B-Box C-terminal domain; Coiled coil region C-terminal to (some) B-Box domains

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928129864   253 QRMLLEGVTTQVAHKKSSLQTSAKQIEDRIFEVKHQHRKVENQIKMAKMVLMNELNKQANGLIEELEGITNERKRKLEQQ 332
Cdd:smart00502    1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*.
gi 1928129864   333 LQSIMVLNRQFEHVQNFINWAVCSKTSVPFLFSKELIVFQMQRLLE 378
Cdd:smart00502   81 LESLTQKQEKLSHAINFTEEALNSGDPTELLLSKKLIIERLQNLLK 126

B-box-type 2 zinc finger found in tripartite motif-containing protein 66 (TRIM66) and similar proteins; TRIM66, also termed transcriptional intermediary factor 1 delta (TIF1delta), is a novel heterochromatin protein 1 (HP1)-interacting member of the transcriptional intermediary factor 1 (TIF1) family expressed by elongating spermatids. Like other TIF1 proteins, TRIM66 displays a potent trichostatin A (TSA)-sensitive repression function; TSA is a specific inhibitor of histone deacetylases. Moreover, TRIM66 plays an important role in heterochromatin-mediated gene silencing during postmeiotic phases of spermatogenesis. It functions as a negative regulator of postmeiotic genes acting through HP1 isotype gamma (HP1gamma) complex formation and centromere association. TRIM66 belongs to an unclassified TRIM (tripartite motif) family of proteins that do not have RING fingers and thus lack the characteristic tripartite (RING (R), B-box, and coiled coil (CC)) RBCC motif. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1928129864  208 LYCPLHTQEVLKLFCETCDMLTCHSCLVVEHKEHRCRHVEEVL 250
Cdd:cd19794      1 LMCPLHNQEPLKLFCETCDVLVCRSCLLSEHKEHRFKHLDEAL 43

UV excision repair protein Rad23; All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. In humans, Rad23 complexes with the XPC protein. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928129864  710 SQEETLQATDEPPASQGSKPALPldKNTAAALPQASGEETPLSVPPVDSTIQHSSPNVV-RKHSTSLSIMG--------- 779
Cdd:TIGR00601   75 SKPKTGTGKVAPPAATPTSAPTP--TPSPPASPASGMSAAPASAVEEKSPSEESATATApESPSTSVPSSGsdaastlvv 152

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928129864  780 -------FSNTLEMELSSTRLER--------------------PLEPQIQSVSNLTAGAPQAVPSLLSAPPkmvssltSV 832
Cdd:TIGR00601  153 gserettIEEIMEMGYEREEVERalraafnnpdraveylltgiPEDPEQPEPVQQTAASTAAATTETPQHG-------SV 225

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928129864  833 QNQAMPSLTTSHLQTVPSLVHS--------TFQSMPNLISDSPQAMASLASDHPQAGPSL---MSGHTQAVPSLATCPLQ 901
Cdd:TIGR00601  226 FEQAAQGGTEQPATEAAQGGNPleflrnqpQFQQLRQVVQQNPQLLPPLLQQIGQENPQLlqqISQHPEQFLQMLNEPVG 305

                   ....*...
gi 1928129864  902 SIPPVSDM 909
Cdd:TIGR00601  306 ELASESDM 313

B-Box C-terminal domain; Coiled coil region C-terminal to (some) B-Box domains

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928129864   253 QRMLLEGVTTQVAHKKSSLQTSAKQIEDRIFEVKHQHRKVENQIKMAKMVLMNELNKQANGLIEELEGITNERKRKLEQQ 332
Cdd:smart00502    1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*.
gi 1928129864   333 LQSIMVLNRQFEHVQNFINWAVCSKTSVPFLFSKELIVFQMQRLLE 378
Cdd:smart00502   81 LESLTQKQEKLSHAINFTEEALNSGDPTELLLSKKLIIERLQNLLK 126

bromo domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928129864  1194 DQKKCEKLVLSLCCNN----LSLPFHEPVSP-LARHYYQIIKRPMDLSIIRRKLQKKdpaHYTTPEEVVSDVRLMFWNCA 1268
Cdd:smart00297    4 LQKKLQELLKAVLDKLdshpLSWPFLKPVSRkEAPDYYDIIKKPMDLKTIKKKLENG---KYSSVEEFVADFNLMFSNAR 80

                            90       100
                    ....*....|....*....|....*..
gi 1928129864  1269 KFNYPDSEVAEAGRCLEVFFEGWLKEI 1295
Cdd:smart00297   81 TYNGPDSEVYKDAKKLEKFFEKKLREL 107

Bromodomain; Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928129864 1198 CEKLVLSLCCNNLSLPFHEPVSPLAR-HYYQIIKRPMDLSIIRRKLQKKdpaHYTTPEEVVSDVRLMFWNCAKFNYPDSE 1276
Cdd:pfam00439    1 CLEILDKLMEHPIAAPFLEPVDPDEYpDYYSVIKKPMDLSTIKKKLENG---EYKSLAEFLADVKLIFSNARTYNGPGSV 77

                   ....*.
gi 1928129864 1277 VAEAGR 1282
Cdd:pfam00439   78 IYKAAE 83

B-box-type 1 zinc finger found in tripartite motif-containing protein 66 (TRIM66) and similar proteins; TRIM66, also termed transcriptional intermediary factor 1 delta (TIF1delta), is a novel heterochromatin protein 1 (HP1)-interacting member of the transcriptional intermediary factor 1 (TIF1) family, and is expressed by elongating spermatids. Like other TIF1 proteins, TRIM66 displays a potent trichostatin A (TSA)-sensitive repression function; TSA is a specific inhibitor of histone deacetylases. Moreover, TRIM66 plays an important role in heterochromatin-mediated gene silencing during postmeiotic phases of spermatogenesis. It functions as a negative regulator of postmeiotic genes acting through HP1 isotype gamma (HP1gamma) complex formation and centromere association. TRIM66 belongs to an unclassified TRIM (tripartite motif) family of proteins that do not have RING fingers and thus lack the characteristic tripartite (RING (R), B-box, and coiled coil (CC)) RBCC motif. The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif.

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1928129864  149 NCSECKEKRAAHILCTYCNRWLCSSCTEEHRHSPVPG 185
Cdd:cd19811      1 SCSECKEKRPAHSLCTTCNKWLCSSCTEEHRHGKSTS 37

PHD zinc finger; The plant homeodomain (PHD) finger is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in epigenetics and chromatin-mediated transcriptional regulation. The PHD finger binds two zinc ions using the so-called 'cross-brace' motif and is thus structurally related to the RING finger and the FYVE finger. It is not yet known if PHD fingers have a common molecular function. Several reports suggest that it can function as a protein-protein interacton domain and it was recently demonstrated that the PHD finger of p300 can cooperate with the adjacent BROMO domain in nucleosome binding in vitro. Other reports suggesting that the PHD finger is a ubiquitin ligase have been refuted as these domains were RING fingers misidentified as PHD fingers.

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*..
gi 1928129864  1120 FCAVC---LNGGELLCCDRCPKVFHLSCHVPALLSF-PGGEWVCTLC 1162
Cdd:smart00249    1 YCSVCgkpDDGGELLQCDGCDRWYHQTCLGPPLLEEePDGKWYCPKC 47

B-box zinc finger;

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1928129864  209 YCPLHTQEVLKLFCETCDMLTCHSCLVVEHKEHRCR 244
Cdd:pfam00643    5 LCPEHEEEPLTLYCNDCQELLCEECSVGEHRGHTVV 40

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928129864  240 EHRCRHVEEVLQNQRMLLEGVTTQVAHKK---SSLQTSAKQIEDRIFEVKHQHRKVENQIKMAKmvlmNelNKQANGLIE 316
Cdd:COG1579     23 EHRLKELPAELAELEDELAALEARLEAAKtelEDLEKEIKRLELEIEEVEARIKKYEEQLGNVR----N--NKEYEALQK 96

                           90       100
                   ....*....|....*....|.
gi 1928129864  317 ELEGITnERKRKLEQQLQSIM 337
Cdd:COG1579     97 EIESLK-RRISDLEDEILELM 116

B-Box C-terminal domain; Coiled coil region C-terminal to (some) B-Box domains

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928129864   253 QRMLLEGVTTQVAHKKSSLQTSAKQIEDRIFEVKHQHRKVENQIKMAKMVLMNELNKQANGLIEELEGITNERKRKLEQQ 332
Cdd:smart00502    1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*.
gi 1928129864   333 LQSIMVLNRQFEHVQNFINWAVCSKTSVPFLFSKELIVFQMQRLLE 378
Cdd:smart00502   81 LESLTQKQEKLSHAINFTEEALNSGDPTELLLSKKLIIERLQNLLK 126

bromo domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928129864  1194 DQKKCEKLVLSLCCNN----LSLPFHEPVSP-LARHYYQIIKRPMDLSIIRRKLQKKdpaHYTTPEEVVSDVRLMFWNCA 1268
Cdd:smart00297    4 LQKKLQELLKAVLDKLdshpLSWPFLKPVSRkEAPDYYDIIKKPMDLKTIKKKLENG---KYSSVEEFVADFNLMFSNAR 80

                            90       100
                    ....*....|....*....|....*..
gi 1928129864  1269 KFNYPDSEVAEAGRCLEVFFEGWLKEI 1295
Cdd:smart00297   81 TYNGPDSEVYKDAKKLEKFFEKKLREL 107

Bromodomain, Brdt_like subfamily, repeat II. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928129864 1195 QKKCEKLV---LSLCCNNLSLPFHEPVSP--LARH-YYQIIKRPMDLSIIRRKLQKKDpahYTTPEEVVSDVRLMFWNCA 1268
Cdd:cd05498      2 LKFCSGILkelFSKKHKAYAWPFYKPVDPeaLGLHdYHDIIKHPMDLSTIKKKLDNRE---YADAQEFAADVRLMFSNCY 78

                           90       100
                   ....*....|....*....|.
gi 1928129864 1269 KFNYPDSEVAEAGRCLEVFFE 1289
Cdd:cd05498     79 KYNPPDHPVHAMARKLQDVFE 99

Bromodomain; Gcn5_like subfamily. Gcn5p is a histone acetyltransferase (HAT) which mediates acetylation of histones at lysine residues; such acetylation is generally correlated with the activation of transcription. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928129864 1211 SLPFHEPVSPL-ARHYYQIIKRPMDLSIIRRKLQKKdpaHYTTPEEVVSDVRLMFWNCAKFNYPDSEVAEAGRCLEVFFE 1289
Cdd:cd05509     19 AWPFLEPVDKEeAPDYYDVIKKPMDLSTMEEKLENG---YYVTLEEFVADLKLIFDNCRLYNGPDTEYYKCANKLEKFFW 95

                   ....*.
gi 1928129864 1290 GWLKEI 1295
Cdd:cd05509     96 KKLKEL 101

PHD finger found in the transcriptional intermediary factor 1 (TIF1) family and similar proteins; The TIF1 family of transcriptional cofactors includes TIF1alpha (TRIM24), TIF1beta (TRIM28), TIF1gamma (TRIM33), and TIF1delta (TRIM66), which are characterized by an N-terminal RING-finger B-box coiled-coil (RBCC/TRIM) motif and plant homeodomain (PHD) finger followed by a bromodomain in the C-terminal region. TIF1 proteins couple chromatin modifications to transcriptional regulation, signaling, and tumor suppression. They exert a deacetylase-dependent silencing effect when tethered to a promoter region. TIF1alpha, TIF1beta, and TIF1delta can homodimerize and contain a PXVXL motif necessary and sufficient for heterochromatin protein 1(HP1) binding. TIF1alpha and TIF1beta bind nuclear receptors and Kruppel-associated boxes (KRAB) specifically and respectively. In contrast, TIF1delta appears to lack nuclear receptor- and KRAB-binding activity. Moreover, TIF1delta is specifically involved in heterochromatin-mediated gene silencing during postmeiotic phases of spermatogenesis. TIF1gamma is structurally closely related to TIF1alpha and TIF1beta, but has very little functional features in common with them. It does not interact with the KRAB silencing domain of KOX1 or the heterochromatinic proteins HP1alpha, beta, and gamma. It cannot bind to nuclear receptors (NRs). This family also includes Sp100/Sp140 family proteins, the nuclear body SP100 and SP140. Sp110 is a leukocyte-specific component of the nuclear body. It may function as a nuclear hormone receptor transcriptional coactivator that may play a role in inducing differentiation of myeloid cells. It is also involved in resisting intracellular pathogens and functions as an important drug target for preventing intracellular pathogen diseases, such as tuberculosis, hepatic veno-occlusive disease, and intracellular cancers. SP140 is an interferon inducible nuclear leukocyte-specific protein involved in primary biliary cirrhosis and a risk factor in chronic lymphocytic leukemia. It is also implicated in innate immune response to human immunodeficiency virus type 1 (HIV-1) by binding to the virus viral infectivity factor (Vif) protein. Both Sp110 and Sp140 contain a SAND domain, a plant homeodomain (PHD) finger, and a bromodomain (BRD).

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1928129864 1120 FCAVCLNGGELLCCDRCPKVFHLSCHVPALLSFPGGEWVCTLC 1162
Cdd:cd15541      1 WCAVCQNGGELLCCDKCPRVFHLDCHIPPIPEFPSGEWSCSLC 43

PHD finger found in transcriptional intermediary factor 1 gamma (TIF1gamma); TIF1gamma, also termed tripartite motif-containing 33 (trim33), or ectodermin, or RFG7, or PTC7, is an E3-ubiquitin ligase that functions as a regulator of transforming growth factor beta (TGFbeta) signaling; it inhibits the Smad4-mediated TGFbeta response by interaction with Smad2/3 or ubiquitylation of Smad4. Moreover, TIF1gamma is an important regulator of transcription during hematopoiesis, as well as a key factor of tumorigenesis. Like other TIF1 family members, TIF1gamma also contains an intrinsic transcriptional silencing function. It can control erythroid cell fate by regulating transcription elongation. It can bind to the anaphase-promoting complex/cyclosome (APC/C) and promotes mitosis. TIF1gamma contains an N-terminal RBCC (RING finger, B-box zinc-fingers, coiled-coil), a plant homeodomain (PHD) finger, followed by a bromodomain in the C-terminal region.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1928129864 1120 FCAVCLNGGELLCCDRCPKVFHLSCHVPALLSFPGGEWVCTLCRSL 1165
Cdd:cd15624      1 WCAVCQNGGDLLCCEKCPKVFHLTCHVPTLLSFPSGDWICTFCRDI 46

PHD finger found in transcription intermediary factor 1-alpha (TIF1-alpha); TIF1-alpha, also termed tripartite motif-containing protein 24 (TRIM24), or E3 ubiquitin-protein ligase TRIM24, or RING finger protein 82, belongs to the TRIM/RBCC protein family. It interacts specifically and in a ligand-dependent manner with the ligand binding domain (LBD) of several nuclear receptors (NRs), including retinoid X (RXR), retinoic acid (RAR), vitamin D3 (VDR), estrogen (ER), and progesterone (PR) receptors. It also associates with heterochromatin-associated factors HP1alpha, MOD1 (HP1beta) and MOD2 (HP1gamma), as well as vertebrate Kruppel-type (C2H2) zinc finger proteins that contain transcriptional silencing domain KRAB. TIF1-alpha is a ligand-dependent co-repressor of retinoic acid receptor (RAR) that interacts with multiple nuclear receptors in vitro via an LXXLL motif, and further acts as a gatekeeper of liver carcinogenesis. It also functions as an E3-ubiquitin ligase targeting p53 and is broadly associated with chromatin silencing. Moreover, it is a chromatin regulator that recognizes specific, combinatorial histone modifications through its C-terminal plant homeodomain (PHD)-Bromodomain (Bromo) region. In addition, it interacts with chromatin and estrogen receptor to activate estrogen-dependent genes associated with cellular proliferation and tumor development. TIF1-alpha contains an N-terminal RBCC (RING finger, B-box zinc-fingers, coiled-coil), a plant homeodomain (PHD) finger, followed by a bromodomain in the C-terminal region.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1928129864 1120 FCAVCLNGGELLCCDRCPKVFHLSCHVPALLSFPGGEWVCTLC 1162
Cdd:cd15622      1 WCAVCQNGGELLCCEKCPKVFHLSCHVPTLMNFPSGEWICTFC 43

Bromodomain; Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928129864 1198 CEKLVLSLCCNNLSLPFHEPVSPLAR-HYYQIIKRPMDLSIIRRKLQKKdpaHYTTPEEVVSDVRLMFWNCAKFNYPDSE 1276
Cdd:pfam00439    1 CLEILDKLMEHPIAAPFLEPVDPDEYpDYYSVIKKPMDLSTIKKKLENG---EYKSLAEFLADVKLIFSNARTYNGPGSV 77

                   ....*.
gi 1928129864 1277 VAEAGR 1282
Cdd:pfam00439   78 IYKAAE 83

Bromodomain, uncharacterized subfamily specific to plants. Might function as a global transcription factor. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928129864 1196 KKCEKLVLSLCCNNLSLPFHEPVSPLA---RHYYQIIKRPMDLSIIRRKLQKKdpaHYTTPEEVVSDVRLMFWNCAKFNY 1272
Cdd:cd05506      3 KQCGTLLRKLMKHKWGWVFNAPVDVVAlglPDYFDIIKKPMDLGTVKKKLEKG---EYSSPEEFAADVRLTFANAMRYNP 79

                           90       100
                   ....*....|....*....|
gi 1928129864 1273 PDSEV-AEAGRCLEVFFEGW 1291
Cdd:cd05506     80 PGNDVhTMAKELLKIFETRW 99

Bromodomain, cbp_like subfamily. Cbp (CREB binding protein or CREBBP) is an acetyltransferase acting on histone, which gives a specific tag for transcriptional activation and also acetylates non-histone proteins. CREBBP binds specifically to phosphorylated CREB protein and augments the activity of phosphorylated CREB to activate transcription of cAMP-responsive genes. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928129864 1211 SLPFHEPVSPLARH---YYQIIKRPMDLSIIRRKLqkkDPAHYTTPEEVVSDVRLMFWNCAKFNYPDSEVAEAG-RCLEV 1286
Cdd:cd05495     22 SLPFRQPVDPKLLGipdYFDIVKNPMDLSTIRRKL---DTGQYQDPWQYVDDVWLMFDNAWLYNRKTSRVYKYCtKLAEV 98

                           90
                   ....*....|.
gi 1928129864 1287 FfegwLKEIYP 1297
Cdd:cd05495     99 F----EQEIDP 105

Bromodomain, TFIID-like subfamily. Human TAFII250 (or TAF250) is the largest subunit of TFIID, a large multi-domain complex, which initiates the assembly of the transcription machinery. TAFII250 contains two bromodomains that specifically bind to acetylated histone H4. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1928129864 1211 SLPFHEPVSP-LARHYYQIIKRPMDLSIIRRKLQKKDpahYTTPEEVVSDVRLMFWNCAKFNYPDS 1275
Cdd:cd05511     18 SWPFHTPVNKkKVPDYYKIIKRPMDLQTIRKKISKHK---YQSREEFLEDIELIVDNSVLYNGPDS 80

B-box-type 2 zinc finger found in transcription intermediary factor 1-alpha (TIF1-alpha); TIF1-alpha, also known as tripartite motif-containing protein 24 (TRIM24), E3 ubiquitin-protein ligase TRIM24, or RING finger protein 82, belongs to the C-VI subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a plant homeodomain (PHD), and a bromodomain (Bromo) positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. TIF1-alpha interacts specifically and in a ligand-dependent manner with the ligand binding domain (LBD) of several nuclear receptors (NRs), including retinoid X (RXR), retinoic acid (RAR), vitamin D3 (VDR), estrogen (ER), and progesterone (PR) receptors. It also associates with heterochromatin-associated factors HP1alpha, MOD1 (HP1beta), and MOD2 (HP1gamma), as well as the vertebrate Kruppel-type (C2H2) zinc finger proteins that contain the transcriptional silencing domain KRAB. TIF1-alpha is a ligand-dependent co-repressor of retinoic acid receptor (RAR) that interacts with multiple nuclear receptors in vitro via an LXXLL motif and further acts as a gatekeeper of liver carcinogenesis. It also functions as an E3-ubiquitin ligase targeting p53, and is broadly associated with chromatin silencing. Moreover, it is a chromatin regulator that recognizes specific, combinatorial histone modifications through its C-terminal PHD-Bromo region. In addition, it interacts with chromatin and estrogen receptor to activate estrogen-dependent genes associated with cellular proliferation and tumor development.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1928129864  208 LYCPLHTQEVLKLFCETCDMLTCHSCLVVEHKEHRCRHVEEVLQNQRMLLE 258
Cdd:cd19828      4 VFCPFHKKEQLKLYCETCDKLTCRDCQLLEHKEHRYQFIEEAFQNQKVIID 54

PHD finger 2 found in class II Chromodomain-Helicase-DNA binding (CHD) proteins; Class II CHD proteins includes chromodomain-helicase-DNA-binding protein CHD3, CHD4, and CHD5, which are nuclear and ubiquitously expressed chromatin remodelling ATPases generally associated with histone deacetylases (HDACs). They are involved in DNA Double Strand Break (DSB) signaling, DSB repair and/or p53-dependent pathways such as apoptosis and senescence, as well as in the maintenance of genomic stability, and/or cancer prevention. They function as subunits of the Nucleosome Remodelling and Deacetylase (NuRD) complex, which is generally associated with gene repression, heterochromatin formation, and overall chromatin compaction. In contrast to the class I CHD enzymes (CHD1 and CHD2), class II CHD proteins lack identifiable DNA-binding domains, but possess a C-terminal coiled-coil region. Moreover, in addition to the tandem chromodomains and a helicase domain, they all harbor tandem plant homeodomain (PHD) zinc fingers involved in the recognition of methylated histone tails. This model corresponds to the second PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1928129864 1120 FCAVCLNGGELLCCDRCPKVFHLSCHVPALLSFPGGEWVCTLC 1162
Cdd:cd15532      1 FCRVCKDGGELLCCDGCPSSYHLHCLNPPLAEIPDGDWFCPRC 43

B-box-type 2 zinc finger found in transcription intermediary factor 1 (TIF1) family; This family corresponds to the TIF1 family of transcriptional cofactors including TIF1-alpha (TRIM24), TIF1-beta (TRIM28), and TIF1-gamma (TRIM33), which belong to the C-VI subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a plant homeodomain (PHD), and a bromodomain (Bromo) positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. TIF1 proteins couple chromatin modifications to transcriptional regulation, signaling, and tumor suppression. They exert a deacetylase-dependent silencing effect when tethered to a promoter region. TIF1alpha and TIF1beta can homodimerize and contain a PXVXL motif necessary and sufficient for heterochromatin protein 1(HP1) binding. They bind nuclear receptors and Kruppel-associated boxes (KRAB) specifically and respectively. TIF1gamma is structurally closely related to TIF1alpha and TIF1beta, but has very little functional features in common with them. It does not interact with the KRAB silencing domain of KOX1 or the heterochromatinic proteins HP1alpha, beta and gamma. It cannot bind to nuclear receptors (NRs).

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1928129864  207 TLYCPLHTQEVLKLFCETCDMLTCHSCLVVEHKEHRCRHVEE 248
Cdd:cd19775      1 PLFCPVHPQEPLKLFCETCDKLTCRDCQLLEHKDHKYQFAEE 42

B-box-type 2 zinc finger found in transcription intermediary factor 1-beta (TIF1-beta); TIF1-beta, also known as Kruppel-associated Box (KRAB)-associated protein 1 (KAP-1), KRAB-interacting protein 1 (KRIP-1), nuclear co-repressor KAP-1, RING finger protein 96, tripartite motif-containing protein 28 (TRIM28), or E3 SUMO-protein ligase TRIM28, belongs to the C-VI subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a plant homeodomain (PHD) and a bromodomain (Bromo) positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. TIF1-beta acts as a nuclear co-repressor that plays a role in transcription and in the DNA damage response. Upon DNA damage, the phosphorylation of KAP-1 on serine 824 by the ataxia telangiectasia-mutated (ATM) kinase enhances cell survival and facilitates chromatin relaxation and heterochromatic DNA repair. It also regulates CHD3 nucleosome remodeling during the DNA double-strand break (DSB) response. Meanwhile, KAP-1 can be dephosphorylated by protein phosphatase PP4C in the DNA damage response. Moreover, KAP-1 is a co-activator of the orphan nuclear receptor NGFI-B (or Nur77) and is involved in NGFI-B-dependent transcription. It is also a coiled-coil binding partner, substrate and activator of the c-Fes protein tyrosine kinase. The N-terminal RBCC domains of TIF1-beta are responsible for the interaction with KRAB zinc finger proteins (KRAB-ZFPs), MDM2, MM1, C/EBPbeta, and the regulation of homo- and heterodimerization. The C-terminal PHD/Bromo domains are involved in interacting with SETDB1, Mi-2alpha and other proteins to form complexes with histone deacetylase or methyltransferase activity.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1928129864  207 TLYCPLHTQEVLKLFCETCDMLTCHSCLVVEHKEHRCRHVEE 248
Cdd:cd19829      1 TVYCSIHKQEPLKLFCETCDTLTCRDCQLNAHKDHQYQFLED 42

Bromodomain, SP100C_like subfamily. The SP100C protein is a splice variant of SP100, a major component of PML-SP100 nuclear bodies (NBs), which are poorly understood. It is covalently modified by SUMO-1 and may play a role in processes at the chromatin level. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928129864 1195 QKKCEKLVLSLCCNNLSlPFHEPVSPLARHYYQIIKRPMDLSIIRRKLQKKDpahYTTPEEVVSDVRLMFWNCAKFnYPD 1274
Cdd:cd05501      4 LLKCEFLLLKVYCMSKS-GFFISKPYYIRDYCQGIKEPMWLNKVKERLNERV---YHTVEGFVRDMRLIFHNHKLF-YKD 78

                           90       100
                   ....*....|....*....|..
gi 1928129864 1275 SEVAEAGRCLEVFFEGWLKEIY 1296
Cdd:cd05501     79 DDFGQVGITLEKKFEKNFKEVF 100

Bromodomain, repeat II in Rsc1/2_like subfamily, specific to fungi. Rsc1 and Rsc2 are components of the RSC complex (remodeling the structure of chromatin), are essential for transcriptional control, and have a specific domain architecture including two bromodomains. The RSC complex has also been linked to homologous recombination and nonhomologous end-joining repair of DNA double strand breaks. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1928129864 1210 LSLPFhEPVSPLARH--YYQIIKRPMDLSIIRRKLQKKdpaHYTTPEEVVSDVRLMFWNCAKFNYPDSEVAEAGRCLE 1285
Cdd:cd05522     24 LTLHF-EKLPDKAREpeYYQEISNPISLDDIKKKVKRR---KYKSFDQFLNDLNLMFENAKLYNENDSQEYKDAVLLE 97

PHD finger found in transcription intermediary factor 1-beta (TIF1-beta); TIF1-beta, also termed Kruppel-associated Box (KRAB)-associated protein 1 (KAP-1), or KRAB-interacting protein 1 (KRIP-1), or nuclear co-repressor KAP-1, or RING finger protein 96, or tripartite motif-containing protein 28 (TRIM28), or E3 SUMO-protein ligase TRIM28, acts as a nuclear co-repressor that plays a role in transcription and in DNA damage response. Upon DNA damage, the phosphorylation of KAP-1 on serine 824 by the ataxia telangiectasia-mutated (ATM) kinase enhances cell survival and facilitates chromatin relaxation and heterochromatic DNA repair. It also regulates CHD3 nucleosome remodeling during DNA double-strand break (DSB) response. Meanwhile, KAP-1 can be dephosphorylated by protein phosphatase PP4C in the DNA damage response. In addition, KAP-1 is a co-activator of the orphan nuclear receptor NGFI-B (or Nur77) and is involved in NGFI-B-dependent transcription. It is also a coiled-coil binding partner, substrate and activator of the c-Fes protein tyrosine kinase. TIF1-beta contains an N-terminal RBCC (RING finger, B-box zinc-fingers, coiled-coil), which can interact with KRAB zinc finger proteins (KRAB-ZFPs), MDM2, MM1, C/EBPbeta, and mediates homo- and heterodimerization, a plant homeodomain (PHD) finger followed by a bromodomain in the C-terminal region, which interact with SETDB1, Mi-2alpha and other proteins to form complexes with histone deacetylase or methyltransferase activity.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1928129864 1121 CAVCLNGGELLCCDRCPKVFHLSCHVPALLSFPGGEWVCTLC 1162
Cdd:cd15623      2 CRVCQKAGALVMCDQCEFCFHLDCHLPALQEVPGEDWKCLLC 43

PHD finger 2 found in monocytic leukemia zinc-finger protein (MOZ) and its factor (MORF); MOZ, also termed histone acetyltransferase KAT6A, YBF2/SAS3, SAS2 and TIP60 protein 3 (MYST-3), or runt-related transcription factor-binding protein 2, or zinc finger protein 220, is a MYST-type histone acetyltransferase (HAT) that functions as a coactivator for acute myeloid leukemia 1 protein (AML1)- and p53-dependent transcription. It possesses intrinsic HAT activity to acetylate both itself and lysine (K) residues on histone H2B, histone H3 (K14) and histone H4 (K5, K8, K12 and K16) in vitro and H3K9 in vivo. MOZ-related factor (MORF), also termed MOZ2, or histone acetyltransferase KAT6B, or MOZ, YBF2/SAS3, SAS2 and TIP60 protein 4 (MYST4), is a ubiquitously expressed transcriptional regulator with intrinsic HAT activity. It can interact with the Runt-domain transcription factor Runx2 and form a tetrameric complex with BRPFs, ING5, and EAF6. Both MOZ and MORF are catalytic subunits of HAT complexes that are required for normal developmental programs, such as hematopoiesis, neurogenesis, and skeletogenesis, and are also implicated in human leukemias. MOZ is also the catalytic subunit of a tetrameric inhibitor of growth 5 (ING5) complex, which specifically acetylates nucleosomal histone H3K14. Moreover, MOZ and MORF are involved in regulating transcriptional activation mediated by Runx2 (or Cbfa1), a Runt-domain transcription factor known to play important roles in T cell lymphomagenesis and bone development, and its homologs. MOZ contains a linker histone 1 and histone 5 domains and two plant homeodomain (PHD) fingers. In contrast, MORF contains an N-terminal region containing two PHD fingers, a putative HAT domain, an acidic region, and a C-terminal Ser/Met-rich domain. The family corresponds to the first PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1928129864 1121 CAVCLNGGE---LLCCDRCPKVFHLSCHVPALLSFPGGEWVCTLC 1162
Cdd:cd15527      2 CSVCQDSGNadnLLFCDACDKGFHMECHDPPLTRMPKGKWVCQIC 46

Bromodomain, polybromo repeat IV. Polybromo is a nuclear protein of unknown function, which contains 6 bromodomains. The human ortholog BAF180 is part of a SWI/SNF chromatin-remodeling complex, and it may carry out the functions of Yeast Rsc-1 and Rsc-2. It was shown that polybromo bromodomains bind to histone H3 at specific acetyl-lysine positions. Bromodomains are found in many chromatin-associated proteins and in nuclear histone acetyltransferases. They interact specifically with acetylated lysine, but not all the bromodomains in polybromo may bind to acetyl-lysine.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1928129864 1225 YYQIIKRPMDLSIIRRKLQKKdpaHYTTPEEVVSDVRLMFWNCAKFNYPDSEVAEAGRCLE 1285
Cdd:cd05518     39 YYKIILEPIDLKTIEHNIRND---KYATEEELMDDFKLMFRNARHYNEEGSQVYEDANILE 96

Bromodomain; WDR9 repeat II_like subfamily. WDR9 is a human gene located in the Down Syndrome critical region-2 of chromosome 21. It encodes for a nuclear protein containing WD40 repeats and two bromodomains, which may function as a transcriptional regulator involved in chromatin remodeling and play a role in embryonic development. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928129864 1196 KKCEKLVLSLCCNNLSLPFHEPVSPLAR-HYYQIIKRPMDLSIIRRKLqkkDPAHYTTPEEVVSDVRLMFWNCAKFNyPD 1274
Cdd:cd05496      8 KQCKELVNLMWDCEDSEPFRQPVDLLKYpDYRDIIDTPMDLGTVKETL---FGGNYDDPMEFAKDVRLIFSNSKSYT-PN 83

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1928129864 1275 --SEVAEAGRCLEVFFEGWLKEIYPEKRFAQPRQ 1306
Cdd:cd05496     84 krSRIYSMTLRLSALFEEHIKKIISDWKSALKRN 117

Bromodomain, repeat I in Rsc1/2_like subfamily, specific to fungi. Rsc1 and Rsc2 are components of the RSC complex (remodeling the structure of chromatin), are essential for transcriptional control, and have a specific domain architecture including two bromodomains. The RSC complex has also been linked to homologous recombination and nonhomologous end-joining repair of DNA double strand breaks. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1928129864 1225 YYQIIKRPMDLSIIRRKLQkkdpaHYTTPEEVVSDVRLMFWNCAKFNYPDSEV 1277
Cdd:cd05521     40 YYKIIKNPLSLNTVKKRLP-----HYTNAQEFVNDLAQIPWNARLYNTKGSVI 87

B-box-type 2 zinc finger (Bbox2); The B-box-type zinc finger is a short zinc binding domain of around 40 amino acid residues in length. It has been found in transcription factors, ribonucleoproteins and proto-oncoproteins, such as in TRIM (tripartite motif) proteins that consist of an N-terminal RING finger (originally called an A-box), followed by 1-2 B-box domains and a coiled-coil domain (also called RBCC for Ring, B-box, Coiled-Coil). The B-box-type zinc finger often presents in combination with other motifs, like RING zinc finger, NHL motif, coiled-coil or RFP domain in functionally unrelated proteins, most likely mediating protein-protein interaction. Based on different consensus sequence and the spacing of the 7-8 zinc-binding residues, B-box-type zinc fingers can be divided into two groups, type 1 (Bbox1: C6H2) and type 2 (Bbox2: CHC3H2). The family corresponds to type 2 B-box (Bbox2).

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1928129864  209 YCPLHTQEVLKLFCETCDMLTCHSCLV-VEHKEHRCR 244
Cdd:cd19756      1 LCPEHPEEPLKLFCETCQELVCVLCLLsGEHRGHKVV 37

PHD finger 1 found in Saccharomyces cerevisiae transcriptional regulatory protein Rco1 and similar proteins; Rco1 is a component of the Rpd3S histone deacetylase complex that plays an important role at actively transcribed genes. Rco1 contains two plant homeodomain (PHD) fingers, which are required for the methylation of histone H3 lysine 36 (H3K36) nucleosome recognition by Rpd3S. This model corresponds to the first PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1928129864 1120 FCAVCLNGGELLCCDRCPKVFHLSCHVPAL--LSFPGGEWVCTLC 1162
Cdd:cd15535      1 FCSACGGYGSFLCCDGCPRSFHFSCLDPPLeeDNLPDDEWFCNEC 45

PHD finger 1 found in bromodomain and PHD finger-containing transcription factor (BPTF); BPTF, also termed nucleosome-remodeling factor subunit BPTF, or fetal Alz-50 clone 1 protein (FAC1), or fetal Alzheimer antigen, functions as a transcriptional regulator that exhibits altered expression and subcellular localization during neuronal development and neurodegenerative diseases such as Alzheimer's disease. It interacts with the human orthologue of the Kelch-like Ech-associated protein (Keap1). Its function and subcellular localization can be regulated by Keap1. Moreover, BPTF is a novel DNA-binding protein that recognizes the DNA sequence CACAACAC and represses transcription through this site in a phosphorylation-dependent manner. Furthermore, BPTF interacts with the Myc-associated zinc finger protein (ZF87/MAZ) and alters its transcriptional activity, which has been implicated in gene regulation in neurodegeneration. Some family members contain two or three plant homeodomain (PHD) fingers, which may be involved in complex formation with histone H3 trimethylated at K4 (H3K4me3). This family corresponds to the first PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1928129864 1121 CAVCLNGGELLCCDRCPKVFHLSCHVPALLSFPGGEWVCTLC 1162
Cdd:cd15559      2 CRVCHKLGDLLCCETCSAVYHLECVDPPLEEVPEEDWQCEVC 43

Bromodomain, brd7_like subgroup. The BRD7 gene encodes a nuclear protein that has been shown to inhibit cell growth and the progression of the cell cycle by regulating cell-cycle genes at the transcriptional level. BRD7 has been identified as a gene involved in nasopharyngeal carcinoma. The protein interacts with acetylated histone H3 via its bromodomain. Bromodomains are 110 amino acid long domains that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1928129864 1214 FHEPVSP-LARHYYQIIKRPMDLSIIRRKLQKKDpahYTTPEEVVSDVRLMFWNCAKFNYPDS 1275
Cdd:cd05513     22 FAFPVTDfIAPGYSSIIKHPMDFSTMKEKIKNND---YQSIEEFKDDFKLMCENAMKYNKPDT 81