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
                 ....*....|....*....|....*....|....*....|....*...
gi 189458898 571 IKKPMSASALFVQDHRPQFLIENPKTSLEDATLQIEELWKTLSEEEKL 618
Cdd:cd21985    2 IRKPMSASALFEQETRPQFLAENPKASLQDITLKIEERWKNLSEEEKK 49

Histidine kinase-like ATPase domain of DNA mismatch repair proteins Escherichia coli MutL, human MutL homologs (MLH/ PMS), and related domains; This family includes the histidine kinase-like ATPase (HATPase) domains of Escherichia coli MutL, human MLH1 (mutL homolog 1), human PMS1 (PMS1 homolog 1, mismatch repair system component), human MLH3 (mutL homolog 3), and human PMS2 (PMS1 homolog 2, mismatch repair system component). MutL homologs (MLH/PMS) participate in MMR (DNA mismatch repair), and in addition have role(s) in DNA damage signaling and suppression of homologous recombination (recombination between partially homologous parental DNAs). The primary role of MutL in MMR is to mediate protein-protein interactions during mismatch recognition and strand removal; a ternary complex is formed between MutS, MutL, and the mismatched DNA, which activates the MutH endonuclease.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898   8 TVRLLSSSQIITSVVSVVKELIENSLDAGATSVDVKLENYGFDKIEVRDNGEGIKAVDAPVMAMKYYTSKINSHEDLENL 87
Cdd:cd16926    1 VVNKIAAGEVIERPASVVKELVENSIDAGATRIDVEIEEGGLKLIRVTDNGSGISREDLELAFERHATSKISSFEDLFSI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898  88 TTYGFRGEALGSICCIAEVLITTRTAADNFSTQYVLDGSGHILSQKPSHLGQGTTVTALRLFKNLPVRKQFYSTAKKckd 167
Cdd:cd16926   81 TTLGFRGEALASIASVSRLTITTRTADDDVGTRLVVDGGGIIEEVKPAAAPVGTTVTVRDLFYNTPARRKFLKSPKT--- 157

                        170       180
                 ....*....|....*....|....*.
gi 189458898 168 EIKKIQDLLMSFGILKPDLRIVFVHN 193
Cdd:cd16926  158 ELSKILDLVQRLALAHPDVSFSLTHD 183

DNA mismatch repair endonuclease MutL;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898   2 KQLPAATVrllssSQI-----ITSVVSVVKELIENSLDAGATSVDVKLENYGFDKIEVRDNGEGIKAVDAPVMAMKYYTS 76
Cdd:PRK00095   4 QLLPPQLA-----NQIaagevVERPASVVKELVENALDAGATRIDIEIEEGGLKLIRVRDNGCGISKEDLALALARHATS 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898  77 KINSHEDLENLTTYGFRGEALGSICCIAEVLITTRTAADNFSTQYVLDGsGHILSQKPSHLGQGTTVTALRLFKNLPVRK 156
Cdd:PRK00095  79 KIASLDDLEAIRTLGFRGEALPSIASVSRLTLTSRTADAAEGWQIVYEG-GEIVEVKPAAHPVGTTIEVRDLFFNTPARR 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898 157 QFYSTAKKckdEIKKIQDLLMSFGILKPDLRIVFVHNKAVIWQKSRVSDHKMALMSVLGTAVMNNMESFqyHSEESQIYL 236
Cdd:PRK00095 158 KFLKSEKT---ELGHIDDVVNRLALAHPDVAFTLTHNGKLVLQTRGAGQLLQRLAAILGREFAENALPI--DAEHGDLRL 232

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898 237 SGF--LPKCdadhsftSLSTPERSFIFINSRPVHQKDILKLIRHHYnlkclkeSTRL----YPVFFLKIDVPTADVDVNL 310
Cdd:PRK00095 233 SGYvgLPTL-------SRANRDYQYLFVNGRYVRDKLLNHAIRQAY-------HDLLprgrYPAFVLFLELDPHQVDVNV 298

                        330
                 ....*....|....*
gi 189458898 311 TPDKSQVLLQNKESV 325
Cdd:PRK00095 299 HPAKHEVRFRDERLV 313

DNA mismatch repair protein, C-terminal domain; This family represents the C-terminal domain of the mutL/hexB/PMS1 family. This domain has a ribosomal S5 domain 2-like fold.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898  211 MSVLGTAVMNNMESFQYHSEesQIYLSGFLPKcdadHSFTSlSTPERSFIFINSRPVHQKDILKLIRHHYNLKclkESTR 290
Cdd:pfam01119   1 AAIYGKEFAENLLPIEKEDD--GLRLSGYISK----PTLSR-SNRDYQYLFVNGRPVRDKLLSHAIREAYRDL---LPKG 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 189458898  291 LYPVFFLKIDVPTADVDVNLTPDKSQVLLQNKESVLIALEN 331
Cdd:pfam01119  71 RYPVAVLFLEIDPELVDVNVHPTKREVRFRDEREVYDFIKE 111

HMG (high mobility group) box;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 189458898  571 IKKPMSASALFVQDHRPQFLIENPKTSLEDATLQIEELWKTLSEEEK 617
Cdd:pfam00505   1 PKRPMSAFFLFSKEQRAKLKAENPGLKNAEISKILGEKWKALSEEEK 47

Histidine kinase-like ATPases; Histidine kinase-, DNA gyrase B-, phytochrome-like ATPases.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898    24 VVKELIENSLDAGATS--VDVKLENYGFD-KIEVRDNGEGIKAVDAPVMAMKYYTSKINSHEdlenlttygFRGEALG-S 99
Cdd:smart00387   9 VLSNLLDNAIKYTPEGgrITVTLERDGDHvEITVEDNGPGIPPEDLEKIFEPFFRTDKRSRK---------IGGTGLGlS 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 189458898   100 ICciaevlittRTAADNFstqyvlDGSGHILSQkpshLGQGTTVT 144
Cdd:smart00387  80 IV---------KKLVELH------GGEISVESE----PGGGTTFT 105

Histidine kinase-like ATPase domain of DNA mismatch repair proteins Escherichia coli MutL, human MutL homologs (MLH/ PMS), and related domains; This family includes the histidine kinase-like ATPase (HATPase) domains of Escherichia coli MutL, human MLH1 (mutL homolog 1), human PMS1 (PMS1 homolog 1, mismatch repair system component), human MLH3 (mutL homolog 3), and human PMS2 (PMS1 homolog 2, mismatch repair system component). MutL homologs (MLH/PMS) participate in MMR (DNA mismatch repair), and in addition have role(s) in DNA damage signaling and suppression of homologous recombination (recombination between partially homologous parental DNAs). The primary role of MutL in MMR is to mediate protein-protein interactions during mismatch recognition and strand removal; a ternary complex is formed between MutS, MutL, and the mismatched DNA, which activates the MutH endonuclease.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898   8 TVRLLSSSQIITSVVSVVKELIENSLDAGATSVDVKLENYGFDKIEVRDNGEGIKAVDAPVMAMKYYTSKINSHEDLENL 87
Cdd:cd16926    1 VVNKIAAGEVIERPASVVKELVENSIDAGATRIDVEIEEGGLKLIRVTDNGSGISREDLELAFERHATSKISSFEDLFSI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898  88 TTYGFRGEALGSICCIAEVLITTRTAADNFSTQYVLDGSGHILSQKPSHLGQGTTVTALRLFKNLPVRKQFYSTAKKckd 167
Cdd:cd16926   81 TTLGFRGEALASIASVSRLTITTRTADDDVGTRLVVDGGGIIEEVKPAAAPVGTTVTVRDLFYNTPARRKFLKSPKT--- 157

                        170       180
                 ....*....|....*....|....*.
gi 189458898 168 EIKKIQDLLMSFGILKPDLRIVFVHN 193
Cdd:cd16926  158 ELSKILDLVQRLALAHPDVSFSLTHD 183

DNA mismatch repair endonuclease MutL;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898   2 KQLPAATVrllssSQI-----ITSVVSVVKELIENSLDAGATSVDVKLENYGFDKIEVRDNGEGIKAVDAPVMAMKYYTS 76
Cdd:PRK00095   4 QLLPPQLA-----NQIaagevVERPASVVKELVENALDAGATRIDIEIEEGGLKLIRVRDNGCGISKEDLALALARHATS 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898  77 KINSHEDLENLTTYGFRGEALGSICCIAEVLITTRTAADNFSTQYVLDGsGHILSQKPSHLGQGTTVTALRLFKNLPVRK 156
Cdd:PRK00095  79 KIASLDDLEAIRTLGFRGEALPSIASVSRLTLTSRTADAAEGWQIVYEG-GEIVEVKPAAHPVGTTIEVRDLFFNTPARR 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898 157 QFYSTAKKckdEIKKIQDLLMSFGILKPDLRIVFVHNKAVIWQKSRVSDHKMALMSVLGTAVMNNMESFqyHSEESQIYL 236
Cdd:PRK00095 158 KFLKSEKT---ELGHIDDVVNRLALAHPDVAFTLTHNGKLVLQTRGAGQLLQRLAAILGREFAENALPI--DAEHGDLRL 232

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898 237 SGF--LPKCdadhsftSLSTPERSFIFINSRPVHQKDILKLIRHHYnlkclkeSTRL----YPVFFLKIDVPTADVDVNL 310
Cdd:PRK00095 233 SGYvgLPTL-------SRANRDYQYLFVNGRYVRDKLLNHAIRQAY-------HDLLprgrYPAFVLFLELDPHQVDVNV 298

                        330
                 ....*....|....*
gi 189458898 311 TPDKSQVLLQNKESV 325
Cdd:PRK00095 299 HPAKHEVRFRDERLV 313

MutL_Trans: transducer domain, having a ribosomal S5 domain 2-like fold, conserved in the C-terminal domain of DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to be important in nucleotide hydrolysis and the transduction of structural signals from ATP-binding site to the DNA breakage/reunion regions of the enzymes. Included in this group are proteins similar to human MLH1, hPMS2, hPMS1, hMLH3 and E. coli MutL, MLH1 forms heterodimers with PMS2, PMS1 and MLH3. These three complexes have distinct functions in meiosis. hMLH1-hPMS2 also participates in the repair of all DNA mismatch repair (MMR) substrates. Roles for hMLH1-hPMS1 or hMLH1-hMLH3 in MMR have not been established. Cells lacking either hMLH1 or hPMS2 have a strong mutator phenotype and display microsatellite instability (MSI). Mutation in hMLH1 causes predisposition to HNPCC, Muir-Torre syndrome and Turcot syndrome (HNPCC variant). Mutation in hPMS2 causes predisposition to HPNCC and Turcot syndrome. Mutation in hMLH1 accounts for a large fraction of HNPCC families. There is no convincing evidence to support hPMS1 having a role in HNPCC predisposition. It has been suggested that hMLH3 may be a low risk gene for colorectal cancer; however there is little evidence to support it having a role in classical HNPCC. It has been suggested that during initiation of DNA mismatch repair in E. coli, the mismatch recognition protein MutS recruits MutL in the presence of ATP. The MutS(ATP)-MutL ternary complex formed, then recruits the latent endonuclease MutH.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898 206 HKMALMSVLGTAVMNNMESFQYhsEESQIYLSGFLPKCDAdhsftSLSTPERSFIFINSRPVHQKDILKLIRHHYNLKCL 285
Cdd:cd00782    1 LKDRIAQVYGKEVAKNLIEVEL--ESGDFRISGYISKPDF-----GRSSKDRQFLFVNGRPVRDKLLSKAINEAYRSYLP 73

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 189458898 286 KestRLYPVFFLKIDVPTADVDVNLTPDKSQVLLQNKESVLIALENLMTTCY 337
Cdd:cd00782   74 K---GRYPVFVLNLELPPELVDVNVHPTKREVRFSDEEEVLELIREALRSAL 122

DNA mismatch repair protein, C-terminal domain; This family represents the C-terminal domain of the mutL/hexB/PMS1 family. This domain has a ribosomal S5 domain 2-like fold.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898  211 MSVLGTAVMNNMESFQYHSEesQIYLSGFLPKcdadHSFTSlSTPERSFIFINSRPVHQKDILKLIRHHYNLKclkESTR 290
Cdd:pfam01119   1 AAIYGKEFAENLLPIEKEDD--GLRLSGYISK----PTLSR-SNRDYQYLFVNGRPVRDKLLSHAIREAYRDL---LPKG 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 189458898  291 LYPVFFLKIDVPTADVDVNLTPDKSQVLLQNKESVLIALEN 331
Cdd:pfam01119  71 RYPVAVLFLEIDPELVDVNVHPTKREVRFRDEREVYDFIKE 111

MutL_Trans: transducer domain, having a ribosomal S5 domain 2-like fold, conserved in the C-terminal domain of type II DNA topoisomerases (Topo II) and DNA mismatch repair (MutL/MLH1/PMS2) proteins. This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to be important in nucleotide hydrolysis and the transduction of structural signals from ATP-binding site to the DNA breakage/reunion regions of the enzymes. The GyrB dimerizes in response to ATP binding, and is homologous to the N-terminal half of eukaryotic Topo II and the ATPase fragment of MutL. Type II DNA topoisomerases catalyze the ATP-dependent transport of one DNA duplex through another, in the process generating transient double strand breaks via covalent attachments to both DNA strands at the 5' positions. Included in this group are proteins similar to human MLH1 and PMS2. MLH1 forms a heterodimer with PMS2 which functions in meiosis and in DNA mismatch repair (MMR). Cells lacking either hMLH1 or hPMS2 have a strong mutator phenotype and display microsatellite instability (MSI). Mutation in hMLH1 accounts for a large fraction of Lynch syndrome (HNPCC) families.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898 206 HKMALMSVLGTAVMNNMESFQyhSEESQIYLSGFLPKCDADHSftslsTPERSFIFINSRPVHQ-KDILKLIRHHYNLKC 284
Cdd:cd00329    1 LKDRLAEILGDKVADKLIYVE--GESDGFRVEGAISYPDSGRS-----SKDRQFSFVNGRPVREgGTHVKAVREAYTRAL 73

                         90       100       110
                 ....*....|....*....|....*....|....
gi 189458898 285 LKESTRLYPVFFLKIDVPTADVDVNLTPDKSQVL 318
Cdd:cd00329   74 NGDDVRRYPVAVLSLKIPPSLVDVNVHPTKEEVR 107

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 189458898 573 KPMSASALFVQDHRPQFLIENPKTSLEDATLQIEELWKTLSEEEKlnlfngSHYLDvlyKMTADDQRY 640
Cdd:cd00084    1 RPLSAYLLFSKEKRPKLKKENPDLSFTEISKLLGERWKELSEEEK------QPYEE---KAKEDKERY 59

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 189458898 572 KKPMSASALFVQDHRPQFLIENPKTSLEDATLQIEELWKTLSEEEK 617
Cdd:cd22012    3 KRPASAYFLFAKEVRPKLKEENPNEKYTDITKLISEKWRSLDESEK 48

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
                 ....*....|....*....|....*....|....*....|....*..
gi 189458898 572 KKPMSASALFVQDHRPQFLIENPKTSLEDATLQIEELWKTLSEEEKL 618
Cdd:cd21979    4 KRPPSAFFLFCSEHRPKIKGEHPGLSIGDVAKKLGEMWNNTSAKDKQ 50

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
                  ....*....|....*....|....*....|....*....|....*.
gi 189458898  572 KKPMSASALFVQDHRPQFLIENPKTSLEDATLQIEELWKTLSEEEK 617
Cdd:pfam09011   5 KRARNAYAFFVQEMIPEHKRQNPVIGFAEVSKLCSERWKNLSEEEK 50

MutL_Trans_MLH3: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH3 (MutL homologue 3). MLH3 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to be important in nucleotide hydrolysis and the transduction of structural signals from ATP-binding site to the DNA breakage/reunion regions of the enzymes. MLH1 forms heterodimers with MLH3. The MLH1-MLH3 complex plays a role in meiosis. A role for hMLH1-hMLH3 in DNA mismatch repair (MMR) has not been established. It has been suggested that hMLH3 may be a low risk gene for colorectal cancer; however there is little evidence to support it having a role in classical HNPCC.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189458898 209 ALMSVLGTAVMNNMESFQyhSEESQIYLSGFLPKCdadhsftslstPERS----FIFINSRPVHQKDILKLI-------- 276
Cdd:cd03486    5 VFKQIYGLVLAQKLKEVS--AKFQEYEVSGYISSE-----------GHYSksfqFIYVNGRLYLKTRFHKLInklfrkts 71

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 189458898 277 --------RHHYNLKCLKESTRLYPVFFLKIDVPTADVDVNLTPDKSQVLLQNKESVLIALENLMTT 335
Cdd:cd03486   72 avaknkssPQSKSSRRGKRSQESYPVFVLNITCPASEYDLSQEPSKTIIEFKDWKTLLPLILEVVKS 138

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
                 ....*....|....*....|....*....|....*....|....*.
gi 189458898 572 KKPMSASALFVQDHRPQFLIENPKTSLEDATLQIEELWKTLSEEEK 617
Cdd:cd22005    1 KRPPTAFFLFLADFRKTYKKKNPDKSVKAVGKAAGEKWKSMSDEEK 46

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
                 ....*....|....*....|....*....|....*....|....*.
gi 189458898 572 KKPMSASALFVQDHRPQFLIENPKTSLEDATLQIEELWKTLSEEEK 617
Cdd:cd22010    2 KRPLSAYFLYFQEHRSDFVKENPDAKMTEISKIGGDKWKNLSADDK 47

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        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 189458898 571 IKKPMSASALFVQDHRPQFLIENPKTSLEDATLQIEELWKTLSEEEKLNLFNGSHYLDVLYKMTADDQRYS 641
Cdd:cd22033    2 IKRPMNAFMVWARIHRPALAKANPNANNADISVQLGEEWNKLTEEQKKPYYDEAQKLKEQHRKEHPGWVYQ 72

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 189458898 572 KKPMSASALFVQDHRPQFLIENPKTSLEDATLQIEELWKTLSEEEKLNLFNGSHYL 627
Cdd:cd21982    2 KKNMSAYQVFCKEYRVSIVAEHPGIDFGELSKKLAEVWKQLPEKDKLVWKQKAQYL 57

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.

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gi 189458898 571 IKKPMSASALFVQDHRPQFLIENPKTSLEDATLQIEELWKTLSEEEK 617
Cdd:cd01389    1 IPRPPNAFILFRKEKHKQLRAQNPGLTNSEISKIIGKMWKNLSEEEK 47

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 189458898 572 KKPMSASALFVQDHRPQFLIENPKTSLEDATLQIEELWKTLSEEEKlnlfngSHYLDvlyKMTADDQRY 640
Cdd:cd21980    3 KAPLTGYVRFLNERREKLRAENPDLSFPEITKILGAEWSSLSAEEK------QKYLD---EAEKDKERY 62

Histidine kinase-like ATPase domain of type IIB topoisomerase, Topo VI, subunit B; This family includes the histidine kinase-like ATPase (HATPase) domain of the B subunit of topoisomerase VI (Topo VIB). Topo VI is a heterotetrameric complex composed of two TopVIA and two TopVIB subunits and is categorized as a type II B DNA topoisomerase. It is found in archaea and also in plants. Type II enzymes cleave both strands of a DNA duplex and pass a second duplex through the resulting break in an ATP-dependent mechanism. DNA cleavage by Topo VI generates two-nucleotide 5'-protruding ends.

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gi 189458898  18 ITSVVSVVKELIENSLDAGATS-------VDVKLENYGFDKIEVRDNGEGIKAVDAP-VMAMKYYTSK 77
Cdd:cd16933   17 IRSLYTTVRELVENSLDATEEAgilpdikVEIEEIGKDHYKVIVEDNGPGIPEEQIPkVFGKVLYGSK 84

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.

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gi 189458898 572 KKPMSASALFVQDHRPQFLIENPKTSLEDATLQIEELWKTLSEEEK 617
Cdd:cd22008   11 KKPASSYLLFGKEYRKKLQEERPGANNATVTALISLKWKELGEEEK 56

high mobility group (HMG)-box found in group A, group B and group G of SRY-related high-mobility group (HMG) box (Sox) transcription factors; This subfamily includes SoxA, SoxB, and SoxG proteins. SRY is the only member of group A SRY-related high-mobility group (HMG) box (Sox) transcription factors. SRY, also called testis-determining factor, is a transcriptional regulator that controls a genetic switch in male development. It promotes DNA bending and is also involved in pre-mRNA splicing. The SRY HMG box recognizes DNA by partial intercalation in the minor groove. It binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3'. 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-5 is the only member of group G Sox transcription factors. It is also called SOX-12, SOX-20, SOX-26, or SOX-27. SOX-5 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.

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gi 189458898 571 IKKPMSASALFVQDHRPQFLIENPKTSLEDATLQIEELWKTLSEEEK 617
Cdd:cd22028    2 VKRPMNAFMVWSREQRRKIAQENPKMHNSEISKRLGAEWKQLSEDEK 48

Histidine kinase-like ATPase domain of two-component sensor histidine kinases similar to Escherichia coli K-12 DpiB, DcuS, and Bacillus subtilis CitS, DctS, and YufL; This family includes histidine kinase-like ATPase domains of Escherichia coli K-12 DpiB and DcuS, and Bacillus subtilis CitS, DctS and MalK histidine kinases (HKs) all of which are two component transduction systems (TCSs). E. coli K-12 DpiB (also known as CitA) is the histidine kinase (HK) of DpiA-DpiB, a two-component signal transduction system (TCS) required for the expression of citrate-specific fermentation genes and genes involved in plasmid inheritance. E. coli K-12 DcuS (also known as YjdH) is the HK of DcuS-DcuR, a TCS that in the presence of the extracellular C4-dicarboxlates, activates the expression of the genes of anaerobic fumarate respiration and of aerobic C4-dicarboxylate uptake. CitS is the HK of Bacillus subtilis CitS-CitT, a TCS which regulates expression of CitM, the Mg-citrate transporter. Bacillus subtilis DctS forms a tripartite sensor unit (DctS/DctA/DctB) for sensing C4 dicarboxylates. Bacillus subtilis MalK (also known as YfuL) is the HK of MalK-MalR (YufL-YufM) a TCS which regulates the expression of the malate transporters MaeN (YufR) and YflS, and is essential for utilization of malate in minimal medium. Proteins having this DpiB-CitA-like HATPase domain generally have sensor domains such as Cache and PAS, and a histidine kinase A (HisKA)-like SpoOB-type, alpha-helical domain.

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gi 189458898  21 VVSVVKELIENSLDAGATS------VDVKLENYGFD-KIEVRDNGEGIKAVDAPVMAMKYYTSKINSH 81
Cdd:cd16915    1 LITIVGNLIDNALDALAATgapnkqVEVFLRDEGDDlVIEVRDTGPGIAPELRDKVFERGVSTKGQGE 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.

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gi 189458898 572 KKPMSASALFVQDHRPQFLIENPKTSLEDATL--QIEELWKTLSEEEK 617
Cdd:cd21978    3 RGKMSSYAFFVQTCREEHKKKHPNESVNFSEFskKCSERWKTMSAKEK 50