core domain of the SPFH (stomatin, prohibitin, flotillin, and HflK/C) superfamily; This model summarizes proteins similar to stomatin, prohibitin, flotillin, HflK/C (SPFH) and podocin. The conserved domain common to the SPFH superfamily has also been referred to as the Band 7 domain. Many superfamily members are associated with lipid rafts. Individual proteins of the SPFH superfamily may cluster to form membrane microdomains which may in turn recruit multiprotein complexes. Microdomains formed from flotillin proteins may in addition be dynamic units with their own regulatory functions. Flotillins have been implicated in signal transduction, vesicle trafficking, cytoskeleton rearrangement and are known to interact with a variety of proteins. Stomatin interacts with and regulates members of the degenerin/epithelia Na+ channel family in mechanosensory cells of Caenorhabditis elegans and vertebrate neurons, and participates in trafficking of Glut1 glucose transporters. Prohibitin may act as a chaperone for the stabilization of mitochondrial proteins. Prokaryotic HflK/C plays a role in the decision between lysogenic and lytic cycle growth during lambda phage infection. Flotillins have been implicated in the progression of prion disease, in the pathogenesis of neurodegenerative diseases such as Parkinson's and Alzheimer's disease, and in cancer invasion and metastasis. Mutations in the podocin gene give rise to autosomal recessive steroid resistant nephritic syndrome.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2103785783  56 KAREAKVREENE-QAAISSVLLRAQIEADRIRREAEAKAERM----KGEiAARKEGIsYNEYQN 114
Cdd:cd03404   181 AARQDKERLINEaQAYANEVIPRARGEAARIIQEAEAYKAEVvaraEGD-AARFLAL-LAEYRK 242

High frequency of lysogenization K (HflK) family; SPFH (stomatin, prohibitin, flotillin, and HflK/C) superfamily; This model characterizes proteins similar to prokaryotic HflK (High frequency of lysogenization K). Although many members of the SPFH (or band 7) superfamily are lipid raft associated, prokaryote plasma membranes lack cholesterol and are unlikely to have lipid raft domains. Individual proteins of this SPFH domain superfamily may cluster to form membrane microdomains which may in turn recruit multiprotein complexes. Escherichia coli HflK is an integral membrane protein which may localize to the plasma membrane. HflK associates with another SPFH superfamily member (HflC) to form an HflKC complex. HflKC interacts with FtsH in a large complex termed the FtsH holo-enzyme. FtsH is an AAA ATP-dependent protease which exerts progressive proteolysis against membrane-embedded and soluble substrate proteins. HflKC can modulate the activity of FtsH. HflKC plays a role in the decision between lysogenic and lytic cycle growth during lambda phage infection.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2103785783  56 KAREAKVREENE-QAAISSVLLRAQIEADRIRREAEAKAERM----KGEiAARKEGIsYNEYQN 114
Cdd:cd03404   181 AARQDKERLINEaQAYANEVIPRARGEAARIIQEAEAYKAEVvaraEGD-AARFLAL-LAEYRK 242

F0F1 ATP synthase subunit B; Validated

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2103785783  52 EAETKAREAKVREENEQAAISSvllrAQIEADRIRREAEAKAERMKGEIAARKE 105
Cdd:PRK07352   61 EAEERLRQAAQALAEAQQKLAQ----AQQEAERIRADAKARAEAIRAEIEKQAI 110

High frequency of lysogenization K (HflK) family; SPFH (stomatin, prohibitin, flotillin, and HflK/C) superfamily; This model characterizes proteins similar to prokaryotic HflK (High frequency of lysogenization K). Although many members of the SPFH (or band 7) superfamily are lipid raft associated, prokaryote plasma membranes lack cholesterol and are unlikely to have lipid raft domains. Individual proteins of this SPFH domain superfamily may cluster to form membrane microdomains which may in turn recruit multiprotein complexes. Escherichia coli HflK is an integral membrane protein which may localize to the plasma membrane. HflK associates with another SPFH superfamily member (HflC) to form an HflKC complex. HflKC interacts with FtsH in a large complex termed the FtsH holo-enzyme. FtsH is an AAA ATP-dependent protease which exerts progressive proteolysis against membrane-embedded and soluble substrate proteins. HflKC can modulate the activity of FtsH. HflKC plays a role in the decision between lysogenic and lytic cycle growth during lambda phage infection.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2103785783  56 KAREAKVREENE-QAAISSVLLRAQIEADRIRREAEAKAERM----KGEiAARKEGIsYNEYQN 114
Cdd:cd03404   181 AARQDKERLINEaQAYANEVIPRARGEAARIIQEAEAYKAEVvaraEGD-AARFLAL-LAEYRK 242

F0F1 ATP synthase subunit B; Validated

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2103785783  52 EAETKAREAKVREENEQAAISSvllrAQIEADRIRREAEAKAERMKGEIAARKE 105
Cdd:PRK07352   61 EAEERLRQAAQALAEAQQKLAQ----AQQEAERIRADAKARAEAIRAEIEKQAI 110

Prohibitin family; SPFH (stomatin, prohibitin, flotillin, and HflK/C) superfamily; This model characterizes proteins similar to prohibitin (a lipid raft-associated integral membrane protein). Individual proteins of the SPFH (band 7) domain superfamily may cluster to form membrane microdomains which may in turn recruit multiprotein complexes. These microdomains, in addition to being stable scaffolds, may also be dynamic units with their own regulatory functions. Prohibitin is a mitochondrial inner-membrane protein which may act as a chaperone for the stabilization of mitochondrial proteins. Human prohibitin forms a hetero-oligomeric complex with Bap-37 (prohibitin 2, an SPFH domain carrying homolog). This complex may protect non-assembled membrane proteins against proteolysis by the m-AAA protease. Prohibitin and Bap-37 yeast homologs have been implicated in yeast longevity and in the maintenance of mitochondrial morphology.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 2103785783  55 TKAREAKVREENEQAAISSVLLRAQIEADRIRREAEAKAE 94
Cdd:cd03401   154 EKAIEAKQVAEQEAERAKFELEKAEQEAERKVIEAEGEAE 193