Uncharacterized conserved protein, LON_N-like domain, ASCH/PUA-like superfamily [Function unknown];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574280908 309 YPTVPCPLHIFEPCYRLMIRRCIETGtRQFGMCL------GDPVKGFAEYGCILEIRNVQFFADGRSVVDSIGKRRFRVL 382
Cdd:COG2802   17 FPGGRLPLHIFEPRYLDMVRDCLAGD-RPFGVVLiregreVGGPPPLYDVGTLARITDFEELEDGRLDITLRGVQRFRIL 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574280908 383 HQSQR-DGYNTADIEYIEDQkvqgedcaelmglhncVYQQASLWFHSLKLSLKnRILNHFGPMPEKDADPQMNPngPAW- 460
Cdd:COG2802   96 EELQEdDPYRVAEVEWLPDE----------------PDLPVPEELEALRERLL-RLLRRYPELAGLEADPDLDD--PEWl 156

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 574280908 461 CWWMLAVLPLESRAQLPFLAMRSLKDRLNGIRRVLAF 497
Cdd:COG2802  157 SNRLAELLPLDPEEKQALLEAPDLLERLELLLALLER 193

RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574280908 189 TDQGDKPALSLP-LASFDASDLeCALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPLCKD-----------GLSQCL 256
Cdd:COG5432    6 TDPSDWNQTKIPsLKGLDSMLR-CRICDCRISIPCETTCGHTFCSLCIRRHLGTQPFCPVCREdpcesrlrgssGSREIN 84

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 574280908 257 ASRKYSKNVIMEEL-IAKFLPEELKERRKLYEEEMEE 292
Cdd:COG5432   85 ESHARNRDLLRKVLeSLCRLPRPIKEERPCRWETVIA 121

Uncharacterized conserved protein, LON_N-like domain, ASCH/PUA-like superfamily [Function unknown];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574280908 309 YPTVPCPLHIFEPCYRLMIRRCIETGtRQFGMCL------GDPVKGFAEYGCILEIRNVQFFADGRSVVDSIGKRRFRVL 382
Cdd:COG2802   17 FPGGRLPLHIFEPRYLDMVRDCLAGD-RPFGVVLiregreVGGPPPLYDVGTLARITDFEELEDGRLDITLRGVQRFRIL 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574280908 383 HQSQR-DGYNTADIEYIEDQkvqgedcaelmglhncVYQQASLWFHSLKLSLKnRILNHFGPMPEKDADPQMNPngPAW- 460
Cdd:COG2802   96 EELQEdDPYRVAEVEWLPDE----------------PDLPVPEELEALRERLL-RLLRRYPELAGLEADPDLDD--PEWl 156

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 574280908 461 CWWMLAVLPLESRAQLPFLAMRSLKDRLNGIRRVLAF 497
Cdd:COG2802  157 SNRLAELLPLDPEEKQALLEAPDLLERLELLLALLER 193

ATP-dependent protease La (LON) substrate-binding domain; This domain has been shown to be part of the PUA superfamily. This domain represents a general protein and polypeptide interaction domain for the ATP-dependent serine peptidase, LON, Peptidase_S16, pfam05362. ATP-dependent Lon proteases are conserved in all living organizms and catalyze rapid turnover of short-lived regulatory proteins and many damaged or denatured proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574280908  299 NVPIFVC--TMAYPTVPCPLHIFEPCYRLMIRRCIETGtRQFGMCL---------GDPVKGFAEYGCILEIRNVQFFADG 367
Cdd:pfam02190   1 ELPLLPLrnTVLFPGMVLPLFVGRPRSIAAIEAALNKD-KLYGVLLvsqkdaedeEPTPDDLYEVGTVAKIVQILKLPDG 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574280908  368 RSVVDSIGKRRFRVLH-QSQRDGYNTADIEYIEDQKVQGEDcaELMGLHncvyqqaslwfhslkLSLKNRILNHFGPMPE 446
Cdd:pfam02190  80 TYKVLVEGLERVRIVElVKKEEPYLRAEVEDLPEDSDELSE--ALKALV---------------KELIEKLRRLLKLLLP 142

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 574280908  447 KDADPQMN--PNGPAWCWWMLAVLPLESRAQLPFLAMRSLKDRLngiRRVLAFISR 500
Cdd:pfam02190 143 LELLLKIKdiENPGRLADLVAAILPLSPEEKQELLETLDVKERL---EKVLELLNR 195

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 574280908  210 ECALCMRLFYEP-VTTPCGHTFCLKCLERCLDHNAKCPLC 248
Cdd:pfam13923   1 MCPICMDMLKDPsTTTPCGHVFCQDCILRALEASNECPLC 40

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
                   ....*....|....*....|....*....|....*....|
gi 574280908   211 CALCM-RLFYEPVTTPCGHTFCLKCLERCLD-HNAKCPLC 248
Cdd:smart00184   1 CPICLeEYLKDPVILPCGHTFCRSCIRKWLEsGNNTCPIC 40

N1R/p28-like protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 574280908 205 DASDLECALCMRLFYEP--------VTTPCGHTFCLKCLERCLDHNAKCPLCKDGLSQCLASRKYSK 263
Cdd:PHA02929 171 RSKDKECAICMEKVYDKeiknmyfgILSNCNHVFCIECIDIWKKEKNTCPVCRTPFISVIKSRFFTK 237

Uncharacterized conserved protein, LON_N-like domain, ASCH/PUA-like superfamily [Function unknown];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574280908 309 YPTVPCPLHIFEPCYRLMIRRCIETGtRQFGMCL------GDPVKGFAEYGCILEIRNVQFFADGRSVVDSIGKRRFRVL 382
Cdd:COG2802   17 FPGGRLPLHIFEPRYLDMVRDCLAGD-RPFGVVLiregreVGGPPPLYDVGTLARITDFEELEDGRLDITLRGVQRFRIL 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574280908 383 HQSQR-DGYNTADIEYIEDQkvqgedcaelmglhncVYQQASLWFHSLKLSLKnRILNHFGPMPEKDADPQMNPngPAW- 460
Cdd:COG2802   96 EELQEdDPYRVAEVEWLPDE----------------PDLPVPEELEALRERLL-RLLRRYPELAGLEADPDLDD--PEWl 156

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 574280908 461 CWWMLAVLPLESRAQLPFLAMRSLKDRLNGIRRVLAF 497
Cdd:COG2802  157 SNRLAELLPLDPEEKQALLEAPDLLERLELLLALLER 193

ATP-dependent protease La (LON) substrate-binding domain; This domain has been shown to be part of the PUA superfamily. This domain represents a general protein and polypeptide interaction domain for the ATP-dependent serine peptidase, LON, Peptidase_S16, pfam05362. ATP-dependent Lon proteases are conserved in all living organizms and catalyze rapid turnover of short-lived regulatory proteins and many damaged or denatured proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574280908  299 NVPIFVC--TMAYPTVPCPLHIFEPCYRLMIRRCIETGtRQFGMCL---------GDPVKGFAEYGCILEIRNVQFFADG 367
Cdd:pfam02190   1 ELPLLPLrnTVLFPGMVLPLFVGRPRSIAAIEAALNKD-KLYGVLLvsqkdaedeEPTPDDLYEVGTVAKIVQILKLPDG 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574280908  368 RSVVDSIGKRRFRVLH-QSQRDGYNTADIEYIEDQKVQGEDcaELMGLHncvyqqaslwfhslkLSLKNRILNHFGPMPE 446
Cdd:pfam02190  80 TYKVLVEGLERVRIVElVKKEEPYLRAEVEDLPEDSDELSE--ALKALV---------------KELIEKLRRLLKLLLP 142

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 574280908  447 KDADPQMN--PNGPAWCWWMLAVLPLESRAQLPFLAMRSLKDRLngiRRVLAFISR 500
Cdd:pfam02190 143 LELLLKIKdiENPGRLADLVAAILPLSPEEKQELLETLDVKERL---EKVLELLNR 195

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574280908  189 TDQGDKPALSLP-LASFDASdLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPLCKDGLSQClasrKYSKNVIM 267
Cdd:TIGR00599   7 TDSSDWLTTPIPsLYPLDTS-LRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPKCPLCRAEDQES----KLRSNWLV 81

                  ....*..
gi 574280908  268 EELIAKF 274
Cdd:TIGR00599  82 SEIVESF 88

HC subclass of RING (RING-HC) finger 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 a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers 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 serve as scaffolds 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
                 ....*....|....*....|....*....|....*....|.
gi 574280908 209 LECALCMRLFYEPVTTPCGHTFCLKCLERCLDH-NAKCPLC 248
Cdd:cd16449    1 LECPICLERLKDPVLLPCGHVFCRECIRRLLESgSIKCPIC 41

RING finger, HC subclass, found in tripartite motif-containing protein TRIM25 and similar proteins; TRIM25, also known as estrogen-responsive finger protein (EFP), RING finger protein 147 (RNF147), or RING-type E3 ubiquitin transferase, is an E3 ubiquitin/ISG15 ligase that is induced by estrogen and is therefore particularly abundant in placenta and uterus. TRIM25 regulates various cellular processes through E3 ubiquitin ligase activity, transferring ubiquitin and ISG15 to target proteins. It mediates K63-linked polyubiquitination of retinoic acid inducible gene I (RIG-I) that is crucial for downstream antiviral interferon signaling. It is also required for melanoma differentiation-associated gene 5 (MDA5) and mitochondrial antiviral signaling (MAVS, also known as IPS-1, VISA, Cardiff) mediated activation of nuclear factor-kappaB (NF-kappaB) and interferon production. Upon UV irradiation, TRIM25 interacts with mono-ubiquitinated PCNA and promotes its ISG15 modification (ISGylation), suggesting a crucial role in termination of error-prone translesion DNA synthesis. TRIM25 also functions as a novel regulator of p53 and Mdm2. It enhances p53 and Mdm2 abundance by inhibiting their ubiquitination and degradation in 26S proteasomes. Meanwhile, it inhibits p53's transcriptional activity and dampens the response to DNA damage, and is essential for medaka development and this dependence is rescued by silencing of p53. Moreover, TRIM25 is involved in the host cellular innate immune response against retroviral infection. It interferes with the late stage of feline leukemia virus (FeLV) replication. Furthermore, TRIM25 acts as an oncogene in gastric cancer. Its blockade by RNA interference inhibits migration and invasion of gastric cancer cells through transforming growth factor-beta (TGF-beta) signaling, suggesting it presents a novel target for the detection and treatment of gastric cancer. In addition, TRIM25 acts as an RNA-specific activator for Lin28a/TuT4-mediated uridylation. TRIM25 belongs to the C-IV 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 C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 574280908 208 DLECALCMRLFYEPVTTPCGHTFCLKCLER----CLDHNAKCPLCK 249
Cdd:cd16597    5 ELTCSICLELFKDPVTLPCGHNFCGVCIEKtwdsQHGSEYSCPQCR 50

RING finger, HC subclass, found in tripartite motif-containing proteins, TRIM7, TRIM11 and TRIM27, and similar proteins; TRIM7, TRIM11 and TRIM27, closely related tripartite motif-containing proteins, belong to the C-IV subclass of the 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 C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM7, also known as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90), is an E3 ubiquitin-protein ligase that mediates c-Jun/AP-1 activation by Ras signalling. Its phosphorylation and activation by MSK1 in response to direct activation by the Ras-Raf-MEK-ERK pathway can stimulate TRIM7 E3 ubiquitin ligase activity in mediating Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilization. Moreover, TRIM7 binds and activates glycogenin, the self-glucosylating initiator of glycogen biosynthesis. TRIM11, also known as protein BIA1, or RING finger protein 92 (RNF92), is an E3 ubiquitin-protein ligase involved in the development of the central nervous system. It is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 acts as a potential therapeutic target for congenital central hypoventilation syndrome (CCHS) by mediating the degradation of CCHS-associated polyalanine-expanded Phox2b. TRIM11 modulates the function of neurogenic transcription factor Pax6 through the ubiquitin-proteosome system, and thus plays an essential role for Pax6-dependent neurogenesis. It also binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105), humanin, a neuroprotective peptide against Alzheimer's disease-relevant insults, and further regulates ARC105 function in transforming growth factor beta (TGFbeta) signaling. Moreover, TRIM11 negatively regulates retinoic acid-inducible gene-I (RIG-I)-mediated interferon-beta (IFNbeta) production and antiviral activity by targeting TANK-binding kinase-1 (TBK1). It may contribute to the endogenous restriction of retroviruses in cells. It enhances N-tropic murine leukemia virus (N-MLV) entry by interfering with Ref1 restriction. It also suppresses the early steps of human immunodeficiency virus HIV-1 transduction, resulting in decreased reverse transcripts. TRIM27, also known as RING finger protein 76 (RNF76), RET finger protein (RFP), or zinc finger protein RFP, is a nuclear E3 ubiquitin-protein ligase that is highly expressed in testis and in various tumor cell lines. Expression of TRIM27 is associated with prognosis of colon and endometrial cancers. TRIM27 was first identified as a fusion partner of the RET receptor tyrosine kinase. It functions as a transcriptional repressor and associates with several proteins involved in transcriptional activity, such as enhancer of polycomb 1 (Epc1), a member of the Polycomb group proteins, and Mi-2beta, a main component of the nucleosome remodeling and deacetylase (NuRD) complex, and the cell cycle regulator retinoblastoma protein (RB1). It also interacts with HDAC1, leading to downregulation of thioredoxin binding protein 2 (TBP-2), which inhibits the function of thioredoxin. Moreover, TRIM27 mediates Pax7-induced ubiquitination of MyoD in skeletal muscle atrophy. In addition, it inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. TRIM27 promotes a non-canonical polyubiquitination of PTEN, a lipid phosphatase that catalyzes PtdIns(3,4,5)P3 (PIP3) to PtdIns(4,5)P2 (PIP2). It is an IKKepsilon-interacting protein that regulates IkappaB kinase (IKK) function and negatively regulates signaling involved in the antiviral response and inflammation. TRIM27 also forms a protein complex with MBD4 or MBD2 or MBD3, and thus plays an important role in the enhancement of transcriptional repression through MBD proteins in tumorigenesis, spermatogenesis, and embryogenesis. It is a component of an estrogen receptor 1 (ESR1) regulatory complex that is involved in estrogen receptor-mediated transcription in MCF-7 cells.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 574280908 208 DLECALCMRLFYEPVTTPCGHTFCLKCLERC---LDHNAKCPLCKDGLSQ 254
Cdd:cd16594    5 ELTCPICLDYFTDPVTLDCGHSFCRACIARCweePETSASCPQCRETCPQ 54

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 574280908  210 ECALCMRLFYEP-VTTPCGHTFCLKCLERCLDHNAKCPLC 248
Cdd:pfam13923   1 MCPICMDMLKDPsTTTPCGHVFCQDCILRALEASNECPLC 40

RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also known as RING finger protein 53 (RNF53), is a RING finger protein encoded by the tumor suppressor gene BRCA1 that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT (BRCA1 C-terminus domain) repeats at the C-terminus.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574280908 209 LECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAK---CPLCKDGLSQclasRKYSKNVIMEELIAKFL 275
Cdd:cd16498   17 LECPICLELLKEPVSTKCDHQFCRFCILKLLQKKKKpapCPLCKKSVTK----RSLQESTRFKQLVEAVK 82

Modified RING finger, HC subclass (C3HC3D-type), found in ligand of Numb protein LNX1, LNX2, and similar proteins; The ligand of Numb protein X (LNX) family, also known as PDZ and RING (PDZRN) family, includes LNX1-5, which can interact with Numb, a key regulator of neurogenesis and neuronal differentiation. LNX5 (also known as PDZK4 or PDZRN4L) shows high sequence homology to LNX3 and LNX4, but it lacks the RING domain. LNX1-4 proteins function as E3 ubiquitin ligases and have a unique domain architecture consisting of an N-terminal RING-HC finger for E3 ubiquitin ligase activity and either two or four PDZ domains necessary for substrate-binding. LNX1/LNX2-like proteins contain a modified C3HC3D-type RING-HC finger and four PDZ domains. This model corresponds to the RING finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 574280908 208 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPL 247
Cdd:cd16637    1 DLTCHICLQPLVEPLDTPCGHTFCYKCLTNYLKIQQCCPL 40

RING finger, HC subclass, found in tripartite motif-containing protein 47 (TRIM47) and similar proteins; TRIM47, also known as gene overexpressed in astrocytoma protein (GOA) or RING finger protein 100 (RNF100), belongs to the C-IV subclass of the 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 C3HC4-type RING-HC finger, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. It plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. This subfamily also includes RING finger protein 135 (RNF135). RNF135, also known as RIG-I E3 ubiquitin ligase (REUL) or Riplet, is a widely expressed E3 ubiquitin-protein ligase that consists of an N-terminal C3HC4-type RING-HC finger and C-terminal B30.2/SPRY and PRY motifs, but lacks the B-box and coiled-coil domains that are also typically present in TRIM proteins. RNF135 serves as a specific retinoic acid-inducible gene-I (RIG-I)-interacting protein that ubiquitinates RIG-I and specifically stimulates RIG-I-mediated innate antiviral activity to produce antiviral type-I interferon (IFN) during the early phase of viral infection. It also has been identified as a bio-marker and therapy target of glioblastoma. It associates with the ERK signal transduction pathway and plays a role in glioblastoma cell proliferation, migration and cell cycle.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 574280908 209 LECALCMRLFYEPVTTPCGHTFCLKCLERCLDHN----AKCPLCKDGLS 253
Cdd:cd16604    1 LSCPICLDLLKDPVTLPCGHSFCMGCLGALWGAGrggrASCPLCRQTFP 49

RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 belongs to the C-IV subclass of the 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 C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 574280908 208 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAK--CPLCKDGLS 253
Cdd:cd16599    4 ELLCPICYEPFREAVTLRCGHNFCKGCVSRSWERQPRapCPVCKEASS 51

RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574280908 189 TDQGDKPALSLP-LASFDASDLeCALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPLCKD-----------GLSQCL 256
Cdd:COG5432    6 TDPSDWNQTKIPsLKGLDSMLR-CRICDCRISIPCETTCGHTFCSLCIRRHLGTQPFCPVCREdpcesrlrgssGSREIN 84

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 574280908 257 ASRKYSKNVIMEEL-IAKFLPEELKERRKLYEEEMEE 292
Cdd:COG5432   85 ESHARNRDLLRKVLeSLCRLPRPIKEERPCRWETVIA 121

RING finger, HC subclass, found in tripartite motif-containing protein 77 (TRIM77) and similar proteins; TRIM77 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including two consecutive zinc-binding domains, a C3HC4-type RING-HC finger and Bbox2, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 574280908 207 SDLECALCMRLFYEPVTTPCGHTFCLKCLERCLDH---NAKCPLCKDGLSQC 255
Cdd:cd16543    2 DQLTCSICLDLLKDPVTIPCGHSFCMNCITLLWDRkqgVPSCPQCRESFPPR 53

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
                   ....*....|....*....|....*....|....*....|
gi 574280908   211 CALCM-RLFYEPVTTPCGHTFCLKCLERCLD-HNAKCPLC 248
Cdd:smart00184   1 CPICLeEYLKDPVILPCGHTFCRSCIRKWLEsGNNTCPIC 40

RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; RNF213, also known as ALK lymphoma oligomerization partner on chromosome 17 or Moyamoya steno-occlusive disease-associated AAA+ and RING finger protein (mysterin), is an intracellular soluble protein that functions as an E3 ubiquitin-protein ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. It plays a unique role in endothelial cells for proper gene expression in response to inflammatory signals from the environment. Mutations in RNF213 may be associated with Moyamoya disease (MMD), an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. It also acts as a nuclear marker for acanthomorph phylogeny. RNF213 contains two tandem enzymatically active AAA+ ATPase modules and a C3HC4-type RING-HC finger. It can form a huge ring-shaped oligomeric complex.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 574280908 210 ECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPLCK 249
Cdd:cd16561    4 ECSICLEDLNDPVKLPCDHVFCEECIRQWLPGQMSCPLCR 43

Variant RING finger, HC subclass (C4C4-type), found in retinoblastoma-binding protein 6 (RBBP6) and similar proteins; RBBP6, also known as proliferation potential-related protein, protein P2P-R, retinoblastoma-binding Q protein 1 (RBQ-1), or p53-associated cellular protein of testis (PACT), is a nuclear E3 ubiquitin-protein ligase involved in multiple processes, such as the control of gene expression, mitosis, cell differentiation, and cell apoptosis. It plays a role in both promoting and inhibiting apoptosis in many human cancers, including esophageal, lung, hepatocellular, and colon cancers, familial myeloproliferative neoplasms, as well as in human immunodeficiency virus-associated nephropathy (HIVAN). It functions as an Rb- and p53-binding protein that plays an important role in chaperone-mediated ubiquitination and possibly in protein quality control. It acts as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in an increase of MDM2-mediated ubiquitination and degradation of p53/TP53, and leading to both apoptosis and cell growth. It is also a double-stranded RNA-binding protein that plays a role in mRNA processing by regulating the human polyadenylation machinery and modulating expression of mRNAs with AU-rich 3' untranslated regions (UTRs). Moreover, RBBP6 ubiquitinates and destabilizes the transcriptional repressor ZBTB38 that negatively regulates transcription and levels of the MCM10 replication factor on chromatin. Furthermore, RBBP6 is involved in tunicamycin-induced apoptosis by mediating protein kinase (PKR) activation. RBBP6 contains an N-terminal ubiquitin-like domain and a C4C4-type RING finger, whose overall folding is similar to that of the typical C3HC4-type RING-HC finger. RBBP6 interacts with chaperones Hsp70 and Hsp40 through its N-terminal ubiquitin-like domain. It promotes the ubiquitination of p53 by Hdm2 in an E4-like manner through its RING finger. It also interacts directly with the pro-proliferative transcription factor Y-box-binding protein-1 (YB-1) via its RING finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 574280908 207 SDLECALCMRLFYEPVTTP-CGHTFCLKCLERCL-DHNAKCPLCK 249
Cdd:cd16620    2 DELKCPICKDLMKDAVLTPcCGNSFCDECIRTALlEEDFTCPTCK 46

RING finger, HC subclass, found in ligand of numb protein X 3 (LNX3); LNX3, also known as PDZ domain-containing RING finger protein 3 (PDZRN3), or Semaphorin cytoplasmic domain-associated protein 3 (SEMACAP3), is an E3 ubiquitin-protein ligase that was first identified as a Semaphorin-binding partner. It is also responsible for the ubiquitination and degradation of Numb, a component of the Notch signaling pathway that functions in the specification of cell fates during development and is known to control cell numbers during neurogenesis in vertebrates. LNX3 acts as a negative regulator of osteoblast differentiation by inhibiting Wnt-beta-catenin signaling. LNX3 also plays an important role in neuromuscular junction formation. It interacts with and ubiquitinates the muscle specific tyrosine kinase (MuSK), thus promoting its endocytosis and negatively regulating the cell surface expression of this key regulator of postsynaptic assembly. LNX3 contains an N-terminal C3HC4-type RING-HC finger, two PDZ domains, and a C-terminal LNX3 homology (LNX3H) domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 574280908 208 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPL 247
Cdd:cd16718    4 DFKCNLCNKVLEDPLTTPCGHVFCAGCVLPWVVQQGSCPV 43

RING finger, HC subclass, found in RING finger protein RNF5, RNF185 and similar proteins; RNF5 and RNF185 are E3 ubiquitin-protein ligases that are anchored to the outer membrane of the endoplasmic reticulum (ER). RNF5 acts at early stages of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) biosynthesis, and functions as a target for therapeutic modalities to antagonize mutant CFTR proteins in CF patients carrying the F508del allele. RNF185 controls the degradation of CFTR and CFTR F508del allele in a RING- and proteasome-dependent manner, but does not control that of other classical endoplasmic reticulum-associated degradation (ERAD) model substrates. Moreover, both RNF5 and RNF185 play important roles in cell adhesion and migration through the modulation of cell migration by ubiquitinating paxillin. Arabidopsis thaliana RING membrane-anchor proteins (AtRMAs) are also included in this family. They possess E3 ubiquitin-protein ligase activity and may play a role in the growth and development of Arabidopsis. All members of this family contain a C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 574280908 210 ECALCMRLFYEPVTTPCGHTFCLKCLERCLD---HNAKCPLCK 249
Cdd:cd16534    2 ECNICLDTASDPVVTMCGHLFCWPCLYQWLEtrpDRQTCPVCK 44

RING finger, HC subclass, found in ligand of numb protein X 4 (LNX4); LNX4, also known as PDZ domain-containing RING finger protein 4 (PDZRN4), or SEMACAP3-like protein (SEMCAP3L), is an E3 ubiquitin-protein ligase responsible for the ubiquitination and degradation of Numb, a component of the Notch signaling pathway that functions in the specification of cell fates during development and is known to control cell numbers during neurogenesis in vertebrates. LNX4 contains an N-terminal C3HC4-type RING-HC finger, two PDZ domains, and a C-terminal LNX3 homology (LNX3H) domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 574280908 206 ASDLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPL 247
Cdd:cd16719    2 DPDLKCKLCGKVLEEPLSTPCGHVFCAGCLLPWAVQRRLCPL 43

RING finger, HC subclass, found in tripartite motif-containing protein 39 (TRIM39) and similar proteins; TRIM39, also known as RING finger protein 23 (RNF23) or testis-abundant finger protein, is an E3 ubiquitin-protein ligase that plays a role in controlling DNA damage-induced apoptosis through inhibition of the anaphase promoting complex (APC/C), a multiprotein ubiquitin ligase that controls multiple cell cycle regulators, including cyclins, geminin, and others. TRIM39 also functions as a regulator of several key processes in the proliferative cycle. It directly regulates p53 stability. It modulates cell cycle progression and DNA damage responses via stabilizing p21. Moreover, TRIM39 negatively regulates the nuclear factor kappaB (NFkappaB)-mediated signaling pathway through stabilization of Cactin, an inhibitor of NFkappaB- and Toll-like receptor (TLR)-mediated transcription, which is induced by inflammatory stimulants such as tumor necrosis factor alpha. Furthermore, TRIM39 is a MOAP-1-binding protein that can promote apoptosis signaling through stabilization of MOAP-1 via the inhibition of its poly-ubiquitination process. TRIM39 belongs to the C-IV subclass of the 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 C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 574280908 211 CALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAK---CPLC 248
Cdd:cd16601    4 CSLCKEYLKDPVIIECGHNFCRACITRFWEELDGdfpCPQC 44

RING finger, HC subclass, found in Arabidopsis thaliana RING membrane-anchor proteins (AtRMAs) and similar proteins; AtRMAs, including AtRma1, AtRma2, and AtRma3, are endoplasmic reticulum (ER)-localized Arabidopsis homologs of human outer membrane of the ER-anchor E3 ubiquitin-protein ligase, RING finger protein 5 (RNF5). AtRMAs possess E3 ubiquitin ligase activity, and may play a role in the growth and development of Arabidopsis. The AtRMA1 and AtRMA3 genes are predominantly expressed in major tissues, such as cotyledons, leaves, shoot-root junction, roots, and anthers, while AtRMA2 expression is restricted to the root tips and leaf hydathodes. AtRma1 probably functions with the Ubc4/5 subfamily of E2. AtRma2 is likely involved in the cellular regulation of ABP1 expression levels through interacting with auxin binding protein 1 (ABP1). AtRMA proteins contain an N-terminal C3HC4-type RING-HC finger and a trans-membrane-anchoring domain in their extreme C-terminal region.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 574280908 210 ECALCMRLFYEPVTTPCGHTFCLKCLERCLD---HNAKCPLCK 249
Cdd:cd16745    2 ECNICLDLAQDPVVTLCGHLFCWPCLHKWLRrqsSQPECPVCK 44

RING finger, HC subclass, found in RING finger protein 166 (RNF166) and similar proteins; RNF166 is encoded by the gene RNF166 targeted by thyroid hormone receptor alpha1 (TRalpha1), which is important in brain development. It plays an important role in RNA virus-induced interferon-beta production by enhancing the ubiquitination of TRAF3 and TRAF6. RNF166, together with three closely related proteins: RNF114, RNF125 and RNF138, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 574280908 211 CALCMRLFYEPV-TTPCGHTFCLKCLERCLDHNA-KCPLCK 249
Cdd:cd16549    4 CPICLEVYHKPVvITSCGHTFCGECLQPCLQVASpLCPLCR 44

RING finger, HC subclass, found in RING finger protein 125 (RNF125); RNF125, also known as T-cell RING activation protein 1 (TRAC-1), is an E3 ubiquitin-protein ligase that is predominantly expressed in lymphoid cells, and functions as a positive regulator of T cell activation. It also down-modulates HIV replication and inhibits pathogen-induced cytokine production. It negatively regulates type I interferon signaling, which conjugates Lys(48)-linked ubiquitination to retinoic acid-inducible gene-I (RIG-I) and subsequently leads to the proteasome-dependent degradation of RIG-I. Further, RNF125 conjugates ubiquitin to melanoma differentiation-associated gene 5 (MDA5), a family protein of RIG-I. It thus acts as a negative regulator of RIG-I signaling, and is a direct target of miR-15b in the context of Japanese encephalitis virus (JEV) infection. Moreover, RNF125 binds to and ubiquitinates JAK1, prompting its degradation and inhibition of receptor tyrosine kinase (RTK) expression. It also negatively regulates p53 function through physical interaction and ubiquitin-mediated proteasome degradation. Mutations in RNF125 may lead to overgrowth syndromes (OGS). RNF125, together with three closely related proteins: RNF114, RNF138 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM). The UIM of RNF125 binds K48-linked poly-ubiquitin chains and is, together with the RING domain, required for auto-ubiquitination.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 574280908 208 DLECALCMRLFYEPVTTPCGHTFCLKCLERCL-DHNAKCPLCKDGLS 253
Cdd:cd16542    1 NFDCAVCLEVLHQPVRTRCGHVFCRPCIATSLrNNTWTCPYCRAYLS 47

RING finger, HC subclass, found in RING finger protein 114 (RNF114) and similar proteins; RNF114, also known as zinc finger protein 228 (ZNF228) or zinc finger protein 313 (ZNF313), is a p21(WAF1)-targeting ubiquitin E3 ligase that interacts with X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) and may play a role in p53-mediated cell-fate decisions. It is involved in the immune response to double-stranded RNA in disease pathogenesis. Moreover, RNF114 interacts with A20 and modulates its ubiquitylation. It negatively regulates nuclear factor-kappaB (NF-kappaB)-dependent transcription and positively regulates T-cell activation. RNF114 may play a putative role in the regulation of immune responses, since it corresponds to a novel psoriasis susceptibility gene, ZNF313. RNF114, together with three closely related proteins: RNF125, RNF138 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 574280908 208 DLECALCMRLFYEPVTTPCGHTFCLKCLERCL-DHNAKCPLCKDGL 252
Cdd:cd16540    1 RFTCPVCLEIFETPVRVPCGHVFCNACLQECLkPKKPVCAVCRSPL 46

RING finger, HC subclass, found in Arabidopsis thaliana BRCA1-associated RING domain protein 1 (AtBARD1) and similar proteins; AtBARD1, also called protein REPRESSOR OF WUSCHEL 1, binds specifically to H3K4me3 regions of target gene (e.g. WUS and WOX5) promoters to repress their transcription via chromatin remodeling. It is required for the shoot apical meristem (SAM) organization and maintenance, by confining WUS expression to the organizing center, and for the quiescent center (QC) development in the root apical meristem (RAM), by repressing WOX5 expression in the root proximal meristem. AtBARD1 plays a role in DNA repair and in cell-cycle control. It is required for the repair of DNA double-strand breaks (DSBs), both natural and induced by genotoxic stress, by homologous recombination (HR). AtBARD1 contains a typical C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 574280908 208 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPLCK 249
Cdd:cd23146    4 ELKCPICLKLLNRPVLLPCDHIFCSSCITDSTKVGSDCPVCK 45

RING finger, HC subclass, found in Mus musculus tripartite motif-containing protein 43 (TRIM43) and similar propteins; This subfamily includes TRIM43A, TRIM43B and TRIM43C, which are expressed specifically in mouse preimplantation embryos. They contain a typical C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 574280908 208 DLECALCMRLFYEPVTTPCGHTFCLKCL---ERCLDHNAKCPLCKDGLSQ 254
Cdd:cd23133    3 TLTCSICQGIFMNPVYLRCGHKFCEACLllfQEDIKFPAYCPMCRQPFNQ 52

RING finger, HC subclass, found in RING finger protein 146 (RNF146) and similar proteins; RNF146, also known as dactylidin, or iduna, is a cytoplasmic E3 ubiquitin-protein ligase that is responsible for PARylation-dependent ubiquitination (PARdU). It displays neuroprotective property due to its inhibition of Parthanatos, a PAR dependent cell death, via binding with Poly(ADP-ribose) (PAR). It also modulates PAR polymerase-1 (PARP-1)-mediated oxidative cell injury in cardiac myocytes. Moreover, RNF146 mediates tankyrase-dependent degradation of axin, thereby positively regulating Wnt signaling. It also facilitates DNA repair and protects against cell death induced by DNA damaging agents or gamma-irradiation by translocating to the nucleus after cellular injury and promoting the ubiquitination and degradation of various nuclear proteins involved in DNA damage repair. Furthermore, RNF146 is implicated in neurodegenerative disease and cancer development. It regulates the development and progression of non-small cell lung cancer (NSCLC) by enhancing cell growth, invasion, and survival. RNF146 contains an N-terminal C3HC4-type RING-HC finger followed by a WWE domain with a poly(ADP-ribose) (PAR) binding motif at the tail.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 574280908 209 LECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPLCK 249
Cdd:cd16546    1 PECPICLQTCIHPVKLPCGHIFCYLCVKGVAWQSKRCALCR 41

RING finger, HC subclass, found in RING finger protein 169 (RNF169) and similar proteins; RNF169 is an uncharacterized E3 ubiquitin-protein ligase paralogous to RNF168. It functions as a negative regulator of the DNA damage signaling cascade. RNF169 recognizes polyubiquitin structures but does not itself contribute to double-strand break (DSB)-induced chromatin ubiquitylation. It contributes to regulation of the DSB repair pathway utilization via functionally competing with recruiting repair factors, 53BP1 and RAP80-BRCA1, for association with RNF168-modified chromatin independent of its catalytic activity, limiting the magnitude of the RNF8/RNF168-dependent signaling response to DSBs. RNF169 contains an N-terminal C3HC4-type RING-HC finger and a C-terminal MIU (motif interacting with ubiquitin) domain.

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gi 574280908 208 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNA---KCPLCK 249
Cdd:cd16551    1 ELTCAGCLEVPVEPATLPCGHTLCRGCANRALDAAEagpTCPRCR 45

RING finger, HC subclass, found in ligand of Numb protein LNX3, LNX4, and similar proteins; The ligand of Numb protein X (LNX) family, also known as PDZ and RING (PDZRN) family, includes LNX1-5, which can interact with Numb, a key regulator of neurogenesis and neuronal differentiation. LNX5 (also known as PDZK4, or PDZRN4L) shows high sequence homology to LNX3 and LNX4, but it lacks the RING domain. LNX1-4 proteins function as E3 ubiquitin ligases and have a unique domain architecture consisting of an N-terminal RING-HC finger for E3 ubiquitin ligase activity and either two or four PDZ domains necessary for the substrate-binding. This family corresponds to LNX3/LNX4-like proteins, which contains a C3HC4-type RING-HC finger and two PDZ domains.

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                 ....*....|....*....|....*....|....*....
gi 574280908 209 LECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPL 247
Cdd:cd16512    1 LKCKLCLGVLEEPLATPCGHVFCAGCVLPWVVRNGSCPL 39

RING finger, HC subclass, found in Arabidopsis thaliana protein BREAST CANCER SUSCEPTIBILITY 1 homolog (AtBRCA1) and similar proteins; AtBRCA1 plays a role in DNA repair and in cell-cycle control. It is required for the repair of DNA double-strand breaks (DSBs), both natural and induced by genotoxic stress, by homologous recombination (HR). AtBRCA1 contains a typical C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 574280908 208 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPLCK 249
Cdd:cd23147    4 ELKCPICLSLFKSAANLSCNHCFCAGCIGESLKLSAICPVCK 45

RING finger, HC subclass, found in tripartite motif-containing protein 69 (TRIM69) and similar proteins; TRIM69, also known as RFP-like domain-containing protein trimless or RING finger protein 36 (RNF36), is a testis E3 ubiquitin-protein ligase that plays a specific role in apoptosis and may also play an important role in germ cell homeostasis during spermatogenesis. TRIM69 belongs to the C-IV subclass of the 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 C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

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                 ....*....|....*....|....*....|....*....|....*
gi 574280908 208 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAK---CPLCK 249
Cdd:cd16611    4 ELHCPLCLDFFRDPVMLSCGHNFCQSCITGFWELQAEdttCPECR 48

Modified RING finger, HC subclass (C3HC3D-type), found in ligand of numb protein X 1 (LNX1); LNX1, also known as numb-binding protein 1 or PDZ domain-containing RING finger protein 2, is a PDZ domain-containing RING-type E3 ubiquitin ligase responsible for the ubiquitination and degradation of Numb, a component of the Notch signaling pathway that functions in the specification of cell fates during development and is known to control cell numbers during neurogenesis in vertebrates. LNX1 contains an N-terminal modified C3HC3D-type RING-HC finger, a NPAY motif for Numb-LNX interaction, and four PDZ domains necessary for the binding of substrates, including CAR, ErbB2, SKIP, JAM4, CAST, c-Src, Claudins, RhoC, KCNA4, PAK6, PLEKHG5, PKC-alpha1, TYK2, PDZ-binding kinase (PBK), LNX2, and itself.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 574280908 208 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPL 247
Cdd:cd16779    1 DLICHICLQALIQPLDTPCGHTYCTLCLTNFLVEKDFCPM 40

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 2(RNFT2); RNFT2, also known as transmembrane protein 118 (TMEM118), is a multi-pass membrane protein containing a C3HC4-type RING-HC finger. Its biological role remains unclear.

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gi 574280908 211 CALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPLCK 249
Cdd:cd16742   16 CAICQAEFREPLILICQHVFCEECLCLWFDRERTCPLCR 54

RING finger, HC subclass, found in tripartite motif-containing protein 62 (TRIM62) and similar proteins; TRIM62, also known as Ductal Epithelium Associated Ring Chromosome 1 (DEAR1), is a cytoplasmic E3 ubiquitin-protein ligase that was identified as a dominant regulator of acinar morphogenesis in the mammary gland. It is implicated in the inflammatory response of immune cells by regulating the Toll-like receptor 4 (TLR4) signaling pathway, leading to increased activity of the activator protein 1 (AP-1) transcription factor in primary macrophages. It is also involved in muscular protein homeostasis, especially during inflammation-induced atrophy, and may play a role in the pathogenesis of ICU-acquired weakness (ICUAW) by activating and maintaining inflammation in myocytes. Moreover, TRIM62 facilitates K27-linked poly-ubiquitination of CARD9 and also regulates CARD9-mediated anti-fungal immunity and intestinal inflammation. It also functions as a chromosome 1p35 tumor suppressor and negatively regulates transforming growth factor beta (TGFbeta)-driven epithelial-mesenchymal transition (EMT) by binding to and promoting the ubiquitination of SMAD3, a major effector of TGFbeta-mediated EMT. TRIM62 belongs to the C-IV subclass of the 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 C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

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                 ....*....|....*....|....*....|....*....|....*..
gi 574280908 208 DLECALCMRLFYEPVTTPCGHTFCLKCLErclDHNAK-----CPLCK 249
Cdd:cd16608    6 ELLCSICLSIYQDPVSLGCEHYFCRQCIT---EHWSRsehrdCPECR 49

RING finger, HC subclass, found in Caenorhabditis elegans RING finger protein NHL-1 and similar proteins; NHL-1 functions as an E3 ubiquitin-protein ligase in the presence of both UBC-13 and UBC-1 within the ubiquitin pathway of Caenorhabditis elegans. It acts in chemosensory neurons to promote stress resistance in distal tissues by the transcription factor DAF-16 activation but is dispensable for the activation of heat shock factor 1 (HSF-1). NHL-1 belongs to the TRIM (tripartite motif)-NHL family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil domain, as well as an NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 574280908 209 LECALCMRLFYEPVTTPCGHTFCLK-CLERCLDH---NAKCPLCK 249
Cdd:cd16524    6 LTCPICLDRYRRPKLLPCQHTFCLSpCLEGLVDYvtrKLKCPECR 50

RING finger, HC subclass, found in RING finger protein 185 (RNF185) and similar proteins; RNF185 is an E3 ubiquitin-protein ligase of endoplasmic reticulum-associated degradation (ERAD) that targets cystic fibrosis transmembrane conductance regulator (CFTR). It controls the degradation of CFTR and CFTR F508del allele in a RING- and proteasome-dependent manner, but does not control that of other classical ERAD model substrates. It also negatively regulates osteogenic differentiation by targeting dishevelled2 (Dvl2), a key mediator of the Wnt signaling pathway, for degradation. Moreover, RNF185 regulates selective mitochondrial autophagy through interaction with the Bcl-2 family protein BNIP1. It also plays an important role in cell adhesion and migration through the modulation of cell migration by ubiquitinating paxillin. RNF185 contains a C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 574280908 210 ECALCMRLFYEPVTTPCGHTFCLKCLERCLD---HNAKCPLCKDGLSQ 254
Cdd:cd16744    2 ECNICLDTAKDAVVSLCGHLFCWPCLHQWLEtrpNRQVCPVCKAGISR 49

RING finger, HC subclass, found in peroxin-10 (PEX10) and similar proteins; PEX10, also known as peroxisome biogenesis factor 10, peroxisomal biogenesis factor 10, peroxisome assembly protein 10, or RING finger protein 69 (RNF69), is an integral peroxisomal membrane protein with two transmembrane regions and a C3HC4-type RING-HC finger within its cytoplasmically exposed C-terminus. It plays an essential role in peroxisome assembly, import of target substrates, and recycling or degradation of protein complexes and amino acids. It is an essential component of the spinal locomotor circuit, and thus its mutations may be involved in peroxisomal biogenesis disorders (PBD). Mutations in human PEX10 also result in autosomal recessive ataxia. Moreover, PEX10 functions as an E3-ubiquitin ligase with an E2, UBCH5C. It mono- or poly-ubiquitinates PEX5, a key player in peroxisomal matrix protein import, in a UBC4-dependent manner, to control PEX5 receptor recycling or degradation. It also links the E2 ubiquitin conjugating enzyme PEX4 to the protein import machinery of the peroxisome.

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                 ....*....|....*....|....*....|....*...
gi 574280908 211 CALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPLC 248
Cdd:cd16527    3 CSLCLEERRHPTATPCGHLFCWSCITEWCNEKPECPLC 40

RING finger, HC subclass, found in midline-1 (MID1) and similar proteins; MID1, also known as midin, midline 1 RING finger protein, putative transcription factor XPRF, RING finger protein 59 (RNF59), or tripartite motif-containing protein 18 (TRIM18), is a microtubule-associated E3 ubiquitin-protein ligase implicated in epithelial-mesenchymal differentiation, cell migration and adhesion, and programmed cell death along specific regions of the ventral midline during embryogenesis. It monoubiquinates the alpha4 subunit of protein phosphatase 2A (PP2A), promoting proteosomal degradation of the catalytic subunit of PP2A (PP2Ac) and preventing the A and B subunits from forming an active complex. It promotes allergen and rhinovirus-induced asthma through the inhibition of PP2A activity. It is strongly upregulated in cytotoxic lymphocytes (CTLs) and directs lytic granule exocytosis and cytotoxicity of killer T cells. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (XLOS) syndrome characterized by defective midline development during embryogenesis. MID1 belongs to the C-I subclass of the 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 C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. MID1 hetero-dimerizes in vitro with its paralog MID2.

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 574280908 207 SDLECALCMRLFYEPVTTPCGHTFCLKCLERCL-DHNA-----------KCPLCK 249
Cdd:cd16753    4 SELTCPICLELFEDPLLLPCAHSLCFNCAHRILvSHCAsnesvesitafQCPTCR 58

RING finger, HC subclass, found in topoisomerase I-binding arginine/serine-rich protein (Topors) and similar proteins; Topors, also known as topoisomerase I-binding RING finger protein, tumor suppressor p53- binding protein 3, or p53-binding protein 3 (p53BP3), is a ubiquitously expressed nuclear E3 ubiquitin-protein ligase that can ligate both ubiquitin and small ubiquitin-like modifier (SUMO) to substrate proteins in the nucleus. It contains an N-terminal C3HC4-type RING-HC finger which ligates ubiquitin to its target proteins including DNA topoisomerase I, p53, NKX3.1, H2AX, and the AAV-2 Rep78/68 proteins. As a RING-dependent E3 ubiquitin ligase, Topors works with the E2 enzymes UbcH5a, UbcH5c, and UbcH6, but not with UbcH7, CDC34, or UbcH2b. Topors acts as a tumor suppressor in various malignancies. It regulates p53 modification, suggesting it may be responsible for astrocyte elevated gene-1 (AEG-1, also known as metadherin, or LYRIC) ubiquitin modification. Plk1-mediated phosphorylation of Topors inhibits Topors-mediated sumoylation of p53, whereas p53 ubiquitination is enhanced, leading to p53 degradation. It also functions as a negative regulator of the prostate tumor suppressor NKX3.1. Moreover, Topors is associated with promyelocytic leukemia nuclear bodies, and may be involved in the cellular response to camptothecin. It also plays a key role in the turnover of H2AX protein, discriminating the type of DNA damaging stress. Furthermore, Topors is a cilia-centrosomal protein associated with autosomal dominant retinal degeneration. Mutations in TOPORS cause autosomal dominant retinitis pigmentosa (adRP).

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gi 574280908 208 DLECALCMRLFYEP--VTTPCGHTFCLKCLERCLDHNAKCPLCK 249
Cdd:cd16574    1 DSSCPICLDRFENEkaFLDGCFHAFCFTCILEWSKVKNECPLCK 44