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Conserved domains on  [gi|767905874|ref|XP_011540381|]
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complement component C8 alpha chain isoform X2 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
MACPF super family cl02616
membrane-attack complex / perforin;
289-366 7.07e-30

membrane-attack complex / perforin;


The actual alignment was detected with superfamily member smart00457:

Pssm-ID: 470633  Cd Length: 195  Bit Score: 113.68  E-value: 7.07e-30
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767905874   289 FTRIFTKVQTAHFKMRKDDIMLDEGMLQSLMELPDQYNYGMYAKFINDYGTHYITSGSMGGIYEYILVIDKAKMESLG 366
Cdd:smart00457   1 FLVARDTVRNRLYSVKLDELPLALEFLKALRDLPDTYNRGAYARFIDDYGTHYITSATLGGEYSLLLVLDKESLERKG 78
LDLa cd00112
Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central ...
 96-130 2.31e-08

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: 49.51  E-value: 2.31e-08
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 767905874  96 CGQD-FQCKeTGRCLKRHLVCNGDQDCLDGSDEDDC 130
Cdd:cd00112    1 CPPNeFRCA-NGRCIPSSWVCDGEDDCGDGSDEENC 35
TSP1_spondin super family cl46269
Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an ...
 39-74 4.11e-05

Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an alternative disulphide binding pattern compared to the canonical TSP1 domain.


The actual alignment was detected with superfamily member pfam19028:

Pssm-ID: 480609  Cd Length: 52  Bit Score: 40.73  E-value: 4.11e-05
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 767905874   39 CQLSNWSEWTDC-FPCQD-KKYRHRSLLQPNKFGGTIC 74
Cdd:pfam19028   1 CVVSEWSEWSECsVTCGGgVQTRTRTVIVEPQNGGRPC 38
 
Name Accession Description Interval E-value
MACPF smart00457
membrane-attack complex / perforin;
289-366 7.07e-30

membrane-attack complex / perforin;


Pssm-ID: 214671  Cd Length: 195  Bit Score: 113.68  E-value: 7.07e-30
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767905874   289 FTRIFTKVQTAHFKMRKDDIMLDEGMLQSLMELPDQYNYGMYAKFINDYGTHYITSGSMGGIYEYILVIDKAKMESLG 366
Cdd:smart00457   1 FLVARDTVRNRLYSVKLDELPLALEFLKALRDLPDTYNRGAYARFIDDYGTHYITSATLGGEYSLLLVLDKESLERKG 78
MACPF pfam01823
MAC/Perforin domain; The membrane-attack complex (MAC) of the complement system forms ...
 267-367 5.80e-25

MAC/Perforin domain; The membrane-attack complex (MAC) of the complement system forms transmembrane channels. These channels disrupt the phospholipid bilayer of target cells, leading to cell lysis and death. A number of proteins participate in the assembly of the MAC. Freshly activated C5b binds to C6 to form a C5b-6 complex, then to C7 forming the C5b-7 complex. The C5b-7 complex binds to C8, which is composed of three chains (alpha, beta, and gamma), thus forming the C5b-8 complex. C5b-8 subsequently binds to C9 and acts as a catalyst in the polymerization of C9. Active MAC has a subunit composition of C5b-C6-C7-C8-C9{n}. Perforin is a protein found in cytolytic T-cell and killer cells. In the presence of calcium, perforin polymerizes into transmembrane tubules and is capable of lysing, non-specifically, a variety of target cells. There are a number of regions of similarity in the sequences of complement components C6, C7, C8-alpha, C8-beta, C9 and perforin. The X-ray crystal structure of a MACPF domain reveals that it shares a common fold with bacterial cholesterol dependent cytolysins (pfam01289) such as perfringolysin O. Three key pieces of evidence suggests that MACPF domains and CDCs are homologous: Functional similarity (pore formation), conservation of three glycine residues at a hinge in both families and conservation of a complex core fold.


Pssm-ID: 460349  Cd Length: 211  Bit Score: 100.94  E-value: 5.80e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767905874  267 VSHSQDTSFLNELNKYNEKKFIFTRIFTKVQTAHFKM-RKDDIMLDEGMLQSLMELPDQYNYGM---YAKFINDYGTHYI 342
Cdd:pfam01823   1 GSFSASSEFKKMSDKSKQKKKSLIISKSTCSLYQFTLkRSNKLQLSDEFLQALSDLPDNYDYAAkatYIQFFDKYGTHYI 80

                          90       100
                  ....*....|....*....|....*
gi 767905874  343 TSGSMGGIYEYILVIDKAKMESLGS 367
Cdd:pfam01823  81 TSVTLGGKIVYVLKLDKSQLEDLKL 105
LDLa cd00112
Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central ...
 96-130 2.31e-08

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: 49.51  E-value: 2.31e-08
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 767905874  96 CGQD-FQCKeTGRCLKRHLVCNGDQDCLDGSDEDDC 130
Cdd:cd00112    1 CPPNeFRCA-NGRCIPSSWVCDGEDDCGDGSDEENC 35
Ldl_recept_a pfam00057
Low-density lipoprotein receptor domain class A;
95-130 2.54e-08

Low-density lipoprotein receptor domain class A;


Pssm-ID: 395011  Cd Length: 37  Bit Score: 49.17  E-value: 2.54e-08
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 767905874   95 QCGQD-FQCkETGRCLKRHLVCNGDQDCLDGSDEDDC 130
Cdd:pfam00057   2 TCSPNeFQC-GSGECIPRSWVCDGDPDCGDGSDEENC 37
LDLa smart00192
Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density ...
 95-127 4.05e-07

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: 45.70  E-value: 4.05e-07
                           10        20        30
                   ....*....|....*....|....*....|....
gi 767905874    95 QCGQD-FQCKeTGRCLKRHLVCNGDQDCLDGSDE 127
Cdd:smart00192   1 TCPPGeFQCD-NGRCIPSSWVCDGVDDCGDGSDE 33
TSP1_spondin pfam19028
Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an ...
 39-74 4.11e-05

Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an alternative disulphide binding pattern compared to the canonical TSP1 domain.


Pssm-ID: 465948  Cd Length: 52  Bit Score: 40.73  E-value: 4.11e-05
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 767905874   39 CQLSNWSEWTDC-FPCQD-KKYRHRSLLQPNKFGGTIC 74
Cdd:pfam19028   1 CVVSEWSEWSECsVTCGGgVQTRTRTVIVEPQNGGRPC 38
 
Name Accession Description Interval E-value
MACPF smart00457
membrane-attack complex / perforin;
289-366 7.07e-30

membrane-attack complex / perforin;


Pssm-ID: 214671  Cd Length: 195  Bit Score: 113.68  E-value: 7.07e-30
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767905874   289 FTRIFTKVQTAHFKMRKDDIMLDEGMLQSLMELPDQYNYGMYAKFINDYGTHYITSGSMGGIYEYILVIDKAKMESLG 366
Cdd:smart00457   1 FLVARDTVRNRLYSVKLDELPLALEFLKALRDLPDTYNRGAYARFIDDYGTHYITSATLGGEYSLLLVLDKESLERKG 78
MACPF pfam01823
MAC/Perforin domain; The membrane-attack complex (MAC) of the complement system forms ...
 267-367 5.80e-25

MAC/Perforin domain; The membrane-attack complex (MAC) of the complement system forms transmembrane channels. These channels disrupt the phospholipid bilayer of target cells, leading to cell lysis and death. A number of proteins participate in the assembly of the MAC. Freshly activated C5b binds to C6 to form a C5b-6 complex, then to C7 forming the C5b-7 complex. The C5b-7 complex binds to C8, which is composed of three chains (alpha, beta, and gamma), thus forming the C5b-8 complex. C5b-8 subsequently binds to C9 and acts as a catalyst in the polymerization of C9. Active MAC has a subunit composition of C5b-C6-C7-C8-C9{n}. Perforin is a protein found in cytolytic T-cell and killer cells. In the presence of calcium, perforin polymerizes into transmembrane tubules and is capable of lysing, non-specifically, a variety of target cells. There are a number of regions of similarity in the sequences of complement components C6, C7, C8-alpha, C8-beta, C9 and perforin. The X-ray crystal structure of a MACPF domain reveals that it shares a common fold with bacterial cholesterol dependent cytolysins (pfam01289) such as perfringolysin O. Three key pieces of evidence suggests that MACPF domains and CDCs are homologous: Functional similarity (pore formation), conservation of three glycine residues at a hinge in both families and conservation of a complex core fold.


Pssm-ID: 460349  Cd Length: 211  Bit Score: 100.94  E-value: 5.80e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767905874  267 VSHSQDTSFLNELNKYNEKKFIFTRIFTKVQTAHFKM-RKDDIMLDEGMLQSLMELPDQYNYGM---YAKFINDYGTHYI 342
Cdd:pfam01823   1 GSFSASSEFKKMSDKSKQKKKSLIISKSTCSLYQFTLkRSNKLQLSDEFLQALSDLPDNYDYAAkatYIQFFDKYGTHYI 80

                          90       100
                  ....*....|....*....|....*
gi 767905874  343 TSGSMGGIYEYILVIDKAKMESLGS 367
Cdd:pfam01823  81 TSVTLGGKIVYVLKLDKSQLEDLKL 105
LDLa cd00112
Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central ...
 96-130 2.31e-08

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: 49.51  E-value: 2.31e-08
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 767905874  96 CGQD-FQCKeTGRCLKRHLVCNGDQDCLDGSDEDDC 130
Cdd:cd00112    1 CPPNeFRCA-NGRCIPSSWVCDGEDDCGDGSDEENC 35
Ldl_recept_a pfam00057
Low-density lipoprotein receptor domain class A;
95-130 2.54e-08

Low-density lipoprotein receptor domain class A;


Pssm-ID: 395011  Cd Length: 37  Bit Score: 49.17  E-value: 2.54e-08
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 767905874   95 QCGQD-FQCkETGRCLKRHLVCNGDQDCLDGSDEDDC 130
Cdd:pfam00057   2 TCSPNeFQC-GSGECIPRSWVCDGDPDCGDGSDEENC 37
LDLa smart00192
Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density ...
 95-127 4.05e-07

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: 45.70  E-value: 4.05e-07
                           10        20        30
                   ....*....|....*....|....*....|....
gi 767905874    95 QCGQD-FQCKeTGRCLKRHLVCNGDQDCLDGSDE 127
Cdd:smart00192   1 TCPPGeFQCD-NGRCIPSSWVCDGVDDCGDGSDE 33
TSP1_spondin pfam19028
Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an ...
 39-74 4.11e-05

Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an alternative disulphide binding pattern compared to the canonical TSP1 domain.


Pssm-ID: 465948  Cd Length: 52  Bit Score: 40.73  E-value: 4.11e-05
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 767905874   39 CQLSNWSEWTDC-FPCQD-KKYRHRSLLQPNKFGGTIC 74
Cdd:pfam19028   1 CVVSEWSEWSECsVTCGGgVQTRTRTVIVEPQNGGRPC 38
 
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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