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        60        70        80
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 3702826  15 RVKKGGKAKDPNAPKRAMSAFFFWMQENRERIKK--PGMGVADVAKAAGVEWGKLTDKSR--WEKKAADDKKRYEVDIAN 90
Cdd:cd01390  1 KKKKGRKKKDPNAPKRGLSAYMFFSQDNREKVKEenPDATFGEVGKLLGEKWKELSEEEKapYEEKAAKDKKRYEEEKAA 80

               .
gi 3702826  91 Y 91
Cdd:cd01390 81 Y 81

high mobility group (HMG)-box found in Saccharomyces cerevisiae non-histone chromosomal proteins NHP6A, NHP6B and similar proteins; This subfamily includes Saccharomyces cerevisiae high-mobility-group proteins NHP6A and its closely related paralog NHP6B. NHP6A and NHP6B seem to be functionally redundant. They are DNA-binding proteins that induce severe bending of DNA and are required for DNA-binding by the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. They augment the fidelity of transcription by RNA polymerase III independently of any role in the FACT complex. They may also play essential roles in transcriptional initiation fidelity of some but not all tRNA genes.

                       10        20        30        40        50        60        70        80
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 3702826  15 RVKKGGKAKDPNAPKRAMSAFFFWMQENRERIKK--PGMGVADVAKAAGVEWGKLTDKSR--WEKKAADDKKRYEVDIAN 90
Cdd:cd01390  1 KKKKGRKKKDPNAPKRGLSAYMFFSQDNREKVKEenPDATFGEVGKLLGEKWKELSEEEKapYEEKAAKDKKRYEEEKAA 80

               .
gi 3702826  91 Y 91
Cdd:cd01390 81 Y 81

HMG (high mobility group) box;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 3702826    28 PKRAMSAFFFWMQENRERIKK--PGMGVADVAKAAGVEWGKLTD--KSRWEKKAADDKKRYEVDIANY 91
Cdd:pfam00505  1 PKRPMSAFFLFSKEQRAKLKAenPGLKNAEISKILGEKWKALSEeeKKPYEEKAEKEKARYEKEHPEY 68

high mobility group protein; Provisional

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 3702826   13 VKRVKKGGKAKDPNAPKRAMSAFFFWMQENRERI--KKPGMG--VADVAKAAGVEWGKLTDKSR--WEKKAADDKKRYEV 86
Cdd:PTZ00199  8 VLVRKNKRKKKDPNAPKRALSAYMFFAKEKRAEIiaENPELAkdVAAVGKMVGEAWNKLSEEEKapYEKKAQEDKVRYEK 87

                ....*..
gi 3702826   87 DIANYKK 93
Cdd:PTZ00199 88 EKAEYAK 94

high mobility group (HMG)-box found in Saccharomyces cerevisiae non-histone chromosomal proteins NHP6A, NHP6B and similar proteins; This subfamily includes Saccharomyces cerevisiae high-mobility-group proteins NHP6A and its closely related paralog NHP6B. NHP6A and NHP6B seem to be functionally redundant. They are DNA-binding proteins that induce severe bending of DNA and are required for DNA-binding by the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. They augment the fidelity of transcription by RNA polymerase III independently of any role in the FACT complex. They may also play essential roles in transcriptional initiation fidelity of some but not all tRNA genes.

                       10        20        30        40        50        60        70        80
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 3702826  15 RVKKGGKAKDPNAPKRAMSAFFFWMQENRERIKK--PGMGVADVAKAAGVEWGKLTDKSR--WEKKAADDKKRYEVDIAN 90
Cdd:cd01390  1 KKKKGRKKKDPNAPKRGLSAYMFFSQDNREKVKEenPDATFGEVGKLLGEKWKELSEEEKapYEEKAAKDKKRYEEEKAA 80

               .
gi 3702826  91 Y 91
Cdd:cd01390 81 Y 81

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 3702826  30 RAMSAFFFWMQENRERIKK--PGMGVADVAKAAGVEWGKLT--DKSRWEKKAADDKKRYEVDIANYK 92
Cdd:cd21994  1 RPMSAYMLWLNENREKIKKenPGISVTEISKKAGEIWKELDeeDKEKWEQKAEKAKERYDKAMKEYK 67

Chromatin-associated proteins containing the HMG domain [Chromatin structure and dynamics];

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 3702826   21 KAKDPNAPKRAMSAFFFWMQENRERIKK--PGMGVADVAKAAGVEWGKLTD--KSRWEKKAADDKKRYEVDIANYKKS 94
Cdd:COG5648  64 KKKDPNGPKRPLSAYFLYSAENRDEIRKenPKLTFGEVGKLLSEKWKELTDeeKEPYYKEANSDRERYQREKEEYNKK 141

high mobility group;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 3702826     27 APKRAMSAFFFWMQENRERIKK--PGMGVADVAKAAGVEWGKLT--DKSRWEKKAADDKKRYEVDIANYK 92
Cdd:smart00398  1 KPKRPMSAFMLFSQENRAKIKAenPDLSNAEISKKLGERWKLLSeeEKAPYEEKAKKDKERYEEEMPEYK 70

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 3702826  21 KAKDPNAPKRAMSAFFFWMQENRERIK------KPGMGVADVAKAAGVEWGKL--TDKSRWEKKAADDKKRYEVDIANY 91
Cdd:cd22016  1 KEKDPNAPKRPANAFFLFCQEQREKVReeykeeHQEIDHHDLTKALAQAWRNLdaEDKKPYYELYEKDKERYEKEMEEY 79

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 3702826  27 APKRAMSAFFFWMQENRERIKK--PGMGVADVAKAAGVEWGKLT--DKSRWEKKAADDKKRYEVDIANYKKS 94
Cdd:cd21980  1 APKAPLTGYVRFLNERREKLRAenPDLSFPEITKILGAEWSSLSaeEKQKYLDEAEKDKERYVKELEAYQQT 72

high mobility group (HMG)-box found in high mobility group protein 20A (HMG20A) and similar proteins; HMG20A, also called HMG box-containing protein 20A, HMG domain-containing protein 1 (HMGXB1), 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 3702826   17 KKGGKAKDPNAPKRAMSAFFFWMQENRE--RIKKPGMGVADVAKAAGVEWGKL--TDKSRWEKKAADDKKRYEVDIANYK 92
Cdd:cd22017  10 KRKKPLRDSNAPKAPLTGYVRFMNERREqlRAERPDVPFPEITRMLGNEWSKLpaEEKQRYLDEAEKDKERYMKELEQYQ 89

                ...
gi 3702826   93 KSQ 95
Cdd:cd22017  90 KTE 92

first high mobility group (HMG)-box found in Saccharomyces cerevisiae mitochondrial ARS-binding factor 2 (ABF2) 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. ABF2 contains two HMG-box domains. This model corresponds to the first one.

                       10        20        30        40        50        60
               ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 3702826  28 PKRAMSAFFFWMQENRERIKK--PGMGVADVAKAAGVEWGKLT--DKSRWEKKAADDKKRYEVDIANY 91
Cdd:cd22010  1 PKRPLSAYFLYFQEHRSDFVKenPDAKMTEISKIGGDKWKNLSadDKKKYEDDFQRELSEYQKAKAEF 68

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 3702826  29 KRAMSAFFFWMQENRERIKK--PGMGVADVAKAAGVEWGKLTD--KSRWEKKAADDKKRY 84
Cdd:cd22005  1 KRPPTAFFLFLADFRKTYKKknPDKSVKAVGKAAGEKWKSMSDeeKAPYVEKAEKEKAEY 60

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 3702826  28 PKRAMSAFFFWMQENRERIKK--PGMGVADVAKAAGVEWGKLTD--KSRWEKKAADDKKRYEVDIANY 91
Cdd:cd22007  1 PKRPQSAYFLYANDRRAALKEenKNVKITEIAKMLGAEWKNLSDakKKPYEEKAKKLKEAYLQEMEEY 68

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
               ....*....|....*....|....*....|....*....|....*...
gi 3702826  27 APKRAMSAFFFWMQENRERIKK--PGMGVADVAKAAGVEWGKLTDKSR 72
Cdd:cd22012  1 PPKRPASAYFLFAKEVRPKLKEenPNEKYTDITKLISEKWRSLDESEK 48

first 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 first one.

                       10        20        30        40        50        60
               ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 3702826  29 KRAMSAFFFWMQENRERIKK--PGMGVADVAKAAGVEWGKLTDKsrwEKKAADDKkrYEVDIANYKK 93
Cdd:cd22006  1 KKPKTAYFLWCKDQREEVKKenPNADFSEVSKILGAKWKNLSEE---EKKPYEEK--YKEEKEKYLK 62

high mobility group (HMG)-box found in sex-determining region Y (SRY)-box (SOX) family transcription factors; The SOX gene family of transcription factors are characterized by the evolutionarily conserved SRY-type HMG box, which is a DNA binding domain that binds the minor groove of DNA on a common consensus site, (A/T)(A/T)CAA(A/T)G but with different levels of efficiency. Members include SRY and its homologs identified in mammals that can be subdivided into 8 groups (A, B1, B2, C, D, E, F, G, H). They are involved in embryonic development, regulating processes such as cell differentiation, maintenance of stemness, sex determination, and development of the central nervous, haematopoietic and other organ systems. The SOX gene family has a crucial role in carcinogenesis and cancer progression.

                       10        20        30        40        50        60
               ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 3702826  29 KRAMSAFFFWMQENRERIKK--PGMGVADVAKAAGVEWGKLTD--KSRWEKKAADDKKRYEVDIANYK 92
Cdd:cd22004  3 KRPMNAFMVWSQQERKKIAKqnPKLHNSEISKILGKEWKKLTEeeKRPYVEEAERLREEHKKEYPDYK 70

high mobility group (HMG)-box found in sex determining region Y (SRY)-box 30 (SOX30) and similar proteins; SOX-30 is a crucial transcription factor that controls the transition from a late meiotic to a post-meiotic gene expression program and subsequent round spermatid development. It specially prevents Wnt-signaling to suppress metastasis. SOX-30 binds to the DNA sequence 5'-ACAAT-3' and shows a preference for guanine residues surrounding this core motif. SOX-30 is the only member of the group H of SRY-related high-mobility group (HMG) box (Sox) transcription factors.

                       10        20        30        40
               ....*....|....*....|....*....|....*....|...
gi 3702826  29 KRAMSAFFFWMQENRERIKK--PGMGVADVAKAAGVEWGKLTD 69
Cdd:cd22033  3 KRPMNAFMVWARIHRPALAKanPNANNADISVQLGEEWNKLTE 45

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 3702826  28 PKRAMSAFFFWMQENRERIKKPG----MGVADVAKAAGVEWGKLTD--KSRWEKKAADDKKRYE 85
Cdd:cd21978  2 PRGKMSSYAFFVQTCREEHKKKHpnesVNFSEFSKKCSERWKTMSAkeKKKFEDMAKKDKARYE 65