high mobility group (HMG)-box found in high mobility group protein 20B (HMG20B) and similar proteins; HMG20B, also called SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related, SMARCE1-related protein (SMARCE1R), BRCA2-associated factor 35 (BRAF35), HMG box-containing protein 20B, HMG domain-containing protein 2 (HMGXB2), HMG domain-containing protein HMGX2, Sox-like transcriptional factor, or structural DNA-binding protein BRAF35, is a DNA binding factor that acts as a repressor of erythroid differentiation. It is required for correct progression through the G2 phase of the cell cycle and entry into mitosis. It is also required for RCOR1/CoREST mediated repression of neuronal specific gene promoters. HMG20B is a core subunit of the Lys-specific demethylase 1/REST co-repressor 1 (LSD1-CoREST) histone demethylase complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1497485697  64 GPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQQSEAYKMCTE 143
Cdd:cd22018     1 GPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQPHEKQRYLDEAERDKQQYMKELREYQQSEAYKMCTE 80

                  ....*
gi 1497485697 144 KIQEK 148
Cdd:cd22018    81 KIQEK 85

GIPC-homology 2 (GH2) domain found in the GIPC family; The GIPC family includes PDZ domain-containing proteins, GIPC1 (also called GAIP C-terminus-interacting protein, RGS-GAIP-interacting protein, RGS19-interacting protein 1, RGS19IP1, synectin, tax interaction protein 2, or TIP-2), GIPC2, and GIPC3, which may act as scaffold proteins linking heterotrimeric G-proteins to seven-transmembrane-type WNT receptor or to receptor tyrosine kinases. They might play key roles in carcinogenesis and embryogenesis through modulation of growth factor signaling and cell adhesion. GIPCs are proteins with a GIPC homology 1 (GH1) domain, a central PDZ domain and a GH2 domain. This model corresponds to the GH2 domain, which mediates the interaction with myosin VI and is involved in homodimerization in the autoinhibited state.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1497485697 519 AARRVDDLLESYMGIRDSELASTMVEVAKDSPSVAQLAQGLDSVLGEFAFPPEFVAEVWAAV 580
Cdd:cd21180     4 AIEKIDDLLESYMGIRDDELAQTIVELGKDKSNPDEFAEALDESLGDFAFPDEFVFDVWGAI 65

high mobility group (HMG)-box found in high mobility group protein 20B (HMG20B) and similar proteins; HMG20B, also called SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related, SMARCE1-related protein (SMARCE1R), BRCA2-associated factor 35 (BRAF35), HMG box-containing protein 20B, HMG domain-containing protein 2 (HMGXB2), HMG domain-containing protein HMGX2, Sox-like transcriptional factor, or structural DNA-binding protein BRAF35, is a DNA binding factor that acts as a repressor of erythroid differentiation. It is required for correct progression through the G2 phase of the cell cycle and entry into mitosis. It is also required for RCOR1/CoREST mediated repression of neuronal specific gene promoters. HMG20B is a core subunit of the Lys-specific demethylase 1/REST co-repressor 1 (LSD1-CoREST) histone demethylase complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1497485697  64 GPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQQSEAYKMCTE 143
Cdd:cd22018     1 GPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQPHEKQRYLDEAERDKQQYMKELREYQQSEAYKMCTE 80

                  ....*
gi 1497485697 144 KIQEK 148
Cdd:cd22018    81 KIQEK 85

GIPC-homology 2 (GH2) domain found in the GIPC family; The GIPC family includes PDZ domain-containing proteins, GIPC1 (also called GAIP C-terminus-interacting protein, RGS-GAIP-interacting protein, RGS19-interacting protein 1, RGS19IP1, synectin, tax interaction protein 2, or TIP-2), GIPC2, and GIPC3, which may act as scaffold proteins linking heterotrimeric G-proteins to seven-transmembrane-type WNT receptor or to receptor tyrosine kinases. They might play key roles in carcinogenesis and embryogenesis through modulation of growth factor signaling and cell adhesion. GIPCs are proteins with a GIPC homology 1 (GH1) domain, a central PDZ domain and a GH2 domain. This model corresponds to the GH2 domain, which mediates the interaction with myosin VI and is involved in homodimerization in the autoinhibited state.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1497485697 519 AARRVDDLLESYMGIRDSELASTMVEVAKDSPSVAQLAQGLDSVLGEFAFPPEFVAEVWAAV 580
Cdd:cd21180     4 AIEKIDDLLESYMGIRDDELAQTIVELGKDKSNPDEFAEALDESLGDFAFPDEFVFDVWGAI 65

high mobility group;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1497485697   65 PKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREY 132
Cdd:smart00398   2 PKRPMSAFMLFSQENRAKIKAENPDLSNAEISKKLGERWKLLSEEEKAPYEEKAKKDKERYEEEMPEY 69

high mobility group protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1497485697  53 KGKKRKKILPNGPKAPVTGYVRFLNERREQIRTQHPDLP--FPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELR 130
Cdd:PTZ00199   11 RKNKRKKKDPNAPKRALSAYMFFAKEKRAEIIAENPELAkdVAAVGKMVGEAWNKLSEEEKAPYEKKAQEDKVRYEKEKA 90

                  ....
gi 1497485697 131 EYQQ 134
Cdd:PTZ00199   91 EYAK 94

PDZ domain; PDZ domains are found in diverse signaling proteins.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1497485697 398 LGLTI---TDNGAGYAFIKRIKEGSIINRlQTVSVGDSIEAINDHTIVGCRHYEVARMLRE 455
Cdd:pfam00595  12 LGFSLkggSDQGDPGIFVSEVLPGGAAEA-GGLKVGDRILSINGQDVENMTHEEAVLALKG 71

high mobility group (HMG)-box found in high mobility group protein 20B (HMG20B) and similar proteins; HMG20B, also called SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related, SMARCE1-related protein (SMARCE1R), BRCA2-associated factor 35 (BRAF35), HMG box-containing protein 20B, HMG domain-containing protein 2 (HMGXB2), HMG domain-containing protein HMGX2, Sox-like transcriptional factor, or structural DNA-binding protein BRAF35, is a DNA binding factor that acts as a repressor of erythroid differentiation. It is required for correct progression through the G2 phase of the cell cycle and entry into mitosis. It is also required for RCOR1/CoREST mediated repression of neuronal specific gene promoters. HMG20B is a core subunit of the Lys-specific demethylase 1/REST co-repressor 1 (LSD1-CoREST) histone demethylase complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1497485697  64 GPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQQSEAYKMCTE 143
Cdd:cd22018     1 GPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQPHEKQRYLDEAERDKQQYMKELREYQQSEAYKMCTE 80

                  ....*
gi 1497485697 144 KIQEK 148
Cdd:cd22018    81 KIQEK 85

PDZ domain of GIPC family proteins; GIPC1/GIPC (GAIP/RGS19-interacting protein), GIPC2, and GIPC3 (also known as C19orf64) constitute the GIPC family. These proteins contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc1 and Gipc2 genes have been linked to cancer, while mutations in the Gipc3 gene cause nonsyndromic hearing loss. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GIPC family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1497485697 383 RGETKEVEVTKTEDALGLTITDNGAGYAFIKRIKEGSIINRLQTVSVGDSIEAINDHTIVGCRHYEVARMLRELPRAQPF 462
Cdd:cd06707     1 KGQPKEIEVTKSEDALGLTITDNGAGYAFIKRIKEGSIMDKVPAICVGDHIEKINGESLVGCRHYEVARMLKEIPIGETF 80

                  ....*....
gi 1497485697 463 TLRLVQPKK 471
Cdd:cd06707    81 TLRLVEPKK 89

high mobility group (HMG)-box found in the high mobility group protein 20 (HMG20) subfamily; The HMG20 subfamily includes HMG20A and HMG20B. HMG20A, also called HMG box-containing protein 20A, HMG domain-containing protein 1, HMG domain-containing protein HMGX1, HMGXB1, or iBRAF, is a chromatin-associated protein involved in neuronal differentiation and maturation. It is required for SNAI1-mediated epithelial to mesenchymal transition. HMG20A acts as an inhibitor of HMG20B. HMG20B, also called SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related, SMARCE1-related protein (SMARCE1R), BRCA2-associated factor 35 (BRAF35), HMG box-containing protein 20B, HMG domain-containing protein 2, HMG domain-containing protein HMGX2, Sox-like transcriptional factor, or structural DNA-binding protein BRAF35, is a DNA binding factor that acts as a repressor of erythroid differentiation. It is required for correct progression through the G2 phase of the cell cycle and entry into mitosis. It is also required for RCOR1/CoREST mediated repression of neuronal specific gene promoters. HMG20B is a core subunit of the Lys-specific demethylase 1/REST co-repressor 1 (LSD1-CoREST) histone demethylase complex. Both HMG20A and HMG20B contain one HMG-box.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1497485697  65 PKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQQSEAYKM 140
Cdd:cd21980     2 PKAPLTGYVRFLNERREKLRAENPDLSFPEITKILGAEWSSLSAEEKQKYLDEAEKDKERYVKELEAYQQTEAYKA 77

PDZ domain of PDZ domain-containing protein GIPC2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GIPC2, and related domains. GIPC2 belongs to the GIPC family, members of which contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc2 gene have been linked to cancer. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GIPC2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1497485697 381 HVRGETKEVEVTKTEDALGLTITDNGAGYAFIKRIKEGSIINRLQTVSVGDSIEAINDHTIVGCRHYEVARMLRELPRAQ 460
Cdd:cd23078     1 HVKGIKKEVNVYKSEDSLGLTITDNGVGYAFIKRIKDGSVIDSVKTICVGDHIECINGENIVGWRHYEVAKKLKELKKEE 80

                          90
                  ....*....|...
gi 1497485697 461 PFTLRLVQPKKAF 473
Cdd:cd23078    81 LFTLKLIEPKKAF 93

HMG (high mobility group) box;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1497485697  65 PKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREY 132
Cdd:pfam00505   1 PKRPMSAFFLFSKEQRAKLKAENPGLKNAEISKILGEKWKALSEEEKKPYEEKAEKEKARYEKEHPEY 68

high mobility group;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1497485697   65 PKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREY 132
Cdd:smart00398   2 PKRPMSAFMLFSQENRAKIKAENPDLSNAEISKKLGERWKLLSEEEKAPYEEKAKKDKERYEEEMPEY 69

high mobility group (HMG)-box domain superfamily; The High Mobility Group (HMG)-box is found in a variety of eukaryotic chromosomal proteins and transcription factors. HMGs bind to the minor groove of DNA and have been classified by DNA binding preferences. Two phylogenetically distinct groups of Class I proteins bind DNA in a sequence specific fashion and contain a single HMG box. One group (SOX-TCF) includes transcription factors, TCF-1, -3, -4, and also SRY and LEF-1, which bind four-way DNA junctions and duplex DNA targets. The second group (MATA) includes fungal mating type gene products MC, MATA1 and Ste11. Class II and III proteins (HMGB-UBF) bind DNA in a non-sequence specific fashion and contain two or more tandem HMG boxes. Class II members include non-histone chromosomal proteins, HMG1 and HMG2, which bind to bent or distorted DNA such as four-way DNA junctions, synthetic DNA cruciforms, kinked cisplatin-modified DNA, DNA bulges, cross-overs in supercoiled DNA, and can cause looping of linear DNA. Class III members include nucleolar and mitochondrial transcription factors, UBF and mtTF1, which bind four-way DNA junctions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1497485697  68 PVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQY 125
Cdd:cd00084     2 PLSAYLLFSKEKRPKLKKENPDLSFTEISKLLGERWKELSEEEKQPYEEKAKEDKERY 59

high mobility group (HMG)-box found in structure-specific recognition protein 1 (SSRP1) and similar proteins; SSRP1, also called FACT complex subunit SSRP1, chromatin-specific transcription elongation factor 80 kDa subunit, facilitates chromatin transcription complex 80 kDa subunit (FACT 80 kDa subunit or FACTp80), facilitates chromatin transcription complex subunit SSRP1, recombination signal sequence recognition protein 1, or T160, is a factor that facilitates transcript elongation through nucleosomes. It is a component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication, and DNA repair.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1497485697  68 PVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQ 133
Cdd:cd21994     2 PMSAYMLWLNENREKIKKENPGISVTEISKKAGEIWKELDEEDKEKWEQKAEKAKERYDKAMKEYK 67

high mobility group (HMG)-box found in Saccharomyces cerevisiae non-histone protein 10 (NHP10) and similar proteins; NHP10, also called high mobility group protein 2, is probably involved in transcription regulation via its interaction with the INO80 complex, a chromatin remodeling complex.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1497485697  62 PNGPKAPVTGYVRFLNERREQIRT----QHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREY 132
Cdd:cd22016     5 PNAPKRPANAFFLFCQEQREKVREeykeEHQEIDHHDLTKALAQAWRNLDAEDKKPYYELYEKDKERYEKEMEEY 79

second high mobility group (HMG)-box found in Arabidopsis thaliana high mobility group B protein 6 (HMGB6) and similar proteins; HMGB6, also called nucleosome/chromatin assembly factor group D 06 (or D 6), WRKY transcription factor 53 (WRKY53), or WRKY DNA-binding protein 53, is a master regulator of age-induced leaf senescence. It acts in a complex transcription factor signaling network regulating senescence specific gene expression; hydrogen peroxide might be involved in signal transduction. The subfamily also includes Arabidopsis thaliana HMGB13 (also known as nucleosome/chromatin assembly factor group D 13). Both HMGB6 and HMGB13 contain three HMG-box domains. This model corresponds to the second one.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1497485697  65 PKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREY 132
Cdd:cd22007     1 PKRPQSAYFLYANDRRAALKEENKNVKITEIAKMLGAEWKNLSDAKKKPYEEKAKKLKEAYLQEMEEY 68

first high mobility group (HMG)-box found in Saccharomyces cerevisiae intrastrand cross-link recognition protein (Ixr1) and similar proteins; Ixr1, also called structure-specific recognition protein (SSRP), is a homolog of the yeast mitochondrial regulator ABF2. It binds to platinated DNA and confers sensitivity to the anticancer drug cisplatin. Ixr1 contains two HMG-box domains. This model corresponds to the first one.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1497485697  65 PKAPVTGYVRFLNERREQIRTQ-HPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREY 132
Cdd:cd22011     1 PKRPSSAYFLFSQEIRKNLKSQgSPEEKVPELSKRAAEQWRSLTLAEKQPYYDEVEVLKKQYDVEKEEY 69

first high mobility group (HMG)-box found in upstream-binding factor 1 (UBF1) and similar proteins; UBF1, also called UBTF, nucleolar transcription factor 1, or auto-antigen NOR-90, is a nucleolar transcription factor that recognizes the ribosomal RNA gene promoter and activates transcription mediated by RNA polymerase I through cooperative interactions with the transcription factor SL1/TIF-IB complex. It binds specifically to the upstream control element. UBF1 contains six HMG-box domains. This model corresponds to the first one. This model also includes the first HMG-box domain of upstream-binding factor 1-like protein 1 (UBTFL1), which contains two HMG-box domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1497485697  62 PNGPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQQ 134
Cdd:cd21998     1 PDFPKKPLTPYFRFFMEKRAKYAKKHPEMSNLELTKILSKKYKELPEKKKQKYIQDYEKEKEEYEQKMARFRE 73

second high mobility group (HMG)-box found in Saccharomyces cerevisiae mitochondrial ARS-binding factor 2 (ABF2), intrastrand cross-link recognition protein (Ixr1) and similar proteins; ABF2 is a close relative of the nuclear, chromosomal high-mobility group protein HMG1 in yeast mitochondria. It specifically binds to the autonomously replicating sequence 1 (ARS1). It might play a positive role in gene expression and replication. Ixr1, also called structure-specific recognition protein (SSRP), is a homolog of the yeast mitochondrial regulator ABF2. It binds to platinated DNA and confers sensitivity to the anticancer drug cisplatin. Both ABF2 and Ixr1 contain two HMG-box domains. This model corresponds to the second one.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1497485697  64 GPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDeaerekqQYMKELREYQQ 134
Cdd:cd22012     1 PPKRPASAYFLFAKEVRPKLKEENPNEKYTDITKLISEKWRSLDESEKEPYQE-------EYEKALEEYEE 64

high mobility group (HMG)-box found in sex determining region Y (SRY)-box 7 (SOX7) and similar proteins; SOX-7 is an endothelial-associated transcription factor that acts as a tumor suppressor in a number of cancer types. It binds the DNA sequence 5'-AACAAT-3'. SOX-7 belongs to the group F of SRY-related high-mobility group (HMG) box (Sox) transcription factors.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1497485697  66 KAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQ 133
Cdd:cd22046    13 RRPMNAFMVWAKDERKRLAVQNPDLHNAELSKMLGKSWKALTPSQKRPYVEEAERLRVQHMQDYPNYK 80

second high mobility group (HMG)-box found in the high mobility group protein B (HMGB) family; HMGB proteins are chromatin-associated nuclear proteins that act as architectural factors in nucleoprotein structures, which regulate DNA-dependent processes including transcription. In mammals, four family members are present: HMGB1, HMGB2, HMGB3 and HMGB4. They regulate the expression of a wide range of genes through architectural remodeling of the chromatin structure. HMGB1, also called high mobility group protein 1 (HMG-1), is a prototypical alarmin or damage-associated molecular pattern (DAMP) molecule when released from cells. It plays important roles in the regulation of a wide range of processes, including transcription, replication, DNA repair, and nucleosome formation, in the nucleus. It also plays multiple roles in regulating inflammation and responses to cell and tissue stress. HMGB2, also called high mobility group protein 2 (HMG-2), has been implicated in numerous cellular processes, including proliferation, differentiation, apoptosis, and tumor growth. It acts as a chromatin-associated nonhistone protein involved in transcriptional regulation and nucleic-acid-mediated innate immune responses in mammalian. It binds DNA to stabilize nucleosomes and promote transcription. HMGB3, also called high mobility group protein 2a (HMG-2a), or high mobility group protein 4 (HMG-4), is an X-linked member of HMGB family and functions as a universal sentinel for nucleic acid-mediated innate immune responses. HMGB3 has been implicated in the regulation of cellular proliferation and differentiation, as well as inflammatory response. HMGB4 is expressed by neuronal cells and affects the expression of genes involved in neural differentiation. It is a factor that regulates chromatin and expression of neuronal differentiation markers. The family also includes high mobility group protein B1 pseudogene 1 (HMGB1P1) and nuclear auto-antigen Sp-100. HMGB1P1, also called putative high mobility group protein B1-like 1 (HMGB1L1), or putative high mobility group protein 1-like 1 (HMG-1L1), is an HMG-box containing protein that binds preferentially single-stranded DNA and unwinds double-stranded DNA. Sp-100, also called nuclear dot-associated Sp100 protein, or speckled 100 kDa. It is a tumor suppressor that is a major constituent of the promyelocytic leukemia (PML) bodies, a subnuclear organelle involved in many physiological processes including cell growth, differentiation and apoptosis. Through the regulation of ETS1, Sp-100 may play a role in angiogenesis, controlling endothelial cell motility and invasion. It may also play roles in the regulation of telomeres lengthening, TP53-mediated transcription, FAS-mediated apoptosis, etc. In addition, the family includes Drosophila melanogaster high mobility group protein DSP1 (dDSP1) and similar proteins. dDSP1, also called protein dorsal switch 1, is a Drosophila HMG1 protein that binds preferentially single-stranded DNA and unwinds double-stranded DNA. It converts Dorsal and nuclear factor (NF)-kappa B from transcriptional activators to repressors. Members of the HMGB family contain two HMG-box domains. This model corresponds to the second one.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1497485697  63 NGPKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREY 132
Cdd:cd21979     1 NAPKRPPSAFFLFCSEHRPKIKGEHPGLSIGDVAKKLGEMWNNTSAKDKQPYEKKAAKLKEKYEKDIAAY 70

high mobility group (HMG)-box found in sex determining region Y (SRY)-box 17 (SOX17) and similar proteins; SOX-17 is a developmental transcription regulator involved in endoderm formation, angiogenesis, and carcinogenesis. It acts as a tumor suppressor and modulates WNT signaling. SOX-17 binds target promoter DNA and bends the DNA. It binds to the sequences 5'-AACAAT-'3 or 5'-AACAAAG-3'. SOX-17 belongs to the group F of SRY-related high-mobility group (HMG) box (Sox) transcription factors.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1497485697  66 KAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQ 133
Cdd:cd22047     8 RRPMNAFMVWAKDERKRLAQQNPDLHNAELSKMLGKSWKALTLAEKRPFVEEAERLRVQHMQDHPNYK 75

fourth high mobility group (HMG)-box found in upstream-binding factor 1 (UBF1) and similar proteins; UBF1, also called UBTF, nucleolar transcription factor 1, or auto-antigen NOR-90, is a nucleolar transcription factor that recognizes the ribosomal RNA gene promoter and activates transcription mediated by RNA polymerase I through cooperative interactions with the transcription factor SL1/TIF-IB complex. It binds specifically to the upstream control element. UBF1 contains six HMG-box domains. This model corresponds to the fourth one.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1497485697  65 PKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKE 128
Cdd:cd22001     3 PKRPISAMFIYSKEKRSKLKKKHPELSEQELTRLLAKKYNELPDKKKAKYKKKEALAKAEYEKK 66

high mobility group (HMG)-box found in Saccharomyces cerevisiae high mobility group protein 1 (HMO1) and similar proteins; HMO1, also called high spontaneous mutagenesis protein 2 (HSM2), is a DNA-binding protein that is probably part of the rDNA transcription apparatus. It acts synergetically with the RPA49 subunit of RNA polymerase I during rDNA transcription. It may participate in mutagenesis control.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1497485697  65 PKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREY 132
Cdd:cd22015     1 PKKPLTPYFAFSNHVRPQLKAERPKASPTEIAEEISERWANLSDEEKQLWEDKYEEEMKEYQKALEAY 68

high mobility group (HMG)-box found in Saccharomyces cerevisiae repressor ROX1 and similar proteins; This family includes class I members of the HMG-box superfamily of DNA-binding proteins, including Saccharomyces cerevisiae repressor ROX1, Schizosaccharomyces pombe mating-type M-specific polypeptide Mc (mat-Mc), Schizosaccharomyces pombe transcription factor ste11, Podospora anserina MAT+ sexual cell fertilization-promoting factor (FPR1), Podospora anserina sporulation minus regulator 2 (SMR2) and Candida albicans repressor of filamentous growth 1 (RFG1). These proteins contain a single HMG box, and bind the minor groove of DNA in a highly sequence-specific manner. ROX1, also called heme-dependent repression factor, or hypoxic function repressor, is a transcription factor that represses the expression of HEM13, COX5B, ANB1, CYC7 or AAC3. It binds to the DNA sequence 5'-RRRTAACAAGAG-3'. mat-Mc belongs to the mating type protein family, which contains sequence specific DNA-binding proteins that act as master switches in yeast differentiation by controlling gene expression in a cell type-specific fashion. mat-Mc is a positive regulator of MFM genes and is required for conjugation and efficient meiosis. Its HMG box recognizes the DNA sequence 5'-AACAAAG-3'. Ste11 is a key transcription factor for sexual development. It activates the transcription of the matp, matm, mei2, mfm, ste6 and rgs1 genes. It binds specifically to a DNA fragment carrying a 10-base motif 5'-TTCTTTGTTY-3'. FPR1 controls fertilization, probably by determining the mating type. SMR2 is a transcription factor that is required for post-fertilization events. It is required for the developmental events that occur in the female organ after fertilization. RFG1 is a transcription regulator that functions in both the positive and negative regulation of filamentous growth, depending upon environmental conditions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1497485697  75 FLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKE 128
Cdd:cd01389    11 FRKEKHKQLRAQNPGLTNSEISKIIGKMWKNLSEEEKEPYKELAEEEKEEHKLK 64

high mobility group (HMG)-box found in group C SRY-related high-mobility group (HMG) box (Sox) transcription factors; SoxC transcription factors includes three members: SOX4, SOX11 and SOX12. They play key roles, often in redundancy, in multiple developmental pathways, including neurogenesis and skeletogenesis. SOX-4 is a transcriptional activator that promotes neuronal differentiation both in the adult and embryonic neural progenitors. It binds with high affinity to the T-cell enhancer motif 5'-AACAAAG-3' motif. SOX-4 is abnormally expressed in various cancers. SOX-11 is a neural transcriptional factor involved in precursor survival, neuronal fate determination, migration and morphogenesis. SOX-12, also called SOX-22, is a transcription factor essential for embryonic development and cell fate determination. It binds to the sequence 5'-AACAAT-3'.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1497485697  78 ERReQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQ 133
Cdd:cd22029    16 ERR-KIMEQQPDMHNAEISKRLGKRWKLLSDSEKIPFIEEAERLRLLHMQEYPDYK 70

high mobility group (HMG)-box found in sex determining region Y (SRY)-box 15 (SOX15) and similar proteins; SOX-15, also called SOX-12, SOX-20, SOX-26, or SOX-27, is a crucial transcription factor involved in the regulation of embryonic development and in cell fate determination. It binds to the 5'-AACAAT-3' sequence. SOX-15 can be a tumor suppressor in multiple cancer types. SOX-5 is the only member of group G SRY-related high-mobility group (HMG) box (Sox) transcription factors.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1497485697  66 KAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQ 133
Cdd:cd22035     9 KRPMNAFMVWSSAQRRQMAQEHPKMHNSEISKRLGAAWKLLPEAEKRPFVEEAKRLRARHMRDYPDYK 76

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1497485697 388 EVEVTKTEDA-LGLTIT--DNGAGYAFIKRIKEGSIINRLQTVSVGDSIEAINDHTIVGCRHYEVARMLRELPRaqpfTL 464
Cdd:cd00136     1 TVTLEKDPGGgLGFSIRggKDGGGGIFVSRVEPGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAGG----EV 76

                  ...
gi 1497485697 465 RLV 467
Cdd:cd00136    77 TLT 79

high mobility group (HMG)-box found in HMG box-containing protein 2 (HBP2) and similar proteins; HBP2, also called HMG box transcription factor BBX, or Bobby sox homolog, is a transcription factor that is necessary for cell cycle progression from the G1 to S phase.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1497485697  66 KAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKE 128
Cdd:cd21989     1 RRPMNAFLLFCKRHRSLVRERHPRLDNRGITKILGDWWAVLDPDEKQKYTDLAKQYKEAFMKA 63

high mobility group (HMG)-box found in the TOX high mobility group box family; The TOX family includes four members: TOX, TOX2, TOX3 and TOX4. TOX, also called thymus high mobility group box protein TOX, is a transcriptional regulator with a major role in neural stem cell commitment and corticogenesis as well as in lymphoid cell development and lymphoid tissue organogenesis. It binds to GC-rich DNA sequences in the proximity of transcription start sites and may alter chromatin structure, modifying access of transcription factors to DNA. TOX2, also called granulosa cell HMG box protein 1 (GCX-1), is a putative transcriptional activator involved in the hypothalamic-pituitary-gonadal system. TOX3, also called CAG trinucleotide repeat-containing gene F9 protein (CAGF9), or trinucleotide repeat-containing gene 9 protein (TNRC9), is a transcriptional coactivator of the p300/CBP-mediated transcription complex. It activates transactivation through cAMP response element (CRE) sites. It protects against cell death by inducing anti-apoptotic and repressing pro-apoptotic transcripts. TOX4, also called epidermal Langerhans cell protein LCP1, is a component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. All family members contain one HMG-box domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1497485697  68 PVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQQS 135
Cdd:cd21995     3 PVSAYALFFRDTQAAIKGQNPNATFGEVSKIVASMWDSLDEEQKQVYKKKTEAAKKEYLKALAAYRAS 70

high mobility group (HMG)-box found in Arabidopsis thaliana high mobility group B protein 1 (HMGB1) and similar proteins; This subfamily contains a group of Arabidopsis thaliana HMGB family proteins, including HMGB1, 2, 3, 4, 5, 7, 12 and 14. They bind preferentially to double-stranded DNA. HMGB1 modulates general plant growth and stress tolerance and confers sensitivity to salt and genotoxic (methyl methanesulfonate, MMS) stresses. HMGB2 and HMGB5 confer sensitivity to salt and drought stresses. HMGB7 is required for karyogamy during female gametophyte development, when the two polar nuclei fuse to form the diploid central cell nucleus. Members of this subfamily contain only one HMG-box domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1497485697  66 KAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQY 125
Cdd:cd22005     1 KRPPTAFFLFLADFRKTYKKKNPDKSVKAVGKAAGEKWKSMSDEEKAPYVEKAEKEKAEY 60

high mobility group (HMG)-box found in sex determining region Y (SRY)-box 12 (SOX12) and similar proteins; SOX-12, also called SOX-22, is a transcription factor essential for embryonic development and cell fate determination. It binds to the sequence 5'-AACAAT-3'. SOX-12 belongs to the group C of SRY-related high-mobility group (HMG) box (Sox) transcription factors.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1497485697  62 PNGP-KAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQ 133
Cdd:cd22038     8 PSGHiKRPMNAFMVWSQIERRKIMEQWPDMHNAEISKRLGRRWKLLQDYEKIPFIKEAERLRLKHMADYPDYK 80

high mobility group (HMG)-box found in basic helix-loop-helix and HMG box domain-containing protein 1 (BHMG1) and similar proteins; BHMG1 is an uncharacterized HMG-box containing protein that contains a degenerate basic motif not likely to bind DNA.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1497485697  65 PKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQ 124
Cdd:cd21977     1 KKKWVNGFIMFCRLNRKNYIDKHPGLASTELTKELGQLWRELSAEEKKPYCVRARELSQL 60

PDZ domain of connector enhancer of kinase suppressor of ras 1 (CNK1), CNK2, CNK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CNK1 (also known as connector enhancer of KSR 1 (CNKSR1), CNK homolog protein 1, connector enhancer of KSR-like), CNK2 (also known as CNKSR2, CNK homolog protein 2), and CNK3 (also known as CNKSR3, CNK homolog protein 3, CNKSR family member 3, maguin-like). CNK proteins modulate Ras-mediated signaling, acting downstream of Ras as a scaffold for the Raf/MEK/ERK kinase cascade. They also modulate signaling mediated via Rho family small GTPases, through interactions with various guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), and modulate the insulin signaling pathway through interactions with the Arf guanine nucleotide exchange factors. CNK proteins also regulate cell proliferation and migration by acting as scaffolds for the PI3K/Akt and JNK signaling cascades. CNK2 plays a role in the molecular processes that govern morphology of the postsynaptic density (PSD), and influences subcellular localization of the regulatory NCK-interacting kinase TNIK. TNIK binds a region of CNK2 including the PDZ and the DUF domain; this region also binds the kinase MINK1. CNK2 may also influence the membrane localization of MINK1. CNK3 plays a part in transepithelial sodium transport; it coordinates assembly of an epithelial sodium channel (ENaC)-regulatory complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This CNK1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1497485697 393 KTEDALGLTITDNGAGYAFIKRIKEGSIINRLQTVSVGDSIEAINDHTIVGCRHYEVARMLRELPRAQPFTLR 465
Cdd:cd06748     9 KPEEGLGLEIKSTYNGLHVITGTKENSPADRCGKIHAGDEVIQVNYQTVVGWQLKNLVRALREDPHGVTLTLK 81

high mobility group (HMG)-box found in sex determining region Y (SRY)-box 4 (SOX4) and similar proteins; SOX-4 is a transcriptional activator that promotes neuronal differentiation both in the adult and embryonic neural progenitors. It binds with high affinity to the T-cell enhancer motif 5'-AACAAAG-3' motif. SOX-4 is abnormally expressed in various cancers. SOX-4 belongs to group C SRY-related high-mobility group (HMG) box (Sox) transcription factors.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1497485697  66 KAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELREYQ 133
Cdd:cd22036     4 KRPMNAFMVWSQIERRKIMEQSPDMHNAEISKRLGKRWKLLKDSDKIPFIREAERLRLKHMADYPDYK 71

first high mobility group (HMG)-box found in the high mobility group protein B (HMGB) family; HMGB proteins are chromatin-associated nuclear proteins that act as architectural factors in nucleoprotein structures, which regulate DNA-dependent processes including transcription. In mammals, four family members are present: HMGB1, HMGB2, HMGB3 and HMGB4. They regulate the expression of a wide range of genes through architectural remodeling of the chromatin structure. HMGB1, also called high mobility group protein 1 (HMG-1), is a prototypical alarmin or damage-associated molecular pattern (DAMP) molecule when released from cells. It plays important roles in the regulation of a wide range of processes, including transcription, replication, DNA repair, and nucleosome formation, in the nucleus. It also plays multiple roles in regulating inflammation and responses to cell and tissue stress. HMGB2, also called high mobility group protein 2 (HMG-2), has been implicated in numerous cellular processes, including proliferation, differentiation, apoptosis, and tumor growth. It acts as a chromatin-associated nonhistone protein involved in transcriptional regulation and nucleic-acid-mediated innate immune responses in mammalian cells. It binds DNA to stabilize nucleosomes and promote transcription. HMGB3, also called high mobility group protein 2a (HMG-2a), or high mobility group protein 4 (HMG-4), is an X-linked member of the HMGB family that functions as a universal sentinel for nucleic acid-mediated innate immune responses. HMGB3 has been implicated in the regulation of cellular proliferation and differentiation, as well as inflammatory responses. HMGB4 is expressed by neuronal cells and affects the expression of genes involved in neural differentiation. It is a factor that regulates chromatin and expression of neuronal differentiation markers. This family also includes high mobility group protein B1 pseudogene 1 (HMGB1P1) and nuclear auto-antigen Sp-100. HMGB1P1, also called putative high mobility group protein B1-like 1 (HMGB1L1), or putative high mobility group protein 1-like 1 (HMG-1L1), is an HMG-box containing protein that binds preferentially single-stranded DNA and unwinds double-stranded DNA. Sp-100, also called nuclear dot-associated Sp100 protein, or speckled 100 kDa, is a tumor suppressor that is a major constituent of promyelocytic leukemia (PML) bodies, a subnuclear organelle involved in many physiological processes including cell growth, differentiation and apoptosis. Through the regulation of ETS1, Sp-100 may play a role in angiogenesis, controlling endothelial cell motility and invasion. It may also play roles in the regulation of telomere lengthening, TP53-mediated transcription, FAS-mediated apoptosis, etc. In addition, the family includes Drosophila melanogaster high mobility group protein DSP1 (dDSP1) and similar proteins. dDSP1, also called protein dorsal switch 1, binds preferentially to single-stranded DNA and unwinds double-stranded DNA. It converts Dorsal and nuclear factor (NF)-kappa B from transcriptional activators to repressors. Members of the HMGB family contain two HMG-box domains. This model corresponds to the first one.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1497485697  65 PKAPVTGYVRFLNERREQIRTQHPDLP--FPEITKMLGAEWSKLQLSEKQRYLDEAEREKQQYMKELR 130
Cdd:cd21978     2 PRGKMSSYAFFVQTCREEHKKKHPNESvnFSEFSKKCSERWKTMSAKEKKKFEDMAKKDKARYEREMK 69

PDZ domain 3 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1497485697 389 VEVTKTE-DALGLTITD---NGAGYAFIKRIKEGSIINRLQTVSVGDSIEAINDHTIVGCRHYEVARMLR 454
Cdd:cd06684     5 VEIEKTPgSSLGITLSTsthRNKQVIVIDSIKPASIADRCGALHVGDHILSIDGTSVEHCSLAEATQLLA 74

PDZ domain 4 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, -B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1497485697 388 EVEVTKTED-ALGLTI--TDNGAGYAFIKRIKEGSIINRLQTVSVGDSIEAINDHTIVGCRHYEVARMLRE 455
Cdd:cd06734     3 DVTLTRRENeGFGFVIisSVNKKSGSKIGRIIPGSPADRCGQLKVGDRILAVNGISILNLSHGDIVNLIKD 73

second high mobility group (HMG)-box found in upstream-binding factor 1 (UBF1) and similar proteins; UBF1, also called UBTF, nucleolar transcription factor 1, or auto-antigen NOR-90, is a nucleolar transcription factor that recognizes the ribosomal RNA gene promoter and activates transcription mediated by RNA polymerase I through cooperative interactions with the transcription factor SL1/TIF-IB complex. It binds specifically to the upstream control element. UBF1 contains six HMG-box domains. This model corresponds to the second one.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1497485697  65 PKAPVTGYVRFLNERREQIRTQHPDLPfpEITKMLGAEWSklQLSEKQR--YLDEAEREKQQYMKELREYQQS 135
Cdd:cd21999     1 PKKPKTPFQLFYNKELKKLEPGTPDKK--ELKEKLREKWK--QMSDKKKlkWINKALEDEKRYEEELKEYKKE 69