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Conserved domains on  [gi|478247123|pdb|2M2F|A]
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Chain A, Disintegrin and metalloproteinase domain-containing protein 17

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
ADAM17_MPD pfam16698
Membrane-proximal domain, switch, for ADAM17; ADAM17_MPD is the membrane-proximal domain of a ...
 27-88 2.85e-27

Membrane-proximal domain, switch, for ADAM17; ADAM17_MPD is the membrane-proximal domain of a family of disintegrin and metalloproteinase domain-containing protein 17 found in metazoan species. ADAM17 is a major sheddase that is responsible for the regulation of a wide range of biological processes, such as cellular differentiation, regeneration, and cancer progression. This MPD region acts as the sheddase switch. PDI or protein-disulfide isomerase interacts with ADAM17 and to down-regulate its enzymatic activity. The interaction is directly with the MPD, the region of dimerization and substrate recognition, where it catalyzes an isomerization of disulfide bridges within the thioredoxin motif CXXC. this isomerization results in a major structural change between an active, open state and an inactive, closed state of the MPD. This change is thought to act as a molecular switch, allowing a global reorientation of the extracellular domains in ADAM17 and regulating its shedding activity.


:

Pssm-ID: 465239  Cd Length: 62  Bit Score: 93.95  E-value: 2.85e-27
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
2M2F_A        27 FCEREQQLESCACNETDNSCKVCCRDLSGRCVPYVDAEQKNLFLRKGKPCTVGFCDMNGKCE 88
Cdd:pfam16698  1 FCETKSGLQSCACNETDDSCKVCCRDLNGTCSPYLDANGSFLYLRDGKPCTVGFCDGKGKCE 62
 
Name Accession Description Interval E-value
ADAM17_MPD pfam16698
Membrane-proximal domain, switch, for ADAM17; ADAM17_MPD is the membrane-proximal domain of a ...
 27-88 2.85e-27

Membrane-proximal domain, switch, for ADAM17; ADAM17_MPD is the membrane-proximal domain of a family of disintegrin and metalloproteinase domain-containing protein 17 found in metazoan species. ADAM17 is a major sheddase that is responsible for the regulation of a wide range of biological processes, such as cellular differentiation, regeneration, and cancer progression. This MPD region acts as the sheddase switch. PDI or protein-disulfide isomerase interacts with ADAM17 and to down-regulate its enzymatic activity. The interaction is directly with the MPD, the region of dimerization and substrate recognition, where it catalyzes an isomerization of disulfide bridges within the thioredoxin motif CXXC. this isomerization results in a major structural change between an active, open state and an inactive, closed state of the MPD. This change is thought to act as a molecular switch, allowing a global reorientation of the extracellular domains in ADAM17 and regulating its shedding activity.


Pssm-ID: 465239  Cd Length: 62  Bit Score: 93.95  E-value: 2.85e-27
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
2M2F_A        27 FCEREQQLESCACNETDNSCKVCCRDLSGRCVPYVDAEQKNLFLRKGKPCTVGFCDMNGKCE 88
Cdd:pfam16698  1 FCETKSGLQSCACNETDDSCKVCCRDLNGTCSPYLDANGSFLYLRDGKPCTVGFCDGKGKCE 62
ADAM17_MPD cd14246
Membrane-proximal domain of a disintegrin and metalloprotease 17 (ADAM17); ADAM17 is a ...
 27-88 2.04e-18

Membrane-proximal domain of a disintegrin and metalloprotease 17 (ADAM17); ADAM17 is a multi-domain protein that acts as a sheddase; is involved in the cleavage and release of the soluble ectodomain of tumor necrosis factor alpha from the cell surface and in the trans-Golgi network, as well as in the release of various other targets such as cytokines and cell adhesion molecules. This links ADAM17 to a variety of biological processes, including cellular differentiation and the progression of cancer. It was shown that the enzymatic activity of ADAM17 is regulated via a protein-disulfide isomerase (PDI). Specifically, the disulfide bridges within a CxxC motif of the membrane-proximal domain (MPD) are isomerized by PDI; the conversion triggers a conformational change between a closed and an opened form of the MPD, which may constitute a molecular switch that triggers the shedding activity of ADAM17.


Pssm-ID: 271205  Cd Length: 60  Bit Score: 71.64  E-value: 2.04e-18
                       10        20        30        40        50        60
               ....*....|....*....|....*....|....*....|....*....|....*....|..
2M2F_A      27 FCEReQQLESCACNETDNSCKVCCRDLSGRCVPYVDAEQKnLFLRKGKPCTVGFCDMnGKCE 88
Cdd:cd14246  2 FCER-ENLQSCACNEVENSCKRCCRDSNGTCSPYVDAGPF-LYLRDGKPCTVGFCDS-GKCE 60
 
Name Accession Description Interval E-value
ADAM17_MPD pfam16698
Membrane-proximal domain, switch, for ADAM17; ADAM17_MPD is the membrane-proximal domain of a ...
 27-88 2.85e-27

Membrane-proximal domain, switch, for ADAM17; ADAM17_MPD is the membrane-proximal domain of a family of disintegrin and metalloproteinase domain-containing protein 17 found in metazoan species. ADAM17 is a major sheddase that is responsible for the regulation of a wide range of biological processes, such as cellular differentiation, regeneration, and cancer progression. This MPD region acts as the sheddase switch. PDI or protein-disulfide isomerase interacts with ADAM17 and to down-regulate its enzymatic activity. The interaction is directly with the MPD, the region of dimerization and substrate recognition, where it catalyzes an isomerization of disulfide bridges within the thioredoxin motif CXXC. this isomerization results in a major structural change between an active, open state and an inactive, closed state of the MPD. This change is thought to act as a molecular switch, allowing a global reorientation of the extracellular domains in ADAM17 and regulating its shedding activity.


Pssm-ID: 465239  Cd Length: 62  Bit Score: 93.95  E-value: 2.85e-27
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
2M2F_A        27 FCEREQQLESCACNETDNSCKVCCRDLSGRCVPYVDAEQKNLFLRKGKPCTVGFCDMNGKCE 88
Cdd:pfam16698  1 FCETKSGLQSCACNETDDSCKVCCRDLNGTCSPYLDANGSFLYLRDGKPCTVGFCDGKGKCE 62
ADAM17_MPD cd14246
Membrane-proximal domain of a disintegrin and metalloprotease 17 (ADAM17); ADAM17 is a ...
 27-88 2.04e-18

Membrane-proximal domain of a disintegrin and metalloprotease 17 (ADAM17); ADAM17 is a multi-domain protein that acts as a sheddase; is involved in the cleavage and release of the soluble ectodomain of tumor necrosis factor alpha from the cell surface and in the trans-Golgi network, as well as in the release of various other targets such as cytokines and cell adhesion molecules. This links ADAM17 to a variety of biological processes, including cellular differentiation and the progression of cancer. It was shown that the enzymatic activity of ADAM17 is regulated via a protein-disulfide isomerase (PDI). Specifically, the disulfide bridges within a CxxC motif of the membrane-proximal domain (MPD) are isomerized by PDI; the conversion triggers a conformational change between a closed and an opened form of the MPD, which may constitute a molecular switch that triggers the shedding activity of ADAM17.


Pssm-ID: 271205  Cd Length: 60  Bit Score: 71.64  E-value: 2.04e-18
                       10        20        30        40        50        60
               ....*....|....*....|....*....|....*....|....*....|....*....|..
2M2F_A      27 FCEReQQLESCACNETDNSCKVCCRDLSGRCVPYVDAEQKnLFLRKGKPCTVGFCDMnGKCE 88
Cdd:cd14246  2 FCER-ENLQSCACNEVENSCKRCCRDSNGTCSPYVDAGPF-LYLRDGKPCTVGFCDS-GKCE 60
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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