MACPF membrane-attack complex / perforin
SMART ACC:	SM000457
Description:	-
InterPro ACC:	IPR020864
InterPro abstract:	The membrane attack complex/perforin (MACPF) domain is conserved in bacteria, fungi, mammals and plants. It was originally identified and named as being common to five complement components (C6, C7, C8-alpha, C8-beta, and C9) and perforin. These molecules perform critical functions in innate and adaptive immunity. The MAC family proteins and perforin are known to participate in lytic pore formation. … expand The membrane attack complex/perforin (MACPF) domain is conserved in bacteria, fungi, mammals and plants. It was originally identified and named as being common to five complement components (C6, C7, C8-alpha, C8-beta, and C9) and perforin. These molecules perform critical functions in innate and adaptive immunity. The MAC family proteins and perforin are known to participate in lytic pore formation. In response to pathogen infection, a sequential and highly specific interaction between the constituent elements occurs to form transmembrane channels which are known as the membrane-attack complex (MAC).Only a few other MACPF proteins have been characterised and several are thought to form pores for invasion or protection [ PUBMED:16900325 PUBMED:17717151 PUBMED:18440555 ]. Examples are proteins from malarial parasites [ PUBMED:15659064 ], the cytolytic toxins from sea anemones [ PUBMED:17368498 ], and proteins that provide plant immunity [ PUBMED:16900325 PUBMED:15799997 ]. Functionally uncharacterised MACPF proteins are also evident in pathogenic bacteria such as Chlamydia spp [ PUBMED:10608922 ] and Photorhabdus luminescens (Xenorhabdus luminescens) [ PUBMED:17717151 ]. The MACPF domain is commonly found to be associated with other N- and C-terminal domains, such as TSP1 LDLRA EGF-like,Sushi/CCP/SCR FIMAC or C2. They probably control or target MACPF function [ PUBMED:17717151 PUBMED:17872444 ]. The MACPF domain oligomerizes, undergoes conformational change, and is required for lytic activity. The MACPF domain consists of a central kinked four-stranded antiparallel β sheet surrounded by α helices and β strands, forming two structural segments. Overall, the MACPF domain has a thin L-shaped appearance. MACPF domains exhibit limited sequence similarity but contain a signature [YW]-G-[TS]-H-[FY]-x(6)-G-G motif [ PUBMED:17717151 PUBMED:18440555 PUBMED:17872444 ]. Some proteins known to contain a MACPF domain are listed below: Vertebrate complement proteins C6 to C9. Complement factors C6 to C9 assemble to form a scaffold, the membrane attack complex (MAC), that permits C9 polymerisation into pores that lyse Gram-negative pathogens [ PUBMED:18440555 PUBMED:17872444 ]. Vertebrate perforin. It is delivered by natural killer cells and cytotoxic T lymphocytes and forms oligomeric pores (12 to 18 monomers) in the plasma membrane of either virus-infected or transformed cells. Arabidopsis thaliana (Mouse-ear cress) constitutively activated cell death 1 (CAD1) protein. It is likely to act as a mediator that recognises plant signals for pathogen infection [ PUBMED:15799997 ]. Arabidopsis thaliana (Mouse-ear cress) necrotic spotted lesions 1 (NSL1) protein [ PUBMED:16900325 ]. Venomous sea anemone Phyllodiscus semoni (Night anemone) toxins PsTX-60A and PsTX-60B [ PUBMED:17368498 ]. Venomous sea anemone Actineria villosa (Okinawan sea anemone) toxin AvTX-60A [ PUBMED:17368498 ]. Plasmodium sporozoite microneme protein essential for cell traversal 2 (SPECT2). It is essential for the membrane-wounding activity of the sporozoite and is involved in its traversal of the sinusoidal cell layer prior to hepatocyte-infection [ PUBMED:15659064 ]. P. luminescens Plu-MACPF. Although nonlytic, it was shown to bind to cell membranes [ PUBMED:17717151 ]. Chlamydial putative uncharacterised protein CT153 [ PUBMED:10608922 ]. collapse
Family alignment:	View the Family alignment or the Alignment consensus sequence
There are 3 546 MACPF domains in 3 539 proteins in SMART's NRDB database.

Taxonomic distribution of proteins containing MACPF domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing MACPF domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Relevant references for this domain

Primary literature for the MACPF domain is listed below. Automatically-derived, secondary literature is also available.

Disease genes where sequence variants are found in this domain

UniRef sequences and OMIM curated human diseases associated with missense mutations within the MACPF domain.

Protein	Description	Disease / phenotype
PERF_HUMAN		OMIM:170280 : Hemophagocytic lymphohistiocytosis, familial, 2
PERF_HUMAN		OMIM:603553 : no description

KEGG pathways involving proteins which contain this domain

This information is based on the mapping of SMART genomic protein database to KEGG orthologous groups. Percentages are related to the number of proteins containing a MACPF domain which could be assigned to a KEGG orthologous group, and not all proteins containing MACPF domains. Please note that proteins can be included in multiple pathways, ie. the numbers below will not add to 100%.

KEGG pathways

KEGG orthologous groups

3D structures in PDB containing this domain

Links to other resources describing this domain

PROSITE	MAC_PERFORIN
InterPro	IPR020864