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 1784428954 549 RPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYEKAMKEYE 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 1784428954 197 DAICIFRELQCLTPRGRYDIRIYPTFLHLHGKTFDYKIPYTTVLRLFLLPHKDQRQMFFVISLDPPIKQGQTRYHFLILL 276
Cdd:cd13230     4 DAIVTFEDILCLTPRGRYDIEMYPSFLRLHGKTYDYKIQYKSISRLFLLPKPDDRHVFFVISLDPPIRQGQTRYPFLVMQ 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1784428954 277 FSKDEDISLTLNMNEEEVEKRFEGRLTKNMSGSLYEMVSRVMKALVNRKITVPG 330
Cdd:cd13230    84 FDKDEEVELELNLTEEELEEKYKGKLEKEMSGPLYEVVSRVFKGLTGKKITVPG 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 1784428954 106 GWNWGTVKFGGQLLSFDIGDQPVFEIPLSNVSQCT-TGKNEVTLEFHQNDDAEVS---LMEVRFYVPPT 170
Cdd:pfam03531   1 GWNWGKADFEGSELSFNVDNKPAFEIPLSDVSNSNlPGKNEVALEFHQDDDADVNgdeLVEMRFYVPGT 69

high mobility group;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1784428954  546 APKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYEKAMKEYE 615
Cdd:smart00398   1 KPKRPMSAFMLFSQENRAKIKAENPDLSNAEISKKLGERWKLLSEEEKAPYEEKAKKDKERYEEEMPEYK 70

high mobility group protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1784428954 525 MAKDRKSRKKPVevKKGKDPNAPKRPMSAYMLWLNASREKIKSDHPGIS--ITDLSKKAGEIWKGMSKEKKEEWDRKAED 602
Cdd:PTZ00199    3 KKQGKVLVRKNK--RKKKDPNAPKRALSAYMFFAKEKRAEIIAENPELAkdVAAVGKMVGEAWNKLSEEEKAPYEKKAQE 80

                          90
                  ....*....|...
gi 1784428954 603 ARRDYEKAMKEYE 615
Cdd:PTZ00199   81 DKVRYEKEKAEYA 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 1784428954 197 DAICIFRELQCLTPRGRYDIRIYPTFLHLHGKTFDYKIPYTTVLRLFLLPHKDQRQMFFVISLDPPIKQGQTRYHFLILL 276
Cdd:cd13230     4 DAIVTFEDILCLTPRGRYDIEMYPSFLRLHGKTYDYKIQYKSISRLFLLPKPDDRHVFFVISLDPPIRQGQTRYPFLVMQ 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1784428954 277 FSKDEDISLTLNMNEEEVEKRFEGRLTKNMSGSLYEMVSRVMKALVNRKITVPG 330
Cdd:cd13230    84 FDKDEEVELELNLTEEELEEKYKGKLEKEMSGPLYEVVSRVFKGLTGKKITVPG 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 1784428954 549 RPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYEKAMKEYE 615
Cdd:cd21994     1 RPMSAYMLWLNENREKIKKENPGISVTEISKKAGEIWKELDEEDKEKWEQKAEKAKERYDKAMKEYK 67

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 1784428954 340 CITCSYKASSGLLYPLERGFIY-VHKPPVHIRFDEISFVNFARGTTTTRSFDFEIETKQGTQYTFSSIEREEYGKLFDFV 418
Cdd:pfam08512   2 GVKCSRKAKEGYLYPLEKCLLFgFKKPPLVIPLSDIESVSFERVSFTLRTFDLVIVLKKDPEYEFSMIDQEELDGIKDFL 81

                  ...
gi 1784428954 419 NAK 421
Cdd:pfam08512  82 KSK 84

HMG (high mobility group) box;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1784428954 547 PKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYEKAMKEY 614
Cdd:pfam00505   1 PKRPMSAFFLFSKEQRAKLKAENPGLKNAEISKILGEKWKALSEEEKKPYEEKAEKEKARYEKEHPEY 68

high mobility group;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1784428954  546 APKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYEKAMKEYE 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 1784428954 525 MAKDRKSRKKPVEVKKGKDPNAPKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDAR 604
Cdd:COG5648    49 LTKPRKKTKSKRLVRKKKDPNGPKRPLSAYFLYSAENRDEIRKENPKLTFGEVGKLLSEKWKELTDEEKEPYYKEANSDR 128

                          90
                  ....*....|.
gi 1784428954 605 RDYEKAMKEYE 615
Cdd:COG5648   129 ERYQREKEEYN 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 1784428954 545 NAPKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYEKAMKEY 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 1784428954 546 APKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWdrkaedaRRDYEKAMKEYE 615
Cdd:cd22012     1 PPKRPASAYFLFAKEVRPKLKEENPNEKYTDITKLISEKWRSLDESEKEPY-------QEEYEKALEEYE 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 1784428954 539 KKGKDPNAPKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYEKAMKEY 614
Cdd:cd22008     2 NKNVDPNKPKKPASSYLLFGKEYRKKLQEERPGANNATVTALISLKWKELGEEEKQVYNDKAAVLMEKYKKEVEEY 77

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 1784428954 547 PKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYEKAMKEY 614
Cdd:cd22010     1 PKRPLSAYFLYFQEHRSDFVKENPDAKMTEISKIGGDKWKNLSADDKKKYEDDFQRELSEYQKAKAEF 68

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 1784428954 540 KGKDPNAPKRPMSAYMLWLNASREKIKSD----HPGISITDLSKKAGEIWKGMSKE-KKEEWDRKAEDARRdYEKAMKEY 614
Cdd:cd22016     1 KEKDPNAPKRPANAFFLFCQEQREKVREEykeeHQEIDHHDLTKALAQAWRNLDAEdKKPYYELYEKDKER-YEKEMEEY 79

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 1784428954 547 PKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYEK 609
Cdd:cd22001     3 PKRPISAMFIYSKEKRSKLKKKHPELSEQELTRLLAKKYNELPDKKKAKYKKKEALAKAEYEK 65

high mobility group (HMG)-box found in SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1) and similar proteins; SMARCE1, also called BRG1-associated factor 57 (BAF57), is a ubiquitously expressed protein involved in transcriptional activation and repression of select genes by chromatin remodeling. It is a component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. SMARCE1 has a single HMG domain that displays non-specific DNA-binding characteristics. It also contains a kinesin-like coiled-coil (KLCC) domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1784428954 543 DPNAPKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYEKAMKEY 614
Cdd:cd21983     1 PPKPPEKPLMPYMRYSRKVWDQVKASNPDLKLWEIGKIIGQMWRELSDEEKQEYIEEYEAEKVEYEEQMKAY 72

high mobility group (HMG)-box found in group E SRY-related high-mobility group (HMG) box (Sox) transcription factors; SoxE transcription factors includes three members: Sox8, Sox9, and Sox10. They function as important transcriptional regulators of neural differentiation and nervous system development. They regulate mammalian development directing sex determination, gliogenesis, pancreas specification and neural crest development. SOX-8 is specifically expressed by M cells in the intestinal epithelium. It acts as a transcription factor necessary for the maintenance of spermatogenesis. It may play a role in central nervous system, limb and facial development. SOX-9 is involved in cell differentiation, sex determination, and tumorigenesis. It plays a role in chondrocyte differentiation and skeletal development. SOX-10 plays a central role in the development of melanocytes and glial cells from neural crest precursors.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1784428954 548 KRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYEKAMKEY 614
Cdd:cd22031     3 KRPMNAFMVWAQAARRKLADQYPHLHNAELSKTLGKLWRLLSESEKRPFIEEAERLRVQHKKDHPDY 69

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 1784428954 527 KDRKsRKKPVevkkgKDPNAPKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWkgmSKEKKEEWDRKAEDARRD 606
Cdd:cd22017     7 KGRK-RKKPL-----RDSNAPKAPLTGYVRFMNERREQLRAERPDVPFPEITRMLGNEW---SKLPAEEKQRYLDEAEKD 77

                  ....*....
gi 1784428954 607 YEKAMKEYE 615
Cdd:cd22017    78 KERYMKELE 86

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 1784428954 547 PKRPMSAYMLWLNASREKIKSDHPGISI--TDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYEKAMK 612
Cdd:cd21978     2 PRGKMSSYAFFVQTCREEHKKKHPNESVnfSEFSKKCSERWKTMSAKEKKKFEDMAKKDKARYEREMK 69

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 1784428954 548 KRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYEKAMKEY 614
Cdd:cd22006     1 KKPKTAYFLWCKDQREEVKKENPNADFSEVSKILGAKWKNLSEEEKKPYEEKYKEEKEKYLKVVGEE 67

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 1784428954 544 PNAPKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWdrkaedaRRDYEKAMKEYE 615
Cdd:cd21998     1 PDFPKKPLTPYFRFFMEKRAKYAKKHPEMSNLELTKILSKKYKELPEKKKQKY-------IQDYEKEKEEYE 65

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 1784428954 541 GKDP-NAPKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWdrkAEDARRDYEKAMKEY 614
Cdd:cd22035     1 GGDPlEKVKRPMNAFMVWSSAQRRQMAQEHPKMHNSEISKRLGAAWKLLPEAEKRPF---VEEAKRLRARHMRDY 72

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1784428954 547 PKRPMSAYMLWLNASREKIKSDHPgiSITDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYEKAMKEY 614
Cdd:cd21999     1 PKKPKTPFQLFYNKELKKLEPGTP--DKKELKEKLREKWKQMSDKKKLKWINKALEDEKRYEEELKEY 66

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 1784428954 547 PKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYEKAMKEYE 615
Cdd:cd22018     2 PKAPVTGYVRFLNERREQIRTQHPDLPFPEITKMLGAEWSKLQPHEKQRYLDEAERDKQQYMKELREYQ 70

high mobility group (HMG)-box found in group F SRY-related high-mobility group (HMG) box (Sox) transcription factors; SoxF transcription factors includes three members: Sox7, Sox17, and Sox18. They regulate endothelial cell fate as well as development and differentiation of the developing heart, blood cells, and lymphatic vessels.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1784428954 548 KRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYekaMKEY 614
Cdd:cd22032     3 RRPMNAFMVWAKDERKRLADENPDLHNAELSKMLGKKWKSLSLAEKRPFVEEAERLRVQH---MQDY 66

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 1784428954 548 KRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYEKAMK 612
Cdd:cd21985     3 RKPMSASALFEQETRPQFLAENPKASLQDITLKIEERWKNLSEEEKKKYEEKAAKDLERYNSQKK 67

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 1784428954 548 KRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWdrkAEDARRDYEKAMKEY 614
Cdd:cd01388     4 KRPMNAFMVWSRGQRRKMAQENPKMHNSEISKRLGAEWKLLSEAEKRPF---IDEAKRLRALHMKEH 67

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1784428954 539 KKGKDPNApKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARRDYekaMKEY 614
Cdd:cd22046     5 EKGSEPRI-RRPMNAFMVWAKDERKRLAVQNPDLHNAELSKMLGKSWKALTPSQKRPYVEEAERLRVQH---MQDY 76

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
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1784428954 548 KRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDAR 604
Cdd:cd22047     8 RRPMNAFMVWAKDERKRLAQQNPDLHNAELSKMLGKSWKALTLAEKRPFVEEAERLR 64

first high mobility group (HMG)-box found in mitochondrial transcription factor A (TFA) and similar proteins; TFA, also called TFAM, mitochondrial transcription factor 1 (TF1), transcription factor 6 (TCF-6), or transcription factor 6-like 2, binds to the mitochondrial light strand promoter and functions in mitochondrial transcription regulation. It is a component of the mitochondrial transcription initiation complex, composed of at least TFB2M, TFAM and POLRMT that is required for basal transcription of mitochondrial DNA. TFA is required for accurate and efficient promoter recognition by the mitochondrial RNA polymerase. It can unwind DNA. It bends the mitochondrial light strand promoter DNA into a U-turn shape via its HMG boxes. TFA is required for maintenance of normal levels of mitochondrial DNA and may play a role in organizing and compacting mitochondrial DNA. TFA contains two HMG-box domains. This model corresponds to the first one.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1784428954 547 PKRPMSAYMLWLN---ASREKIKSDhpgiSITDLSKKAGEIWKGMSKEKKeewdRKAEDARR-DYEKAMKEY 614
Cdd:cd21986     1 PKRPLSPYLRFYReqlPSFPAQNPD----ATTDLSKRIGERWRELPDSQK----KKYQDAYKaEWQKYKEEI 64

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1784428954 547 PKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKAEDARR 605
Cdd:cd21977     1 KKKWVNGFIMFCRLNRKNYIDKHPGLASTELTKELGQLWRELSAEEKKPYCVRARELSQ 59