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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966908    253 QRMLLEGVTTQVAHKKSSLQTSAKQIEDRIFEVKHQHRKVENQIKMAKMVLMNELNKQANGLIEELEGITNERKRKLEQQ 332
Cdd:smart00502    1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*.
gi 767966908    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 767966908  208 LYCPLHTQEVLKLFCETCDMLTCHSCLVVEHKEHRCRHVEEVL 250
Cdd:cd19794     1 LMCPLHNQEPLKLFCETCDVLVCRSCLLSEHKEHRFKHLDEAL 43

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966908    253 QRMLLEGVTTQVAHKKSSLQTSAKQIEDRIFEVKHQHRKVENQIKMAKMVLMNELNKQANGLIEELEGITNERKRKLEQQ 332
Cdd:smart00502    1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*.
gi 767966908    333 LQSIMVLNRQFEHVQNFINWAVCSKTSVPFLFSKELIVFQMQRLLE 378
Cdd:smart00502   81 LESLTQKQEKLSHAINFTEEALNSGDPTELLLSKKLIIERLQNLLK 126

bromo domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966908   1222 DQKKCEKLVLSLCCNN----LSLPFHEPVSP-LARHYYQIIKRPMDLSIIRRKLQKKdpaHYTTPEEVVSDVRLMFWNCA 1296
Cdd:smart00297    4 LQKKLQELLKAVLDKLdshpLSWPFLKPVSRkEAPDYYDIIKKPMDLKTIKKKLENG---KYSSVEEFVADFNLMFSNAR 80

                            90       100
                    ....*....|....*....|....*..
gi 767966908   1297 KFNYPDSEVAEAGRCLEVFFEGWLKEI 1323
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 767966908  1226 CEKLVLSLCCNNLSLPFHEPVSPLAR-HYYQIIKRPMDLSIIRRKLQKKdpaHYTTPEEVVSDVRLMFWNCAKFNYPDSE 1304
Cdd:pfam00439    1 CLEILDKLMEHPIAAPFLEPVDPDEYpDYYSVIKKPMDLSTIKKKLENG---EYKSLAEFLADVKLIFSNARTYNGPGSV 77

                   ....*.
gi 767966908  1305 VAEAGR 1310
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 767966908  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 767966908   1148 FCAVC---LNGGELLCCDRCPKVFHLSCHVPALLSF-PGGEWVCTLC 1190
Cdd:smart00249    1 YCSVCgkpDDGGELLQCDGCDRWYHQTCLGPPLLEEePDGKWYCPKC 47

B-box zinc finger;

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 767966908   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 767966908  240 EHRCRHVEEVLQNQRMLLEGVTTQVAHKK---SSLQTSAKQIEDRIFEVKHQHRKVENQIKMAKmvlmNelNKQANGLIE 316
Cdd:COG1579    23 EHRLKELPAELAELEDELAALEARLEAAKtelEDLEKEIKRLELEIEEVEARIKKYEEQLGNVR----N--NKEYEALQK 96

                          90       100
                  ....*....|....*....|.
gi 767966908  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 767966908    253 QRMLLEGVTTQVAHKKSSLQTSAKQIEDRIFEVKHQHRKVENQIKMAKMVLMNELNKQANGLIEELEGITNERKRKLEQQ 332
Cdd:smart00502    1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*.
gi 767966908    333 LQSIMVLNRQFEHVQNFINWAVCSKTSVPFLFSKELIVFQMQRLLE 378
Cdd:smart00502   81 LESLTQKQEKLSHAINFTEEALNSGDPTELLLSKKLIIERLQNLLK 126

bromo domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966908   1222 DQKKCEKLVLSLCCNN----LSLPFHEPVSP-LARHYYQIIKRPMDLSIIRRKLQKKdpaHYTTPEEVVSDVRLMFWNCA 1296
Cdd:smart00297    4 LQKKLQELLKAVLDKLdshpLSWPFLKPVSRkEAPDYYDIIKKPMDLKTIKKKLENG---KYSSVEEFVADFNLMFSNAR 80

                            90       100
                    ....*....|....*....|....*..
gi 767966908   1297 KFNYPDSEVAEAGRCLEVFFEGWLKEI 1323
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 767966908 1223 QKKCEKLV---LSLCCNNLSLPFHEPVSP--LARH-YYQIIKRPMDLSIIRRKLQKKDpahYTTPEEVVSDVRLMFWNCA 1296
Cdd:cd05498     2 LKFCSGILkelFSKKHKAYAWPFYKPVDPeaLGLHdYHDIIKHPMDLSTIKKKLDNRE---YADAQEFAADVRLMFSNCY 78

                          90       100
                  ....*....|....*....|.
gi 767966908 1297 KFNYPDSEVAEAGRCLEVFFE 1317
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 767966908 1239 SLPFHEPVSPL-ARHYYQIIKRPMDLSIIRRKLQKKdpaHYTTPEEVVSDVRLMFWNCAKFNYPDSEVAEAGRCLEVFFE 1317
Cdd:cd05509    19 AWPFLEPVDKEeAPDYYDVIKKPMDLSTMEEKLENG---YYVTLEEFVADLKLIFDNCRLYNGPDTEYYKCANKLEKFFW 95

                  ....*.
gi 767966908 1318 GWLKEI 1323
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 767966908 1148 FCAVCLNGGELLCCDRCPKVFHLSCHVPALLSFPGGEWVCTLC 1190
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 767966908 1148 FCAVCLNGGELLCCDRCPKVFHLSCHVPALLSFPGGEWVCTLCRSL 1193
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 767966908 1148 FCAVCLNGGELLCCDRCPKVFHLSCHVPALLSFPGGEWVCTLC 1190
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 767966908  1226 CEKLVLSLCCNNLSLPFHEPVSPLAR-HYYQIIKRPMDLSIIRRKLQKKdpaHYTTPEEVVSDVRLMFWNCAKFNYPDSE 1304
Cdd:pfam00439    1 CLEILDKLMEHPIAAPFLEPVDPDEYpDYYSVIKKPMDLSTIKKKLENG---EYKSLAEFLADVKLIFSNARTYNGPGSV 77

                   ....*.
gi 767966908  1305 VAEAGR 1310
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 767966908 1224 KKCEKLVLSLCCNNLSLPFHEPVSPLA---RHYYQIIKRPMDLSIIRRKLQKKdpaHYTTPEEVVSDVRLMFWNCAKFNY 1300
Cdd:cd05506     3 KQCGTLLRKLMKHKWGWVFNAPVDVVAlglPDYFDIIKKPMDLGTVKKKLEKG---EYSSPEEFAADVRLTFANAMRYNP 79

                          90       100
                  ....*....|....*....|
gi 767966908 1301 PDSEV-AEAGRCLEVFFEGW 1319
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 767966908 1239 SLPFHEPVSPLARH---YYQIIKRPMDLSIIRRKLqkkDPAHYTTPEEVVSDVRLMFWNCAKFNYPDSEVAEAG-RCLEV 1314
Cdd:cd05495    22 SLPFRQPVDPKLLGipdYFDIVKNPMDLSTIRRKL---DTGQYQDPWQYVDDVWLMFDNAWLYNRKTSRVYKYCtKLAEV 98

                          90
                  ....*....|.
gi 767966908 1315 FfegwLKEIYP 1325
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 767966908 1239 SLPFHEPVSP-LARHYYQIIKRPMDLSIIRRKLQKKDpahYTTPEEVVSDVRLMFWNCAKFNYPDS 1303
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 767966908  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 767966908 1148 FCAVCLNGGELLCCDRCPKVFHLSCHVPALLSFPGGEWVCTLC 1190
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 767966908  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 767966908  207 TLYCPLHTQEVLKLFCETCDMLTCHSCLVVEHKEHRCRHVEE 248
Cdd:cd19829     1 TVYCSIHKQEPLKLFCETCDTLTCRDCQLNAHKDHQYQFLED 42

B-box-type 2 zinc finger found in tripartite motif-containing protein 45 (TRIM45) and similar proteins; TRIM45, also known as RING finger protein 99 (RNF99), is a novel receptor for activated C-kinase (RACK1)-interacting protein that suppresses transcriptional activities of Elk-1 and AP-1 and downregulates mitogen-activated protein kinase (MAPK) signal transduction by inhibiting RACK1/PKC (protein kinase C) complex formation. It also negatively regulates tumor necrosis factor alpha (TNFalpha)-induced nuclear factor-kappaB (NF-kappa B)-mediated transcription and suppresses cell proliferation. TRIM45 belongs to the C-X subclass of TRIM (tripartite motif) family that is 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 filamin-type immunoglobulin (IG-FLMN) domain and NHL repeats positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 767966908  209 YCPLHTQEVLKLFCETCDMLTCHSCLVVEHKEHRCRHVEEV 249
Cdd:cd19785     3 LCPFHPAEELRLFCETCDKPVCRDCVLVEHRGHQCDFTSDV 43

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 767966908 1238 LSLPFhEPVSPLARH--YYQIIKRPMDLSIIRRKLQKKdpaHYTTPEEVVSDVRLMFWNCAKFNYPDSEVAEAGRCLE 1313
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 767966908 1149 CAVCLNGGELLCCDRCPKVFHLSCHVPALLSFPGGEWVCTLC 1190
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 767966908 1149 CAVCLNGGE---LLCCDRCPKVFHLSCHVPALLSFPGGEWVCTLC 1190
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 767966908 1253 YYQIIKRPMDLSIIRRKLQKKdpaHYTTPEEVVSDVRLMFWNCAKFNYPDSEVAEAGRCLE 1313
Cdd:cd05518    39 YYKIILEPIDLKTIEHNIRND---KYATEEELMDDFKLMFRNARHYNEEGSQVYEDANILE 96

Bromodomain; Williams syndrome transcription factor-like subfamily (WSTF-like). The Williams-Beuren syndrome deletion transcript 9 is a putative transcriptional regulator. WSTF was found to play a role in vitamin D-mediated transcription as part of two chromatin remodeling complexes, WINAC and WICH. 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 767966908 1222 DQKKCEKLVLSLCCNNLSLPFHEPVSPL-ARHYYQIIKRPMDLSIIRRKLQKKDpahYTTPEEVVSDVRLMFWNCAKFNY 1300
Cdd:cd05505     1 ELQKCEEILSKILKYRFSWPFREPVTADeAEDYKKVITNPMDLQTMQTKCSCGS---YSSVQEFLDDMKLVFSNAEKYYE 77

                  ....*
gi 767966908 1301 PDSEV 1305
Cdd:cd05505    78 NGSYV 82

B-box-type 2 zinc finger found in Drosophila melanogaster brain tumor protein (BRAT) and similar proteins; BRAT is a NHL-domain family protein that functions as a translational repressor to inhibit cell proliferation. This family also contains Caenorhabditis elegans B-box type zinc finger protein ncl-1, a C. elegans Brat homolog which functions as a translational repressor that inhibits protein synthesis. BRAT contains Bbox1 and Bbox2 zinc fingers and NHL repeats. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 767966908  208 LYCPLHTQEVLKLFCETCDMLTCHSCLVVEHK--EHRCRHV 246
Cdd:cd19798     4 VFCPKHPNEVLKFFCKTCNIPICKDCTLLDHNkgLHDYEYL 44

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 767966908  209 YCPLHTQEVLKLFCETCDMLTCHSCLV-VEHKEHRCR 244
Cdd:cd19756     1 LCPEHPEEPLKLFCETCQELVCVLCLLsGEHRGHKVV 37

PHD finger 5 found in nuclear receptor-binding SET domain-containing (NSD) proteins; The nuclear receptor binding SET domain (NSD) protein is a family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1, that are critical in maintaining chromatin integrity. Reducing NSD activity through specific lysine-HMTase inhibitors appears promising to help suppress cancer growth. NSD proteins have specific mono- and dimethylase activities for H3K36, and they play non-redundant roles during development. NSD1 plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. NSD2 is involved in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. NSD3 is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD proteins contain a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). This model corresponds to the fifth PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 767966908 1148 FCAVCLNGGELLCCDR--CPKVFHLSChvPALLSFPGGEWVC 1187
Cdd:cd15568     1 ECFRCGDGGDLVLCDFkgCPKVYHLSC--LGLEKPPGGKWIC 40

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 767966908 1149 CAVCLNGGELLCCDRCPKVFHLSCHVPALLSFPGGEWVCTLC 1190
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 767966908 1242 FHEPVSP-LARHYYQIIKRPMDLSIIRRKLQKKDpahYTTPEEVVSDVRLMFWNCAKFNYPDS 1303
Cdd:cd05513    22 FAFPVTDfIAPGYSSIIKHPMDFSTMKEKIKNND---YQSIEEFKDDFKLMCENAMKYNKPDT 81

B-box zinc finger;

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 767966908   209 YCPLHTQEVLKLFCETCDMLTCHSCLVVEHKEHRCR 244
Cdd:pfam00643    5 LCPEHEEEPLTLYCNDCQELLCEECSVGEHRGHTVV 40

PHD finger superfamily; The PHD finger superfamily includes a canonical plant homeodomain (PHD) finger typically characterized as Cys4HisCys3, and a non-canonical extended PHD finger, characterized as Cys2HisCys5HisCys2His. Variations include the RAG2 PHD finger characterized by Cys3His2Cys2His and the PHD finger 5 found in nuclear receptor-binding SET domain-containing proteins characterized by Cys4HisCys2His. The PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. Single or multiple copies of PHD fingers have been found in a variety of eukaryotic proteins involved in the control of gene transcription and chromatin dynamics. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins. They also function as epigenome readers controlling gene expression through molecular recruitment of multi-protein complexes of chromatin regulators and transcription factors. The PHD finger domain SF is structurally similar to the RING and FYVE_like superfamilies.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 767966908 1148 FCAVCLNGG----ELLCCDRCPKVFHLSCHVPALLSF-PGGEWVCTLC 1190
Cdd:cd15489     1 SCIVCGKGGdlggELLQCDGCGKWFHADCLGPPLSSFvPNGKWICPVC 48