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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1953376059 571 VKKPMSASALFVQDHRAQFLTENSKTSLEDATVQIEELWKTLSEEEKLKYEEKATKDLERYNRQIKRAIEQE 642
Cdd:cd21985     2 IRKPMSASALFEQETRPQFLAENPKASLQDITLKIEERWKNLSEEEKKKYEEKAAKDLERYNSQKKRAAEQP 73

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 1953376059   8 TVRLLSSSQIITSVVSVVKELLENSLDAGATSIDVKLENYGFDKIEVRDNGEGIKAIDAPVMAVKYYTSKINSHEDLENL 87
Cdd:cd16926     1 VVNKIAAGEVIERPASVVKELVENSIDAGATRIDVEIEEGGLKLIRVTDNGSGISREDLELAFERHATSKISSFEDLFSI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953376059  88 TTYGFRGEALGSICCVAEVLITTRTASDNFSTQYVLDGSGHIISQKPSHLGQGTTVTVLKLFKNLPVRKQFYSTAKKckd 167
Cdd:cd16926    81 TTLGFRGEALASIASVSRLTITTRTADDDVGTRLVVDGGGIIEEVKPAAAPVGTTVTVRDLFYNTPARRKFLKSPKT--- 157

                         170       180
                  ....*....|....*....|....*.
gi 1953376059 168 EIKKVQDLLISYGILKPELRIVFIHN 193
Cdd:cd16926   158 ELSKILDLVQRLALAHPDVSFSLTHD 183

DNA mismatch repair endonuclease MutL;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953376059   2 KQLPAATVrllssSQI-----ITSVVSVVKELLENSLDAGATSIDVKLENYGFDKIEVRDNGEGIKAIDAPVMAVKYYTS 76
Cdd:PRK00095    4 QLLPPQLA-----NQIaagevVERPASVVKELVENALDAGATRIDIEIEEGGLKLIRVRDNGCGISKEDLALALARHATS 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953376059  77 KINSHEDLENLTTYGFRGEALGSICCVAEVLITTRTASDNFSTQYVLDGsGHIISQKPSHLGQGTTVTVLKLFKNLPVRK 156
Cdd:PRK00095   79 KIASLDDLEAIRTLGFRGEALPSIASVSRLTLTSRTADAAEGWQIVYEG-GEIVEVKPAAHPVGTTIEVRDLFFNTPARR 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953376059 157 QFYSTAKKckdEIKKVQDLLISYGILKPELRIVFIHN-KAVIwqKTR-VSDRQVALRAVLGTAVMGNMEPFQYHPEDsqI 234
Cdd:PRK00095  158 KFLKSEKT---ELGHIDDVVNRLALAHPDVAFTLTHNgKLVL--QTRgAGQLLQRLAAILGREFAENALPIDAEHGD--L 230

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953376059 235 YLSGF--LPkhdvdhsSTSLSTPERSFIFINNRPVHQKDILKLIRHYYnlkclkeASRL----YPIFFLKIDVPTADVDV 308
Cdd:PRK00095  231 RLSGYvgLP-------TLSRANRDYQYLFVNGRYVRDKLLNHAIRQAY-------HDLLprgrYPAFVLFLELDPHQVDV 296

                         330
                  ....*....|....*..
gi 1953376059 309 NITPDKSQVLIQNKEAV 325
Cdd:PRK00095  297 NVHPAKHEVRFRDERLV 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 1953376059 211 RAVLGTAVMGNMEPFQYhpEDSQIYLSGFLPKHDvdhssTSLSTPERSFIFINNRPVHQKDILKLIRHYYNLKclkEASR 290
Cdd:pfam01119   1 AAIYGKEFAENLLPIEK--EDDGLRLSGYISKPT-----LSRSNRDYQYLFVNGRPVRDKLLSHAIREAYRDL---LPKG 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1953376059 291 LYPIFFLKIDVPTADVDVNITPDKSQVLIQNKEAVLIALEN 331
Cdd:pfam01119  71 RYPVAVLFLEIDPELVDVNVHPTKREVRFRDEREVYDFIKE 111

HMG (high mobility group) box;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1953376059 571 VKKPMSASALFVQDHRAQFLTENSKTSLEDATVQIEELWKTLSEEEKLKYEEKATKDLERYNRQIKR 637
Cdd:pfam00505   1 PKRPMSAFFLFSKEQRAKLKAENPGLKNAEISKILGEKWKALSEEEKKPYEEKAEKEKARYEKEHPE 67

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953376059   24 VVKELLENSLDAGATS--IDVKLENYGFD-KIEVRDNGEGIKAIDAPVMAVKYYTSKINSHEdlenlttygFRGEALG-S 99
Cdd:smart00387   9 VLSNLLDNAIKYTPEGgrITVTLERDGDHvEITVEDNGPGIPPEDLEKIFEPFFRTDKRSRK---------IGGTGLGlS 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1953376059  100 ICcvaevlittRTASDNFstqyvlDGSGHIISQkpshLGQGTTVTV 145
Cdd:smart00387  80 IV---------KKLVELH------GGEISVESE----PGGGTTFTI 106

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 1953376059   8 TVRLLSSSQIITSVVSVVKELLENSLDAGATSIDVKLENYGFDKIEVRDNGEGIKAIDAPVMAVKYYTSKINSHEDLENL 87
Cdd:cd16926     1 VVNKIAAGEVIERPASVVKELVENSIDAGATRIDVEIEEGGLKLIRVTDNGSGISREDLELAFERHATSKISSFEDLFSI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953376059  88 TTYGFRGEALGSICCVAEVLITTRTASDNFSTQYVLDGSGHIISQKPSHLGQGTTVTVLKLFKNLPVRKQFYSTAKKckd 167
Cdd:cd16926    81 TTLGFRGEALASIASVSRLTITTRTADDDVGTRLVVDGGGIIEEVKPAAAPVGTTVTVRDLFYNTPARRKFLKSPKT--- 157

                         170       180
                  ....*....|....*....|....*.
gi 1953376059 168 EIKKVQDLLISYGILKPELRIVFIHN 193
Cdd:cd16926   158 ELSKILDLVQRLALAHPDVSFSLTHD 183

DNA mismatch repair endonuclease MutL;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953376059   2 KQLPAATVrllssSQI-----ITSVVSVVKELLENSLDAGATSIDVKLENYGFDKIEVRDNGEGIKAIDAPVMAVKYYTS 76
Cdd:PRK00095    4 QLLPPQLA-----NQIaagevVERPASVVKELVENALDAGATRIDIEIEEGGLKLIRVRDNGCGISKEDLALALARHATS 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953376059  77 KINSHEDLENLTTYGFRGEALGSICCVAEVLITTRTASDNFSTQYVLDGsGHIISQKPSHLGQGTTVTVLKLFKNLPVRK 156
Cdd:PRK00095   79 KIASLDDLEAIRTLGFRGEALPSIASVSRLTLTSRTADAAEGWQIVYEG-GEIVEVKPAAHPVGTTIEVRDLFFNTPARR 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953376059 157 QFYSTAKKckdEIKKVQDLLISYGILKPELRIVFIHN-KAVIwqKTR-VSDRQVALRAVLGTAVMGNMEPFQYHPEDsqI 234
Cdd:PRK00095  158 KFLKSEKT---ELGHIDDVVNRLALAHPDVAFTLTHNgKLVL--QTRgAGQLLQRLAAILGREFAENALPIDAEHGD--L 230

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953376059 235 YLSGF--LPkhdvdhsSTSLSTPERSFIFINNRPVHQKDILKLIRHYYnlkclkeASRL----YPIFFLKIDVPTADVDV 308
Cdd:PRK00095  231 RLSGYvgLP-------TLSRANRDYQYLFVNGRYVRDKLLNHAIRQAY-------HDLLprgrYPAFVLFLELDPHQVDV 296

                         330
                  ....*....|....*..
gi 1953376059 309 NITPDKSQVLIQNKEAV 325
Cdd:PRK00095  297 NVHPAKHEVRFRDERLV 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 1953376059 209 ALRAVLGTAVMGNMEPFQYhpEDSQIYLSGFLPKHDVDHSStslstPERSFIFINNRPVHQKDILKLIRHYYNLKCLKea 288
Cdd:cd00782     4 RIAQVYGKEVAKNLIEVEL--ESGDFRISGYISKPDFGRSS-----KDRQFLFVNGRPVRDKLLSKAINEAYRSYLPK-- 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1953376059 289 sRLYPIFFLKIDVPTADVDVNITPDKSQVLIQNKEAVLIALENLMTTCY 337
Cdd:cd00782    75 -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 1953376059 211 RAVLGTAVMGNMEPFQYhpEDSQIYLSGFLPKHDvdhssTSLSTPERSFIFINNRPVHQKDILKLIRHYYNLKclkEASR 290
Cdd:pfam01119   1 AAIYGKEFAENLLPIEK--EDDGLRLSGYISKPT-----LSRSNRDYQYLFVNGRPVRDKLLSHAIREAYRDL---LPKG 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1953376059 291 LYPIFFLKIDVPTADVDVNITPDKSQVLIQNKEAVLIALEN 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 1953376059 209 ALRAVLGTAVMGNMEPFQYHPEDsqIYLSGFLPKHDVDHSStslstPERSFIFINNRPVHQ-KDILKLIRHYYNLKCLKE 287
Cdd:cd00329     4 RLAEILGDKVADKLIYVEGESDG--FRVEGAISYPDSGRSS-----KDRQFSFVNGRPVREgGTHVKAVREAYTRALNGD 76

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1953376059 288 ASRLYPIFFLKIDVPTADVDVNITPDKSQVL 318
Cdd:cd00329    77 DVRRYPVAVLSLKIPPSLVDVNVHPTKEEVR 107

Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase; This family represents the structurally related ATPase domains of histidine kinase, DNA gyrase B and HSP90.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953376059  24 VVKELLENSLD--AGATSIDVKLENYGFDKIEVRDNGEGIKAIDAPVMAVKYYTSKINSHEdlenlttygfrGEALG-SI 100
Cdd:pfam02518   9 VLSNLLDNALKhaAKAGEITVTLSEGGELTLTVEDNGIGIPPEDLPRIFEPFSTADKRGGG-----------GTGLGlSI 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1953376059 101 CcvaevlittRTASDNFstqyvldgSGHIisQKPSHLGQGTTVTV 145
Cdd:pfam02518  78 V---------RKLVELL--------GGTI--TVESEPGGGTTVTL 103

HMG (high mobility group) box;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1953376059 571 VKKPMSASALFVQDHRAQFLTENSKTSLEDATVQIEELWKTLSEEEKLKYEEKATKDLERYNRQIKR 637
Cdd:pfam00505   1 PKRPMSAFFLFSKEQRAKLKAENPGLKNAEISKILGEKWKALSEEEKKPYEEKAEKEKARYEKEHPE 67

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1953376059 572 KKPMSASALFVQDHRAQFLTENSKTSLEDATVQIEELWKTLSEEEKLKYEEKATKDLERYNRQIK 636
Cdd:COG5648    72 KRPLSAYFLYSAENRDEIRKENPKLTFGEVGKLLSEKWKELTDEEKEPYYKEANSDRERYQREKE 136

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1953376059 572 KKPMSASALFVQDHRAQFLTENSKTSLEDATVQIEELWKTLSEEEKLKYEEKATKDLERYNRQIKR 637
Cdd:cd01390    15 KRGLSAYMFFSQDNREKVKEENPDATFGEVGKLLGEKWKELSEEEKAPYEEKAAKDKKRYEEEKAA 80

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 1953376059 573 KPMSASALFVQDHRAQFLTENSKTSLEDATVQIEELWKTLSEEEKLKYEEKATKDLERYNRQIK 636
Cdd:cd21994     1 RPMSAYMLWLNENREKIKKENPGISVTEISKKAGEIWKELDEEDKEKWEQKAEKAKERYDKAMK 64

Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase; This family represents, additionally, the structurally related ATPase domains of histidine kinase, DNA gyrase B and HSP90.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1953376059  23 SVVKELLENSLDAGATSIDVKLENY--GFDKIEVRDNGEGI 61
Cdd:pfam13589   3 GALAELIDNSIDADATNIKIEVNKNrgGGTEIVIEDDGHGM 43

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1953376059 572 KKPMSASALFVQDHRAQFLTENSKTSLEDATVQIEELWKTLSEEEKLKYEEKATKDLERYNRQI 635
Cdd:cd21979     4 KRPPSAFFLFCSEHRPKIKGEHPGLSIGDVAKKLGEMWNNTSAKDKQPYEKKAAKLKEKYEKDI 67

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1953376059  21 VVSVVKELLENSLDAGATS------IDVKLENYGFD-KIEVRDNGEGIKAIDAPVMAVKYYTSKINSH 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1953376059 572 KKPMSASALFVQDHRAqfltENSKTSlEDATVQIEEL-------WKTLSEEEKLKYEEKATKDLERYNRQIK 636
Cdd:cd21978     3 RGKMSSYAFFVQTCRE----EHKKKH-PNESVNFSEFskkcserWKTMSAKEKKKFEDMAKKDKARYEREMK 69