A-macroglobulin TED domain; This entry corresponds to the TED domain of the complement ...
1186-1550
2.45e-90
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.
The actual alignment was detected with superfamily member pfam07678:
Pssm-ID: 462227 [Multi-domain] Cd Length: 311 Bit Score: 296.52 E-value: 2.45e-90
Alpha-2-macroglobulin bait region domain; Alpha-2-macroglobulins (A2Ms) are plasma proteins ...
692-826
1.05e-25
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: 104.35 E-value: 1.05e-25
Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central ...
911-938
1.64e-06
Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure
:
Pssm-ID: 238060 Cd Length: 35 Bit Score: 46.05 E-value: 1.64e-06
A-macroglobulin TED domain; This entry corresponds to the TED domain of the complement ...
1186-1550
2.45e-90
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: 296.52 E-value: 2.45e-90
Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy ...
1203-1550
7.46e-55
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: 193.56 E-value: 7.46e-55
Alpha-2-macroglobulin bait region domain; Alpha-2-macroglobulins (A2Ms) are plasma proteins ...
692-826
1.05e-25
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: 104.35 E-value: 1.05e-25
MG2 domain; This is the MG2 (macroglobulin) domain of alpha-2-macroglobulin in eukaryotes. ...
230-320
2.46e-13
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: 67.34 E-value: 2.46e-13
Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central ...
911-938
1.64e-06
Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure
Pssm-ID: 238060 Cd Length: 35 Bit Score: 46.05 E-value: 1.64e-06
Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density ...
911-935
7.89e-04
Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. The N-terminal type A repeats in LDL receptor bind the lipoproteins. Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. Mutations in the LDL receptor gene cause familial hypercholesterolemia.
Pssm-ID: 197566 Cd Length: 33 Bit Score: 38.38 E-value: 7.89e-04
A-macroglobulin TED domain; This entry corresponds to the TED domain of the complement ...
1186-1550
2.45e-90
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: 296.52 E-value: 2.45e-90
Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy ...
1203-1550
7.46e-55
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: 193.56 E-value: 7.46e-55
Proteins similar to alpha2-macroglobulin (alpha (2)-M). Alpha (2)-M is a major carrier ...
1203-1550
5.90e-49
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: 176.42 E-value: 5.90e-49
Proteins similar to C3, C4 and C5 of vertebrate complement. The vertebrate complement system, ...
1206-1550
7.09e-42
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: 156.28 E-value: 7.09e-42
This group contains class II terpene cyclases, protein prenyltransferases beta subunit, two ...
1211-1550
7.57e-31
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: 124.59 E-value: 7.57e-31
Alpha-2-macroglobulin bait region domain; Alpha-2-macroglobulins (A2Ms) are plasma proteins ...
692-826
1.05e-25
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: 104.35 E-value: 1.05e-25
MG2 domain; This is the MG2 (macroglobulin) domain of alpha-2-macroglobulin in eukaryotes. ...
230-320
2.46e-13
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: 67.34 E-value: 2.46e-13
Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central ...
911-938
1.64e-06
Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure
Pssm-ID: 238060 Cd Length: 35 Bit Score: 46.05 E-value: 1.64e-06
Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density ...
911-935
7.89e-04
Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. The N-terminal type A repeats in LDL receptor bind the lipoproteins. Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. Mutations in the LDL receptor gene cause familial hypercholesterolemia.
Pssm-ID: 197566 Cd Length: 33 Bit Score: 38.38 E-value: 7.89e-04
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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