alpha-2-macroglobulin-like protein may function as a proteinase inhibitor via a trapping mechanism. A peptide stretch serves as the bait region and contains cleavage sites for various proteinases; as soon as a proteinase cleaves the bait region, a conformational change traps the proteinase and significantly reduces its activity against high molecular weight substrates
Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy ...
1176-1464
4.04e-145
Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy zone protein (PZP). Alpha(2)-M and PZP are broadly specific proteinase inhibitors. Alpha (2)-M is a major carrier protein in serum. The structural thioester of alpha (2)-M, is involved in the immobilization and entrapment of proteases. PZP is a trace protein in the plasma of non-pregnant females and males which is elevated in pregnancy. Alpha (2)-M and PZ bind to placental protein-14 and may modulate its activity in T-cell growth and cytokine production contributing to fetal survival. It has been suggested that thioester bond cleavage promotes the binding of PZ and alpha (2)-M to the CD91 receptor clearing them from circulation.
:
Pssm-ID: 239227 Cd Length: 292 Bit Score: 450.49 E-value: 4.04e-145
Farnesoic acid 0-methyl transferase; This domain family is found in bacteria and eukaryotes, ...
1020-1121
4.71e-32
Farnesoic acid 0-methyl transferase; This domain family is found in bacteria and eukaryotes, and is approximately 110 amino acids in length.Farnesoic acid O-methyl transferase (FAMeT) is the enzyme that catalyzes the formation of methyl farnesoate (MF) from farnesoic acid (FA) in the biosynthetic pathway of juvenile hormone (JH).
:
Pssm-ID: 463505 Cd Length: 104 Bit Score: 121.21 E-value: 4.71e-32
Alpha-2-macroglobulin bait region domain; Alpha-2-macroglobulins (A2Ms) are plasma proteins ...
490-661
6.16e-28
Alpha-2-macroglobulin bait region domain; Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad range of proteases and are major components of the eukaryotic innate immune system. However, A2M-like proteins were identified in pathogenically invasive bacteria and species that colonize higher eukaryotes. This domain is found in eukaryotic and bacterial proteins. In human A2Ms, this domain encompasses macroglobulin-like domain MG5 and 6 including bait region. In Salmonella enterica ser A2Ms, this domain encompasses MG7 and MG8 including the bait region. The Bait region is cleaved by proteases, followed by a large conformational change that blocks the target protease within a cage-like complex. This model of protease entrapment is recognized as the Venus flytrap mechanism.
:
Pssm-ID: 462235 [Multi-domain] Cd Length: 139 Bit Score: 110.90 E-value: 6.16e-28
MG2 domain; This is the MG2 (macroglobulin) domain of alpha-2-macroglobulin in eukaryotes. ...
164-256
5.24e-12
MG2 domain; This is the MG2 (macroglobulin) domain of alpha-2-macroglobulin in eukaryotes. Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad range of proteases and are major components of the eukaryotic innate immune system. However, A2M-like proteins were identified in pathogenically invasive bacteria and species that colonize higher eukaryotes. This domain is found in eukaryotic and bacterial proteins. In human A2Ms, this domain is termed macroglobulin-like (MG) domain 2 and in Salmonella enterica ser A2Ms, this is domain 4.
:
Pssm-ID: 426464 [Multi-domain] Cd Length: 95 Bit Score: 63.87 E-value: 5.24e-12
Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy ...
1176-1464
4.04e-145
Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy zone protein (PZP). Alpha(2)-M and PZP are broadly specific proteinase inhibitors. Alpha (2)-M is a major carrier protein in serum. The structural thioester of alpha (2)-M, is involved in the immobilization and entrapment of proteases. PZP is a trace protein in the plasma of non-pregnant females and males which is elevated in pregnancy. Alpha (2)-M and PZ bind to placental protein-14 and may modulate its activity in T-cell growth and cytokine production contributing to fetal survival. It has been suggested that thioester bond cleavage promotes the binding of PZ and alpha (2)-M to the CD91 receptor clearing them from circulation.
Pssm-ID: 239227 Cd Length: 292 Bit Score: 450.49 E-value: 4.04e-145
A-macroglobulin TED domain; This entry corresponds to the TED domain of the complement ...
1155-1464
5.35e-130
A-macroglobulin TED domain; This entry corresponds to the TED domain of the complement components such as C3, C4 and C5. This domain contains a short highly conserved region of proteinase-binding alpha-macro-globulins contains the cysteine and a glutamine of a thiol-ester bond that is cleaved at the moment of proteinase binding, and mediates the covalent binding of the alpha-macro-globulin to the proteinase. The GCGEQ motif is highly conserved.
Pssm-ID: 462227 [Multi-domain] Cd Length: 311 Bit Score: 409.38 E-value: 5.35e-130
Farnesoic acid 0-methyl transferase; This domain family is found in bacteria and eukaryotes, ...
1020-1121
4.71e-32
Farnesoic acid 0-methyl transferase; This domain family is found in bacteria and eukaryotes, and is approximately 110 amino acids in length.Farnesoic acid O-methyl transferase (FAMeT) is the enzyme that catalyzes the formation of methyl farnesoate (MF) from farnesoic acid (FA) in the biosynthetic pathway of juvenile hormone (JH).
Pssm-ID: 463505 Cd Length: 104 Bit Score: 121.21 E-value: 4.71e-32
Alpha-2-macroglobulin bait region domain; Alpha-2-macroglobulins (A2Ms) are plasma proteins ...
490-661
6.16e-28
Alpha-2-macroglobulin bait region domain; Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad range of proteases and are major components of the eukaryotic innate immune system. However, A2M-like proteins were identified in pathogenically invasive bacteria and species that colonize higher eukaryotes. This domain is found in eukaryotic and bacterial proteins. In human A2Ms, this domain encompasses macroglobulin-like domain MG5 and 6 including bait region. In Salmonella enterica ser A2Ms, this domain encompasses MG7 and MG8 including the bait region. The Bait region is cleaved by proteases, followed by a large conformational change that blocks the target protease within a cage-like complex. This model of protease entrapment is recognized as the Venus flytrap mechanism.
Pssm-ID: 462235 [Multi-domain] Cd Length: 139 Bit Score: 110.90 E-value: 6.16e-28
MG2 domain; This is the MG2 (macroglobulin) domain of alpha-2-macroglobulin in eukaryotes. ...
164-256
5.24e-12
MG2 domain; This is the MG2 (macroglobulin) domain of alpha-2-macroglobulin in eukaryotes. Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad range of proteases and are major components of the eukaryotic innate immune system. However, A2M-like proteins were identified in pathogenically invasive bacteria and species that colonize higher eukaryotes. This domain is found in eukaryotic and bacterial proteins. In human A2Ms, this domain is termed macroglobulin-like (MG) domain 2 and in Salmonella enterica ser A2Ms, this is domain 4.
Pssm-ID: 426464 [Multi-domain] Cd Length: 95 Bit Score: 63.87 E-value: 5.24e-12
Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit ...
1751-1791
2.32e-08
Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the cognate enzyme as substrate. The reactive site peptide bond is a combining loop which has an identical conformation in all Kazal inhibitors and in all enzyme/inhibitor complexes. These Kazal domains (small hydrophobic core of alpha/beta structure with 3 to 4 disulfide bonds) often occur in tandem arrays. Similar domains are also present in follistatin (FS) and follistatin-like family members, which play an important role in tissue specific regulation. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a Kazal-like domain and has five disulfide bonds. Although the Kazal-like FS substructure is similar to Kazal proteinase inhibitors, no FS domain has yet been shown to be a proteinase inhibitor. Follistatin-like family members include SPARC, also known as, BM-40 or osteonectin, the Gallus gallus Flik protein, as well as, agrin which has a long array of FS domains. The kazal-type inhibitor domain has also been detected in an extracellular loop region of solute carrier 21 (SLC21) family members (organic anion transporters) , which may regulate the specificity of anion uptake. The distant homolog, Ascidian trypsin inhibitor, is included in this CD.
Pssm-ID: 238052 [Multi-domain] Cd Length: 41 Bit Score: 51.50 E-value: 2.32e-08
Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. ...
1744-1779
2.26e-07
Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides.
Pssm-ID: 400135 Cd Length: 50 Bit Score: 49.03 E-value: 2.26e-07
Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy ...
1176-1464
4.04e-145
Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy zone protein (PZP). Alpha(2)-M and PZP are broadly specific proteinase inhibitors. Alpha (2)-M is a major carrier protein in serum. The structural thioester of alpha (2)-M, is involved in the immobilization and entrapment of proteases. PZP is a trace protein in the plasma of non-pregnant females and males which is elevated in pregnancy. Alpha (2)-M and PZ bind to placental protein-14 and may modulate its activity in T-cell growth and cytokine production contributing to fetal survival. It has been suggested that thioester bond cleavage promotes the binding of PZ and alpha (2)-M to the CD91 receptor clearing them from circulation.
Pssm-ID: 239227 Cd Length: 292 Bit Score: 450.49 E-value: 4.04e-145
A-macroglobulin TED domain; This entry corresponds to the TED domain of the complement ...
1155-1464
5.35e-130
A-macroglobulin TED domain; This entry corresponds to the TED domain of the complement components such as C3, C4 and C5. This domain contains a short highly conserved region of proteinase-binding alpha-macro-globulins contains the cysteine and a glutamine of a thiol-ester bond that is cleaved at the moment of proteinase binding, and mediates the covalent binding of the alpha-macro-globulin to the proteinase. The GCGEQ motif is highly conserved.
Pssm-ID: 462227 [Multi-domain] Cd Length: 311 Bit Score: 409.38 E-value: 5.35e-130
Proteins similar to alpha2-macroglobulin (alpha (2)-M). Alpha (2)-M is a major carrier ...
1176-1464
5.64e-109
Proteins similar to alpha2-macroglobulin (alpha (2)-M). Alpha (2)-M is a major carrier protein in serum. It is a broadly specific proteinase inhibitor. The structural thioester of alpha (2)-M, is involved in the immobilization and entrapment of proteases. This group contains another broadly specific proteinase inhibitor: pregnancy zone protein (PZP). PZP is a trace protein in the plasma of non-pregnant females and males which is elevated in pregnancy. Alpha (2)-M and PZ bind to placental protein-14 and may modulate its activity in T-cell growth and cytokine production thereby protecting the allogeneic fetus from attack by the maternal immune system. This group also contains C3, C4 and C5 of vertebrate complement. The vertebrate complement is an effector of both the acquired and innate immune systems The point of convergence of the classical, alternative and lectin pathways of the complement system is the proteolytic activation of C3. C4 plays a key role in propagating the classical and lectin pathways. C5 participates in the classical and alternative pathways. The thioester bond located within the structure of C3 and C4 is central to the function of complement. C5 does not contain an active thioester bond.
Pssm-ID: 239221 [Multi-domain] Cd Length: 282 Bit Score: 348.61 E-value: 5.64e-109
Proteins similar to C3, C4 and C5 of vertebrate complement. The vertebrate complement system, ...
1176-1464
4.00e-94
Proteins similar to C3, C4 and C5 of vertebrate complement. The vertebrate complement system, comprised of a large number of distinct plasma proteins, is an effector of both the acquired and innate immune systems. The point of convergence of the classical, alternative and lectin pathways of the complement system is the proteolytic activation of C3. C4 plays a key role in propagating the classical and lectin pathways. C5 participates in the classical and alternative pathways. The thioester bond located within the structure of C3 and C4 is central to the function of complement. C5 does not contain an active thioester bond.
Pssm-ID: 239226 [Multi-domain] Cd Length: 297 Bit Score: 306.89 E-value: 4.00e-94
This group contains class II terpene cyclases, protein prenyltransferases beta subunit, two ...
1179-1464
5.14e-64
This group contains class II terpene cyclases, protein prenyltransferases beta subunit, two broadly specific proteinase inhibitors alpha2-macroglobulin (alpha (2)-M) and pregnancy zone protein (PZP) and, the C3 C4 and C5 components of vertebrate complement. Class II terpene cyclases include squalene cyclase (SQCY) and 2,3-oxidosqualene cyclase (OSQCY), these integral membrane proteins catalyze a cationic cyclization cascade converting linear triterpenes to fused ring compounds. The protein prenyltransferases include protein farnesyltransferase (FTase) and geranylgeranyltransferase types I and II (GGTase-I and GGTase-II) which catalyze the carboxyl-terminal lipidation of Ras, Rab, and several other cellular signal transduction proteins, facilitating membrane associations and specific protein-protein interactions. Alpha (2)-M is a major carrier protein in serum and involved in the immobilization and entrapment of proteases. PZP is a pregnancy associated protein. Alpha (2)-M and PZP are known to bind to and, may modulate, the activity of placental protein-14 in T-cell growth and cytokine production thereby protecting the allogeneic fetus from attack by the maternal immune system.
Pssm-ID: 238362 [Multi-domain] Cd Length: 300 Bit Score: 220.50 E-value: 5.14e-64
Farnesoic acid 0-methyl transferase; This domain family is found in bacteria and eukaryotes, ...
1020-1121
4.71e-32
Farnesoic acid 0-methyl transferase; This domain family is found in bacteria and eukaryotes, and is approximately 110 amino acids in length.Farnesoic acid O-methyl transferase (FAMeT) is the enzyme that catalyzes the formation of methyl farnesoate (MF) from farnesoic acid (FA) in the biosynthetic pathway of juvenile hormone (JH).
Pssm-ID: 463505 Cd Length: 104 Bit Score: 121.21 E-value: 4.71e-32
Alpha-2-macroglobulin bait region domain; Alpha-2-macroglobulins (A2Ms) are plasma proteins ...
490-661
6.16e-28
Alpha-2-macroglobulin bait region domain; Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad range of proteases and are major components of the eukaryotic innate immune system. However, A2M-like proteins were identified in pathogenically invasive bacteria and species that colonize higher eukaryotes. This domain is found in eukaryotic and bacterial proteins. In human A2Ms, this domain encompasses macroglobulin-like domain MG5 and 6 including bait region. In Salmonella enterica ser A2Ms, this domain encompasses MG7 and MG8 including the bait region. The Bait region is cleaved by proteases, followed by a large conformational change that blocks the target protease within a cage-like complex. This model of protease entrapment is recognized as the Venus flytrap mechanism.
Pssm-ID: 462235 [Multi-domain] Cd Length: 139 Bit Score: 110.90 E-value: 6.16e-28
MG2 domain; This is the MG2 (macroglobulin) domain of alpha-2-macroglobulin in eukaryotes. ...
164-256
5.24e-12
MG2 domain; This is the MG2 (macroglobulin) domain of alpha-2-macroglobulin in eukaryotes. Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad range of proteases and are major components of the eukaryotic innate immune system. However, A2M-like proteins were identified in pathogenically invasive bacteria and species that colonize higher eukaryotes. This domain is found in eukaryotic and bacterial proteins. In human A2Ms, this domain is termed macroglobulin-like (MG) domain 2 and in Salmonella enterica ser A2Ms, this is domain 4.
Pssm-ID: 426464 [Multi-domain] Cd Length: 95 Bit Score: 63.87 E-value: 5.24e-12
Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit ...
1751-1791
2.32e-08
Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the cognate enzyme as substrate. The reactive site peptide bond is a combining loop which has an identical conformation in all Kazal inhibitors and in all enzyme/inhibitor complexes. These Kazal domains (small hydrophobic core of alpha/beta structure with 3 to 4 disulfide bonds) often occur in tandem arrays. Similar domains are also present in follistatin (FS) and follistatin-like family members, which play an important role in tissue specific regulation. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a Kazal-like domain and has five disulfide bonds. Although the Kazal-like FS substructure is similar to Kazal proteinase inhibitors, no FS domain has yet been shown to be a proteinase inhibitor. Follistatin-like family members include SPARC, also known as, BM-40 or osteonectin, the Gallus gallus Flik protein, as well as, agrin which has a long array of FS domains. The kazal-type inhibitor domain has also been detected in an extracellular loop region of solute carrier 21 (SLC21) family members (organic anion transporters) , which may regulate the specificity of anion uptake. The distant homolog, Ascidian trypsin inhibitor, is included in this CD.
Pssm-ID: 238052 [Multi-domain] Cd Length: 41 Bit Score: 51.50 E-value: 2.32e-08
Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. ...
1744-1779
2.26e-07
Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides.
Pssm-ID: 400135 Cd Length: 50 Bit Score: 49.03 E-value: 2.26e-07
The kazal-type serine protease inhibitor domain has been detected in an extracellular loop ...
1743-1770
1.08e-03
The kazal-type serine protease inhibitor domain has been detected in an extracellular loop region of solute carrier 21 (SLC21) family members (organic anion transporters) , which may regulate the specificity of anion uptake. The KAZAL_SLC21 domain is a member of the superfamily of kazal-like proteinase inhibitors and follistatin-like proteins.
Pssm-ID: 238650 [Multi-domain] Cd Length: 54 Bit Score: 38.82 E-value: 1.08e-03
Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. ...
1748-1770
3.87e-03
Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides. Alignment also includes a single domain from transporters in the OATP/PGT family.
Pssm-ID: 395004 Cd Length: 49 Bit Score: 36.88 E-value: 3.87e-03
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.
of the residues that compose this conserved feature have been mapped to the query sequence.
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