Histidine kinase-like ATPase domain; This superfamily includes the histidine kinase-like ATPase (HATPase) domains of several ATP-binding proteins such as histidine kinase, DNA gyrase B, topoisomerases, heat shock protein 90 (HSP90), phytochrome-like ATPases and DNA mismatch repair proteins. Domains belonging to this superfamily are also referred to as GHKL (gyrase, heat-shock protein 90, histidine kinase, MutL) ATPase domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002273471 229 YLRTLSQTHAgWVFGAIAELIDNSRDADASRLNIsvksLFSKKADKK-IPVLSVIDDGHGMTCAEMMRMISFGHKRPDKQ 307
Cdd:cd16931     1 FLHSNSTTHS-WPFGAVAELVDNARDADATRLDI----FIDDINLLRgGFMLSFLDDGNGMTPEEAHHMISFGFSDKRSD 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1002273471 308 RQDQIGRFGIGFKTGAMKLGRDAIVLTQTSSSRSVAFLSQSFN 350
Cdd:cd16931    76 DHDHIGRYGNGFKSGSMRLGRDVIVFTKKDESQSCGLLSQTFL 118

CW-type Zinc Finger; This domain appears to be a zinc finger. The alignment shows four conserved cysteine residues and a conserved tryptophan. It was first identified by, and is predicted to be a "highly specialized mononuclear four-cysteine zinc finger...that plays a role in DNA binding and/or promoting protein-protein interactions in complicated eukaryotic processes including...chromatin methylation status and early embryonic development." Weak homology to pfam00628 further evidences these predictions (personal obs: C Yeats). Twelve different CW-domain-containing protein subfamilies are described, with different subfamilies being characteriztic of vertebrates, higher plants and other animals in which these domain is found.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1002273471 634 WVQCYSCRKWRILNAGFDTKSLPDEWFCYM---PPFNgKCEVAEQQ 676
Cdd:pfam07496   2 WVQCDSCLKWRRLPTEIDPYELPEPWYCSMnpdPKYN-SCDAPEEI 46

Histidine kinase-like ATPase domain of human microrchidia (MORC) family CW-type zinc finger proteins MORC1-4, and related domains; This family includes the histidine kinase-like ATPase (HATPase) domain of human microrchidia (MORC) family CW-type zinc finger proteins MORC1-4, and related domains. In addition to the HATPase domain, MORC family proteins have a CW-type zinc finger domain containing four conserved cysteines and two conserved tryptophans, and coiled-coil domains at the carboxy-terminus. MORC1 has cross-species differential methylation in association with early life stress, and genome-wide association with major depressive disorder (MDD). MORC2 is involved in several nuclear processes, including transcription modulation and DNA damage repair, and exhibits a cytosolic function in lipogenesis, adipogenic differentiation, and lipid homeostasis by increasing the activity of ACLY. MORC3 regulates p53, and is an antiviral factor which plays an important role during HSV-1 and HCMV infection, and is a positive regulator of influenza virus transcription. MORC4 is highly expressed in a subset of diffuse large B-cell lymphomas and has potential as a lymphoma biomarker.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002273471 229 YLRTLSQTHAgWVFGAIAELIDNSRDADASRLNIsvksLFSKKADKK-IPVLSVIDDGHGMTCAEMMRMISFGHKRPDKQ 307
Cdd:cd16931     1 FLHSNSTTHS-WPFGAVAELVDNARDADATRLDI----FIDDINLLRgGFMLSFLDDGNGMTPEEAHHMISFGFSDKRSD 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1002273471 308 RQDQIGRFGIGFKTGAMKLGRDAIVLTQTSSSRSVAFLSQSFN 350
Cdd:cd16931    76 DHDHIGRYGNGFKSGSMRLGRDVIVFTKKDESQSCGLLSQTFL 118

Morc6 ribosomal protein S5 domain 2-like; This domain is found in MORC6 proteins in eukaryotes. Arabidopsis microrchidia (MORC) ATPase family proteins are conserved among plants and animals and are involved in transcriptional silencing. In Arabidopsis, MORC6/DMS11 was reported to function in the condensation of pericentromeric heterochromatin, thereby facilitating transcriptional silencing. Further studies demonstrate that MORC6 and its homologs MORC1 and MORC2 form a complex which associates with SUVH9, required for Pol V occupancy in the RdDM (RNA-directed DNA methylation) pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002273471 471 YSLQSYLEVMFLN--PRMKISVQGSSVKTRPLAKTLNKTSVI-----SGEIMGRTIQLTLG------RSNVewdrmnCGI 537
Cdd:pfam17942   1 YSLRAYASILYLRlpPNFQIILRGKKVEHHNIADDLKYPEKItykpqVGGGKEVVVITTIGflkeapHINV------HGF 74

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1002273471 538 FLYWHGRLIESYKRVGGQkhNADMGRGVIGV--ADITDLIDDedgnswvlnsKQGFQDCEMYAKLEEWLGRKADEYW 612
Cdd:pfam17942  75 NVYHKNRLIKPFWRVGNQ--AGSKGRGVIGVleANFIEPTHD----------KQDFERTSLYQRLEARLKQMLKEYW 139

Molecular chaperone, HSP90 family [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002273471 247 ELIDNSRDA-DASR-LNISVKSLFSKKADKKIPV--------LSVIDDGHGMTCAEMMRMIS---------FGHKRPDKQ 307
Cdd:COG0326    33 ELISNASDAiDKLRfLALTDPELKEEDGDLKIRIevdkeaktLTISDNGIGMTREEVIENLGtiaksgtreFLEKLKGDQ 112

                          90
                  ....*....|....
gi 1002273471 308 RQDQ--IGRFGIGF 319
Cdd:COG0326   113 KKDSdlIGQFGVGF 126

PHD finger found in Transcription factor 19 (TCF-19), Lysine-specific demethylase KDM5A and KDM5B, and other similar proteins; TCF-19 was identified as a putative trans-activating factor with expression beginning at the late G1-S boundary in dividing cells. It functions as a novel islet factor necessary for proliferation and survival in the INS-1 beta cell line. It plays an important role in susceptibility to both Type 1 Diabetes Mellitus (T1DM) and Type 2 Diabetes Mellitus (T2DM); it has been suggested that it may positively impact beta cell mass under conditions of beta cell stress and increased insulin demand. KDM5A was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation. It is involved in transcription through interaction with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK, and BMAL1. KDM5B has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of the pregnant female and has been shown to be upregulated in breast cancer, prostate cancer, and lung cancer, suggesting a potential role in tumorigenesis. Both KDM5A and KDM5B function as trimethylated histone H3 lysine 4 (H3K4me3) demethylases. This family also includes Caenorhabditis elegans Lysine-specific demethylase 7 homolog (ceKDM7A). ceKDM7A (also termed JmjC domain-containing protein 1.2, PHD finger protein 8 homolog, or PHF8 homolog) is a plant homeodomain (PHD)- and JmjC domain-containing protein that functions as a histone demethylase specific for H3K9me2 and H3K27me2. The binding of the PHD finger to H3K4me3 guides H3K9me2- and H3K27me2-specific demethylation by its catalytic JmjC domain in a trans-histone regulation mechanism. In addition, this family includes plant protein OBERON 1 and OBERON 2, Alfin1-like (AL) proteins, histone acetyltransferases (HATs) HAC, and AT-rich interactive domain-containing protein 4 (ARID4).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1002273471 624 GSERYKADHEWVQCYSCRKW------RILNAGFDTkslPDEWFC 661
Cdd:cd15517     6 NLETAAVDELWVQCDGCDKWfhqfclGLSNERYAD---EDKFKC 46

Histidine kinase-like ATPase domain of human microrchidia (MORC) family CW-type zinc finger proteins MORC1-4, and related domains; This family includes the histidine kinase-like ATPase (HATPase) domain of human microrchidia (MORC) family CW-type zinc finger proteins MORC1-4, and related domains. In addition to the HATPase domain, MORC family proteins have a CW-type zinc finger domain containing four conserved cysteines and two conserved tryptophans, and coiled-coil domains at the carboxy-terminus. MORC1 has cross-species differential methylation in association with early life stress, and genome-wide association with major depressive disorder (MDD). MORC2 is involved in several nuclear processes, including transcription modulation and DNA damage repair, and exhibits a cytosolic function in lipogenesis, adipogenic differentiation, and lipid homeostasis by increasing the activity of ACLY. MORC3 regulates p53, and is an antiviral factor which plays an important role during HSV-1 and HCMV infection, and is a positive regulator of influenza virus transcription. MORC4 is highly expressed in a subset of diffuse large B-cell lymphomas and has potential as a lymphoma biomarker.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002273471 229 YLRTLSQTHAgWVFGAIAELIDNSRDADASRLNIsvksLFSKKADKK-IPVLSVIDDGHGMTCAEMMRMISFGHKRPDKQ 307
Cdd:cd16931     1 FLHSNSTTHS-WPFGAVAELVDNARDADATRLDI----FIDDINLLRgGFMLSFLDDGNGMTPEEAHHMISFGFSDKRSD 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1002273471 308 RQDQIGRFGIGFKTGAMKLGRDAIVLTQTSSSRSVAFLSQSFN 350
Cdd:cd16931    76 DHDHIGRYGNGFKSGSMRLGRDVIVFTKKDESQSCGLLSQTFL 118

Morc6 ribosomal protein S5 domain 2-like; This domain is found in MORC6 proteins in eukaryotes. Arabidopsis microrchidia (MORC) ATPase family proteins are conserved among plants and animals and are involved in transcriptional silencing. In Arabidopsis, MORC6/DMS11 was reported to function in the condensation of pericentromeric heterochromatin, thereby facilitating transcriptional silencing. Further studies demonstrate that MORC6 and its homologs MORC1 and MORC2 form a complex which associates with SUVH9, required for Pol V occupancy in the RdDM (RNA-directed DNA methylation) pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002273471 471 YSLQSYLEVMFLN--PRMKISVQGSSVKTRPLAKTLNKTSVI-----SGEIMGRTIQLTLG------RSNVewdrmnCGI 537
Cdd:pfam17942   1 YSLRAYASILYLRlpPNFQIILRGKKVEHHNIADDLKYPEKItykpqVGGGKEVVVITTIGflkeapHINV------HGF 74

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1002273471 538 FLYWHGRLIESYKRVGGQkhNADMGRGVIGV--ADITDLIDDedgnswvlnsKQGFQDCEMYAKLEEWLGRKADEYW 612
Cdd:pfam17942  75 NVYHKNRLIKPFWRVGNQ--AGSKGRGVIGVleANFIEPTHD----------KQDFERTSLYQRLEARLKQMLKEYW 139

Molecular chaperone, HSP90 family [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002273471 247 ELIDNSRDA-DASR-LNISVKSLFSKKADKKIPV--------LSVIDDGHGMTCAEMMRMIS---------FGHKRPDKQ 307
Cdd:COG0326    33 ELISNASDAiDKLRfLALTDPELKEEDGDLKIRIevdkeaktLTISDNGIGMTREEVIENLGtiaksgtreFLEKLKGDQ 112

                          90
                  ....*....|....
gi 1002273471 308 RQDQ--IGRFGIGF 319
Cdd:COG0326   113 KKDSdlIGQFGVGF 126

heat shock protein 90; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002273471 247 ELIDNSRDAdASRLN---ISVKSLFSKKADKKIPV--------LSVIDDGHGMTCAEMMRMI---------SFGHKRPDK 306
Cdd:PRK05218   33 ELISNASDA-IDKLRfeaLTDPALYEGDGDLKIRIsfdkeartLTISDNGIGMTREEVIENLgtiaksgtkEFLEKLKGD 111

                          90
                  ....*....|....*
gi 1002273471 307 QRQDQ--IGRFGIGF 319
Cdd:PRK05218  112 QKKDSqlIGQFGVGF 126

PHD finger found in Transcription factor 19 (TCF-19), Lysine-specific demethylase KDM5A and KDM5B, and other similar proteins; TCF-19 was identified as a putative trans-activating factor with expression beginning at the late G1-S boundary in dividing cells. It functions as a novel islet factor necessary for proliferation and survival in the INS-1 beta cell line. It plays an important role in susceptibility to both Type 1 Diabetes Mellitus (T1DM) and Type 2 Diabetes Mellitus (T2DM); it has been suggested that it may positively impact beta cell mass under conditions of beta cell stress and increased insulin demand. KDM5A was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation. It is involved in transcription through interaction with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK, and BMAL1. KDM5B has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of the pregnant female and has been shown to be upregulated in breast cancer, prostate cancer, and lung cancer, suggesting a potential role in tumorigenesis. Both KDM5A and KDM5B function as trimethylated histone H3 lysine 4 (H3K4me3) demethylases. This family also includes Caenorhabditis elegans Lysine-specific demethylase 7 homolog (ceKDM7A). ceKDM7A (also termed JmjC domain-containing protein 1.2, PHD finger protein 8 homolog, or PHF8 homolog) is a plant homeodomain (PHD)- and JmjC domain-containing protein that functions as a histone demethylase specific for H3K9me2 and H3K27me2. The binding of the PHD finger to H3K4me3 guides H3K9me2- and H3K27me2-specific demethylation by its catalytic JmjC domain in a trans-histone regulation mechanism. In addition, this family includes plant protein OBERON 1 and OBERON 2, Alfin1-like (AL) proteins, histone acetyltransferases (HATs) HAC, and AT-rich interactive domain-containing protein 4 (ARID4).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1002273471 624 GSERYKADHEWVQCYSCRKW------RILNAGFDTkslPDEWFC 661
Cdd:cd15517     6 NLETAAVDELWVQCDGCDKWfhqfclGLSNERYAD---EDKFKC 46