first BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also termed RING finger protein 53 (RNF53), is a RING finger protein encoded by BRCA1, a tumor suppressor gene 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. The family corresponds to the first BRCT domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1950431363 1684 MSIVASGLNQRELLLVQKFARKTQSTLSNQITEGTTHVIMKTDMELVCERTLKYFLGIAGRKWVVSYEWIVQSFKEGKIL 1763
Cdd:cd17735      1 MSMVASGLTPEELMLVQKFARKTGSTLTSQFTEETTHVIMKTDAELVCERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                           90
                   ....*....|....*..
gi 1950431363 1764 DEYDFEVRGDVINGRNH 1780
Cdd:cd17735     81 PEHDFEVRGDVVNGRNH 97

second (C-terminal) BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also termed RING finger protein 53 (RNF53), is a RING finger protein encoded by BRCA1, a tumor suppressor gene 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 repeats at the C-terminus. The family corresponds to the second BRCT domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1950431363 1793 KLFKDIEICCYGPFTDMRTGDLEWMVELCGASVVKQPHLFTHKANSTAVIVVQPDAWLEYAGYRVIQQKCTAM-VTREWV 1871
Cdd:cd17721      2 LLFRGFEICCYGPFTNMTKDQLEWLLELCGATVVKEPSLFTAKPGKKRLIVVQPDAWTEDNDYNAIYRRYKALvVTREWV 81

                           90
                   ....*....|....*..
gi 1950431363 1872 LDSVACYECQEFDTYLV 1888
Cdd:cd17721     82 LDSVALYKVQPLDAYLL 98

first BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also termed RING finger protein 53 (RNF53), is a RING finger protein encoded by BRCA1, a tumor suppressor gene 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. The family corresponds to the first BRCT domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1950431363 1684 MSIVASGLNQRELLLVQKFARKTQSTLSNQITEGTTHVIMKTDMELVCERTLKYFLGIAGRKWVVSYEWIVQSFKEGKIL 1763
Cdd:cd17735      1 MSMVASGLTPEELMLVQKFARKTGSTLTSQFTEETTHVIMKTDAELVCERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                           90
                   ....*....|....*..
gi 1950431363 1764 DEYDFEVRGDVINGRNH 1780
Cdd:cd17735     81 PEHDFEVRGDVVNGRNH 97

second (C-terminal) BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also termed RING finger protein 53 (RNF53), is a RING finger protein encoded by BRCA1, a tumor suppressor gene 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 repeats at the C-terminus. The family corresponds to the second BRCT domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1950431363 1793 KLFKDIEICCYGPFTDMRTGDLEWMVELCGASVVKQPHLFTHKANSTAVIVVQPDAWLEYAGYRVIQQKCTAM-VTREWV 1871
Cdd:cd17721      2 LLFRGFEICCYGPFTNMTKDQLEWLLELCGATVVKEPSLFTAKPGKKRLIVVQPDAWTEDNDYNAIYRRYKALvVTREWV 81

                           90
                   ....*....|....*..
gi 1950431363 1872 LDSVACYECQEFDTYLV 1888
Cdd:cd17721     82 LDSVALYKVQPLDAYLL 98

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
                   ....*....|....*....|....*....|....*....|...
gi 1950431363   24 CPICLELIKEPV-STKCDHIFCRFCMFKLLSKKKKgpaQCPLC 65
Cdd:pfam00097    1 CPICLEEPKDPVtLLPCGHLFCSKCIRSWLESGNV---TCPLC 40

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1950431363  1793 KLFKDIEICCYGPFTDMRTGDLEWMVELCGASVVKQPHLFThkansTAVIVVQPDAWLEYAGYRVIQQKCtAMVTREWVL 1872
Cdd:smart00292    2 KLFKGKTFYITGSFDKEERDELKELIEALGGKVTSSLSSKT-----TTHVIVGSPEGGKLELLKAIALGI-PIVKEEWLL 75

                    ...
gi 1950431363  1873 DSV 1875
Cdd:smart00292   76 DCL 78

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1950431363   21 NLECPICLELIKEPVSTKCDHIFCRFCMFKLLSKKKkgPAQCPLCKTEV 69
Cdd:COG5574    215 DYKCFLCLEEPEVPSCTPCGHLFCLSCLLISWTKKK--YEFCPLCRAKV 261

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1950431363   15 LLAMQKNLECPICLELIKEPVSTKCDHIFCRFCMFKLLSKKKKgpaqCPLCKTEVTKRSLQENPRFKQLIEG 86
Cdd:TIGR00599   20 LYPLDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPK----CPLCRAEDQESKLRSNWLVSEIVES 87

first BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also termed RING finger protein 53 (RNF53), is a RING finger protein encoded by BRCA1, a tumor suppressor gene 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. The family corresponds to the first BRCT domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1950431363 1684 MSIVASGLNQRELLLVQKFARKTQSTLSNQITEGTTHVIMKTDMELVCERTLKYFLGIAGRKWVVSYEWIVQSFKEGKIL 1763
Cdd:cd17735      1 MSMVASGLTPEELMLVQKFARKTGSTLTSQFTEETTHVIMKTDAELVCERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                           90
                   ....*....|....*..
gi 1950431363 1764 DEYDFEVRGDVINGRNH 1780
Cdd:cd17735     81 PEHDFEVRGDVVNGRNH 97

second (C-terminal) BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also termed RING finger protein 53 (RNF53), is a RING finger protein encoded by BRCA1, a tumor suppressor gene 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 repeats at the C-terminus. The family corresponds to the second BRCT domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1950431363 1793 KLFKDIEICCYGPFTDMRTGDLEWMVELCGASVVKQPHLFTHKANSTAVIVVQPDAWLEYAGYRVIQQKCTAM-VTREWV 1871
Cdd:cd17721      2 LLFRGFEICCYGPFTNMTKDQLEWLLELCGATVVKEPSLFTAKPGKKRLIVVQPDAWTEDNDYNAIYRRYKALvVTREWV 81

                           90
                   ....*....|....*..
gi 1950431363 1872 LDSVACYECQEFDTYLV 1888
Cdd:cd17721     82 LDSVALYKVQPLDAYLL 98

first BRCT domain of BRCA1-associated RING domain protein 1 (Bard1) and similar proteins; Bard1, also termed BARD-1, or RING-type E3 ubiquitin transferase BARD1, is a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. It associates with BRCA1 (breast cancer-1) to form a heterodimeric BRCA1/BARD1 complex that is responsible for maintaining genomic stability through nuclear functions involving DNA damage signaling and repair, transcriptional regulation, and cell cycle control. The BRCA1/BARD1 complex catalyzes autoubiquitination of BRCA1 and trans ubiquitination of other protein substrates. Its E3 ligase activity is dramatically reduced in the presence of UBX domain protein 1 (UBXN1). BARD-1 contains an N-terminal C3HC4-type RING-HC finger that binds BRCA1, and a C-terminal region with three ankyrin repeats and tandem BRCT domains that bind CstF-50 (cleavage stimulation factor) to modulate mRNA processing and RNAP II stability in response to DNA damage. The family corresponds to the first BRCT domain.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1950431363 1686 IVASGLNQRELLLVQKFARKTQSTLSNQITEGTTHVIMKTDMELVCERTLKYFLGIAGRKWVVSYEWIVQSFKEGKIL 1763
Cdd:cd17734      3 LLGSGLSSEQKKLLEKLAQLLKAKVVTEFSPEVTHVVVPADERGVCPRTMKYLMGILAGKWIVSFEWVEACLKAKKLV 80

RING finger, HC subclass, found in RING finger protein 10 (RNF10) and similar proteins; RNF10 is an E3 ubiquitin-protein ligase that interacts with mesenchyme Homeobox 2 (MEOX2) transcription factor, a regulator of the proliferation, differentiation and migration of vascular smooth muscle cells and cardiomyocytes; it enhances Meox2 activation of the p21 promoter. It also regulates the expression of myelin-associated glycoprotein (MAG) genes and is required for myelin production in Schwann cells of the peripheral nervous system. Moreover, RNF10 regulates retinoic acid-induced neuronal differentiation and the cell cycle exit of P19 embryonic carcinoma cells. RNF10 contains a C3HC4-type RING-HC finger and three putative nuclear localization signals.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1950431363   23 ECPICLElikEPVS---TKCDHIFCRFCMFKLLSKKKKGPAQCPLCKTEVTKRSLQ 75
Cdd:cd16536      2 QCPICLE---PPVApriTRCGHIFCWPCILRYLSLSEKKWRKCPICFESIHKKDLR 54

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 1950431363   22 LECPICLELIKEPVSTKCDHIFCRFCMFKLLskkKKGPAQCPLC 65
Cdd:cd16449      1 LECPICLERLKDPVLLPCGHVFCRECIRRLL---ESGSIKCPIC 41

RING finger, HC subclass, found in helicase-like transcription factor (HLTF) and similar proteins; HLTF, also known as DNA-binding protein/plasminogen activator inhibitor 1 regulator, HIP116, RING finger protein 80, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 3, or sucrose nonfermenting protein 2-like 3, is a yeast RAD5 homolog found in mammals. It has both E3 ubiquitin ligase and DNA helicase activities, and plays a pivotal role in the template-switching pathway of DNA damage tolerance. It is involved in Lys-63-linked poly-ubiquitination of proliferating cell nuclear antigen (PCNA) at Lys-164 and in the regulation of DNA damage tolerance. It shows double-stranded DNA translocase activity with 3'-5' polarity, thereby facilitating regression of the replication fork. HLTF contains an N-terminal HIRAN (HIP116 and RAD5 N-terminal) domain, a SWI/SNF helicase domain that is divided into N- and C-terminal parts by an insertion of a C3HC4-type RING-HC finger involved in the poly-ubiquitination of PCNA.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1950431363   23 ECPICLELIKEPVSTKCDHIFCRFCMFKLLSKKKkgpAQCPLCKTEVTKRSL 74
Cdd:cd16509      5 ECAICLDSLTNPVITPCAHVFCRRCICEVIQREK---AKCPMCRAPLSASDL 53

second RING finger, HC subclass, found in the LON peptidase N-terminal domain and RING finger protein family; The LON peptidase N-terminal domain and RING finger protein family includes LONRF1 (also known as RING finger protein 191 or RNF191), LONRF2 (also known as RING finger protein 192, RNF192, or neuroblastoma apoptosis-related protease), LONRF3 (also known as RING finger protein 127 or RNF127), which are characterized by containing two C3HC4-type RING-HC fingers, four tetratricopeptide (TPR) repeats, and an ATP-dependent protease La (LON) substrate-binding domain at the C-terminus. Their biological functions remain unclear. This model corresponds to the second RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1950431363   22 LECPICLELIKEPVSTKCDHIFCRFCMFKLLSKKKKgpaqCPLCKT 67
Cdd:cd16514      2 LECSLCLRLLYEPVTTPCGHTFCRACLERCLDHSPK----CPLCRT 43

RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; RNF138, also known as Nemo-like kinase-associated RING finger protein (NARF) or NLK-associated RING finger protein, is an E3 ubiquitin-protein ligase that plays an important role in glioma cell proliferation, apoptosis, and cell cycle. It specifically cooperates with the E2 conjugating enzyme E2-25K (Hip-2/UbcH1), regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF), and further suppresses Wnt-beta-catenin signaling. RNF138, together with three closely related proteins: RNF114, RNF125 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        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1950431363   22 LECPICLELIKEPVST-KCDHIFCRFCmfkLLSKKKKGPAQCPLCKTEVTKR 72
Cdd:cd16544      3 LTCPVCQEVLKDPVELpPCRHIFCKAC---ILLALRSSGARCPLCRGPVGKT 51

RING finger, HC subclass, found in tripartite motif-containing protein 40 (TRIM40) and similar proteins; TRIM40, also known as probable E3 NEDD8-protein ligase or RING finger protein 35 (RNF35), is highly expressed in the gastrointestinal tract including the stomach, small intestine, and large intestine. It enhances neddylation of inhibitor of nuclear factor kappaB kinase subunit gamma (IKKgamma), inhibits the activity of nuclear factor-kappaB (NF-kappaB)-mediated transcription, and thus prevents inflammation-associated carcinogenesis in the gastrointestinal tract. TRIM40 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1950431363   24 CPICLELIKEPVSTKCDHIFCRFCMFKLLSK-KKKGPAQCPLCKTEVTKRSLQEN 77
Cdd:cd16583      8 CPICQEPLKEAVSTDCGHLFCRMCLTQHAKKaSASGVFSCPVCRKPCSEGVLGDG 62

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 1950431363   23 ECPICLELIKEPVSTKCDHIFCRFCMFKLLSKKKKGPaQCPLCK 66
Cdd:cd16745      2 ECNICLDLAQDPVVTLCGHLFCWPCLHKWLRRQSSQP-ECPVCK 44

RING finger, HC subclass, found in Ret finger protein-like 4B (RFPL4B) and similar proteins; RFPL4B, also called RING finger protein 211 (RNF211), is an uncharacterized RING finger protein containing a typical C3HC4-type RING-HC finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1950431363   18 MQKNLECPICLELIKEPVSTKCDHIFCRFCMFKLLSKKKKGPAQCPLCKTEVTKRSLQE 76
Cdd:cd16623      5 LEMEATCPICLDFFSHPISLSCAHIFCFDCIQKWMTKREDSILTCPLCRKEQKKPVLEE 63

RING finger, HC subclass, found in constitutive photomorphogenesis protein 1 (COP1) and similar proteins; COP1, also known as RING finger and WD repeat domain protein 2 (RFWD2) or RING finger protein 200 (RNF200), is a central regulator of photomorphogenic development in plants, which targets key transcription factors for proteasome-dependent degradation. It is localized predominantly in the nucleus, but may also be present in the cytosol. Mammalian COP1 functions as an E3 ubiquitin-protein ligase that interacts with Jun transcription factors and modulates their transcriptional activity. It also interacts with and negatively regulates the tumor-suppressor protein p53. Moreover, COP1 associates with COP9 signalosome subunit 6 (CSN6), and is involved in 14-3-3sigma ubiquitin-mediated degradation. The CSN6-COP1 link enhances ubiquitin-mediated degradation of p27(Kip1), a critical CDK inhibitor involved in cell cycle regulation, to promote cancer cell growth. Furthermore, COP1 functions as the negative regulator of ETV1 and influences prognosis in triple-negative breast cancer. COP1 contains an N-terminal extension, a C3HC4-type RING-HC finger, a coiled coil domain, and seven WD40 repeats. In human COP1, a classic leucine-rich NES, and a novel bipartite NLS is bridged by the RING-HC finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1950431363   20 KNLECPICLELIKEPVSTKCDHIFCRFCMFKLLSKKKKgpaqCPLCKTEVT 70
Cdd:cd16504      1 NDFLCPICFDIIKEAFVTKCGHSFCYKCIVKHLEQKNR----CPKCNFYLT 47

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM5, TRIM6, TRIM22, TRIM34 and similar proteins; TRIM5, TRIM6, TRIM22, and TRIM34, four 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, 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. TRIM5, also known as RING finger protein 88 (RNF88), is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. Its retroviral restriction activity correlates with the ability to activate TAK1-dependent innate immune signaling. TRIM5 also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Moreover, TRIM5 plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. It also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction. TRIM6, also known as RING finger protein 89 (RNF89), is an E3-ubiquitin ligase that cooperates with the E2-ubiquitin conjugase UbE2K to catalyze the synthesis of unanchored K48-linked polyubiquitin chains, and further stimulates the interferon-I kappa B kinase epsilon (IKKepsilon) kinase-mediated antiviral response. It also regulates the transcriptional activity of Myc during the maintenance of embryonic stem (ES) cell pluripotency, and may act as a novel regulator for Myc-mediated transcription in ES cells. TRIM22, also known as 50 kDa-stimulated trans-acting factor (Staf-50) or RING finger protein 94 (RNF94), is an E3 ubiquitin-protein ligase that plays an integral role in the host innate immune response to viruses. It has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. TRIM22 acts as a suppressor of basal HIV-1 long terminal repeat (LTR)-driven transcription by preventing the transcription factor specificity protein 1 (Sp1) binding to the HIV-1 promoter. It also controls FoxO4 activity and cell survival by directing Toll-like receptor 3 (TLR3)-stimulated cells toward type I interferon (IFN) type I gene induction or apoptosis. Moreover, TRIM22 can activate the noncanonical nuclear factor-kappaB (NF-kappaB) pathway by activating I kappa B kinase alpha (IKKalpha). It also regulates nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-kappaB. TRIM34, also known as interferon-responsive finger protein 1 or RING finger protein 21 (RNF21), may function as antiviral protein that contribute to the defense against retroviral infections.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1950431363   18 MQKNLECPICLELIKEPVSTKCDHIFCRFCMF--KLLSKKKKGPAQCPLCKTEVTKRSLQENPRFKQLIE 85
Cdd:cd16591      3 IKEEVTCPICLELLTEPLSLDCGHSFCQACITanHKESVNQEGESSCPVCRTSYQPENLRPNRHLANIVE 72

RING finger, HC subclass, found in tripartite motif-containing protein TRIM21 and similar proteins; TRIM21, also known as 52 kDa Ro protein, 52 kDa ribonucleoprotein autoantigen Ro/SS-A, Ro(SS-A), RING finger protein 81 (RNF81), or Sjoegren syndrome type A antigen (SS-A), is a ubiquitously expressed E3 ubiquitin-protein ligase and a high affinity antibody receptor uniquely expressed in the cytosol of mammalian cells. As a cytosolic Fc receptor, TRIM21 binds the Fc of virus-associated antibodies and targets the complex in the cytosol for proteasomal degradation in a process known as antibody-dependent intracellular neutralization (ADIN), and provides an intracellular immune response to protect host defense against pathogen infection. It shows remarkably broad isotype specificity as it does not only bind IgG, but also IgM and IgA. Moreover, TRIM21 promotes the cytosolic DNA sensor cGAS and the cytosolic RNA sensor RIG-I sensing of viral genomes during infection by antibody-opsonized virus. It stimulates inflammatory signaling and activates innate transcription factors, such as nuclear factor-kappaB (NF-kappaB). TRIM21 also plays an essential role in p62-regulated redox homeostasis, suggesting it may be a viable target for treating pathological conditions resulting from oxidative damage. Furthermore, TRIM21 may have implications for various autoimmune diseases associated with uncontrolled antiviral signaling through the regulation of Nmi-IFI35 complex-mediated inhibition of innate antiviral response. TRIM21 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        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1950431363   18 MQKNLECPICLELIKEPVSTKCDHIFCRFCMFKLlskKKKGPAQCPLCKTEVTKRSLQENPRFKQLIEGL 87
Cdd:cd16596      6 MWEEVTCPICLDPFVEPVSIECGHSFCQECISQV---GKGGGSVCPVCRQRFLLKNLRPNRQLANMVNNL 72

RING finger, HC subclass, found in really interesting new gene 1 protein (RING1) and similar proteins; RING1, also known as polycomb complex protein RING1, RING finger protein 1 (RNF1), or RING finger protein 1A (RING1A), was identified as a transcriptional repressor that is associated with the Polycomb group (PcG) protein complex involved in stable repression of gene activity. It is a core component of polycomb repressive complex 1 (PRC1) that functions as an E3-ubuiquitin ligase that transferring the mono-ubuiquitin mark to the C-terminal tail of Histone H2A at K118/K119. PRC1 is also capable of chromatin compaction, a function not requiring histone tails, and this activity appears important in gene silencing. RING1 interacts with multiple PcG proteins and displays tumorigenic activity. It also shows zinc-dependent DNA binding activity. Moreover, RING1 inhibits transactivation of the DNA-binding protein recombination signal binding protein-Jkappa (RBP-J) by Notch through interaction with the LIM domains of KyoT2. RING1 contains a C3HC4-type RING-HC finger.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1950431363   19 QKNLECPICLELIKEPVSTK-CDHIFCRFCMFKLLskkKKGPAQCPLCKTE-VTKRSLQENPRFKQLI 84
Cdd:cd16739      1 HSELMCPICLDMLKNTMTTKeCLHRFCSDCIVTAL---RSGNKECPTCRKKlVSKRSLRPDPNFDALI 65

RING finger, HC subclass, found in RING finger protein 180 (RNF180) and similar proteins; RNF180, also known as Rines, is a membrane-bound E3 ubiquitin-protein ligase well conserved among vertebrates. It is a critical regulator of the monoaminergic system, as well as emotional and social behavior. It interacts with brain monoamine oxidase A (MAO-A) and targets it for ubiquitination and degradation. It also functions as a novel tumor suppressor in gastric carcinogenesis. The hypermethylated CpG site count of the RNF180 DNA promoter can be used to predict survival of gastric cancer. RNF180 contains a novel conserved dual specificity protein phosphatase Rines conserved (DSPRC) domain, a basic coiled-coil domain, a C3HC4-type RING-HC finger, and a C-terminal hydrophobic region that is predicted to be a transmembrane domain.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1950431363   21 NLECPICLELIKEP-VSTKCDHIFCRFCMfKLLSKKKKGPAQCPLCKTEVTKRSLQEN 77
Cdd:cd16554      2 SLTCPVCLDLYYDPyMCYPCGHIFCEPCL-RQLAKSSPKNTPCPLCRTTIRRVFFQEE 58

RING finger, HC subclass, found in tripartite motif-containing protein 26 (TRIM26) and similar proteins; TRIM26, also known as acid finger protein (AFP), RING finger protein 95 (RNF95), or zinc finger protein 173 (ZNF173), is an E3 ubiquitin-protein ligase that negatively regulates interferon-beta production and antiviral response through polyubiquitination and degradation of nuclear transcription factor IRF3. It functions as an important regulator for RNA virus-triggered innate immune response by bridging TBK1 to NEMO (NF-kappaB essential modulator, also known as IKKgamma) and mediating TBK1 activation. It also acts as a novel tumor suppressor of hepatocellular carcinoma by regulating cancer cell proliferation, colony forming ability, migration, and invasion. TRIM26 belongs 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.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1950431363   18 MQKNLECPICLELIKEPVSTKCDHIFCRFCMFKLLSKK-KKGPAQCPLCKTEVTKRSLQENprfKQL 83
Cdd:cd16598      1 LEEEVTCSICLDYLRDPVTIDCGHNFCRSCITDYCPISgGHERPVCPLCRKPFKKENIRPN---WQL 64

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM41, TRIM52 and similar proteins; TRIM41 and TRIM52, two closely related tripartite motif-containing proteins, have dramatically expanded RING domains compared with the rest of the TRIM family proteins. TRIM41 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. In contrast, TRIM52 lacks the putative viral recognition SPRY/B30.2 domain, and thus has been classified to the C-V subclass of the TRIM family that contains only RBCC domains. TRIM41, also known as RING finger-interacting protein with C kinase (RINCK), is an E3 ubiquitin-protein ligase that promotes the ubiquitination of protein kinase C (PKC) isozymes in cells. It specifically recognizes the C1 domain of PKC isozymes. It controls the amplitude of PKC signaling by controlling the amount of PKC in the cell. TRIM52, also known as RING finger protein 102 (RNF102), is encoded by a novel, noncanonical antiviral TRIM52 gene in primate genomes with unique specificity determined by the rapidly evolving RING domain.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1950431363   19 QKNLECPICLELIKEPVSTKCDHIFCRFCMFKLLSkkkkgpAQCPLCKTEVTKRSLQEN 77
Cdd:cd16602      1 QEEAVCAICLDYFKDPVSIGCGHNFCRVCVTQLWG------FTCPQCRKSFPRRSFRPN 53

RING finger, HC subclass, found in tripartite motif-containing protein TRIM65 and similar proteins; TRIM65 is an E3 ubiquitin-protein ligase that interacts with the innate immune receptor MDA5, enhancing its ability to stimulate interferon-beta signaling. It functions as a potential oncogenic protein that negatively regulates p53 through ubiquitination, providing insight into the development of novel approaches targeting TRIM65 for non-small cell lung carcinoma (NSCLC) treatment, and also overcoming chemotherapy resistance. Moreover, TRIM65 negatively regulates microRNA-driven suppression of mRNA translation by targeting TNRC6 proteins for ubiquitination and degradation. TRIM65 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        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1950431363   22 LECPICLELIKEPVSTKCDHIFCRFCMFKLLSKKKKGPAQCPLCKTEVTKR 72
Cdd:cd16609      4 LTCSICLGLYQDPVTLPCQHSFCRACIEDHWRQKDEGSFSCPECRAPFPEG 54

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 1950431363   19 QKNLECPICLELIKEPVSTKCDHIFCRFCMFkLLSKKKKGPAQCPLCKTEVTKR 72
Cdd:cd23133      1 EETLTCSICQGIFMNPVYLRCGHKFCEACLL-LFQEDIKFPAYCPMCRQPFNQE 53

RING finger, HC subclass, found in Arabidopsis thaliana proteolysis 1 protein (PRT1) and similar proteins; PRT1, also called RING-type E3 ubiquitin transferase PRT1, is an E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. It functions in the N-end rule pathway of protein degradation, where it specifically recognizes and ubiquitinates proteins with an N-terminal bulky aromatic amino acid (Phe). It does not act on aliphatic hydrophobic and basic N-terminal residues (Arg or Leu) containing proteins. PRT1 contains a typical C3HC4-type RING-HC finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1950431363   22 LECPICLELIKEPVSTKCDHIFCRFCMFKLLSKKKKgpAQCPLCKTEVTK 71
Cdd:cd23132      3 FLCCICLDLLYKPVVLECGHVFCFWCVHRCMNGYDE--SHCPLCRRPYDH 50

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1950431363  1793 KLFKDIEICCYGPFTDMRTGDLEWMVELCGASVVKQPHLFThkansTAVIVVQPDAWLEYAGYRVIQQKCtAMVTREWVL 1872
Cdd:smart00292    2 KLFKGKTFYITGSFDKEERDELKELIEALGGKVTSSLSSKT-----TTHVIVGSPEGGKLELLKAIALGI-PIVKEEWLL 75

                    ...
gi 1950431363  1873 DSV 1875
Cdd:smart00292   76 DCL 78

RING finger, HC subclass, found in really interesting new gene 2 protein (RING2) and similar proteins; RING2, also known as huntingtin-interacting protein 2-interacting protein 3, HIP2-interacting protein 3, protein DinG, RING finger protein 1B (RING1B), RING finger protein 2 (RNF2), or RING finger protein BAP-1, is an E3 ubiquitin-protein ligase that interacts with both nucleosomal DNA and an acidic patch on histone H4 to achieve the specific monoubiquitination of K119 on histone H2A (H2AK119ub), thereby playing a central role in histone code and gene regulation. RING2 is a core component of polycomb repressive complex 1 (PRC1) that functions as an E3-ubuiquitin ligase transferring the mono-ubuiquitin mark to the C-terminal tail of Histone H2A at K118/K119. PRC1 is also capable of chromatin compaction, a function not requiring histone tails, and this activity appears important in gene silencing. The enzymatic activity of RING2 is enhanced by the interaction with BMI1/PCGF4, and it is dispensable for early embryonic development and much of the gene repression activity of PRC1. Moreover, RING2 plays a key role in terminating neural precursor cell (NPC)-mediated production of subcerebral projection neurons (SCPNs) during neocortical development. It also plays a critical role in nonhomologous end-joining (NHEJ)-mediated end-to-end chromosome fusions. Furthermore, RING2 is essential for expansion of hepatic stem/progenitor cells. It promotes hepatic stem/progenitor cell expansion through simultaneous suppression of cyclin-dependent kinase inhibitors (CDKIs) Cdkn1a and Cdkn2a, known negative regulators of cell proliferation. RING2 also negatively regulates p53 expression through directly binding with both p53 and MDM2 and promoting MDM2-mediated p53 ubiquitination in selective cancer cell types to stimulate tumor development. RING2 contains a C3HC4-type RING-HC finger.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1950431363   17 AMQKNLECPICLELIKEPVSTK-CDHIFCRFCMFKLLskkKKGPAQCPLCKTE-VTKRSLQENPRFKQLI 84
Cdd:cd16740      8 SLHSELMCPICLDMLKNTMTTKeCLHRFCADCIITAL---RSGNKECPTCRKKlVSKRSLRPDPNFDALI 74

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 1950431363   18 MQKNLECPICLELIKEPVSTKCDHIFCRFCmfklLSKKKKGPAQCPLCK 66
Cdd:cd23146      1 MELELKCPICLKLLNRPVLLPCDHIFCSSC----ITDSTKVGSDCPVCK 45

zinc finger of C3HC4-type, RING; This is a family of primate-specific Ret finger protein-like (RFPL) zinc-fingers of the C3HC4 type. Ret finger protein-like proteins are primate-specific target genes of Pax6, a key transcription factor for pancreas, eye and neocortex development. This domain is likely to be DNA-binding. This zinc-finger domain together with the RDM domain, pfam11002, forms a large zinc-finger structure of the RING/U-Box superfamily. RING-containing proteins are known to exert an E3 ubiquitin protein ligase activity with the zinc-finger structure being mandatory for binding to the E2 ubiquitin-conjugating enzyme.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1950431363   24 CPICLELIKEPVSTKCDHIFCRFCMFKLLSKKKKGPAQCPLC 65
Cdd:pfam15227    1 CPICLDYLEKPVSIECGHSFCLSCINSLQKEPDGESLLCPQC 42

Zinc finger, C3HC4 type (RING finger);

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1950431363   23 ECPICLELIKEP-VSTKCDHIFCRFCMFKLLSKKKkgpaQCPLC 65
Cdd:pfam13923    1 MCPICMDMLKDPsTTTPCGHVFCQDCILRALRAGN----ECPLC 40

RING finger, HC subclass, found in postreplication repair protein RAD18 and similar proteins; RAD18, also known as HR18 or RING finger protein 73 (RNF73), is an E3 ubiquitin-protein ligase involved in post replication repair of UV-damaged DNA via its recruitment to stalled replication forks. It associates to the E2 ubiquitin conjugating enzyme UBE2B to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono-ubiquitination of DNA-associated PCNA on K164. It also interacts with another E2 ubiquitin conjugating enzyme RAD6 to form a complex that monoubiquitinates proliferating cell nuclear antigen at stalled replication forks in DNA translesion synthesis. Moreover, Rad18 is a key factor in double-strand break DNA damage response (DDR) pathways via its association with K63-linked polyubiquitylated chromatin proteins. It can function as a mediator for DNA damage response signals to activate the G2/M checkpoint in order to maintain genome integrity and cell survival after ionizing radiation (IR) exposure. RAD18 contains a C3HC4-type RING-HC finger, a ubiquitin-binding zinc finger domain (UBZ), a SAP (SAF-A/B, Acinus and PIAS) domain, and a RAD6-binding domain (R6BD).

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1950431363   22 LECPICLELIK-EPVSTKCDHIFCRFCMFKLLSKKKkgpaQCPLCKTEVTKRSL 74
Cdd:cd16529      5 LRCPICFEYFNtAMMITQCSHNYCSLCIRRFLSYKT----QCPTCRAAVTESDL 54

RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1950431363   24 CPICLELIKEPVsTKCDHIFCRFCMfKLLSKKKKGPAQCP 63
Cdd:pfam13445    1 CPICLELFTDPV-LPCGHTFCRECL-EEMSQKKGGKFKCP 38

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        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1950431363   22 LECPICLELIKEPVSTKCDHIFCRFCMfkLLSKKKKGPAQCPLCKTEVTKRSLQENPRFKQLIE 85
Cdd:cd16599      5 LLCPICYEPFREAVTLRCGHNFCKGCV--SRSWERQPRAPCPVCKEASSSDDLRTNHTLNNLVE 66

RING finger, HC subclass, found in tripartite motif-containing protein TRIM17 and similar proteins; TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (Terf), is a crucial E3 ubiquitin ligase that is necessary and sufficient for neuronal apoptosis and contributes to Mcl-1 ubiquitination in cerebellar granule neurons (CGNs). It interacts in a SUMO-dependent manner with nuclear factor of activated T cell NFATc3 transcription factor, and thus inhibits the activity of NFATc3 by preventing its nuclear localization. In contrast, it binds to and inhibits NFATc4 transcription factor in a SUMO-independent manner. Moreover, TRIM17 stimulates degradation of kinetochore protein ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates cell proliferation. TRIM17 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        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1950431363   18 MQKNLECPICLELIKEPVSTKCDHIFCRFCM--------FKLLSKKKKGPAQCPLCKTEVTKRSLQEN 77
Cdd:cd16595      2 LQEEATCSICLDYFTDPVMTTCGHNFCRACIqlswekarGKKGRRKQKGSFPCPECREMSPQRNLRPN 69

RING finger, HC subclass, found in Equid alphaherpesvirus 1 (Equine herpesvirus 1/EHV-1) regulatory protein and similar proteins; EHV-1 regulatory protein belongs to the Vmw110 (IPC0) protein family. It contains a typical C3HC4-type RING-HC finger and binds zinc stably.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1950431363   23 ECPICLELIK-EPVSTKCDHIFCRFCMFKLLSKKkkgpAQCPLCKTEVT 70
Cdd:cd23130      2 VCPICLDDPEdEAITLPCLHQFCYTCILRWLQTS----PTCPLCKTPVT 46

RING finger, HC subclass, found in tripartite motif-containing protein 10 (TRIM10) and similar proteins; TRIM10, also known as B30-RING finger protein (RFB30), RING finger protein 9 (RNF9), or hematopoietic RING finger 1 (HERF1), is a novel hematopoiesis-specific RING finger protein required for terminal differentiation of erythroid cells. TRIM10 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        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1950431363   18 MQKNLECPICLELIKEPVSTKCDHIFCRFCMFKLLSKKKKG---PAQCPLCK 66
Cdd:cd16593      2 LADEVNCPICQGTLREPVTIDCGHNFCRACLTRYCEIPGPDleePPTCPLCK 53

RING finger, HC subclass, found in RING finger protein 151 (RNF151) and similar proteins; RNF151 is a testis-specific RING finger protein that interacts with dysbindin, a synaptic and microtubular protein that binds brain snapin, a SNARE-binding protein that mediates intracellular membrane fusion in both neuronal and non-neuronal cells. Thus, it may be involved in acrosome formation of spermatids by interacting with multiple proteins participating in membrane biogenesis and microtubule organization. RNF151 contains a C3HC4-type RING finger domain, a putative nuclear localization signal (NLS), and a TNF receptor associated factor (TRAF)-type zinc finger domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1950431363   21 NLECPICLELIKEPVSTKCDHIFCRFCMFKLLSKKKKgpaqCPLCKTEV 69
Cdd:cd16547      3 DLICSICHGVLRCPVRLSCSHIFCKKCILQWLKRQET----CPCCRKEV 47

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 1950431363   24 CPICLELIKEPVSTKCDHIFCRFCMfKLLSKKKKGPAQCPLC 65
Cdd:cd16601      4 CSLCKEYLKDPVIIECGHNFCRACI-TRFWEELDGDFPCPQC 44