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P78536

- ADA17_HUMAN

UniProt

P78536 - ADA17_HUMAN

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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

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. 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
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. 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
Complete GO annotation...

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

BgeeiP78536.
CleanExiHS_ADAM17.
ExpressionAtlasiP78536. baseline and differential.
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. 12 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.
GeneTreeiENSGT00670000097974.
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

        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)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. 12 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 GC02M009628.
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.
GeneTreei ENSGT00670000097974.
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

Bgeei P78536.
CleanExi HS_ADAM17.
ExpressionAtlasi P78536. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 170 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