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 755513512  490 TGTQPPGKMEFHLIPHSLPGFADTQTIRIVYDIPTGIQGPEHPNPGKKFTarGFPRHCYLPNNEKGRKVLRLLITAWERR 569
Cdd:pfam18102   1 TGNQPDGTMTVSTIPTSLPGYENCGTIVITYNIPGGIQGPEHPNPGKPYS--GTPRTAYLPDNEEGRKVLKLLKRAFDQR 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 755513512  570 LIFTIGTSNTTGESDTVVWNEIHHKTEFGSNLTGHGYPDASYLDNVLAELTAQGV 624
Cdd:pfam18102  79 LIFTVGTSRTTGASNVVTWNDIHHKTSISGGPTGFGYPDPDYLKRVKEELAAKGI 133

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755513512    26 VVWEWLNEHSRWRPYTATVCHHIENVLK--EDARGSVVLGQvdaqlvPYIIDLQSMHQFRQDTGTMRPVRRNFYDPSSA 102
Cdd:smart00678   1 YVWEYEGRNGKWWPYDPRVSEDIEEAYAagKKLCELSICGF------PYTIDFNAMTQYNQATGTTRKVRRVTYSPYSK 73

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 755513512  490 TGTQPPGKMEFHLIPHSLPGFADTQTIRIVYDIPTGIQGPEHPNPGKKFTarGFPRHCYLPNNEKGRKVLRLLITAWERR 569
Cdd:pfam18102   1 TGNQPDGTMTVSTIPTSLPGYENCGTIVITYNIPGGIQGPEHPNPGKPYS--GTPRTAYLPDNEEGRKVLKLLKRAFDQR 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 755513512  570 LIFTIGTSNTTGESDTVVWNEIHHKTEFGSNLTGHGYPDASYLDNVLAELTAQGV 624
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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755513512 415 DEDCTICMERLVTASGYEGVLRNKSVRPELVGRLGRCGHMYHLLCLVAMYSNGNkvghKDGSLQCPTCKAIYG 487
Cdd:cd16671    1 DEDCTICMERLVTPSGYEGVLSHKGVKPELVGKLSRCGHMYHLLCLVAMYNNGN----KDGSLQCPTCKAIYG 69

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 755513512   107 IVWEWENDGGAWTAYDMDICITIQNAYEKQHPWLDLSSLGFCYLIYFNSMSQMNRQT 163
Cdd:smart00678   1 YVWEYEGRNGKWWPYDPRVSEDIEEAYAAGKKLCELSICGFPYTIDFNAMTQYNQAT 57

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 755513512  108 VWEWENDGGAWTAYDMDICITIQNAYEKQHPWLDLS--SLGFCYLIYFNSMSQMNRQT 163
Cdd:pfam02825   1 VWEWEDDNGGWHPYDPEVSSLIEEAYQKGKPSVDLSitTAGFPYTIDFKSMTQTNKDT 58

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 755513512  490 TGTQPPGKMEFHLIPHSLPGFADTQTIRIVYDIPTGIQGPEHPNPGKKFTarGFPRHCYLPNNEKGRKVLRLLITAWERR 569
Cdd:pfam18102   1 TGNQPDGTMTVSTIPTSLPGYENCGTIVITYNIPGGIQGPEHPNPGKPYS--GTPRTAYLPDNEEGRKVLKLLKRAFDQR 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 755513512  570 LIFTIGTSNTTGESDTVVWNEIHHKTEFGSNLTGHGYPDASYLDNVLAELTAQGV 624
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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755513512 415 DEDCTICMERLVTASGYEGVLRNKSVRPELVGRLGRCGHMYHLLCLVAMYSNGNkvghKDGSLQCPTCKAIYG 487
Cdd:cd16671    1 DEDCTICMERLVTPSGYEGVLSHKGVKPELVGKLSRCGHMYHLLCLVAMYNNGN----KDGSLQCPTCKAIYG 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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 755513512 417 DCTICMERLVTASGYEGVlrnKSVRPELVGRLGRCGHMYHLLCLVAMYSNGNkvghKDGSLQCPTCKAIYG 487
Cdd:cd16459    1 DCPICCEPLCVASGYEES---KLEGSKVVVRLKKCSHMYHKACLVAMYSNGA----KDGSLQCPTCKTIYG 64

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 755513512   107 IVWEWENDGGAWTAYDMDICITIQNAYEKQHPWLDLSSLGFCYLIYFNSMSQMNRQT 163
Cdd:smart00678   1 YVWEYEGRNGKWWPYDPRVSEDIEEAYAAGKKLCELSICGFPYTIDFNAMTQYNQAT 57

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 755513512  108 VWEWENDGGAWTAYDMDICITIQNAYEKQHPWLDLS--SLGFCYLIYFNSMSQMNRQT 163
Cdd:pfam02825   1 VWEWEDDNGGWHPYDPEVSSLIEEAYQKGKPSVDLSitTAGFPYTIDFKSMTQTNKDT 58

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 755513512 418 CTICMERLVTASgyegvlrnksvrpelVGRLGRCGHMYHLLCLVAMYSNGNKvghkdgslQCPTCK 483
Cdd:cd16448    1 CVICLEEFEEGD---------------VVRLLPCGHVFHLACILRWLESGNN--------TCPLCR 43