MATH (meprin and TRAF-C homology) domain; an independent folding unit with an eight-stranded beta-sandwich structure found in meprins, TRAFs and other proteins. Meprins comprise a class of extracellular metalloproteases which are anchored to the membrane and are capable of cleaving growth factors, extracellular matrix proteins, and biologically active peptides. TRAF molecules serve as adapter proteins that link cell surface receptors of the Tumor Necrosis Factor and 1nterleukin-1/Toll-like families to downstream kinase cascades, which results in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses in the immune and inflammatory systems. Other members include the ubiquitin ligases, TRIM37 and SPOP, and the ubiquitin-specific proteases, HAUSP and Ubp21p. A large number of uncharacterized members mostly from lineage-specific expansions in C. elegans and rice contain MATH and BTB domains, similar to SPOP. The MATH domain has been shown to bind peptide/protein substrates in TRAFs and HAUSP. It is possible that the MATH domain in other members of this superfamily also interacts with various protein substrates. The TRAF domain may also be involved in the trimerization of TRAFs. Based on homology, it is postulated that the MATH domain in meprins may be involved in its tetramer assembly and that the MATH domain, in general, may take part in diverse modular arrangements defined by adjacent multimerization domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907143854  80 CLRVNPKGLDDESKDYLSLYLLLVSCPKSEVRAKFKFSLLNDKREETKAMESQRAYRFVQGKDWGFKKFIRRDFLLDEAN 159
Cdd:cd03774    41 CLRVNPKGLDEESKDYLSLYLLLVSCPKSEVRAKFKFSILNAKGEETKAMESQRAYRFVQGKDWGFKKFIRRDFLLDEAN 120

                          90
                  ....*....|....*....
gi 1907143854 160 GLLPDDKLTLFCEVSVVQD 178
Cdd:cd03774   121 GLLPDDKLTLFCEVSVVQD 139

Speckle-type POZ protein (SPOP) family, MATH domain; composed of proteins with similarity to human SPOP. SPOP was isolated as a novel antigen recognized by serum from a scleroderma patient, whose overexpression in COS cells results in a discrete speckled pattern in the nuclei. It contains an N-terminal MATH domain and a C-terminal BTB (also called POZ) domain. Together with Cul3, SPOP constitutes an ubiquitin E3 ligase which is able to ubiquitinate the PcG protein BMI1, the variant histone macroH2A1 and the death domain-associated protein Daxx. Therefore, SPOP may be involved in the regulation of these proteins and may play a role in transcriptional regulation, apoptosis and X-chromosome inactivation. Cul3 binds to the BTB domain of SPOP whereas Daxx and the macroH2A1 nonhistone region have been shown to bind to the MATH domain. Both MATH and BTB domains are necessary for the nuclear speckled accumulation of SPOP. There are many proteins, mostly uncharacterized, containing both MATH and BTB domains from C. elegans and plants which are excluded from this family.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907143854  80 CLRVNPKGLDDESKDYLSLYLLLVSCPKSEVRAKFKFSLLNDKREETKAMESQRAYRFVQGKDWGFKKFIRRDFLLDEAN 159
Cdd:cd03774    41 CLRVNPKGLDEESKDYLSLYLLLVSCPKSEVRAKFKFSILNAKGEETKAMESQRAYRFVQGKDWGFKKFIRRDFLLDEAN 120

                          90
                  ....*....|....*....
gi 1907143854 160 GLLPDDKLTLFCEVSVVQD 178
Cdd:cd03774   121 GLLPDDKLTLFCEVSVVQD 139

BTB/POZ domain; The BTB (for BR-C, ttk and bab) or POZ (for Pox virus and Zinc finger) domain is present near the N-terminus of a fraction of zinc finger (pfam00096) proteins and in proteins that contain the pfam01344 motif such as Kelch and a family of pox virus proteins. The BTB/POZ domain mediates homomeric dimerization and in some instances heteromeric dimerization. The structure of the dimerized PLZF BTB/POZ domain has been solved and consists of a tightly intertwined homodimer. The central scaffolding of the protein is made up of a cluster of alpha-helices flanked by short beta-sheets at both the top and bottom of the molecule. POZ domains from several zinc finger proteins have been shown to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes including N-CoR and SMRT. The POZ or BTB domain is also known as BR-C/Ttk or ZiN.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907143854 202 LGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEECTKIWVE 254
Cdd:pfam00651   1 LNELREQGELCDVTLVVGDKEFRAHKAVLAACSPYFKALFSGQESESSVSEIT 53

Speckle-type POZ protein (SPOP) family, MATH domain; composed of proteins with similarity to human SPOP. SPOP was isolated as a novel antigen recognized by serum from a scleroderma patient, whose overexpression in COS cells results in a discrete speckled pattern in the nuclei. It contains an N-terminal MATH domain and a C-terminal BTB (also called POZ) domain. Together with Cul3, SPOP constitutes an ubiquitin E3 ligase which is able to ubiquitinate the PcG protein BMI1, the variant histone macroH2A1 and the death domain-associated protein Daxx. Therefore, SPOP may be involved in the regulation of these proteins and may play a role in transcriptional regulation, apoptosis and X-chromosome inactivation. Cul3 binds to the BTB domain of SPOP whereas Daxx and the macroH2A1 nonhistone region have been shown to bind to the MATH domain. Both MATH and BTB domains are necessary for the nuclear speckled accumulation of SPOP. There are many proteins, mostly uncharacterized, containing both MATH and BTB domains from C. elegans and plants which are excluded from this family.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907143854  80 CLRVNPKGLDDESKDYLSLYLLLVSCPKSEVRAKFKFSLLNDKREETKAMESQRAYRFVQGKDWGFKKFIRRDFLLDEAN 159
Cdd:cd03774    41 CLRVNPKGLDEESKDYLSLYLLLVSCPKSEVRAKFKFSILNAKGEETKAMESQRAYRFVQGKDWGFKKFIRRDFLLDEAN 120

                          90
                  ....*....|....*....
gi 1907143854 160 GLLPDDKLTLFCEVSVVQD 178
Cdd:cd03774   121 GLLPDDKLTLFCEVSVVQD 139

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in speckle-type POZ protein (SPOP) and similar proteins; This family includes speckle-type POZ protein (SPOP), speckle-type POZ protein-like (SPOPL), TD and POZ domain-containing proteins (TDPOZ), Drosophila melanogaster protein roadkill and similar proteins. Both, SPOP and SPOPL, serve as adaptors of cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes that mediate the ubiquitination and proteasomal degradation of target proteins. TDPOZ is a family of bipartite animal and plant proteins that contain a tumor necrosis factor receptor-associated factor (TRAF) domain (TD) and a POZ/BTB domains. TDPOZ proteins may be nuclear scaffold proteins probably involved in transcription regulation in early development and other cellular processes. Drosophila melanogaster protein roadkill, also called Hh-induced MATH and BTB domain-containing protein (HIB), is a hedgehog-induced BTB protein that modulates hedgehog signaling by degrading Ci/Gli transcription factor. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907143854 194 PECRLAEDLGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEECTKIWVEV 255
Cdd:cd18279     1 PECRLAEDLGNLWENSRFTDCCLCVGGQEFQAHKAILAARSPVFSAMFEHEMEESKKNRVEI 62

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in speckle-type POZ protein (SPOP); SPOP, also called HIB homolog 1 or Roadkill homolog 1, is a novel nuclear speckle-type protein which serves as an adaptor of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and proteasomal degradation of target proteins, such as BRMS1, DAXX, PDX1/IPF1, GLI2 and GLI3. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907143854 191 LKVPECRLAEDLGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEECTKIWVEV 255
Cdd:cd18342     2 VKVPECRLADELGGLWENSRFTDCCLCVAGQEFQAHKAILAARSPVFSAMFEHEMEESKKNRVEI 66

BTB/POZ domain; The BTB (for BR-C, ttk and bab) or POZ (for Pox virus and Zinc finger) domain is present near the N-terminus of a fraction of zinc finger (pfam00096) proteins and in proteins that contain the pfam01344 motif such as Kelch and a family of pox virus proteins. The BTB/POZ domain mediates homomeric dimerization and in some instances heteromeric dimerization. The structure of the dimerized PLZF BTB/POZ domain has been solved and consists of a tightly intertwined homodimer. The central scaffolding of the protein is made up of a cluster of alpha-helices flanked by short beta-sheets at both the top and bottom of the molecule. POZ domains from several zinc finger proteins have been shown to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes including N-CoR and SMRT. The POZ or BTB domain is also known as BR-C/Ttk or ZiN.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907143854 202 LGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEECTKIWVE 254
Cdd:pfam00651   1 LNELREQGELCDVTLVVGDKEFRAHKAVLAACSPYFKALFSGQESESSVSEIT 53

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in plant BTB/POZ-MATH (BPM) protein family; The BPM protein family includes Arabidopsis thaliana BTB/POZ and MATH domain-containing proteins, AtBPM1-6, and similar proteins from other plants. BPM protein, also called protein BTB-POZ and MATH domain, may act as a substrate-specific adaptor of an E3 ubiquitin-protein ligase complex (CUL3-RBX1-BTB) which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907143854 198 LAEDLGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEE 247
Cdd:cd18280     1 LGQHFGALLESEEGADVTFNVDGEKFRAHKLVLAARSPVFRSMLFGPMRE 50

MATH (meprin and TRAF-C homology) domain; an independent folding unit with an eight-stranded beta-sandwich structure found in meprins, TRAFs and other proteins. Meprins comprise a class of extracellular metalloproteases which are anchored to the membrane and are capable of cleaving growth factors, extracellular matrix proteins, and biologically active peptides. TRAF molecules serve as adapter proteins that link cell surface receptors of the Tumor Necrosis Factor and 1nterleukin-1/Toll-like families to downstream kinase cascades, which results in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses in the immune and inflammatory systems. Other members include the ubiquitin ligases, TRIM37 and SPOP, and the ubiquitin-specific proteases, HAUSP and Ubp21p. A large number of uncharacterized members mostly from lineage-specific expansions in C. elegans and rice contain MATH and BTB domains, similar to SPOP. The MATH domain has been shown to bind peptide/protein substrates in TRAFs and HAUSP. It is possible that the MATH domain in other members of this superfamily also interacts with various protein substrates. The TRAF domain may also be involved in the trimerization of TRAFs. Based on homology, it is postulated that the MATH domain in meprins may be involved in its tetramer assembly and that the MATH domain, in general, may take part in diverse modular arrangements defined by adjacent multimerization domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907143854  80 CLRVNPKGlDDESKDYL----SLYLLLVSCPKSEVRAKFKFSLLNDKREETKAMESQRAYRFVQGKDWGFKKFIRRDFLL 155
Cdd:cd00121    31 RIRIYPNG-DGESGDYLslylELDKGESDLEKWSVRAEFTLKLVNQNGGKSLSKSFTHVFFSEKGSGWGFPKFISWDDLE 109

                          90
                  ....*....|....*...
gi 1907143854 156 DEANglLPDDKLTLFCEV 173
Cdd:cd00121   110 DSYY--LVDDSLTIEVEV 125

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in BTB/POZ domain-containing protein 9 (BTBD9); BTBD9 is a risk factor for Restless Legs Syndrome (RLS) encoding a Cullin-3 substrate adaptor. The BTBD9 gene may be associated with antipsychotic-induced RLS in schizophrenia. Mutations in BTBD9 lead to reduced dopamine, increased locomotion and sleep fragmentation. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907143854 197 RLAEDLGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEE--CTKI 251
Cdd:cd18287     8 FLSEDIGALFLNEEYSDVTFVVEEKRFPAHRVILAARSEYFRALLYGGMREsqQSEI 64

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 40 (KLHL40); KLHL40, also called Kelch repeat and BTB domain-containing protein 5 (KBTBD5) or sarcosynapsin, is a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a key regulator of skeletal muscle development. Mutations in KLHL40 may cause severe autosomal-recessive nemaline myopathy. KLHL40 contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907143854 198 LAEDLGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEECTK 250
Cdd:cd18340    14 LQDGLKDLLDHNKFVDCVLKIKEKEFPCHRLVLAACSPYFRAMFLSDLEESKK 66

first BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Ankyrin repeat and BTB/POZ domain-containing protein 1 (ABTB1); ABTB1, also called elongation factor 1A-binding protein or bood POZ containing gene type 1 (BPOZ-1), is an anti-proliferative factor that may act as a mediator of the phosphatase and tensin homolog (PTEN) growth-suppressive signaling pathway. It may play a role in developmental processes. ABTB1 contains an ankyrin repeat and two BTB domains. This model corresponds to the first BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1907143854 200 EDLGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFE 242
Cdd:cd18295     8 EFLRRLLEQGSYSDVTFNVHGESFPAHRCILSARSPYFAEMFE 50

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 12 (KLHL12); KLHL12, also called CUL3-interacting protein 1 (C3IP1) or DKIR homolog, is a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a negative regulator of the Wnt signaling pathway and ER-Golgi transport. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1907143854 218 VRGKEFKAHKSVLAARSPVFNAMFEHEMEECTKIWVEVYFLS 259
Cdd:cd18242    28 VEGKEFPAHRIVLAACSDYFCAMFTSEMSEKGKSEVELQGLT 69

BTB (Broad-Complex, Tramtrack and Bric a brac) /POZ (poxvirus and zinc finger) domain found in Drosophila melanogaster proteins bric-a-brac 1 (BAB1), bric-a-brac 2 (BAB2), modifier of mdg4 (doom), and similar proteins; BAB1 and BAB2 probably act as transcriptional regulators that are required for specification of the tarsal segment and are involved in antenna development. Doom is a product of the Drosophila mod(mdg4) gene. It induces apoptosis and binds to baculovirus inhibitor-of-apoptosis proteins. This subfamily also includes Drosophila melanogaster sex determination protein fruitless (FRU), protein jim lovell (LOV), zinc finger protein chinmo, transcription factor GAGA, transcription factor Ken, and longitudinals lacking proteins (LOLA). FRU probably acts as a transcriptional regulator that plays a role in male courtship behavior and sexual orientation, and enhances male-specific expression of takeout in brain-associated fat body. LOV, also called tyrosine kinase-related (TKR), has a regulatory role during midline cell development. Chinmo is a functional effector of the JAK/STAT pathway that regulates eye development, tumor formation, and stem cell self-renewal in Drosophila. GAGA is a transcriptional activator that functions by regulating chromatin structure. Ken, also termed protein Ken and Barbie, is a transcription factor required for Terminalia development. LOLA proteins are putative transcription factors required for axon growth and guidance in the central and peripheral nervous systems. Proteins in this subfamily contain a BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1907143854 211 FTDCCFFVRGKEFKAHKSVLAARSPVFNAMFE 242
Cdd:cd18315     1 LVDVTLACEGGSLKAHKLVLAAASPYFAALLK 32

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like ECH-associated protein 1 (KEAP1); KEAP1, also called cytosolic inhibitor of Nrf2 (INrf2) or Kelch-like protein 19 (KLHL19), is a redox-regulated substrate adaptor protein for a Cullin3-dependent ubiquitin ligase complex that targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30
                  ....*....|....*....|....*....|
gi 1907143854 221 KEFKAHKSVLAARSPVFNAMFEHEMEECTK 250
Cdd:cd18248    35 EEFMAHKVVLASSSPYFKAMFTSGLRECGM 64

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch repeat and BTB domain-containing protein 12 (KBTBD12); KBTBD12, also called Kelch domain-containing protein 6 (KLHDC6), contains a BTB domain and kelch repeats, characteristics of a kelch family protein. Its function remains unclear. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907143854 198 LAEDLGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEECTKIWVEVY 256
Cdd:cd18276     8 LLDQLNRMKELAELTDVVLVAEGEKFPCHRLVLAAFSPYFKAMFTCGLMECSQREVVLH 66

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 30 (KLHL30); KLHL30 contains a BTB domain and kelch repeats, characteristics of a kelch family protein. Its function remains unclear. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907143854 200 EDLGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEECTKIWVEV 255
Cdd:cd18259    21 DGLQTLRSNPKLSDVTLLVGGREFPCHRSVLALCSHYFNAMFTGDFVESISARVEI 76

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 25 (KLHL25); KLHL25, also called ectoderm-neural cortex protein 2 (ENC-2), is a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that is required for translational homeostasis. The BCR(KLHL25) ubiquitin ligase complex acts by mediating ubiquitination of hypophosphorylated EIF4EBP1 (4E-BP1). Cullin3-KLHL25 ubiquitin ligase also targets ATP-citrate lyase (ACLY), a key enzyme for lipid synthesis, for degradation to inhibit lipid synthesis and tumor progression. KLHL25 contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907143854 194 PECRLAEdLGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEE 247
Cdd:cd18254     6 PDCVLTH-LNTLRKQCMFTDVTLWAGNRSFPCHRAVLAACSRYFEAMFSNGLRE 58

first BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in leucine-zipper-like transcriptional regulator 1 (LZTR-1); LZTR-1 is a golgi BTB-kelch protein that is degraded upon induction of apoptosis. It may also function as a transcriptional regulator that plays a crucial role in embryogenesis. Germline loss-of-function mutations in LZTR-1 predispose to an inherited disorder of multiple schwannomas. LZTR-1 contains two BTB domains. This model corresponds to the first domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1907143854 194 PECRLAEDLGNLWENTRFTDCCFFV--RGKEFKAHKSVLAARSP 235
Cdd:cd18308     6 PKCTLHDDFGRLLESRQFCDVEFIVgeEEERIPAHIAFVAARSK 49

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 21 (KLHL21); KLHL21 is a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for efficient chromosome alignment and cytokinesis. The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of aurora B. KLHL21 also targets IkappaB kinase-beta to regulate nuclear factor kappa-light chain enhancer of activated B cells (NF-kappaB) signaling negatively. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907143854 202 LGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEECTKIWVEVYFLS 259
Cdd:cd18250    12 LSELRAERKFFDVTLCAGGREFPCHRTVLAAASSYFRAMFAGELRESRADRVVLHGVS 69

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch repeat and BTB domain-containing protein 8 (KBTBD8); KBTBD8, also called T-cell activation kelch repeat protein (TA-KRP), is a BTB-kelch family protein that is located in the Golgi apparatus and translocates to the spindle apparatus during mitosis. It acts as a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of neural crest specification. The BCR(KBTBD8) complex monoubiquitylates NOLC1 and its paralog TCOF1, the mutation of which underlies the neurocristopathy Treacher Collins syndrome. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907143854 196 CRLAEDLGNLWENTRFTDCCFFV-RGKEFKAHKSVLAARSPVFNAMFEHEMEECTKIWVEV 255
Cdd:cd18274     7 CSILQQLKAMYDEGQLTDIVVEVdHGKTFSCHRNVLAAISPYFRSMFTSGLTESTQKEVRI 67

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like proteins, KLHL2 and KLHL3; The family includes Kelch-like proteins, KLHL2 and KLHL3. KLHL2 is a novel actin-binding protein predominantly expressed in brain. It plays a role in the reorganization of the actin cytoskeleton, and promotes growth of cell projections in oligodendrocyte precursors. KLHL2 and KLHL3 each functions as a component of an E3 ubiquitin ligase complex that mediates the ubiquitination of target proteins. They contain a BTB domain and kelch repeat domains, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20
                  ....*....|....*....|....*...
gi 1907143854 220 GKEFKAHKSVLAARSPVFNAMFEHEMEE 247
Cdd:cd18235    30 GVEIPAHRVVLASCSPYFHAMFTGDLSE 57

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in zinc finger and BTB domain-containing protein 11 (ZBTB11); ZBTB11 is a transcriptional repressor of TP53. It is critical for basal and emergency granulopoiesis. It regulates neutrophil development through its integrase-like zinc finger domain. ZBTB11 contains a BTB/POZ domain, a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1907143854 208 NTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMF 241
Cdd:cd18202    16 NNQFCDVTLLIEGEEYKAHKSVLAANSEYFRELF 49

second BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in leucine-zipper-like transcriptional regulator 1 (LZTR-1); LZTR-1 is a golgi BTB-kelch protein that is degraded upon induction of apoptosis. It may also function as a transcriptional regulator that plays a crucial role in embryogenesis. Germline loss-of-function mutations in LZTR-1 predispose to an inherited disorder of multiple schwannomas. LZTR-1 contains two BTB domains. This model corresponds to the second domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1907143854 211 FTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEE 247
Cdd:cd18309    20 FCDITLLLDGHPIPAHKAILAARCSYFEAMFRSFMPE 56

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch repeat and BTB domain-containing protein 2 (KBTBD2); KBTBD2, also called BTB and kelch domain-containing protein 1 (BKLHD1), plays an essential role in the regulation of insulin-signaling pathway. It is a BTB-Kelch family substrate recognition subunit of the Cullin-3-based E3 ubiquitin ligase, which targets p85alpha, the regulatory subunit of the phosphoinositol-3-kinase (PI3K) heterodimer, causing p85alpha ubiquitination and proteasome-mediated degradation. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907143854 198 LAEDLGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEE 247
Cdd:cd18270    13 LLEQLKFFYEQQLLTDIVLIVEGTEFPCHKMVLATCSSYFRAMFMSGLSE 62

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in zinc finger and BTB domain-containing protein 8B (ZBTB8B); ZBTB8B may be involved in transcriptional regulation. It contains a BTB/POZ domain, a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907143854 198 LAEDLGNLWENTR---FTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEE 247
Cdd:cd18330     2 YTKLLGELNEQRKrdfFCDCSIIVEGRIFKAHRNILFANSGYFRALLIHYIQD 54

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in gigaxonin; Gigaxonin, also called Kelch-like protein 16 (KLHL16), may be a cytoskeletal component that directly or indirectly plays an important role in neurofilament architecture. It may also act as a substrate-specific adaptor of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, including tubulin folding cofactor B (TBCB), microtubule-associated protein MAP1B, and glial fibrillary acidic protein (GFAP). Gigaxonin is mutated in giant axonal neuropathy. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1907143854 198 LAEDLGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMF 241
Cdd:cd18245     1 LLRALNSFREEPHLCDATLVVGGEEIPVQKNVLAAASPYFRAKL 44

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 24 (KLHL24); KLHL24, also called kainate receptor-interacting protein for GluR6 (KRIP6) or protein DRE1, is necessary to maintain the balance between intermediate filament stability and degradation, a process that is essential for skin integrity. KLHL24 is a component of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that mediates ubiquitination of KRT14 and controls its levels during keratinocyte differentiation. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907143854 202 LGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEECTKIWVEV 255
Cdd:cd18253     9 FNEFRDSRLFTDVIICVEGREFPCHRAILSACSSYFRAMFCNDHRESREMLVEI 62

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 6 (KLHL6); KLHL6 is a BTB-kelch protein with a lymphoid tissue-restricted expression pattern. It is involved in B-lymphocyte antigen receptor signaling and germinal center formation. It belongs to the KLHL gene family, which is composed of an N-terminal BTB-POZ domain and four to six Kelch motifs in tandem. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907143854 198 LAEDLGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEE 247
Cdd:cd18236    11 LQNGLENLRLENSLTDVILCVDSQEFSCHRVVLAAASNYFRAMFCNDLKE 60

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in zinc finger and BTB domain-containing protein 8 (ZBTB8); There are two ZBTB8 isoforms: ZBTB8A and ZBTB8B. ZBTB8A is a novel proto-oncoprotein that stimulates cell proliferation. ZBTB8B may be involved in transcriptional regulation. They both contain a BTB/POZ domain, a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907143854 202 LGNLWENTR---FTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEECTK 250
Cdd:cd18199     6 LGQLNEQRKqdfFCDCSIIVEGRIFKAHRNVLFASSGYFRMLLSHYIQDTGR 57

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in zinc finger and BTB domain-containing protein 8A (ZBTB8A); ZBTB8A, also called BTB/POZ and zinc-finger domain-containing factor or BTB/POZ and zinc-finger domains factor on chromosome 1 (BOZ-F1), is a novel proto-oncoprotein that stimulates cell proliferation. It binds to all the proximal GC boxes to repress transcription, and it inhibits p53 acetylation without affecting p53 stability. It may be involved in gastric adenocarcinoma cell differentiation, cancer invasion, and metastasis. ZBTB8A contains a BTB/POZ domain, a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907143854 197 RLAEDLGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEECTK 250
Cdd:cd18329     7 RLLQQLDEQRKQELFCDCSILVEGQVFKAHRNVLFASSGYFKMLLSQNAKETGQ 60

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 2 (KLHL2); KLHL2, also called actin-binding protein Mayven, is a novel actin-binding protein predominantly expressed in the brain. It plays a role in the reorganization of the actin cytoskeleton, and promotes growth of cell projections in oligodendrocyte precursors. KLHL2 is a component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, such as NPTXR, leading most often to their proteasomal degradation. It contains a BTB domain and kelch repeat domains, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20
                  ....*....|....*....|....*.
gi 1907143854 222 EFKAHKSVLAARSPVFNAMFEHEMEE 247
Cdd:cd18338    32 EIAAHRVVLAACSPYFHAMFTGEMSE 57

Herpesvirus-associated ubiquitin-specific protease (HAUSP, also known as USP7) family, N-terminal MATH (TRAF-like) domain; composed of proteins similar to human HAUSP, an enzyme that specifically catalyzes the deubiquitylation of p53 and MDM2, hence playing an important role in the p53-MDM2 pathway. It contains an N-terminal TRAF-like domain and a C-terminal catalytic protease (C19 family) domain. The tumor suppressor p53 protein is a transcription factor that responds to many cellular stress signals and is regulated primarily through ubiquitylation and subsequent degradation. MDM2 is a RING-finger E3 ubiquitin ligase that promotes p53 ubiquitinylation. p53 and MDM2 bind to the same site in the N-terminal TRAF-like domain of HAUSP in a mutually exclusive manner. HAUSP also interacts with the Epstein-Barr nuclear antigen 1 (EBNA1) protein of the Epstein-Barr virus (EBV), which efficiently immortalizes infected cells predisposing the host to a variety of cancers. EBNA1 plays several important roles in EBV latent infection and cellular transformation. It binds the same pocket as p53 in the HAUSP TRAF-like domain. Through interactions with p53, MDM2 and EBNA1, HAUSP plays a role in cell proliferation, apoptosis and EBV-mediated immortalization.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1907143854 142 DWGFKKFIRRDFLLDEANGLLPDDKLTLfcEVSVVQD 178
Cdd:cd03772    99 DWGFSNFMTWSEVTDPEKGFIEDDTITL--EVYVQAD 133

first BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Rho-related BTB domain-containing proteins (RhoBTB); RhoBTB proteins constitute a subfamily of atypical members within the Rho family of small guanosine triphosphatases (GTPases), which is characterized by containing a GTPase domain (in most cases, non-functional) followed by a proline-rich region, tandem BTB domains, and a conserved C-terminal region. In vertebrates, the RhoBTB subfamily consists of 3 isoforms: RhoBTB1, RhoBTB2, and RhoBTB3. Orthologs are present in several other eukaryotes, such as Drosophila and Dictyostelium, but have been lost in plants and fungi. This model corresponds to the first BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1907143854 200 EDLGNLWENTRFTDCCFFVRGKE-FKAHKSVLAARSPVFNAMFEHE 244
Cdd:cd18299     1 EDLRNLLHSPSCADVVFILQGGVrIFAHRIVLAAASSVFADLFLMM 46

second BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Rho-related BTB domain-containing proteins (RhoBTB); RhoBTB proteins constitute a subfamily of atypical members within the Rho family of small guanosine triphosphatases (GTPases), which is characterized by containing a GTPase domain (in most cases, non-functional) followed by a proline-rich region, a tandem of 2 BTB domains, and a conserved C-terminal region. In humans, the RhoBTB subfamily consists of 3 isoforms: RhoBTB1, RhoBTB2, and RhoBTB3. Orthologs are present in several other eukaryotes, such as Drosophila and Dictyostelium, but have been lost in plants and fungi. This model corresponds to the second BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1907143854 211 FTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEECTKIWVEVY 256
Cdd:cd18300     9 FSDVTFIVEDGTIPAHKALLVARCDVMAAMFGGNFRESSAKEVELP 54

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in rabankyrin-5 (Rank-5); Rank-5, also called ankyrin repeat and FYVE domain-containing protein 1 (ANKFY1) or ankyrin repeats hooked to a zinc finger motif (ANKHZN), is a Rab5 effector that regulates and coordinates different endocytic mechanisms. It contains an N-terminal BTB domain, followed by a BACK domain, several ankyrin (ANK) repeats and a C-terminal FYVE domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1907143854 197 RLAEDLGNLWENTRFTDCCFFVRGKEFKAHKSVLAARS 234
Cdd:cd18303     4 RLLKTVASLFDKELYSDITIKLADKSIPAHKFVLAARS 41

second BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Ankyrin repeat and BTB/POZ domain-containing protein 1 (ABTB1); ABTB1, also called elongation factor 1A-binding protein or bood POZ containing gene type 1 (BPOZ-1), is an anti-proliferative factor that may act as a mediator of the phosphatase and tensin homolog (PTEN) growth-suppressive signaling pathway. It may play a role in developmental processes. ABTB1 contains an ankyrin repeat and two BTB domains. This model corresponds to the second BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907143854 201 DLGNLWENTR----FTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEECTK 250
Cdd:cd18296     3 DLDELPFPPEqelsFPDVCFQVEGHRFPCHKAFFCGRSDYFKALLRDHFAESEE 56

second BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Rho-related BTB domain-containing protein 3 (RhoBTB3); RhoBTB3 is an atypical Rho family small guanosine triphosphatase (GTPase) and is a member of the RhoBTB subfamily, which is characterized by containing a GTPase domain (in most cases, non-functional) followed by a proline-rich region, tandem BTB domains, and a conserved C-terminal region. The carboxyl terminal extension that harbors two BTB domains is capable of assembling cullin 3-dependent ubiquitin ligase complexes. RhoBTB3 is a Golgi-associated Rho-related ATPase that regulates the S/G2 transition of the cell cycle by targeting cyclin E for ubiquitylation. It is involved in vesicle trafficking and in targeting proteins for degradation in the proteasome. It binds directly to Rab9 GTPase and functions with Rab9 in protein transport from endosomes to the trans Golgi network. It also promotes proteasomal degradation of Hypoxia-inducible factor alpha (HIFalpha) through facilitating hydroxylation and suppresses the Warburg effect. This model corresponds to the second BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907143854 202 LGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEECTKIWVEVYFLS 259
Cdd:cd18360     1 LGLFFNSPLLADVVFKIQGTTVPAHRAVLVARCEVMAAMFNGNYAEAKSFLVPIYGVS 58

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 3 (KLHL3); KLHL3 is a component of an E3 ubiquitin ligase complex that regulates blood pressure by targeting With-No-Lysine (WNK) kinases for degradation. It contains a BTB domain and kelch repeat domains, characteristics of a kelch family protein. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1907143854 222 EFKAHKSVLAARSPVFNAMFEHEMEECTKIWVEV 255
Cdd:cd18339    32 EIEAHRVVLAACSPYFCAMFTGDMSESKAKKIEI 65

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 28 (KLHL28); KLHL28, also called BTB/POZ domain-containing protein 5 (BTBD5), contains a BTB domain and kelch repeats, characteristics of a kelch family protein. Its function remains unclear. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907143854 198 LAEDLGNLWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEECTKIWVE 254
Cdd:cd18257     5 LLQGLNLLRQHHELCDVVLRVGDVKIHAHKVVLASCSPYFKAMFTGNLSEKENSEVE 61

second BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 33 (KLHL33); KLHL33 contains BTB domains and kelch repeats, characteristics of a kelch family protein. Its function remains unclear. KLHL33 gene expression in normal and tumor tissue suggest a significant association with prostate cancer risk. KLHL33 contains two BTB domains. This model corresponds to the second BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1907143854 205 LWENTRFTDCCFFVRGKEFKAHKSVLAARSPVFNAMFEHEMEECTKIWVEVYFLS 259
Cdd:cd18263     7 LWEKGVGCDVQLEADGSIFRVHRVILAAGSDYFRAMFTSGMKESTQSVVQLPTIP 61