CCCH-type zinc finger; This short zinc binding domain has the pattern of three cysteines and one histidine to coordinate the zinc ion. This domain is found in a wide variety of proteins such as E3 ligases.

                          10
                  ....*....|....*....
gi 528487676   53 CRYFQKGGCWFGDRCRYLH 71
Cdd:pfam18044   3 CRYFQKGGCRYGDNCRFSH 21

N1R/p28-like protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528487676 231 FDQSNDVACGICMDKISEKSTaQERRYGILPNCNHAFCIGCIVTWRKTKdfqeeviKGCPQCRVKSSFYIPSK 303
Cdd:PHA02929 169 YNRSKDKECAICMEKVYDKEI-KNMYFGILSNCNHVFCIECIDIWKKEK-------NTCPVCRTPFISVIKSR 233

Cleavage and polyadenylation specificity factor (CPSF) Clipper subunit and related makorin family Zn-finger proteins [General function prediction only];

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 528487676  22 VCRQFINGSCRYGQSCYYLHEFPSVPSFQVQCRYFQ-KGGCWFGDRCRYLHTPQNG 76
Cdd:COG5084  106 VCKFFLRGLCKSGFSCEFLHEYDLRSSQGPPCRSFSlKGSCSSGPSCGYSHIDPDS 161

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 528487676   239 CGICMDKISEKStaqerrygILPNCNHAFCIGCIVTWRKTKDFQeevikgCPQC 292
Cdd:smart00184   1 CPICLEEYLKDP--------VILPCGHTFCRSCIRKWLESGNNT------CPIC 40

Zinc finger domain; This is a zinc finger domain found in Zinc finger CCCH-type with G patch domain-containing proteins such as ZIP. Functional studies indicate that ZIP specifically targets EGFR and represses its transcription, and that the zinc finger and the coiled-coil domains are central to that process.

                          10
                  ....*....|....*....
gi 528487676   23 CRQFINGSCRYGQSCYYLH 41
Cdd:pfam18345   1 CKFFLKGRCRYGDKCRFAH 19

RING finger, HC subclass, found in makorin-1 (MKRN1), makorin-3 (MKRN3), and similar proteins; MKRN1, also known as makorin RING finger protein 1 or RING finger protein 61 (RNF61), is an E3 ubiquitin-protein ligase targeting the telomerase catalytic subunit (TERT) for proteasome processing. It regulates the ubiquitination and degradation of peroxisome-proliferator-activated receptor gamma (PPARgamma), a nuclear receptor that is linked to obesity and metabolic diseases. It also mediates the posttranslational regulation of p14ARF, and thus potentially regulates cellular senescence and tumorigenesis in gastric cancer. Moreover, MKRN1 functions as a differentially negative regulator of p53 and p21, and controls cell cycle arrest and apoptosis. It induces degradation of West Nile virus (WNV) capsid protein to protect cells from WNV. It is a RNA-binding protein involved in the modulation of cellular stress and apoptosis. It predominantly associates with proteins involved in mRNA metabolism including regulators of mRNA turnover, transport, and/or translation, and acts as a component of a ribonucleoprotein complex in embryonic stem cells (ESCs) that is recruited to stress granules upon exposure to environmental stress. MKRN1 interacts with poly(A)-binding protein (PABP), a key component of different ribonucleoprotein complexes, in an RNA-independent manner, and stimulates translation in nerve cells. In addition, MKRN1 is a novel SEREX (serological identification of antigens by recombinant cDNA expression cloning) antigen of esophageal squamous cell carcinoma (SCC). It may be involved in carcinogenesis of the well-differentiated type of tumors possibly via ubiquitination of filamin A interacting protein 1 (L-FILIP). Human MKRN1 contains three N-terminal C3H1-type zinc fingers, a motif rich in Cys and His residues (CH), a C3HC4-type RING-HC finger, and another C3H1-type zinc finger at the C-terminus. MKRN3, also known as makorin RING finger protein 3, RING finger protein 63 (RNF63), or zinc finger protein 127 (ZNF127), is a therian mammal-specific retrocopy of MKRN1. It acts as a putative E3 ubiquitin-protein ligase involved in ubiquitination and cell signaling. MKRN3 shows a potential inhibitory effect on hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Its defects represent the most frequent known genetic cause of familial central precocious puberty (CPP). In contrast to human MKRN1, human MKRN3 lacks the second C3H1-type zinc finger at the N-terminal region. The RING-HC finger of mammalian MKRN4 shows high sequence similarity with that of MKRN3, and is also included in this model.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528487676 236 DVACGICMDKISEKSTAQERRYGILPNCNHAFCIGCIVTWRKTKDFQEEVIKGCPQCRVKS 296
Cdd:cd16730    1 DKVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECRITS 61

RING finger, HC subclass, found in makorin-2 (MKRN2) and similar proteins; MKRN2, also known as makorin RING finger protein 2, RING finger protein 62 (RNF62), or HSPC070, is a putative ribonucleoprotein that acts as a neurogenesis inhibitor acting upstream of glycogen synthase kinase-3beta (GSK-3beta) in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. It also functions in promoting cell proliferation of primary CD34+ progenitor cells and K562 cells, indicating its possible involvement in normal and malignant hematopoiesis. Mammalian MKRN2 contains three N-terminal C3H1-type zinc fingers, a motif rich in Cys and His residues (CH), a C3HC4-type RING-HC finger, and another C3H1-type zinc finger at the C-terminus. The third C3H1-type zinc finger, the CH motif, as well as the RING zinc finger are necessary for its anti-neurogenic activity.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 528487676 236 DVACGICMDKISEKSTAQERRYGILPNCNHAFCIGCIVTWRKTKDFQEEVIKGCPQCR 293
Cdd:cd16731    1 DKVCSICMEVVYEKASASERRFGILSNCNHTYCLSCIRQWRCAKQFENPIIKSCPECR 58

zinc finger-like protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 528487676 231 FDQSNDVACGICMDKISEKSTAQERRYGILPNCNHAFCIGCIVTWRKTKDfQEEVIKGCPQCRVK------SSFY 299
Cdd:PHA02926 165 YRVSKEKECGICYEVVYSKRLENDRYFGLLDSCNHIFCITCINIWHRTRR-ETGASDNCPICRTRfrnitmSKFY 238

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 528487676 236 DVACGICMDKIsekstaqERRYGILPNCNHAFCIGCIVTWRKTKdfqeeviKGCPQCR 293
Cdd:cd16574    1 DSSCPICLDRF-------ENEKAFLDGCFHAFCFTCILEWSKVK-------NECPLCK 44

RING finger, HC subclass, found in really interesting new gene proteins RING1, RING2 and similar proteins; RING1, also known as polycomb complex protein RING1, RING finger protein 1 (RNF1), or RING finger protein 1A (RING1A), is a transcriptional repressor that is associated with the Polycomb group (PcG) protein complex involved in stable repression of gene activity. 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. Both RING1 and RING2 are core components 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. RING2 acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity. Members of this family contain a C3HC4-type RING-HC finger.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 528487676 236 DVACGICMDKISEKSTAQErrygilpnCNHAFCIGCIVTW-RKTKdfqeeviKGCPQCRVKssfyIPSK 303
Cdd:cd16531    1 ELMCPICLGIIKNTMTVKE--------CLHRFCAECIEKAlRLGN-------KECPTCRKH----LPSR 50

Cleavage and polyadenylation specificity factor (CPSF) Clipper subunit and related makorin family Zn-finger proteins [General function prediction only];

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 528487676  22 VCRQFINGSCRYGQSCYYLHEFPSVPSFQVQCRYFQ-KGGCWFGDRCRYLHTPQNG 76
Cdd:COG5084  106 VCKFFLRGLCKSGFSCEFLHEYDLRSSQGPPCRSFSlKGSCSSGPSCGYSHIDPDS 161

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528487676 235 NDVACGICMDKISEKSTaqerrygiLPnCNHAFCIGCIvtwRKTKDFQEEVIKGCPQCRV 294
Cdd:cd16597    4 EELTCSICLELFKDPVT--------LP-CGHNFCGVCI---EKTWDSQHGSEYSCPQCRA 51

RING finger, HC subclass, found in Saccharomyces cerevisiae POB3/SPT16 histone-associated protein 1 (ScPSH1) and similar proteins; ScPSH1 is a Cse4-specific E3 ubiquitin ligase that interacts with the kinetochore protein Pat1 and targets the degradation of budding yeast centromeric histone H3 variant, CENP-ACse4, which is essential for faithful chromosome segregation. ScPSH1 contains a C3HC4-type RING-HC finger and a DNA directed RNA polymerase domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 528487676 239 CGICMDKISEkstaqerryGILPNCNHAFCIGCIVTWrktkdFQEEVIKGCPQCRVK 295
Cdd:cd16568    7 CIICHEYLYE---------PMVTTCGHTYCYTCLNTW-----FKSNRSLSCPDCRTK 49

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 528487676   239 CGICMDKISEKStaqerrygILPNCNHAFCIGCIVTWRKTKDFQeevikgCPQC 292
Cdd:smart00184   1 CPICLEEYLKDP--------VILPCGHTFCRSCIRKWLESGNNT------CPIC 40

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 528487676  239 CGICMDKISEKSTaqerrygILPnCNHAFCIGCIVTWRKTKdfqeevIKGCPQC 292
Cdd:pfam00097   1 CPICLEEPKDPVT-------LLP-CGHLFCSKCIRSWLESG------NVTCPLC 40

Zinc finger C-x8-C-x5-C-x3-H type (and similar);

                          10        20
                  ....*....|....*....|
gi 528487676   53 CRYFQKGG-CWFGDRCRYLH 71
Cdd:pfam00642   6 CRFFLRTGyCKYGDRCKFAH 25

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Deltex3 (DTX3) and similar proteins; DTX3, also known as RING finger protein 154 (RNF154), is an E3 ubiquitin-protein ligase that belongs to the Deltex (DTX) family. In contrast to other DTXs, DTX3 does not contain two N-terminal Notch-binding WWE domains, but a short unique N-terminal domain, suggesting it does not interact with the intracellular domain of Notch. Its C-terminal region includes a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 528487676 236 DVACGICMDKISEKSTaqerrygiLPNCNHAFCIGCIvtwrkTKDFQeeVIKGCPQCR 293
Cdd:cd16711    1 EETCPICLGEIQNKKT--------LDKCKHSFCEDCI-----TRALQ--VKKACPMCG 43

RING finger, H2 subclass, found in Saccharomyces cerevisiae transmembrane E3 ubiquitin-protein ligase 1 (TUL1) and similar proteins; This subfamily includes Saccharomyces cerevisiae TUL1, Schizosaccharomyces pombe DSC E3 ubiquitin ligase complex subunit 1 (DSC1), and Arabidopsis thaliana protein FLYING SAUCER 2 (FLY2). TUL1 is the catalytic component of DSC E3 ubiquitin ligase complexes that tag proteins present in Golgi, endosome and vacuole membranes and function in protein homeostasis under non-stress conditions, and support a role in protein quality control. It mediates ubiquitination of vacuolar proteins such as CPS1, PPN1, PEP12 and other proteins containing exposed hydrophilic residues within their transmembrane domains, leading to their sorting into internal vesicles in late endosomes. TUL1 also targets the unpalmitoylated endosomal SNARE TLG1 to the multivesicular body (MVB) pathway. DSC1, also known as defective for SREBP cleavage protein 1, is the catalytic component of the DSC E3 ubiquitin ligase complex required for the sre1 transcriptional activator proteolytic cleavage to release the soluble transcription factor from the membrane in low oxygen or sterol conditions. FLY2 acts as an E3 ubiquitin-protein ligase that may be involved in xylem development. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 528487676 237 VACGICMDKISEKSTAQERR-YGILPnCNHAFCIGCIVTWRKTKdfQEevikgCPQCR 293
Cdd:cd23117    5 VDCVICMSDIELPSTNSVRRdYMVTP-CNHIFHTNCLERWMDIK--LE-----CPTCR 54

Zinc finger domain; This is a zinc finger domain found in Zinc finger CCCH-type with G patch domain-containing proteins such as ZIP. Functional studies indicate that ZIP specifically targets EGFR and represses its transcription, and that the zinc finger and the coiled-coil domains are central to that process.

                          10
                  ....*....|....*....
gi 528487676   23 CRQFINGSCRYGQSCYYLH 41
Cdd:pfam18345   1 CKFFLKGRCRYGDKCRFAH 19