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 111154063 549 RPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEKAMKEYE 615
Cdd:cd21994    1 RPMSAYMLWLNENREKIKKENPGISVTEISKKAGEIWKELDEEDKEKWEQKAEKAKERYDKAMKEYK 67

Structure Specific Recognition protein 1 (SSRP1) Pleckstrin homology (PH) domain, repeat 1; SSRP1 is a component of FACT (facilitator of chromatin transcription), an essential chromatin reorganizing factor. In yeast FACT (yFACT) is composed of three proteins: Spt16/Cdc68, Pob3, and Nhp6. In metazoans the Pob3 and Nhp6 orthologs are fused to form SSRP1/T160 in human and mouse, respectively. The middle domain of the Pob3 subunit (Pob3-M) has an unusual double pleckstrin homology (PH) architecture. yFACT interacts in a physiologically important way with the central single-strand DNA binding factor RPA to promote a step in DNA Replication. Coordinated function by yFACT and RPA is important during nucleosome deposition. These results support the model that the FACT family has an essential role in constructing nucleosomes during DNA replication, and suggest that RPA contributes to this process. Members of this cd are composed of the first PH-like repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154063 194 ATGDAICIFRELQCLTPRGRYDIRIYPTFLHLHGKTFDYKIPYTTVLRLFLLPHKDQRQMFFVISLDPPIKQGQTRYHFL 273
Cdd:cd13230    1 VTGDAIVTFEDILCLTPRGRYDIEMYPSFLRLHGKTYDYKIQYKSISRLFLLPKPDDRHVFFVISLDPPIRQGQTRYPFL 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 111154063 274 ILLFSKDEDISLTLNMNEEEVEKRFEGRLTKNMSGSLYEMVSRVMKALVNRKITVPG 330
Cdd:cd13230   81 VMQFDKDEEVELELNLTEEELEEKYKGKLEKEMSGPLYEVVSRVFKGLTGKKITVPG 137

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 111154063 549 RPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEKAMKEYE 615
Cdd:cd21994    1 RPMSAYMLWLNENREKIKKENPGISVTEISKKAGEIWKELDEEDKEKWEQKAEKAKERYDKAMKEYK 67

high mobility group;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154063   546 APKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEKAMKEYE 615
Cdd:smart00398   1 KPKRPMSAFMLFSQENRAKIKAENPDLSNAEISKKLGERWKLLSEEEKAPYEEKAKKDKERYEEEMPEYK 70

high mobility group protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154063 523 AKMAKDRKSRRKSSEAKKgkDPNAPKRPMSAYMLWLNASREKIKSDHPGIS--ITDLSKKAGEIWKGMSKEKKEEWDRKA 600
Cdd:PTZ00199   1 MAKKQGKVLVRKNKRKKK--DPNAPKRALSAYMFFAKEKRAEIIAENPELAkdVAAVGKMVGEAWNKLSEEEKAPYEKKA 78

                         90
                 ....*....|....*
gi 111154063 601 EDARREYEKAMKEYE 615
Cdd:PTZ00199  79 QEDKVRYEKEKAEYA 93

Structure Specific Recognition protein 1 (SSRP1) Pleckstrin homology (PH) domain, repeat 1; SSRP1 is a component of FACT (facilitator of chromatin transcription), an essential chromatin reorganizing factor. In yeast FACT (yFACT) is composed of three proteins: Spt16/Cdc68, Pob3, and Nhp6. In metazoans the Pob3 and Nhp6 orthologs are fused to form SSRP1/T160 in human and mouse, respectively. The middle domain of the Pob3 subunit (Pob3-M) has an unusual double pleckstrin homology (PH) architecture. yFACT interacts in a physiologically important way with the central single-strand DNA binding factor RPA to promote a step in DNA Replication. Coordinated function by yFACT and RPA is important during nucleosome deposition. These results support the model that the FACT family has an essential role in constructing nucleosomes during DNA replication, and suggest that RPA contributes to this process. Members of this cd are composed of the first PH-like repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154063 194 ATGDAICIFRELQCLTPRGRYDIRIYPTFLHLHGKTFDYKIPYTTVLRLFLLPHKDQRQMFFVISLDPPIKQGQTRYHFL 273
Cdd:cd13230    1 VTGDAIVTFEDILCLTPRGRYDIEMYPSFLRLHGKTYDYKIQYKSISRLFLLPKPDDRHVFFVISLDPPIRQGQTRYPFL 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 111154063 274 ILLFSKDEDISLTLNMNEEEVEKRFEGRLTKNMSGSLYEMVSRVMKALVNRKITVPG 330
Cdd:cd13230   81 VMQFDKDEEVELELNLTEEELEEKYKGKLEKEMSGPLYEVVSRVFKGLTGKKITVPG 137

Structure-specific recognition protein (SSRP1); SSRP1 has been implicated in transcriptional initiation and elongation and in DNA replication and repair. This domain belongs to the Pleckstrin homology fold superfamily.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 111154063  106 GWNWGTVKFGGQLLSFDIGDQPVFEIPLSNVSQCT-TGKNEVTLEFHQNDDAEVS---LMEVRFYVPPT 170
Cdd:pfam03531   1 GWNWGKADFEGSELSFNVDNKPAFEIPLSDVSNSNlPGKNEVALEFHQDDDADVNgdeLVEMRFYVPGT 69

Histone chaperone Rttp106-like; This family includes Rttp106, a histone chaperone involved in heterochromatin-mediated silencing. This domain belongs to the Pleckstrin homology domain superfamily.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154063  340 CITCSYKASSGLLYPLERGFIY-VHKPPVHIRFDEISFVNFARGTTTTRSFDFEIETKQGTQYTFSSIEREEYGKLFDFV 418
Cdd:pfam08512   2 GVKCSRKAKEGYLYPLEKCLLFgFKKPPLVIPLSDIESVSFERVSFTLRTFDLVIVLKKDPEYEFSMIDQEELDGIKDFL 81

                  ...
gi 111154063  419 NAK 421
Cdd:pfam08512  82 KSK 84

HMG (high mobility group) box;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 111154063  547 PKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEKAMKEY 614
Cdd:pfam00505   1 PKRPMSAFFLFSKEQRAKLKAENPGLKNAEISKILGEKWKALSEEEKKPYEEKAEKEKARYEKEHPEY 68

high mobility group;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154063   546 APKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEKAMKEYE 615
Cdd:smart00398   1 KPKRPMSAFMLFSQENRAKIKAENPDLSNAEISKKLGERWKLLSEEEKAPYEEKAKKDKERYEEEMPEYK 70

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154063 524 KMAKDRKSRRKSSEAKKGKDPNAPKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDA 603
Cdd:COG5648   48 LLTKPRKKTKSKRLVRKKKDPNGPKRPLSAYFLYSAENRDEIRKENPKLTFGEVGKLLSEKWKELTDEEKEPYYKEANSD 127

                         90
                 ....*....|..
gi 111154063 604 RREYEKAMKEYE 615
Cdd:COG5648  128 RERYQREKEEYN 139

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 111154063 545 NAPKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEKAMKEY 614
Cdd:cd21979    1 NAPKRPPSAFFLFCSEHRPKIKGEHPGLSIGDVAKKLGEMWNNTSAKDKQPYEKKAAKLKEKYEKDIAAY 70

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 111154063 546 APKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWdrkaedaRREYEKAMKEYE 615
Cdd:cd22012    1 PPKRPASAYFLFAKEVRPKLKEENPNEKYTDITKLISEKWRSLDESEKEPY-------QEEYEKALEEYE 63

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 111154063 547 PKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEK 609
Cdd:cd01389    1 IPRPPNAFILFRKEKHKQLRAQNPGLTNSEISKIIGKMWKNLSEEEKEPYKELAEEEKEEHKL 63

third 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 third one.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 111154063 539 KKGKDPNAPKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEKAMKEY 614
Cdd:cd22008    2 NKNVDPNKPKKPASSYLLFGKEYRKKLQEERPGANNATVTALISLKWKELGEEEKQVYNDKAAVLMEKYKKEVEEY 77

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 111154063 547 PKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEK 609
Cdd:cd22001    3 PKRPISAMFIYSKEKRSKLKKKHPELSEQELTRLLAKKYNELPDKKKAKYKKKEALAKAEYEK 65

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154063 540 KGKDPNAPKRPMSAYMLWLNASREKIKSD----HPGISITDLSKKAGEIWKGMSKE-KKEEWDRKAEDARReYEKAMKEY 614
Cdd:cd22016    1 KEKDPNAPKRPANAFFLFCQEQREKVREEykeeHQEIDHHDLTKALAQAWRNLDAEdKKPYYELYEKDKER-YEKEMEEY 79

HMG-box domain; This short 71 residue domain is an HMG-box domain. HMG-box domains mediate re-modelling of chromatin-structure. Mammalian HMG-box proteins are of two types: those that are non-sequence-specific DNA-binding proteins with two HMG-box domains and a long highly acidic C-tail; and a diverse group of sequence-specific transcription factor-proteins with either a single HMG-box or up to six copies, and no acidic C-tail.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 111154063  544 PNAPKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEKAMKEYE 615
Cdd:pfam09011   1 PNKPKRARNAYAFFVQEMIPEHKRQNPVIGFAEVSKLCSERWKNLSEEEKEKYEEMAKEDKNRYDREMGTYD 72

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154063 547 PKRPMSAYMLWLNASREKIKSD-HPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEKAMKEYE 615
Cdd:cd22011    1 PKRPSSAYFLFSQEIRKNLKSQgSPEEKVPELSKRAAEQWRSLTLAEKQPYYDEVEVLKKQYDVEKEEYE 70

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 111154063 547 PKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEKAMKEY 614
Cdd:cd22015    1 PKKPLTPYFAFSNHVRPQLKAERPKASPTEIAEEISERWANLSDEEKQLWEDKYEEEMKEYQKALEAY 68

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 111154063 547 PKRPMSAYMLWLNASREKIKSDHPGISI--TDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEKAMK 612
Cdd:cd21978    2 PRGKMSSYAFFVQTCREEHKKKHPNESVnfSEFSKKCSERWKTMSAKEKKKFEDMAKKDKARYEREMK 69

high mobility group (HMG)-box found in WD repeat and HMG-box DNA-binding protein 1 (WDHD1) and similar proteins; WDHD1, also called acidic nucleoplasmic DNA-binding protein 1 (And-1), acts as a replication initiation factor that brings together the MCM2-7 helicase and the DNA polymerase alpha/primase complex in order to initiate DNA replication.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 111154063 546 APKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKA 600
Cdd:cd21993    1 ENKKKKSGFQLWLEENRSSIEEENPELSEAEIIKLAMQRFRALPKEEKQKWNEKA 55

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 111154063 544 PNAPKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEKAMKEY 614
Cdd:cd21998    1 PDFPKKPLTPYFRFFMEKRAKYAKKHPEMSNLELTKILSKKYKELPEKKKQKYIQDYEKEKEEYEQKMARF 71

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111154063 541 GKDP-NAPKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWdrkAEDARREYEKAMKEY 614
Cdd:cd22035    1 GGDPlEKVKRPMNAFMVWSSAQRRQMAQEHPKMHNSEISKRLGAAWKLLPEAEKRPF---VEEAKRLRARHMRDY 72

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 111154063 547 PKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEKAMKEYE 615
Cdd:cd22018    2 PKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQPHEKQRYLDEAERDKQQYMKELREYQ 70

high mobility group (HMG)-box found in HMG domain-containing protein 4 (HMGXB4) and similar proteins; HMGXB4, also called HMG box-containing protein 4, high mobility group protein 2-like 1 (HMG2L1), or protein HMGBCG, is a non-histone chromosomal protein that negatively regulates Wnt/beta-catenin signaling during development. It plays a role in the hematopoietic system.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 111154063 548 KRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAE 601
Cdd:cd21982    2 KKNMSAYQVFCKEYRVSIVAEHPGIDFGELSKKLAEVWKQLPEKDKLVWKQKAQ 55

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 111154063 548 KRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEKAMKEY 614
Cdd:cd21995    1 QKPVSAYALFFRDTQAAIKGQNPNATFGEVSKIVASMWDSLDEEQKQVYKKKTEAAKKEYLKALAAY 67

high mobility group (HMG)-box found in Caenorhabditis elegans protein egg laying defective 13 (EGL-13) and similar proteins; EGL-13 may act as a transcription factor that is required for uterine cell fate decisions in Caenorhabditis elegans. It controls genes required for the specification and differentiation of O(2) and CO(2)-sensing neurons and for maintaining URX sensory neuronal cell fate.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 111154063 548 KRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEW 596
Cdd:cd22042    4 KRPMNAFMVWAKDERRKILKACPDMHNSNISKILGAKWKAMSNAEKQPY 52

high mobility group (HMG)-box found in group B SRY-related high-mobility group (HMG) box (Sox) transcription factors; SoxB transcription factors play critical roles in the regulation of neurogenesis. They can be divided into two main subgroups, SoxB1 (Sox-1/Sox-2/Sox-3) and SoxB2 (SOX-14/SOX-21). SoxB1 proteins suppress neurogenesis by maintaining neural cells in an undifferentiated state. SoxB2 proteins may have the opposite activity and promote neuronal differentiation. SOX-1 is involved in the regulation of embryonic development and cell fate determination. It also acts as a tumor suppressor that plays an anti-tumorigenicity role in different cells and its expression is inhibited in a variety of cancers. SOX-2 plays an important role in various phases of embryonic development, including cell fate and differentiation. Its overexpression and gene amplification may be associated with tumor aggression and metastasis in various cancer types, including breast, prostate, lung, ovarian and colon cancer. SOX-3 is required during the formation of the hypothalamic-pituitary axis. It plays a role in both normal neural development and carcinogenesis. SOX-14, also called SOX-28, acts as a negative regulator of transcription. It is mainly involved in the regulation of neural development. It can also promote proliferation and invasion capacity of cervical cancer cells by activating the Wnt/beta-catenin pathway. SOX-21, also called SOX-A, or SOX-25, promotes the progression of vertebrate neurogenesis.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 111154063 548 KRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWdrkAEDARREYEKAMKEY 614
Cdd:cd01388    4 KRPMNAFMVWSRGQRRKMAQENPKMHNSEISKRLGAEWKLLSEAEKRPF---IDEAKRLRALHMKEH 67

high mobility group (HMG)-box found in PMS1 protein homolog 1 (PMS1) and similar proteins; PMS1, also called DNA mismatch repair protein PMS1, is probably involved in the repair of mismatches in DNA.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111154063 548 KRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEKAMK 612
Cdd:cd21985    3 RKPMSASALFEQETRPQFLAENPKASLQDITLKIEERWKNLSEEEKKKYEEKAAKDLERYNSQKK 67

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111154063 541 GKDPNAPKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARREYEKAMKEYE 615
Cdd:cd22047    1 GKGESRIRRPMNAFMVWAKDERKRLAQQNPDLHNAELSKMLGKSWKALTLAEKRPFVEEAERLRVQHMQDHPNYK 75