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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528513478  268 YREAVKASQQKDSVFYRVHQVIATSTFKVK-SSDLYLSDPFLQFLNSLPLEYNYAL---YRHIFQLFGTHYFSSGTLGGK 343
Cdd:pfam01823   9 FKKMSDKSKQKKKSLIISKSTCSLYQFTLKrSNKLQLSDEFLQALSDLPDNYDYAAkatYIQFFDKYGTHYITSVTLGGK 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528513478  344 YDLLFQFDREELKTFGLKESDSEYCLSdddTLVTFFYNrHKQRNTCGNISMKTKYEGSMVKASERCITSVQGGRTEFAaa 423
Cdd:pfam01823  89 IVYVLKLDKSQLEDLKLKGEDVKICLS---ASAGASIG-SVNLKGCSKNSSSTKEKKSFNQEIESSITLVIGGTPESI-- 162

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528513478  424 lawekkgvSPQSTVYTDWIKSTIENPVVINYELLPLVNLVRGIScavTKRRHFHRALEEY 483
Cdd:pfam01823 163 --------DDDSKTYSDWAESVKDNPMPIDFELTPISELLKGVP---LKKENLRKALEEY 211

factor I membrane attack complex;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528513478   833 CGSDTCYEWETCSVSkTCECKMPRECPKDGKKiYCLKIVRTQTTrsMNLCFMAAMKCSSIEFELQHEGPCA 903
Cdd:smart00057   1 CAKGFCQLWQKCSAS-TCVCKLPYECPKAGTD-VCVEDGRSEKT--LTYCKQGALRCLNQKYKFLHIGSCT 67

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 528513478   83 CQLTEFGPWSECS-SCAK-KSFRIRSVLRPSQFGGADCSqSLMEERAC 128
Cdd:pfam19028   1 CVVSEWSEWSECSvTCGGgVQTRTRTVIVEPQNGGRPCP-ELLERRPC 47

factor I membrane attack complex;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528513478   745 CKPGEINDGTKCVCMTKERCRGYREDLCVYDAGKEtaIMMSLCAFHADRCHGDRLYFMNNGPC 807
Cdd:smart00057   6 CQLWQKCSASTCVCKLPYECPKAGTDVCVEDGRSE--KTLTYCKQGALRCLNQKYKFLHIGSC 66

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 528513478    27 HYPWSTWSQCTKTCDSGTQSRLRDVQYDDHWFK-NSCSQlcQIHDNRVCNVEACP 80
Cdd:smart00209   1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPPPQNGgGPCTG--EDVETRACNEQPCP 53

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528513478  268 YREAVKASQQKDSVFYRVHQVIATSTFKVK-SSDLYLSDPFLQFLNSLPLEYNYAL---YRHIFQLFGTHYFSSGTLGGK 343
Cdd:pfam01823   9 FKKMSDKSKQKKKSLIISKSTCSLYQFTLKrSNKLQLSDEFLQALSDLPDNYDYAAkatYIQFFDKYGTHYITSVTLGGK 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528513478  344 YDLLFQFDREELKTFGLKESDSEYCLSdddTLVTFFYNrHKQRNTCGNISMKTKYEGSMVKASERCITSVQGGRTEFAaa 423
Cdd:pfam01823  89 IVYVLKLDKSQLEDLKLKGEDVKICLS---ASAGASIG-SVNLKGCSKNSSSTKEKKSFNQEIESSITLVIGGTPESI-- 162

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528513478  424 lawekkgvSPQSTVYTDWIKSTIENPVVINYELLPLVNLVRGIScavTKRRHFHRALEEY 483
Cdd:pfam01823 163 --------DDDSKTYSDWAESVKDNPMPIDFELTPISELLKGVP---LKKENLRKALEEY 211

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 528513478   537 WSCWSSWSPCDAT---LKKHRSRTCSNPAPQRGGKPCPGLEKQVEECT 581
Cdd:smart00209   1 WSEWSEWSPCSVTcggGVQTRTRSCCSPPPQNGGGPCTGEDVETRACN 48

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

                         10        20        30
                 ....*....|....*....|....*....|..
gi 528513478 143 DKFTCDTGRCIHADLQCNDQNDCGDNSDERDC 174
Cdd:cd00112    4 NEFRCANGRCIPSSWVCDGEDDCGDGSDEENC 35

Low-density lipoprotein receptor domain class A;

                          10        20        30
                  ....*....|....*....|....*....|..
gi 528513478  143 DKFTCDTGRCIHADLQCNDQNDCGDNSDERDC 174
Cdd:pfam00057   6 NEFQCGSGECIPRSWVCDGDPDCGDGSDEENC 37

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.

                           10        20
                   ....*....|....*....|....*....
gi 528513478   143 DKFTCDTGRCIHADLQCNDQNDCGDNSDE 171
Cdd:smart00192   5 GEFQCDNGRCIPSSWVCDGVDDCGDGSDE 33

Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR); The complement control protein (CCP) modules (also known as short consensus repeats SCRs or SUSHI repeats) contain approximately 60 amino acid residues and have been identified in several proteins of the complement system. A missense mutation in seventh CCP domain causes deficiency of the b subunit of factor XIII.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 528513478   614 CAKPLPPANSHLRINKRQYDYGDHEEIICFTGFELQGFQLIHCLQDGTWEKPKAQC 669
Cdd:smart00032   1 CPPPPDIENGTVTSSSGTYSYGDTVTYSCDPGYTLIGSSTITCLENGTWSPPPPTC 56

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 528513478    27 HYPWSTWSQCTKTCDSGTQSRLRDVQYDDHWFK-NSCSQlcQIHDNRVCNVEACP 80
Cdd:smart00209   1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPPPQNGgGPCTG--EDVETRACNEQPCP 53

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 528513478  540 WSSWSPCDATL---KKHRSRTCSNPaPQRGGKPCPGLEkQVEEC 580
Cdd:pfam19028   6 WSEWSECSVTCgggVQTRTRTVIVE-PQNGGRPCPELL-ERRPC 47

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528513478  268 YREAVKASQQKDSVFYRVHQVIATSTFKVK-SSDLYLSDPFLQFLNSLPLEYNYAL---YRHIFQLFGTHYFSSGTLGGK 343
Cdd:pfam01823   9 FKKMSDKSKQKKKSLIISKSTCSLYQFTLKrSNKLQLSDEFLQALSDLPDNYDYAAkatYIQFFDKYGTHYITSVTLGGK 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528513478  344 YDLLFQFDREELKTFGLKESDSEYCLSdddTLVTFFYNrHKQRNTCGNISMKTKYEGSMVKASERCITSVQGGRTEFAaa 423
Cdd:pfam01823  89 IVYVLKLDKSQLEDLKLKGEDVKICLS---ASAGASIG-SVNLKGCSKNSSSTKEKKSFNQEIESSITLVIGGTPESI-- 162

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528513478  424 lawekkgvSPQSTVYTDWIKSTIENPVVINYELLPLVNLVRGIScavTKRRHFHRALEEY 483
Cdd:pfam01823 163 --------DDDSKTYSDWAESVKDNPMPIDFELTPISELLKGVP---LKKENLRKALEEY 211

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 528513478   537 WSCWSSWSPCDAT---LKKHRSRTCSNPAPQRGGKPCPGLEKQVEECT 581
Cdd:smart00209   1 WSEWSEWSPCSVTcggGVQTRTRSCCSPPPQNGGGPCTGEDVETRACN 48

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

                         10        20        30
                 ....*....|....*....|....*....|..
gi 528513478 143 DKFTCDTGRCIHADLQCNDQNDCGDNSDERDC 174
Cdd:cd00112    4 NEFRCANGRCIPSSWVCDGEDDCGDGSDEENC 35

Low-density lipoprotein receptor domain class A;

                          10        20        30
                  ....*....|....*....|....*....|..
gi 528513478  143 DKFTCDTGRCIHADLQCNDQNDCGDNSDERDC 174
Cdd:pfam00057   6 NEFQCGSGECIPRSWVCDGDPDCGDGSDEENC 37

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.

                           10        20
                   ....*....|....*....|....*....
gi 528513478   143 DKFTCDTGRCIHADLQCNDQNDCGDNSDE 171
Cdd:smart00192   5 GEFQCDNGRCIPSSWVCDGVDDCGDGSDE 33

Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR); The complement control protein (CCP) modules (also known as short consensus repeats SCRs or SUSHI repeats) contain approximately 60 amino acid residues and have been identified in several proteins of the complement system. A missense mutation in seventh CCP domain causes deficiency of the b subunit of factor XIII.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 528513478   614 CAKPLPPANSHLRINKRQYDYGDHEEIICFTGFELQGFQLIHCLQDGTWEKPKAQC 669
Cdd:smart00032   1 CPPPPDIENGTVTSSSGTYSYGDTVTYSCDPGYTLIGSSTITCLENGTWSPPPPTC 56

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 528513478    27 HYPWSTWSQCTKTCDSGTQSRLRDVQYDDHWFK-NSCSQlcQIHDNRVCNVEACP 80
Cdd:smart00209   1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPPPQNGgGPCTG--EDVETRACNEQPCP 53

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 528513478  540 WSSWSPCDATL---KKHRSRTCSNPaPQRGGKPCPGLEkQVEEC 580
Cdd:pfam19028   6 WSEWSECSVTCgggVQTRTRTVIVE-PQNGGRPCPELL-ERRPC 47

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.

                          10        20
                  ....*....|....*....|...
gi 528513478   29 PWSTWSQCTKTCDSGTQSRLRDV 51
Cdd:pfam19028   5 EWSEWSECSVTCGGGVQTRTRTV 27

Thrombospondin type 1 domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 528513478  538 SCWSSWSPCDATL---KKHRSRTCSNPAPqrGGKPCPGLEKQVEECT 581
Cdd:pfam00090   1 SPWSPWSPCSVTCgkgIQVRQRTCKSPFP--GGEPCTGDDIETQACK 45