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.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034561734 122 WFCVKVVQEYERVIIFRLGHLLPGRAKGPGLFFFLPCLDTYHKVDLRLQTLEIPFHE 178
Cdd:cd08827     1 WFCVKVVREYERAVIFRLGHLLQGRARGPGLFFYLPCLDVCHKVDIRLQTLEIPFHM 57

Podocin, a subgroup of the stomatin-like proteins (slipins) family; belonging to the SPFH (stomatin, prohibitin, flotillin, and HflK/C) superfamily; This model summarizes a subgroup of the stomatin-like protein family (SLPs or slipins) that is found in vertebrates. The conserved domain common to the SPFH superfamily has also been referred to as the Band 7 domain. Individual proteins of the SPFH superfamily may cluster to form membrane microdomains which may in turn recruit multiprotein complexes. Podocin is expressed in the kidney and mutations in the gene have been linked to familial idiopathic nephrotic syndrome. Podocin interacts with the TRP ion channel TRPV-6 and may function as a scaffolding protein in the organization of lipid-protein domains.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034561734 122 WFCVKVVQEYERVIIFRLGHLLPGRAKGPGLFFFLPCLDTYHKVDLRLQTLEIPFHE 178
Cdd:cd08827     1 WFCVKVVREYERAVIFRLGHLLQGRARGPGLFFYLPCLDVCHKVDIRLQTLEIPFHM 57

Regulator of protease activity HflC, stomatin/prohibitin superfamily [Posttranslational modification, protein turnover, chaperones];

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034561734 104 LLVLISLLFIIMTfpfsIWFCVKVVQEYERVIIFRLGHLLpgRAKGPGLFFFLPCLDTYHKVDLRLQTLEIP 175
Cdd:COG0330     4 ILLLILLVLVLVL----LFSSVYIVPQGERGVVLRFGKYV--RTLEPGLHFKIPFIDRVRKVDVREQVLDVP 69

SPFH domain / Band 7 family; This family has been called SPFH, Band 7 or PHB domain. Recent phylogenetic analysis has shown this domain to be a slipin or Stomatin-like integral membrane domain conserved from protozoa to mammals.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 1034561734 126 KVVQEYERVIIFRLGhlLPGRAKGPGLFFFLPCLDTYHKVDLRLQTLEIPF 176
Cdd:pfam01145   1 IIVPPGEVGVVTRFG--KLSRVLEPGLHFIIPFIQRVVTVDVRVQTLEVSV 49

Podocin, a subgroup of the stomatin-like proteins (slipins) family; belonging to the SPFH (stomatin, prohibitin, flotillin, and HflK/C) superfamily; This model summarizes a subgroup of the stomatin-like protein family (SLPs or slipins) that is found in vertebrates. The conserved domain common to the SPFH superfamily has also been referred to as the Band 7 domain. Individual proteins of the SPFH superfamily may cluster to form membrane microdomains which may in turn recruit multiprotein complexes. Podocin is expressed in the kidney and mutations in the gene have been linked to familial idiopathic nephrotic syndrome. Podocin interacts with the TRP ion channel TRPV-6 and may function as a scaffolding protein in the organization of lipid-protein domains.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034561734 122 WFCVKVVQEYERVIIFRLGHLLPGRAKGPGLFFFLPCLDTYHKVDLRLQTLEIPFHE 178
Cdd:cd08827     1 WFCVKVVREYERAVIFRLGHLLQGRARGPGLFFYLPCLDVCHKVDIRLQTLEIPFHM 57

Stomatin, a subgroup of the stomatin-like proteins (slipins) family; belonging to the SPFH (stomatin, prohibitin, flotillin, and HflK/C) superfamily; Stomatin (or band 7) is widely expressed and, highly expressed in red blood cells. It localizes predominantly to the plasma membrane and to intracellular vesicles of the endocytic pathway, where it is present in higher order homo-oligomeric complexes (of between 9 and 12 monomers). Stomatin interacts with and regulates members of the degenerin/epithelia Na+ channel family in mechanosensory cells of Caenorhabditis elegans and vertebrate neurons and, is implicated in trafficking of Glut1 glucose transporters. This subgroup found in animals, also contains proteins similar to Caenorhabditis elegans MEC-2. MEC-2 interacts with MEC-4, which is part of the degenerin channel complex required for response to gentle body touch.

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                  ....*....|....*....|....*....|....*
gi 1034561734 144 PGRAKGPGLFFFLPCLDTYHKVDLRLQTLEIPFHE 178
Cdd:cd03403     1 PGGAKGPGLFFILPCIDSYRKVDLRTVSFDVPPQE 35

Slipin-4 (SLP-4), an uncharacterized subgroup of the stomatin-like proteins (slipins) family; belonging to the SPFH (stomatin, prohibitin, flotillin, and HflK/C) superfamily; This model summarizes a subgroup of the stomatin-like protein family (SLPs or slipins) that is found in arthropods. The conserved domain common to the SPFH superfamily has also been referred to as the Band 7 domain. Individual proteins of the SPFH superfamily may cluster to form membrane microdomains which may in turn recruit multiprotein complexes. Members of this divergent slipin subgroup remain largely uncharacterized. It contains Drosophila Mec2, the gene for which was identified in a screen for genes required for nephrocyte function; it may function together with Sns in maintaining nephrocyte diaphragm.

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                  ....*....|....*....|....*....|....
gi 1034561734 145 GRAKGPGLFFFLPCLDTYHKVDLRLQTLEIPFHE 178
Cdd:cd13435     2 GGARGPGVFFVLPCIDNYCKVDLRTVSFDVPPQE 35

High frequency of lysogenization C (HflC) family; SPFH (stomatin, prohibitin, flotillin, and HflK/C) superfamily; This model characterizes proteins similar to prokaryotic HflC (High frequency of lysogenization C). 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 HflC is an integral membrane protein which may localize to the plasma membrane. HflC associates with another SPFH superfamily member (HflK) 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.

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034561734 124 CVKVVQEYERVIIFRLGHLLpGRAKGPGLFFFLPCLDTYHKVDLRLQTLEIP 175
Cdd:cd03405     1 SVFIVDETEQAVVLQFGKPV-RVITEPGLHFKLPFIQNVRKFDKRILTLDGP 51

Stomatin-like protein 1 (SLP-1), a subgroup of the stomatin-like proteins (slipins) family; belonging to the SPFH (stomatin, prohibitin, flotillin, and HflK/C) superfamily; This model summarizes a subgroup of the stomatin-like protein family (SLPs or slipins) that is found in animals. The conserved domain common to the SPFH superfamily has also been referred to as the Band 7 domain. Individual proteins of the SPFH superfamily may cluster to form membrane microdomains which may in turn recruit multiprotein complexes. The family contains human SLP-1, which has been found to be expressed in the brain, and Caenorhabditis elegans UNC-24, which is a lipid raft-associated protein required for normal locomotion. It may mediate the correct localization of UNC-1. Mutations in the unc-24 gene result in abnormal motion and altered patterns of sensitivity to volatile anesthetics.

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                  ....*....|....*....|....*....|....
gi 1034561734 145 GRA---KGPGLFFFLPCLDTYHKVDLRLQTLEIP 175
Cdd:cd13436     1 GRLqkpRGPGIVLILPCIDNFTRVDMRTRAFNVP 34

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.

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034561734 125 VKVVQEYERVIIFRLGHLLPGRAKGPGLFFFLPCLDTYHKVDLRLQTLEIPF 176
Cdd:cd03401     1 FYTVDAGEVGVVFRRGKGVKDEVLGEGLHFKIPWIQVVIIYDVRTQPREITL 52