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 1379060902 109 QEFMCSVCLELLWKPVVLECGHVFCFWCGYQCMNVYDVSRCPLCKNAFDKFP 160
Cdd:cd23132     1 EEFLCCICLDLLYKPVVLECGHVFCFWCVHRCMNGYDESHCPLCRRPYDHFP 52

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 1379060902 109 QEFMCSVCLELLWKPVVLECGHVFCFWCGYQCMNVYDVSRCPLCKNAFDKFP 160
Cdd:cd23132     1 EEFLCCICLDLLYKPVVLECGHVFCFWCVHRCMNGYDESHCPLCRRPYDHFP 52

Zinc finger, ZZ type. Zinc finger present in potassium channel modulatory factor (PCMF) 1 and related proteins. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding. Human potassium channel modulatory factor 1 or FIGC has been shown to possess intrinsic E3 ubiquitin ligase activity and to promote ubiquitination.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1379060902 398 VSCDGCGKMPIVGRRHTCVDCgkaaCDFDLCGACQDAGYNkpgrfNQNHSADHEVRLV 455
Cdd:cd02338     1 VSCDGCGKSNFTGRRYKCLIC----YDYDLCADCYDSGVT-----TERHLFDHPMQCI 49

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 1379060902 113 CSVCLELLWKPVVLECGHVFCFWCGYQ-CMNVYDVS-RCPLC 152
Cdd:pfam15227   1 CPICLDYLEKPVSIECGHSFCLSCINSlQKEPDGESlLCPQC 42

Zinc-binding domain, present in Dystrophin, CREB-binding protein; Putative zinc-binding domain present in dystrophin-like proteins, and CREB-binding protein/p300 homologues. The ZZ in dystrophin appears to bind calmodulin. A missense mutation of one of the conserved cysteines in dystrophin results in a patient with Duchenne muscular dystrophy.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1379060902  394 VHYGVSCDGCGKmPIVGRRHTCVDCGkaacDFDLCGACqdagYNKpGRFNQNHS 447
Cdd:smart00291   1 VHHSYSCDTCGK-PIVGVRYHCLVCP----DYDLCQSC----FAK-GSAGGEHS 44

Zinc finger, ZZ type; Zinc finger present in dystrophin, CBP/p300. ZZ in dystrophin binds calmodulin. Putative zinc finger; binding not yet shown. Four to six cysteine residues in its sequence are responsible for coordinating zinc ions, to reinforce the structure.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1379060902 395 HYGVSCDGCGKMPIVGRRHTCVDCGkaacDFDLCGACqdagynkpgrFNQNHSADHE 451
Cdd:pfam00569   2 HKVYTCNGCSNDPSIGVRYHCLRCS----DYDLCQSC----------FQTHKGGNHQ 44

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 1379060902 109 QEFMCSVCLELLWKPVVLECGHVFCFWCGYQCMNVYDVSRCPLCKNAFDKFP 160
Cdd:cd23132     1 EEFLCCICLDLLYKPVVLECGHVFCFWCVHRCMNGYDESHCPLCRRPYDHFP 52

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
                  ....*....|....*....|....*....|....*....|....*..
gi 1379060902 113 CSVCLELLWKPVVLECGHVFCFWCGYQCMN-VYDVSRCPLCKNAFDK 158
Cdd:cd16498    19 CPICLELLKEPVSTKCDHQFCRFCILKLLQkKKKPAPCPLCKKSVTK 65

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 1379060902 111 FMCSVCLELLWKPVVLECGHVFCFWCGYQCMNvYDVSRCPLC 152
Cdd:cd16449     1 LECPICLERLKDPVLLPCGHVFCRECIRRLLE-SGSIKCPIC 41

Zinc finger, ZZ type. Zinc finger present in potassium channel modulatory factor (PCMF) 1 and related proteins. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding. Human potassium channel modulatory factor 1 or FIGC has been shown to possess intrinsic E3 ubiquitin ligase activity and to promote ubiquitination.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1379060902 398 VSCDGCGKMPIVGRRHTCVDCgkaaCDFDLCGACQDAGYNkpgrfNQNHSADHEVRLV 455
Cdd:cd02338     1 VSCDGCGKSNFTGRRYKCLIC----YDYDLCADCYDSGVT-----TERHLFDHPMQCI 49

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 1379060902 109 QEFMCSVCLELLWKPVVLECGHVFCFWCGYQCMNVYD-VSRCPLCKNAFDKfpRVCRP 165
Cdd:cd16594     4 EELTCPICLDYFTDPVTLDCGHSFCRACIARCWEEPEtSASCPQCRETCPQ--RNLRP 59

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 1379060902 108 EQEFMCSVCLELLWKPVVLECGHVFCFWCGYQCMNVYDVSR--CPLCKNAFDKFPR 161
Cdd:cd16623     6 EMEATCPICLDFFSHPISLSCAHIFCFDCIQKWMTKREDSIltCPLCRKEQKKPVL 61

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 1379060902 111 FMCSVCLELLWKPVVLECGHVFCFWCGYQCMNVYDVSR-CPLCK 153
Cdd:cd16745     1 FECNICLDLAQDPVVTLCGHLFCWPCLHKWLRRQSSQPeCPVCK 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 1379060902 110 EFMCSVCLELLWKPVVL-ECGHVFCFWCGYQCMNVYDvSRCPLCKNAF 156
Cdd:cd16549     1 QFSCPICLEVYHKPVVItSCGHTFCGECLQPCLQVAS-PLCPLCRMPF 47

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
                  ....*....|....*....|....*....|....*....|....*
gi 1379060902 109 QEFMCSVCLELLWKPVVLE-CGHVFCFWCGYQCMNvYDVSRCPLC 152
Cdd:cd16544     1 AELTCPVCQEVLKDPVELPpCRHIFCKACILLALR-SSGARCPLC 44

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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1379060902 108 EQEFMCSVCLELLWKPVVLECGHVFCFWC-GYQCMNVYDVSR--CPLCKNAFDK 158
Cdd:cd16598     2 EEEVTCSICLDYLRDPVTIDCGHNFCRSCiTDYCPISGGHERpvCPLCRKPFKK 55

RING finger, HC subclass, found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is a telomere-associated E3 ubiquitin-protein ligase that plays an important role in DNA double-strand break (DSB) repair via histone ubiquitination. It is localized in the nucleus and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless). It recruits UBC13 for lysine 63-based self polyubiquitylation. Its deficiency causes neuronal pathology and cognitive decline, and its loss results in neuron degeneration. RNF8, together with RNF168, catalyzes a series of ubiquitylation events on substrates such as H2A and H2AX, with the H2AK13/15 ubiquitylation being particularly important for recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of DSBs. RNF8 mediates the ubiquitination of gammaH2AX, and recruits 53BP1 and BRCA1 to DNA damage sites which promotes DNA damage response (DDR) and inhibits chromosomal instability. Moreover, RNF8 interacts with retinoid X receptor alpha (RXR alpha) and enhances its transcription-stimulating activity. It also regulates the rate of exit from mitosis and cytokinesis. RNF8 contains an N-terminal forkhead-associated (FHA) domain and a C-terminal C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1379060902 110 EFMCSVCLELLWKPVVLECGHVFCFWCGYQCMNVYDVsrCPLCKNAF 156
Cdd:cd16535     1 ELQCSICSELFIEAVTLNCSHSFCSYCITEWMKRKKE--CPICRKPI 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 1379060902 108 EQEFMCSVCLELLWKPVVLECGHVFCFWCGYQCM-NVYDVSRCPLCKNAFDKFP 160
Cdd:cd23133     1 EETLTCSICQGIFMNPVYLRCGHKFCEACLLLFQeDIKFPAYCPMCRQPFNQEY 54

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
                  ....*....|....*....|....*....|.
gi 1379060902 111 FMCSVCLELLWKPVVLECGHVFCFWCGYQCM 141
Cdd:cd16540     2 FTCPVCLEIFETPVRVPCGHVFCNACLQECL 32

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 1379060902 108 EQEFMCSVCLELLWKPVVLECGHVFCFWCgyqCMNVYD----VSRCPLCKNAFDKFP 160
Cdd:cd16543     1 EDQLTCSICLDLLKDPVTIPCGHSFCMNC---ITLLWDrkqgVPSCPQCRESFPPRP 54

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 1379060902 113 CSVCLELLWKPVVLECGHVFCFWCgyqcmnVYDVS----RCPLCKNAF 156
Cdd:cd16546     3 CPICLQTCIHPVKLPCGHIFCYLC------VKGVAwqskRCALCRQEI 44

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
                  ....*....|....*....|....*..
gi 1379060902 110 EFMCSVCLELLWKPVVLECGHVFCFWC 136
Cdd:cd16601     1 EASCSLCKEYLKDPVIIECGHNFCRAC 27

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 1379060902 105 EAPEQEFmCSVCLELLWKPVVLECGHVFCFWCGYQCMN---VYDVSRCPLCK 153
Cdd:cd16583     1 DSDEEGV-CPICQEPLKEAVSTDCGHLFCRMCLTQHAKkasASGVFSCPVCR 51

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1379060902 108 EQEFMCSVCLELLWKPVVLECGHVFCFWCGYQ-----CMNVYDVS-----RCPLCK 153
Cdd:cd16753     3 ESELTCPICLELFEDPLLLPCAHSLCFNCAHRilvshCASNESVEsitafQCPTCR 58

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1379060902 112 MCSVCLELLWKPVVL-ECGHVFCFWCGYQCMNvyDVSRCPLC 152
Cdd:pfam13923   1 MCPICMDMLKDPSTTtPCGHVFCQDCILRALR--AGNECPLC 40

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
                  ....*....|....*....|....*....|....*....|....*....
gi 1379060902 108 EQEFMCSVCLELLWKPVVLECGHVFCFWCGYQCMNVYdvSRCPLCKNAF 156
Cdd:TIGR00599  24 DTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQ--PKCPLCRAED 70

first RING finger, HC subclass, found in Arabidopsis thaliana ORTHRUS and similar proteins; This subfamily includes Arabidopsis thaliana ORTHRUS 1-5. They are E3 ubiquitin-protein ligases that may participate in CpG methylation-dependent transcriptional regulation and/or epigenetic transcriptional silencing. ORTHRUS 1 mediates ubiquitination with the E2 ubiquitin-conjugating enzymes UBC11, UBC8 and UBC8 homologs (e.g. UBC10, UBC11, UBC28 and UBC29) but not with UBC27, UBC30, UBC32, UBC34 and UBC36. ORTHRUS 2 and 5 mediate ubiquitination with the E2 ubiquitin-conjugating enzyme UBC11. ORTHRUS 1 and 2 promote methylation-mediated gene silencing leading, for example, to early flowering. They can bind to CpG, CpNpG, and CpNpN DNA motifs, with a strong preference for methylated forms, and with highest affinity for CpG substrates. Members of this subfamily contain two typical C3HC4-type RING-HC fingers. This model corresponds to the first one.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1379060902 110 EFMCSVCLELLWKPVVLECGHVFCF-----WCGYQcmnvydVSRCPLCKNAF 156
Cdd:cd23138     2 ELNCSFCMQLPERPVTTPCGHNFCLkcfqkWMGQG------KKTCGTCRSPI 47

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 1379060902 111 FMCSVCLELLWKPVVLECGHVFCFWCGYQCMNVYDVSR-CPLCKNAFDK 158
Cdd:cd16744     1 FECNICLDTAKDAVVSLCGHLFCWPCLHQWLETRPNRQvCPVCKAGISR 49

Zinc finger, ZZ type. Zinc finger present in Drosophila ref(2)P, NBR1, Human sequestosome 1 and related proteins. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding. Drosophila ref(2)P appears to control the multiplication of sigma rhabdovirus. NBR1 (Next to BRCA1 gene 1 protein) interacts with fasciculation and elongation protein zeta-1 (FEZ1) and calcium and integrin binding protein (CIB), and may function in cell signalling pathways. Sequestosome 1 is a phosphotyrosine independent ligand for the Lck SH2 domain and binds noncovalently to ubiquitin via its UBA domain.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1379060902 398 VSCDGCGKmPIVGRRHTCVDCGkaacDFDLCGAC 431
Cdd:cd02340     1 VICDGCQG-PIVGVRYKCLVCP----DYDLCESC 29

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        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1379060902 108 EQEFMCSVCLELLWKPVVLECGHVFCFWCGYQCMNV--YDVSRCPLCKNAF 156
Cdd:cd16597     3 EEELTCSICLELFKDPVTLPCGHNFCGVCIEKTWDSqhGSEYSCPQCRATF 53

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
                  ....*....|....*....|....*....|....*....|....*..
gi 1379060902 111 FMCSVCLELLWKPVVLECGHVFCFWCGYQCMNvyDVSRCPLCKNAFD 157
Cdd:cd16504     3 FLCPICFDIIKEAFVTKCGHSFCYKCIVKHLE--QKNRCPKCNFYLT 47

Zinc finger, ZZ type. Zinc finger present in ZZZ3 (ZZ finger containing 3) and related proteins. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1379060902 398 VSCDGCGKMPIVGRRHTCVDCGKAacDFDLCGACQDAGynkpgrfnQNHSADH 450
Cdd:cd02341     1 FKCDSCGIEPIPGTRYHCSECDDG--DFDLCQDCVVKG--------ESHQEDH 43

Uncharacterized conserved protein, contains RING and CCCH-type Zn-fingers [General function prediction only];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1379060902  91 NAEDEEEDVrkLTGEAPEQEFMCSVCLELLWKPVVLECGHVFCFWCGYQCMNvyDVSRCPLC 152
Cdd:COG5152   179 NAEYEEAPV--ISGPGEKIPFLCGICKKDYESPVVTECGHSFCSLCAIRKYQ--KGDECGVC 236

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 1379060902 111 FMCSVCLELLWKPVVLECGHVFCFWCGYQCMNVYDVSR--CPLCKNAF 156
Cdd:cd16604     1 LSCPICLDLLKDPVTLPCGHSFCMGCLGALWGAGRGGRasCPLCRQTF 48

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
                  ....*....|....*....|....*....|....*....|..
gi 1379060902 113 CSVCLELLWKPVVLECGHVFCFWC--GYQCMNVYDVSRCPLC 152
Cdd:cd16536     3 CPICLEPPVAPRITRCGHIFCWPCilRYLSLSEKKWRKCPIC 44

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 1379060902 113 CSVCLELLW-KPVVLECGHVFCFWCGYQCMNVydVSRCPLCKNAFD 157
Cdd:cd23130     3 CPICLDDPEdEAITLPCLHQFCYTCILRWLQT--SPTCPLCKTPVT 46

RING finger, HC subclass, found in tripartite motif-containing protein TRIM58 and similar proteins; TRIM58, also known as protein BIA2, is an erythroid E3 ubiquitin-protein ligase induced during late erythropoiesis. It binds and ubiquitinates the intermediate chain of the microtubule motor dynein (DYNC1LI1/DYNC1LI2), stimulating the degradation of the dynein holoprotein complex. It may participate in the erythroblast enucleation process through regulation of nuclear polarization. TRIM58 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        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1379060902 109 QEFMCSVCLELLWKPVVLECGHVFCFWCGYQCMNVYDVSR-----CPLCKNAF 156
Cdd:cd16606     1 EEARCPVCLDFLQEPVSVDCGHSFCLRCISEFCEKSDSAQggvyaCPQCRGPF 53

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 1379060902 109 QEFMCSVCLELLWKPVVLECGHVFCFWCGYQCMNVydVSRCPLCK 153
Cdd:cd23147     3 KELKCPICLSLFKSAANLSCNHCFCAGCIGESLKL--SAICPVCK 45

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
                  ....*....|....*....|....*.
gi 1379060902 111 FMCSVCLELLWKPVVLECGHVFCFWC 136
Cdd:cd16542     2 FDCAVCLEVLHQPVRTRCGHVFCRPC 27

Zinc finger, ZZ type. Zinc finger present in dystrophin and dystrobrevin. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding. Dystrophin attaches actin filaments to an integral membrane glycoprotein complex in muscle cells. The ZZ domain in dystrophin has been shown to be essential for binding to the membrane protein beta-dystroglycan.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1379060902 398 VSCDGCGKMPIVGRRHTCVDCgkaaCDFDLCGACQDAgynkpGRFNQNHSADHEVR 453
Cdd:cd02334     1 AKCNICKEFPITGFRYRCLKC----FNYDLCQSCFFS-----GRTSKSHKNSHPMK 47

RING finger, HC subclass, found in ubiquitin-like PHD and RING finger domain-containing protein 2 (UHRF2); UHRF2, also known as Np95/ICBP90-like RING finger protein (NIRF), Np95-like RING finger protein, nuclear protein 97, nuclear zinc finger protein Np97, RING finger protein 107, or E3 ubiquitin-protein ligase UHRF2, was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation, but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) through interacting with HBV core protein and promoting its degradation. UHRF2 contains an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) domain, a SET- and RING-associated (SRA) domain, and a C-terminal C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1379060902 108 EQEFMCSVCLELLWKPVVLECGHVFCFWCGYQCMNVyDVSRCPLCKNAFDK 158
Cdd:cd16770     1 EESFLCICCQELVYQPVTTECQHNVCKSCLQRSFKA-EVYTCPACRHDLGK 50

RING finger, HC subclass, found in tripartite motif-containing protein 36 (TRIM36) and similar proteins; TRIM36, the human ortholog of mouse Haprin, also known as RING finger protein 98 (RNF98) or zinc-binding protein Rbcc728, is an E3 ubiquitin-protein ligase expressed in the germ plasm. It has been implicated in acrosome reaction, fertilization, and embryogenesis, as well as in carcinogenesis. TRIM36 functions upstream of Wnt/beta-catenin activation, and plays a role in controlling the stability of proteins regulating microtubule polymerization during cortical rotation, and subsequently dorsal axis formation. It is also potentially associated with chromosome segregation by interacting with the kinetochore protein centromere protein-H (CENP-H), and colocalizing with the microtubule protein alpha-tubulin. Its overexpression may cause chromosomal instability and carcinogenesis. It is, thus, a novel regulator affecting cell cycle progression. Moreover, TRIM36 plays a critical role in the arrangement of somites during embryogenesis. TRIM36 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, Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, a PRY domain and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1379060902 108 EQEFMCSVCLELLWKPVVLECGHVFCFWCGYQCMNVYDvsrCPLCKNAFD 157
Cdd:cd16756     1 ERELICPSCKELFTHPLILPCQHSVCHKCVKELLTTFP---CPGCQHDVD 47

RING finger, HC subclass, found in Arabidopsis thaliana protein CHROMATIN REMODELING 27 (CHR27) and similar proteins; CHR27, also called protein SNF2-RING-HELICASE-LIKE 1, is a probable helicase-like transcription factor involved in transcriptional gene silencing. It associates with SUVR2 and contributes to transcriptional gene silencing at RNA-directed DNA methylation (RdDM) target loci but also at RdDM-independent target loci. It may be involved in nucleosome positioning to form ordered nucleosome arrays on chromatin. It associates with SUVR2 and functions redundantly with FRG2. It is required for the efficient methylation of a broad range of RdDM target loci. CHR27 contains a typical C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1379060902 113 CSVCLELLWKPVVLECGHVFCFWCGYQCMNVYDVSR----CPLCKNAF 156
Cdd:cd23142     3 CPICNDPPEDAVVTLCGHVFCCECVFQYLSSDRTCRqfnhCPLCRQKL 50

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM9, TRIM67, and similar proteins; Tripartite motif-containing proteins TRIM9 and TRIM67 belong 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, consisting of 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. TRIM9 (the human ortholog of rat Spring), also known as RING finger protein 91 (RNF91), is a brain-specific E3 ubiquitin-protein ligase collaborating with an E2 ubiquitin conjugating enzyme UBCH5b. TRIM9 plays an important role in the regulation of neuronal functions and participates in neurodegenerative disorders through its ligase activity. TRIM67, also known as TRIM9-like protein (TNL), is a protein selectively expressed in the cerebellum. It interacts with PRG-1, an important molecule in the control of hippocampal excitability dependent on presynaptic LPA2 receptor signaling, and 80K-H, also known as glucosidase II beta, a protein kinase C substrate.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1379060902 108 EQEFMCSVCLELLWKPVVLECGHVFCFwcgyQCMNVYDVSrCPLCK 153
Cdd:cd16576     1 EEELKCPVCGSLFTEPVILPCSHNLCL----GCALNIQLT-CPICH 41

Zinc finger, ZZ type; Zinc finger present in dystrophin, CBP/p300. ZZ in dystrophin binds calmodulin. Putative zinc finger; binding not yet shown. Four to six cysteine residues in its sequence are responsible for coordinating zinc ions, to reinforce the structure.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1379060902 395 HYGVSCDGCGKMPIVGRRHTCVDCGkaacDFDLCGACqdagynkpgrFNQNHSADHE 451
Cdd:pfam00569   2 HKVYTCNGCSNDPSIGVRYHCLRCS----DYDLCQSC----------FQTHKGGNHQ 44

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 1379060902 113 CSVCLELLWKPVV-LECGHVFCFWC---GYQCMNVYdvsrCPLC 152
Cdd:pfam00097   1 CPICLEEPKDPVTlLPCGHLFCSKCirsWLESGNVT----CPLC 40

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

                          10        20
                  ....*....|....*....|.
gi 1379060902 113 CSVCLELLWKPVvLECGHVFC 133
Cdd:pfam13445   1 CPICLELFTDPV-LPCGHTFC 20

RING finger, HC subclass, found in RING finger protein 112 (RNF112) and similar proteins; RNF112, also known as brain finger protein (BFP), zinc finger protein 179 (ZNF179), or neurolastin, is a peripheral membrane protein that is predominantly expressed in the central nervous system and localizes to endosomes. It contains functional GTPase and C3HC4-type RING-HC finger domains and has been identified as a brain-specific dynamin family GTPase that affects endosome size and spine density. Moreover, RNF112 acts as a downstream target of sigma-1 receptor (Sig-1R) regulation and may play a novel role in neuroprotection by mediating the neuroprotective effects of dehydroepiandrosterone (DHEA) and its sulfated analog (DHEAS).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1379060902 113 CSVCLELLWKPVVLECGHVFCFWCgyqcmnvYDVSRCPLC 152
Cdd:cd16538     5 CSICLERLREPISLDCGHDFCIRC-------FSTHRIPGC 37

RING finger, HC subclass, found in ubiquitin-like PHD and RING finger domain-containing proteins, UHRF1 and UHRF2, and similar proteins; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of transcription factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation, but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) by interacting with the HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1379060902 111 FMCSVCLELLWKPVVLECGHVFCFWCGYQCMNVyDVSRCPLCKN 154
Cdd:cd16613     1 FTCICCQELVYKPITTPCKHNICKSCLQRSFKA-EVYTCPACRH 43