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 188219611  472 TGTQPPGKMEYHLIPHSLPGHPDCKTIRIIYSIPPGIQGPEHPNPGKSFSarGFPRHCYLPDSEKGRKVLKLLLVAWDRR 551
Cdd:pfam18102   1 TGNQPDGTMTVSTIPTSLPGYENCGTIVITYNIPGGIQGPEHPNPGKPYS--GTPRTAYLPDNEEGRKVLKLLKRAFDQR 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 188219611  552 LIFAIGTSSTTGESDTVIWNEVHHKTEFGSNLTGHGYPDANYLDNVLAELAAQGI 606
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 188219611     8 VVWEWLNEHGRWRPYSPAVSHHIEAVVRAGPRAGGSVVLGQvdsrlaPYIIDLQSMNQFRQDTGTLRPVRRNYYDPSSA 86
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 188219611  472 TGTQPPGKMEYHLIPHSLPGHPDCKTIRIIYSIPPGIQGPEHPNPGKSFSarGFPRHCYLPDSEKGRKVLKLLLVAWDRR 551
Cdd:pfam18102   1 TGNQPDGTMTVSTIPTSLPGYENCGTIVITYNIPGGIQGPEHPNPGKPYS--GTPRTAYLPDNEEGRKVLKLLKRAFDQR 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 188219611  552 LIFAIGTSSTTGESDTVIWNEVHHKTEFGSNLTGHGYPDANYLDNVLAELAAQGI 606
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 188219611 403 EEDCTICMERLTAPSGYKGPQPT--VKPDLVGKLSRCGHIYHIYCLVAMYNNGNKDGSLQCPTCKTIYG 469
Cdd:cd16671    1 DEDCTICMERLVTPSGYEGVLSHkgVKPELVGKLSRCGHMYHLLCLVAMYNNGNKDGSLQCPTCKAIYG 69

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188219611    9 VWEWLNEHGRWRPYSPAVSHHIEAVVRAGPRaggSVVLGQVDSRlAPYIIDLQSMNQFRQDTGTLRPVRR 78
Cdd:pfam02825   1 VWEWEDDNGGWHPYDPEVSSLIEEAYQKGKP---SVDLSITTAG-FPYTIDFKSMTQTNKDTGTTRPVRR 66

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 188219611    91 VVWEWENDNGSWTPYDMEVGITIQYAYEKQHPWIDLTSIGFSYIIDFSTMGQIN 144
Cdd:smart00678   1 YVWEYEGRNGKWWPYDPRVSEDIEEAYAAGKKLCELSICGFPYTIDFNAMTQYN 54

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 188219611  406 CTICMERLTAPSgykgpqptvkpdlvgKLSRCGHIYHIYCLVAMYNNGNKdgslQCPTC 464
Cdd:pfam00097   1 CPICLEEPKDPV---------------TLLPCGHLFCSKCIRSWLESGNV----TCPLC 40

RING-finger-containing ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188219611 387 PEEVLKKYLQK------VRHPPEEDCTICMERLTapsgyKGPQPTVKPdlvgklsrCGHIYHIYCLVAMYNngnkDGSLQ 460
Cdd:COG5540  301 PTTTTKGSLKPlsieraVEADKGVECAICMSNFI-----KNDRLRVLP--------CDHRFHVGCVDKWLL----GYSNK 363

                 ....*.
gi 188219611 461 CPTCKT 466
Cdd:COG5540  364 CPVCRT 369

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 188219611  472 TGTQPPGKMEYHLIPHSLPGHPDCKTIRIIYSIPPGIQGPEHPNPGKSFSarGFPRHCYLPDSEKGRKVLKLLLVAWDRR 551
Cdd:pfam18102   1 TGNQPDGTMTVSTIPTSLPGYENCGTIVITYNIPGGIQGPEHPNPGKPYS--GTPRTAYLPDNEEGRKVLKLLKRAFDQR 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 188219611  552 LIFAIGTSSTTGESDTVIWNEVHHKTEFGSNLTGHGYPDANYLDNVLAELAAQGI 606
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 188219611 403 EEDCTICMERLTAPSGYKGPQPT--VKPDLVGKLSRCGHIYHIYCLVAMYNNGNKDGSLQCPTCKTIYG 469
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 188219611 405 DCTICMERLTAPSGYKGPQpTVKPDLVGKLSRCGHIYHIYCLVAMYNNGNKDGSLQCPTCKTIYG 469
Cdd:cd16459    1 DCPICCEPLCVASGYEESK-LEGSKVVVRLKKCSHMYHKACLVAMYSNGAKDGSLQCPTCKTIYG 64

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188219611    9 VWEWLNEHGRWRPYSPAVSHHIEAVVRAGPRaggSVVLGQVDSRlAPYIIDLQSMNQFRQDTGTLRPVRR 78
Cdd:pfam02825   1 VWEWEDDNGGWHPYDPEVSSLIEEAYQKGKP---SVDLSITTAG-FPYTIDFKSMTQTNKDTGTTRPVRR 66

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 188219611    91 VVWEWENDNGSWTPYDMEVGITIQYAYEKQHPWIDLTSIGFSYIIDFSTMGQIN 144
Cdd:smart00678   1 YVWEYEGRNGKWWPYDPRVSEDIEEAYAAGKKLCELSICGFPYTIDFNAMTQYN 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 188219611 406 CTICMERLTAPSgykgpqptvkpdlVGKLSRCGHIYHIYCLVAMYNNGNKdgslQCPTCK 465
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 188219611 400 HPPEEDCTICMErltapsgykgpqpTVKPDLVGKLSRCGHIYHIYCLVAMYNNGNKdgslQCPTCK 465
Cdd:cd16473    1 MLECEECAICLE-------------NYQNGDLLRGLPCGHVFHQNCIDVWLERDNH----CCPVCR 49

N1R/p28-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188219611 382 KKGKTPEE-------VLKKYLQKVRHPPEEDCTICMERLTAPSgykgpqptVKPDLVGKLSRCGHIYHIYCLVAMYNNGN 454
Cdd:PHA02929 146 KKGKNYKKflktipsVLSEYEKLYNRSKDKECAICMEKVYDKE--------IKNMYFGILSNCNHVFCIECIDIWKKEKN 217

                         90
                 ....*....|....
gi 188219611 455 KdgslqCPTCKTIY 468
Cdd:PHA02929 218 T-----CPVCRTPF 226

RING finger, H2 subclass, found in vacuolar protein sorting-associated protein 11 homolog (Vps11) and similar proteins; Vps11, also known as RING finger protein 108 (RNF108), is a soluble protein involved in regulation of glycolipid degradation and retrograde toxin transport. It is highly expressed in heart and pancreas. Vps11 associates with Vps16, Vps18, and Vps33 to form a Class C Vps core complex that is required for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE)-mediated membrane fusion at the lysosome-like yeast vacuole. The core complex, together with two additional compartment-specific subunits, forms the tethering complexes HOPS (homotypic vacuole fusion and protein sorting) and CORVET (class C core vacuole/endosome transport). CORVET contains the additional Vps3 and Vps8 subunits. It operates at endosomes, controls traffic into late endosomes and interacts with the Rab5/Vps21-GTP form. HOPS contains the additional Vps39 and Vps41 subunits. It operates at the lysosomal vacuole, controls all traffic from late endosomes into the vacuole and interacts with the Rab7/Ypt7-GTP form. Vps11 is a central scaffold protein upon which both HOPS and CORVET assemble. The HOPS and CORVET complexes disassemble in the absence of Vps11, resulting in massive fragmentation of vacuoles. Vps11 contains a clathrin repeat domain and a C-terminal C3H2C3-type RING-H2 finger. This subfamily also includes Vps11 homologs found in fungi, such as Saccharomyces cerevisiae vacuolar membrane protein Pep5p, also known as carboxypeptidase Y-deficient protein 5, vacuolar morphogenesis protein 1, or vacuolar biogenesis protein END1. Pep5p is essential for vacuolar biogenesis. It associates with Pep3p to form a core Pep3p/Pep5p complex that promotes vesicular docking/fusion reactions in conjunction with SNARE proteins at multiple steps in transport routes to the vacuole.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 188219611 406 CTICMERLTAPSgykgpqptvkpdlVGKLsrCGHIYHIYCLVAMYNNGNKdgslqCPTCKT 466
Cdd:cd16688    3 CSACGSTLDLPS-------------VHFL--CGHSFHQHCLEDYEENDRE-----CPLCAP 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 188219611 403 EEDCTICMERLTAPSgykgpqptvkpdlvgKLSRCGHIYHIYCLvamyNNGNKDGSLqCPTCKTIYGVKTGTQP 476
Cdd:cd16712    3 EDECPICMDRISNKK---------------VLPKCKHVFCAACI----DKAMKYKPV-CPVCGTIYGVIKGNQP 56

RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins; TTC3, also known as protein DCRR1, TPR repeat protein D, TPR repeat protein 3, or RING finger protein 105 (RNF105), is an E3 ubiquitin-protein ligase encoded by a gene within the Down syndrome (DS) critical region on chromosome 21. It affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways. It inhibits the neuronal-like differentiation of pheocromocytoma cells by activating RhoA and by binding to Citron proteins. TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. It contains four N-terminal TPR motifs, a potential coiled-coil region and a Citron binding region in the central part, and a C-terminal C3H2C2-type RING-H2 finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 188219611 406 CTICMERLtapsgykgpqptvKPDLVGKLsRCGHIYHIYCLVAmYNNGNKDgslqCPTC 464
Cdd:cd16481    2 CIICHDDL-------------KPDQLAKL-ECGHIFHKECIKQ-WLKEQST----CPTC 41

RING-finger-containing ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188219611 387 PEEVLKKYLQK------VRHPPEEDCTICMERLTapsgyKGPQPTVKPdlvgklsrCGHIYHIYCLVAMYNngnkDGSLQ 460
Cdd:COG5540  301 PTTTTKGSLKPlsieraVEADKGVECAICMSNFI-----KNDRLRVLP--------CDHRFHVGCVDKWLL----GYSNK 363

                 ....*.
gi 188219611 461 CPTCKT 466
Cdd:COG5540  364 CPVCRT 369