Deltex C-terminal domain; This is the C-terminal domains found in members of the Deltex family of proteins which comprises five members (DTX1, 2, 3, 4, and 3L). This conserved C-terminal region of about 150 residues of the Deltex family, is preceded by a RING E3 ligase domain in four of the members. Crystal structure of the Deltex C-terminal (DTC) domain reveals a fold composed of a central beta-sheet lined with two long parallel alpha-helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071089  369 TGTQPPGKMEYHLIPHSLPGHPDCKTIRIIYSIPPGIQGPEHPNPGKSFSarGFPRHCYLPDSEKGRKVLKLLLVAWDRR 448
Cdd:pfam18102   1 TGNQPDGTMTVSTIPTSLPGYENCGTIVITYNIPGGIQGPEHPNPGKPYS--GTPRTAYLPDNEEGRKVLKLLKRAFDQR 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 663071089  449 LIFAIGTSSTTGESDTVIWNEVHHKTEFGSNLTGHGYPDANYLDNVLAELAAQGI 503
Cdd:pfam18102  79 LIFTVGTSRTTGASNVVTWNDIHHKTSISGGPTGFGYPDPDYLKRVKEELAAKGI 133

WWE domain; The WWE domain is named after three of its conserved residues and is predicted to mediate specific protein- protein interactions in ubiquitin and ADP ribose conjugation systems.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 663071089    1 MEVGITIQHAYEKQHPWIDL--TSIGFSYVIDFNTMGQIN 38
Cdd:pfam02825  16 PEVSSLIEEAYQKGKPSVDLsiTTAGFPYTIDFKSMTQTN 55

Deltex C-terminal domain; This is the C-terminal domains found in members of the Deltex family of proteins which comprises five members (DTX1, 2, 3, 4, and 3L). This conserved C-terminal region of about 150 residues of the Deltex family, is preceded by a RING E3 ligase domain in four of the members. Crystal structure of the Deltex C-terminal (DTC) domain reveals a fold composed of a central beta-sheet lined with two long parallel alpha-helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071089  369 TGTQPPGKMEYHLIPHSLPGHPDCKTIRIIYSIPPGIQGPEHPNPGKSFSarGFPRHCYLPDSEKGRKVLKLLLVAWDRR 448
Cdd:pfam18102   1 TGNQPDGTMTVSTIPTSLPGYENCGTIVITYNIPGGIQGPEHPNPGKPYS--GTPRTAYLPDNEEGRKVLKLLKRAFDQR 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 663071089  449 LIFAIGTSSTTGESDTVIWNEVHHKTEFGSNLTGHGYPDANYLDNVLAELAAQGI 503
Cdd:pfam18102  79 LIFTVGTSRTTGASNVVTWNDIHHKTSISGGPTGFGYPDPDYLKRVKEELAAKGI 133

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase deltex1 (DTX1), deltex4 (DTX4), and similar proteins; DTX1 functions as a Notch downstream transcription regulator that mediates a Notch signal to block differentiation of neural progenitor cells. It interacts with the transcription coactivator p300 and inhibits transcription activation mediated by the neural specific transcription factor MASH1. It is also a transcription target of nuclear factor of activated T cells (NFAT) and participates in T cell anergy and Foxp3 protein level maintenance in vivo. Moreover, DTX1 appears to promote B-cell development at the expense of T-cell development. It also promotes protein kinase C theta degradation and sustains Casitas B-lineage lymphoma expression. DTX4, also known as RING finger protein 155, shares the highest degree of sequence similarity with DTX1 and likely interacts with the intracellular domain of Notch as well. Both DTX1 and DTX4 contain two Notch-binding WWE domains at the N-terminus that physically interact with the Notch ankyrin domains, a proline-rich motif that shares homology with SH3-binding domains, and a C3H2C3-type RING-H2 finger at the C-terminus. They also harbor two nuclear localization signals.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 663071089 300 DEDCTICMERLTAPSGYKGPQPT--VKPDLVGKLSRCGHVYHIYCLVAMYNNGNKDGSLQCPTCKTIYG 366
Cdd:cd16671    1 DEDCTICMERLVTPSGYEGVLSHkgVKPELVGKLSRCGHMYHLLCLVAMYNNGNKDGSLQCPTCKAIYG 69

Domain in Deltex and TRIP12 homologues. Possibly involved in regulation of ubiquitin-mediated proteolysis;

                           10        20        30
                   ....*....|....*....|....*....|..
gi 663071089     7 IQHAYEKQHPWIDLTSIGFSYVIDFNTMGQIN 38
Cdd:smart00678  23 IEEAYAAGKKLCELSICGFPYTIDFNAMTQYN 54

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 663071089   303 CTICMERLTAPsgykgpqPTVKPdlvgklsrCGHVYHIYCLVAMYNNGNKdgslQCPTC 361
Cdd:smart00184   1 CPICLEEYLKD-------PVILP--------CGHTFCRSCIRKWLESGNN----TCPIC 40

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 663071089  303 CTICMERLTAPSgykgpqptvkpdlvgKLSRCGHVYHIYCLVAMYNNGNKdgslQCPTC 361
Cdd:pfam00097   1 CPICLEEPKDPV---------------TLLPCGHLFCSKCIRSWLESGNV----TCPLC 40

Deltex C-terminal domain; This is the C-terminal domains found in members of the Deltex family of proteins which comprises five members (DTX1, 2, 3, 4, and 3L). This conserved C-terminal region of about 150 residues of the Deltex family, is preceded by a RING E3 ligase domain in four of the members. Crystal structure of the Deltex C-terminal (DTC) domain reveals a fold composed of a central beta-sheet lined with two long parallel alpha-helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071089  369 TGTQPPGKMEYHLIPHSLPGHPDCKTIRIIYSIPPGIQGPEHPNPGKSFSarGFPRHCYLPDSEKGRKVLKLLLVAWDRR 448
Cdd:pfam18102   1 TGNQPDGTMTVSTIPTSLPGYENCGTIVITYNIPGGIQGPEHPNPGKPYS--GTPRTAYLPDNEEGRKVLKLLKRAFDQR 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 663071089  449 LIFAIGTSSTTGESDTVIWNEVHHKTEFGSNLTGHGYPDANYLDNVLAELAAQGI 503
Cdd:pfam18102  79 LIFTVGTSRTTGASNVVTWNDIHHKTSISGGPTGFGYPDPDYLKRVKEELAAKGI 133

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase deltex1 (DTX1), deltex4 (DTX4), and similar proteins; DTX1 functions as a Notch downstream transcription regulator that mediates a Notch signal to block differentiation of neural progenitor cells. It interacts with the transcription coactivator p300 and inhibits transcription activation mediated by the neural specific transcription factor MASH1. It is also a transcription target of nuclear factor of activated T cells (NFAT) and participates in T cell anergy and Foxp3 protein level maintenance in vivo. Moreover, DTX1 appears to promote B-cell development at the expense of T-cell development. It also promotes protein kinase C theta degradation and sustains Casitas B-lineage lymphoma expression. DTX4, also known as RING finger protein 155, shares the highest degree of sequence similarity with DTX1 and likely interacts with the intracellular domain of Notch as well. Both DTX1 and DTX4 contain two Notch-binding WWE domains at the N-terminus that physically interact with the Notch ankyrin domains, a proline-rich motif that shares homology with SH3-binding domains, and a C3H2C3-type RING-H2 finger at the C-terminus. They also harbor two nuclear localization signals.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 663071089 300 DEDCTICMERLTAPSGYKGPQPT--VKPDLVGKLSRCGHVYHIYCLVAMYNNGNKDGSLQCPTCKTIYG 366
Cdd:cd16671    1 DEDCTICMERLVTPSGYEGVLSHkgVKPELVGKLSRCGHMYHLLCLVAMYNNGNKDGSLQCPTCKAIYG 69

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase Deltex1 (DTX1), Deltex2 (DTX2), Deltex4 (DTX4), and similar proteins; This subfamily contains the vertebrate homologs of Drosophila melanogaster Deltex, specifically DTX1, DTX2, and DTX4, and other similar proteins mainly from eumetazoa. The vertebrate homologs of Deltex are involved in Notch signaling and neurogenesis. Mammalian DTX1 is most closely related to the Drosophila Deltex. Both of them bind to SH3-domain containing protein Grb2 and further inhibit E2A. DTX1 functions as a Notch downstream transcription regulator. It interacts with the transcription coactivator p300 and inhibits transcription activation mediated by the neural specific transcription factor MASH1. It is also a transcription target of nuclear factor of activated T cells (NFAT) and participates in T cell anergy and Foxp3 protein level maintenance in vivo. Moreover, DTX1 promotes protein kinase C theta degradation and sustains Casitas B-lineage lymphoma expression. DTX4, also known as RING finger protein 155, shares the highest degree of sequence similarity with DTX1. So it likely interacts with the intracellular domain of Notch as well. Like DTX1 and DTX4, DTX2 is expressed in thymocytes. It interacts with the intracellular domain of Notch receptors and acts as a negative regulator of Notch signals in T cells. However, the endogenous levels of DTX1 and DTX2 is not important for regulating Notch signals during thymocyte development. In contrast to other DTXs, DTX3 does not contain two Notch-binding WWE domains at the N-terminus, but rather a short unique N-terminal domain. It does not interact with the intracellular domain of Notch. In addition, it has a different class of RING finger (C3HC4 type or RING-HC subclass), compared with the other DTXs which harbor a C3H2C3-type RING-H2 finger. Thus DTX3 is not included in this subfamily. Drosophila melanogaster Deltex also does not belong to this subfamily.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 663071089 302 DCTICMERLTAPSGYKGPQpTVKPDLVGKLSRCGHVYHIYCLVAMYNNGNKDGSLQCPTCKTIYG 366
Cdd:cd16459    1 DCPICCEPLCVASGYEESK-LEGSKVVVRLKKCSHMYHKACLVAMYSNGAKDGSLQCPTCKTIYG 64

Domain in Deltex and TRIP12 homologues. Possibly involved in regulation of ubiquitin-mediated proteolysis;

                           10        20        30
                   ....*....|....*....|....*....|..
gi 663071089     7 IQHAYEKQHPWIDLTSIGFSYVIDFNTMGQIN 38
Cdd:smart00678  23 IEEAYAAGKKLCELSICGFPYTIDFNAMTQYN 54

H2 subclass of RING (RING-H2) fingers and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serves as a scaffold for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071089 303 CTICMERLTAPSgykgpqptvkpdlVGKLSRCGHVYHIYCLVAMYNNGNKdgslQCPTCK 362
Cdd:cd16448    1 CVICLEEFEEGD-------------VVRLLPCGHVFHLACILRWLESGNN----TCPLCR 43

RING finger, H2 subclass, found in RING finger protein 103 (RNF103) and similar proteins; RNF103, also known as KF-1 or zinc finger protein 103 homolog (Zfp-103), is an endoplasmic reticulum (ER)-resident E3 ubiquitin-protein ligase that is widely expressed in many different organs, including brain, heart, kidney, spleen, and lung. It is involved in the ER-associated degradation (ERAD) pathway by interacting with components of the ERAD pathway, including Derlin-1 and VCP. RNF103 contains several hydrophobic regions at its N-terminal and middle regions, as well as a C-terminal C3H2C3-type RING-H2 finger.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 663071089 297 HPPDEDCTICMErltapsgykgpqpTVKPDLVGKLSRCGHVYHIYCLVAMYNNGNKdgslQCPTCK 362
Cdd:cd16473    1 MLECEECAICLE-------------NYQNGDLLRGLPCGHVFHQNCIDVWLERDNH----CCPVCR 49

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071089   63 PKAQSWPVSPGPATSPPMSPCSCPqcvlvmsvkAAVVNGSTGPLQLPVtrknmPPPGVVKLPPLPGSGAKPLDSTGTIRG 142
Cdd:PHA03247 2608 PRGPAPPSPLPPDTHAPDPPPPSP---------SPAANEPDPHPPPTV-----PPPERPRDDPAPGRVSRPRRARRLGRA 2673

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071089  143 PLKTAPSQVIRRQASSMPTGTTMGS---PASPPGPNSKTGRVALATLNRTNLQRLAIAQSRVLIASGVPTVPVKNLNGSS 219
Cdd:PHA03247 2674 AQASSPPQRPRRRAARPTVGSLTSLadpPPPPPTPEPAPHALVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATPGG 2753

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 663071089  220 PVNPALAGITGILMSAAGLPVCLTRPPKLVLHPPPVSKSE 259
Cdd:PHA03247 2754 PARPARPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSE 2793

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 663071089  303 CTICMERLTAPSgykgpqptvkpdlvgKLSRCGHVYHIYCLVAMYNNGNKdgslQCPTC 361
Cdd:pfam00097   1 CPICLEEPKDPV---------------TLLPCGHLFCSKCIRSWLESGNV----TCPLC 40

second RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, proteins with double RING-H2 fingers may act as scaffolds for binding several proteins that function in the same pathway. This model corresponds to the second RING-H2 finger.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 663071089 302 DCTICMERLTAPSGYKGPQPTVKPDLVgkLSRCGHVYHIYCLVAM--YNNGNKdgsLQCPTCKTIY 365
Cdd:cd16678    1 DCPICLTPLQSSGDSSDAKRVSSRPTV--LLSCSHVFHATCLEAFeeFSVGEE---LVCPVCRSHY 61

RING finger, H2 subclass, found in synoviolin and similar proteins; Synoviolin, also known as synovial apoptosis inhibitor 1 (Syvn1), Hrd1, or Der3, is an endoplasmic reticulum (ER)-anchoring E3 ubiquitin ligase that functions as a suppressor of ER stress-induced apoptosis and plays a role in homeostasis maintenance. It also targets tumor suppressor gene p53 for proteasomal degradation, suggesting crosstalk between ER associated degradation (ERAD) and p53 mediated apoptotic pathway under ER stress. Moreover, synoviolin controls body weight and mitochondrial biogenesis through negative regulation of the thermogenic coactivator peroxisome proliferator-activated receptor coactivator (PGC)-1beta. It upregulates amyloid beta production by targeting a negative regulator of gamma-secretase, Retention in endoplasmic reticulum 1 (Rer1), for degradation. It is also involved in the degradation of endogenous immature nicastrin, and affects amyloid beta-protein generation. Moreover, synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of rheumatoid arthritis (RA). It functions as an anti-apoptotic factor that is responsible for the outgrowth of synovial cells during the development of RA. It promotes inositol-requiring enzyme 1 (IRE1) ubiquitination and degradation in synovial fibroblasts with collagen-induced arthritis. Furthermore, the upregulation of synoviolin may represent a protective response against neurodegeneration in Parkinson's disease (PD). In addition, synoviolin is involved in liver fibrogenesis. Synoviolin contains a C3H2C2-type RING-H2 finger.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 663071089 300 DEDCTICMERLTaPSGYKGPqptvkpdlvgklsrCGHVYHIYCLVAMYNNgnkdgSLQCPTCK 362
Cdd:cd16479    1 DNTCIICREEMT-VGAKKLP--------------CGHIFHLSCLRSWLQR-----QQTCPTCR 43

RING finger, HC subclass, found in protein Deltex-3-like (DTX3L) and similar proteins; DTX3L, also known as B-lymphoma- and BAL-associated protein (BBAP) or Rhysin-2 (Rhysin2), is a RING-domain E3 ubiquitin-protein ligase that regulates endosomal sorting of the G protein-coupled receptor CXCR4 from endosomes to lysosomes. It also regulates subcellular localization of its partner protein, B aggressive lymphoma (BAL), by a dynamic nucleocytoplasmic trafficking mechanism. DTX3L has a unique N-terminus, but lacks the highly basic N-terminal motif and the central proline-rich motif present in other Deltex (DTX) family members, such as DTX1, DTX2, and DTX4. Moreover, its C-terminal region is highly homologous to DTX3. It includes a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain. DTX3L can associate with DTX1 through its unique N-terminus and further enhance self-ubiquitination.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 663071089 301 EDCTICMERLTAPSgykgpqptvkpdlvgKLSRCGHVYHIYCLvamyNNGNKDGSLqCPTCKTIYGVKTGTQP 373
Cdd:cd16712    4 DECPICMDRISNKK---------------VLPKCKHVFCAACI----DKAMKYKPV-CPVCGTIYGVIKGNQP 56

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
                 ....*....|....*....|....*....|
gi 663071089 332 SRCGHVYHIYCLVAMYNNGNKDGSLQCPTC 361
Cdd:cd15489   19 DGCGKWFHADCLGPPLSSFVPNGKWICPVC 48