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 411147393 192 DKVCSICMEVILEKASASERRFGILSNCNHTYCLSCIRQWRCAKQFENPIIKSCPECR 249
Cdd:cd16731    1 DKVCSICMEVVYEKASASERRFGILSNCNHTYCLSCIRQWRCAKQFENPIIKSCPECR 58

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 411147393 257 PSVYWVEDQNKKNELIEAFKQGMGKKACKYF----EQGK----GTCPFGS-KCLYRHAYPDGRLAEPEKprKQLSSQgtv 327
Cdd:COG5252  117 PDLYSDVRDKEEDVPLGKRPWINTDRVCKFFieamESGKygwgWTCPNGNmRCSYIHKLPDGYVLSRDK--IKDSTQ--- 191

                         90       100
                 ....*....|....*....|..
gi 411147393 328 rffNSVRLWDFIENRESRHVPN 349
Cdd:COG5252  192 ---VEISLEEFIELERQSLPEK 210

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 411147393 192 DKVCSICMEVILEKASASERRFGILSNCNHTYCLSCIRQWRCAKQFENPIIKSCPECR 249
Cdd:cd16731    1 DKVCSICMEVVYEKASASERRFGILSNCNHTYCLSCIRQWRCAKQFENPIIKSCPECR 58

N1R/p28-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 411147393 171 KICMLTFEHEMEKAFafQASQDKVCSICMEVILEKASASeRRFGILSNCNHTYCLSCIRQWRCAKqfenpiiKSCPECRV 250
Cdd:PHA02929 155 LKTIPSVLSEYEKLY--NRSKDKECAICMEKVYDKEIKN-MYFGILSNCNHVFCIECIDIWKKEK-------NTCPVCRT 224

                 ....*...
gi 411147393 251 ISEFVIPS 258
Cdd:PHA02929 225 PFISVIKS 232

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 411147393 183 KAFAFQASQDKVCSICMEVIlEKASASErrfgilsnCNHTYCLSCIRQWRCAKQFENpiiksCPECR 249
Cdd:COG5574  206 NGLPFIPLADYKCFLCLEEP-EVPSCTP--------CGHLFCLSCLLISWTKKKYEF-----CPLCR 258

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 411147393  195 CSICMEVILEKASASErrfgilsnCNHTYCLSCIRQWRcakqfeNPIIKSCPEC 248
Cdd:pfam00097   1 CPICLEEPKDPVTLLP--------CGHLFCSKCIRSWL------ESGNVTCPLC 40

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 411147393 192 DKVCSICMEVILEKASASERRFGILSNCNHTYCLSCIRQWRCAKQFENPIIKSCPECR 249
Cdd:cd16731    1 DKVCSICMEVVYEKASASERRFGILSNCNHTYCLSCIRQWRCAKQFENPIIKSCPECR 58

RING finger, HC subclass, found in the makorin (MKRN) proteins; The MKRN protein subfamily includes ribonucleoproteins that are characterized by a variety of zinc-finger motifs, including typical arrays of one to four C3H1-type zinc fingers and a C3HC4-type RING-HC finger. Another motif rich in Cys and His residues (CH), with so far unknown function, is also generally present in MKRN proteins. MKRN proteins may have E3 ubiquitin ligase activity.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 411147393 193 KVCSICMEVILEKasasERRFGILSNCNHTYCLSCIRQWRCAKQFENPIIKSCPECR 249
Cdd:cd16521    1 IECGICMEVVLEK----ERRFGILSNCNHVFCLECIREWRSSKDFENSIVRSCPICR 53

p28-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 411147393 135 ECRFGDACVYLHGEVCEICRLQVLHPFDPEQRKAHEKICMLTFEHEMEKafafqasqdKVCSICMEVILEKaSASERRFG 214
Cdd:PHA03096 130 NCYKGKYCEYLHGDICDICEKYLLHPTDIKQRYNEQKTCLSYQLRLLLS---------KICGICLENIKAK-YIIKKYYG 199

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 411147393 215 ILSNCNHTYCLSCIRQW---RCAKQFENpiikSCPECRVISEFV----------IPSVYWVEDQNKKNELIEAFKQGMGK 281
Cdd:PHA03096 200 ILSEIKHEFNIFCIKIWmteSLYKETEP----ENRRLNTVIVFIekinedlknnIPSRYWIDDKYDKNLLSFRYKKMHIR 275

                 ...
gi 411147393 282 KAC 284
Cdd:PHA03096 276 KVC 278

zinc finger-like protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 411147393 187 FQASQDKVCSICMEVILEKASASERRFGILSNCNHTYCLSCIRQWRCAKQfENPIIKSCPECR 249
Cdd:PHA02926 165 YRVSKEKECGICYEVVYSKRLENDRYFGLLDSCNHIFCITCINIWHRTRR-ETGASDNCPICR 226

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 411147393   195 CSICMEVILEKAsaserrfgILSNCNHTYCLSCIRQWRCAKQfenpiiKSCPEC 248
Cdd:smart00184   1 CPICLEEYLKDP--------VILPCGHTFCRSCIRKWLESGN------NTCPIC 40

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 411147393 192 DKVCSICMEVIlekasasERRFGILSNCNHTYCLSCIRQWrcAKQfENpiikSCPECR 249
Cdd:cd16574    1 DSSCPICLDRF-------ENEKAFLDGCFHAFCFTCILEW--SKV-KN----ECPLCK 44

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 411147393 195 CSICMEVILEKASAserrfgilsNCNHTYCLSCIRQWRCAKqfenpiiKSCPECR 249
Cdd:cd16535    4 CSICSELFIEAVTL---------NCSHSFCSYCITEWMKRK-------KECPICR 42

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        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 411147393 195 CSICMEvilekasasERRFGILSNCNHTYCLSCIRQWRCAKQfenpiiKSCPEC 248
Cdd:cd16449    3 CPICLE---------RLKDPVLLPCGHVFCRECIRRLLESGS------IKCPIC 41

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 411147393 191 QDKVCSICMEVIlekasaserRFGILSNCNHTYCLSCIRQWrCAKQFENpiiKSCPECR 249
Cdd:cd16611    3 EELHCPLCLDFF---------RDPVMLSCGHNFCQSCITGF-WELQAED---TTCPECR 48

RING finger, HC subclass, found in checkpoint with forkhead and RING finger domains protein (CHFR); CHFR, also known as RING finger protein 196 (RNF196), is a checkpoint protein that delays entry into mitosis in response to stress. It functions as an E3 ubiquitin ligase that ubiquitinates and degrades its target proteins, such as Aurora-A, Plk1, Kif22, and PARP-1, which are critical for proper mitotic transitions. It also plays an important role in cell cycle progression and tumor suppression, and is negatively regulated by SUMOylation-mediated proteasomal ubiquitylation. Moreover, CHFR is involved in the early stage of the DNA damage response, which mediates the crosstalk between ubiquitination and poly-ADP-ribosylation. CHFR contains a fork head associated (FHA) domain and a C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 411147393 194 VCSICMEVILEKASASErrfgilsnCNHTYCLSCIRQWRCAKQFEnpiiksCPECRV 250
Cdd:cd16503    4 TCSICQDLLHDCVSLQP--------CMHNFCAACYSDWMERSNTE------CPTCRA 46

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 411147393  195 CSICMEVILEKASASErrfgilsnCNHTYCLSCIRQWRcakqfeNPIIKSCPEC 248
Cdd:pfam00097   1 CPICLEEPKDPVTLLP--------CGHLFCSKCIRSWL------ESGNVTCPLC 40

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 411147393 195 CSICMEVILEKASASerrfgilsnCNHTYCLSCI-RQWRcAKQFENPiikSCPECRV 250
Cdd:cd16597    8 CSICLELFKDPVTLP---------CGHNFCGVCIeKTWD-SQHGSEY---SCPQCRA 51

HRD ubiquitin ligase complex, ER membrane component [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 411147393 189 ASQDKVCSICMEVILEKASASERRFGILSN----CNHTYCLSCIRQWrCAKQfenpiiKSCPECR 249
Cdd:COG5243  284 TNSDRTCTICMDEMFHPDHEPLPRGLDMTPkrlpCGHILHLHCLKNW-LERQ------QTCPICR 341