, spreading of epidermal cells Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Notch signaling pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS07763-MONOMER.
BRENDAi3.4.24.86. 2681.
ReactomeiR-HSA-1251985. Nuclear signaling by ERBB4.
R-HSA-1442490. Collagen degradation.
R-HSA-177929. Signaling by EGFR.
R-HSA-193692. Regulated proteolysis of p75NTR.
R-HSA-2122948. Activated NOTCH1 Transmits Signal to the Nucleus.
R-HSA-2644606. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
R-HSA-2660826. Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant.
R-HSA-2691232. Constitutive Signaling by NOTCH1 HD Domain Mutants.
R-HSA-2894862. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
R-HSA-5362798. Release of Hh-Np from the secreting cell.
R-HSA-75893. TNF signaling.
R-HSA-982772. Growth hormone receptor signaling.
SignaLinkiP78536.
SIGNORiP78536.

Protein family/group databases

MEROPSiM12.217.
TCDBi8.A.77.1.2. the sheddase (sheddase) family.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:195. ADAM17.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini215 – 671ExtracellularSequence analysisAdd BLAST457
Transmembranei672 – 692HelicalSequence analysisAdd BLAST21
Topological domaini693 – 824CytoplasmicSequence analysisAdd BLAST132

GO - Cellular componenti

  • actin cytoskeleton Source: BHF-UCL
  • apical plasma membrane Source: BHF-UCL
  • cell surface Source: BHF-UCL
  • cytoplasm Source: BHF-UCL
  • integral component of plasma membrane Source: BHF-UCL
  • membrane Source: UniProtKB
  • membrane raft Source: BHF-UCL
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Inflammatory skin and bowel disease, neonatal, 1 (NISBD1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:614328

Organism-specific databases

DisGeNETi6868.
MalaCardsiADAM17.
MIMi614328. phenotype.
OpenTargetsiENSG00000151694.
Orphaneti294023. Neonatal inflammatory skin and bowel disease.
PharmGKBiPA24512.

Chemistry databases

ChEMBLiCHEMBL3706.
GuidetoPHARMACOLOGYi1662.

Polymorphism and mutation databases

BioMutaiADAM17.
DMDMi14423632.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17By similarityAdd BLAST17
PropeptideiPRO_000002908818 – 2141 PublicationAdd BLAST197
ChainiPRO_0000029089215 – 824Disintegrin and metalloproteinase domain-containing protein 17Add BLAST610

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi103N-linked (GlcNAc...)Sequence analysis1
Glycosylationi157N-linked (GlcNAc...)Sequence analysis1
Glycosylationi174N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi225 ↔ 3331 Publication
Glycosylationi264N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi365 ↔ 4691 Publication
Disulfide bondi423 ↔ 4531 Publication
Glycosylationi452N-linked (GlcNAc...)Sequence analysis1
Glycosylationi498N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi534 ↔ 555By similarity
Glycosylationi539N-linked (GlcNAc...)Sequence analysis1
Glycosylationi551N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi573 ↔ 582By similarity
Disulfide bondi578 ↔ 591By similarity
Disulfide bondi593 ↔ 600By similarity
Glycosylationi594N-linked (GlcNAc...)Sequence analysis1
Modified residuei735Phosphothreonine; by MAPK142 Publications1
Modified residuei761PhosphothreonineCombined sources1
Modified residuei767PhosphoserineBy similarity1
Modified residuei791PhosphoserineCombined sources1
Modified residuei819Phosphoserine1 Publication1

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.3 Publications

Keywords - PTMi

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

Proteomic databases

EPDiP78536.
MaxQBiP78536.
PaxDbiP78536.
PeptideAtlasiP78536.
PRIDEiP78536.

PTM databases

iPTMnetiP78536.
PhosphoSitePlusiP78536.
SwissPalmiP78536.

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

BgeeiENSG00000151694.
CleanExiHS_ADAM17.
ExpressionAtlasiP78536. baseline and differential.
GenevisibleiP78536. HS.

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

GO - Molecular functioni

  • integrin binding Source: BHF-UCL
  • interleukin-6 receptor binding Source: BHF-UCL
  • Notch binding Source: UniProtKB
  • PDZ domain binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi112731. 18 interactors.
DIPiDIP-31044N.
IntActiP78536. 9 interactors.
MINTiMINT-108290.
STRINGi9606.ENSP00000309968.

Chemistry databases

BindingDBiP78536.

Structurei

Secondary structure

1824
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi220 – 222Combined sources3
Beta strandi224 – 231Combined sources8
Helixi233 – 238Combined sources6
Turni239 – 242Combined sources4
Helixi244 – 263Combined sources20
Beta strandi269 – 271Combined sources3
Beta strandi276 – 284Combined sources9
Beta strandi300 – 302Combined sources3
Beta strandi309 – 311Combined sources3
Helixi314 – 324Combined sources11
Helixi326 – 329Combined sources4
Beta strandi332 – 339Combined sources8
Helixi344 – 346Combined sources3
Beta strandi349 – 354Combined sources6
Beta strandi355 – 357Combined sources3
Beta strandi363 – 365Combined sources3
Beta strandi368 – 371Combined sources4
Turni372 – 375Combined sources4
Beta strandi376 – 379Combined sources4
Beta strandi382 – 389Combined sources8
Helixi396 – 410Combined sources15
Beta strandi418 – 420Combined sources3
Turni421 – 423Combined sources3
Helixi427 – 429Combined sources3
Beta strandi436 – 438Combined sources3
Beta strandi442 – 444Combined sources3
Turni445 – 448Combined sources4
Helixi452 – 469Combined sources18
Helixi583 – 586Combined sources4
Beta strandi589 – 591Combined sources3
Helixi597 – 600Combined sources4
Beta strandi603 – 605Combined sources3
Beta strandi611 – 613Combined sources3
Beta strandi631 – 636Combined sources6
Turni637 – 639Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP78536.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini223 – 474Peptidase M12BPROSITE-ProRule annotationAdd BLAST252
Domaini475 – 563DisintegrinPROSITE-ProRule annotationAdd BLAST89

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni603 – 671Crambin-likeAdd BLAST69

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi182 – 189Cysteine switchBy similarity8
Motifi731 – 738SH3-bindingSequence analysis8
Motifi741 – 748SH3-bindingSequence analysis8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi96 – 99Poly-Val4
Compositional biasi564 – 602Cys-richAdd BLAST39

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.
GeneTreeiENSGT00670000097974.
HOGENOMiHOG000033797.
HOVERGENiHBG050457.
InParanoidiP78536.
KOiK06059.
OMAiDVKVHKN.
OrthoDBiEOG091G03AL.
PhylomeDBiP78536.
TreeFamiTF314733.

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]

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. AlignAdd to basket

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

        10         20         30         40         50
MRQSLLFLTS VVPFVLAPRP PDDPGFGPHQ RLEKLDSLLS DYDILSLSNI
60 70 80 90 100
QQHSVRKRDL QTSTHVETLL TFSALKRHFK LYLTSSTERF SQNFKVVVVD
110 120 130 140 150
GKNESEYTVK WQDFFTGHVV GEPDSRVLAH IRDDDVIIRI NTDGAEYNIE
160 170 180 190 200
PLWRFVNDTK DKRMLVYKSE DIKNVSRLQS PKVCGYLKVD NEELLPKGLV
210 220 230 240 250
DREPPEELVH RVKRRADPDP MKNTCKLLVV ADHRFYRYMG RGEESTTTNY
260 270 280 290 300
LIELIDRVDD IYRNTSWDNA GFKGYGIQIE QIRILKSPQE VKPGEKHYNM
310 320 330 340 350
AKSYPNEEKD AWDVKMLLEQ FSFDIAEEAS KVCLAHLFTY QDFDMGTLGL
360 370 380 390 400
AYVGSPRANS HGGVCPKAYY SPVGKKNIYL 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
CCNSDCTLKE GVQCSDRNSP CCKNCQFETA QKKCQEAINA TCKGVSYCTG
560 570 580 590 600
NSSECPPPGN AEDDTVCLDL GKCKDGKCIP FCEREQQLES CACNETDNSC
610 620 630 640 650
KVCCRDLSGR CVPYVDAEQK NLFLRKGKPC TVGFCDMNGK CEKRVQDVIE
660 670 680 690 700
RFWDFIDQLS INTFGKFLAD NIVGSVLVFS LIFWIPFSIL VHCVDKKLDK
710 720 730 740 750
QYESLSLFHP SNVEMLSSMD SASVRIIKPF PAPQTPGRLQ PAPVIPSAPA
760 770 780 790 800
APKLDHQRMD TIQEDPSTDS HMDEDGFEKD PFPNSSTAAK SFEDLTDHPV
810 820
TRSEKAASFK LQRQNRVDSK ETEC
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)DescriptionActionsGraphical viewLength
Sequence conflicti109V → A in AAC39721 (PubMed:9574564).Curated1
Sequence conflicti563D → N in AAC39721 (PubMed:9574564).Curated1
Sequence conflicti801T → A in AAC39721 (PubMed:9574564).Curated1
Sequence conflicti818D → N in AAC39721 (PubMed:9574564).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051586162K → E.Corresponds to variant rs34431503dbSNPEnsembl.1
Natural variantiVAR_051587202R → G.Corresponds to variant rs2230818dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005478695 – 824Missing in isoform B. 1 PublicationAdd BLAST130

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_003183.5. [P78536-1]
UniGeneiHs.404914.
Hs.570189.
Hs.744980.

Genome annotation databases

EnsembliENST00000310823; ENSP00000309968; ENSG00000151694. [P78536-1]
GeneIDi6868.
KEGGihsa:6868.
UCSCiuc002qzu.5. human. [P78536-1]

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:
EMBLi
GenBanki
DDBJi
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_003183.5. [P78536-1]
UniGeneiHs.404914.
Hs.570189.
Hs.744980.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112731. 18 interactors.
DIPiDIP-31044N.
IntActiP78536. 9 interactors.
MINTiMINT-108290.
STRINGi9606.ENSP00000309968.

Chemistry databases

BindingDBiP78536.
ChEMBLiCHEMBL3706.
GuidetoPHARMACOLOGYi1662.

Protein family/group databases

MEROPSiM12.217.
TCDBi8.A.77.1.2. the sheddase (sheddase) family.

PTM databases

iPTMnetiP78536.
PhosphoSitePlusiP78536.
SwissPalmiP78536.

Polymorphism and mutation databases

BioMutaiADAM17.
DMDMi14423632.

Proteomic databases

EPDiP78536.
MaxQBiP78536.
PaxDbiP78536.
PeptideAtlasiP78536.
PRIDEiP78536.

Protocols and materials databases

DNASUi6868.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000310823; ENSP00000309968; ENSG00000151694. [P78536-1]
GeneIDi6868.
KEGGihsa:6868.
UCSCiuc002qzu.5. human. [P78536-1]

Organism-specific databases

CTDi6868.
DisGeNETi6868.
GeneCardsiADAM17.
HGNCiHGNC:195. ADAM17.
HPAiCAB025906.
HPA010738.
HPA051575.
MalaCardsiADAM17.
MIMi603639. gene.
614328. phenotype.
neXtProtiNX_P78536.
OpenTargetsiENSG00000151694.
Orphaneti294023. Neonatal inflammatory skin and bowel disease.
PharmGKBiPA24512.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3658. Eukaryota.
ENOG410XQWB. LUCA.
GeneTreeiENSGT00670000097974.
HOGENOMiHOG000033797.
HOVERGENiHBG050457.
InParanoidiP78536.
KOiK06059.
OMAiDVKVHKN.
OrthoDBiEOG091G03AL.
PhylomeDBiP78536.
TreeFamiTF314733.

Enzyme and pathway databases

BioCyciZFISH:HS07763-MONOMER.
BRENDAi3.4.24.86. 2681.
ReactomeiR-HSA-1251985. Nuclear signaling by ERBB4.
R-HSA-1442490. Collagen degradation.
R-HSA-177929. Signaling by EGFR.
R-HSA-193692. Regulated proteolysis of p75NTR.
R-HSA-2122948. Activated NOTCH1 Transmits Signal to the Nucleus.
R-HSA-2644606. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
R-HSA-2660826. Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant.
R-HSA-2691232. Constitutive Signaling by NOTCH1 HD Domain Mutants.
R-HSA-2894862. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
R-HSA-5362798. Release of Hh-Np from the secreting cell.
R-HSA-75893. TNF signaling.
R-HSA-982772. Growth hormone receptor signaling.
SignaLinkiP78536.
SIGNORiP78536.

Miscellaneous databases

ChiTaRSiADAM17. human.
EvolutionaryTraceiP78536.
GeneWikiiADAM17.
GenomeRNAii6868.
PROiP78536.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000151694.
CleanExiHS_ADAM17.
ExpressionAtlasiP78536. baseline and differential.
GenevisibleiP78536. HS.

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...

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: November 2, 2016
This is version 193 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

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.