RING finger, H2 subclass, found in RING-box protein 2 (RBX2) and similar proteins; RBX2, also known as CKII beta-binding protein 1 (CKBBP1), RING finger protein 7 (RNF7), regulator of cullins 2 (ROC2), or sensitive to apoptosis gene protein (SAG), is an E3 ubiquitin-protein ligase that protects cells from apoptosis, confers radioresistance, and plays an essential and non-redundant role in embryogenesis and vasculogenesis. It promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1alpha, IkappaBalpha, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes. RBX2 is necessary for ubiquitin ligation activity of the multimeric cullin (Cul)-RING E3 ligases (CRLs). RBX2-containing CRLs are involved in the NEDD8 pathway and RBX2 specifically regulates NEDD8ylation of Cul5. It can bind and activate the HIV-1 Vif-Cullin5 E3 ligase complex in vitro. It is also a substrate of NEDD4-1 E3 ubiquitin ligase and mediates NEDD4-1 induced chemosensitization. The inactivation of RBX2 E3 ubiquitin ligase activity triggers senescence and inhibits Kras-induced immortalization. Endothelial deletion of RBX2 causes embryonic lethality and blocks tumor angiogenesis, and may have potential use in anti-angiogenesis therapy of human cancers. Moreover, as a component of the Cullin 5-RING E3 ubiquitin ligase (CRL5) complex, RBX2 regulates neuronal migration through different CRL5 adaptors, such as SOCS7. RBX2 also functions as a redox inducible antioxidant protein that scavenges oxygen radicals by forming inter- and intra-molecular disulfide bonds when acting alone. It contains a C-terminal C3H2C3-type RING-H2 finger that is essential for its ligase activity.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 157820759  47 CDTCAICRVQVMDACLRCQAENKQEDCVVVWGECNHSFHNCCMSLWVKQNNRCPLCQQDW 106
Cdd:cd16466    1 CDTCAICRVQVMDACLRCQAENKQEDCVVVWGECNHSFHNCCMSLWVKQNNRCPLCQQDW 60

RING finger, H2 subclass, found in RING-box protein 2 (RBX2) and similar proteins; RBX2, also known as CKII beta-binding protein 1 (CKBBP1), RING finger protein 7 (RNF7), regulator of cullins 2 (ROC2), or sensitive to apoptosis gene protein (SAG), is an E3 ubiquitin-protein ligase that protects cells from apoptosis, confers radioresistance, and plays an essential and non-redundant role in embryogenesis and vasculogenesis. It promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1alpha, IkappaBalpha, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes. RBX2 is necessary for ubiquitin ligation activity of the multimeric cullin (Cul)-RING E3 ligases (CRLs). RBX2-containing CRLs are involved in the NEDD8 pathway and RBX2 specifically regulates NEDD8ylation of Cul5. It can bind and activate the HIV-1 Vif-Cullin5 E3 ligase complex in vitro. It is also a substrate of NEDD4-1 E3 ubiquitin ligase and mediates NEDD4-1 induced chemosensitization. The inactivation of RBX2 E3 ubiquitin ligase activity triggers senescence and inhibits Kras-induced immortalization. Endothelial deletion of RBX2 causes embryonic lethality and blocks tumor angiogenesis, and may have potential use in anti-angiogenesis therapy of human cancers. Moreover, as a component of the Cullin 5-RING E3 ubiquitin ligase (CRL5) complex, RBX2 regulates neuronal migration through different CRL5 adaptors, such as SOCS7. RBX2 also functions as a redox inducible antioxidant protein that scavenges oxygen radicals by forming inter- and intra-molecular disulfide bonds when acting alone. It contains a C-terminal C3H2C3-type RING-H2 finger that is essential for its ligase activity.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 157820759  47 CDTCAICRVQVMDACLRCQAENKQEDCVVVWGECNHSFHNCCMSLWVKQNNRCPLCQQDW 106
Cdd:cd16466    1 CDTCAICRVQVMDACLRCQAENKQEDCVVVWGECNHSFHNCCMSLWVKQNNRCPLCQQDW 60

RING-H2 zinc finger domain; There are 8 cysteine/ histidine residues which are proposed to be the conserved residues involved in zinc binding. The protein, of which this domain is the conserved region, participates in diverse functions relevant to chromosome metabolism and cell cycle control.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 157820759   48 DTCAICRVQVMDACLRCQAENKqEDCVVVWGECNHSFHNCCMSLWVKQNNRCPLCQ 103
Cdd:pfam12678   1 DTCAICRNPFMEPCPECQAPGD-DECPVVWGECGHAFHLHCISRWLKTNNTCPLCR 55

RING finger, H2 subclass, found in RING-box protein 2 (RBX2) and similar proteins; RBX2, also known as CKII beta-binding protein 1 (CKBBP1), RING finger protein 7 (RNF7), regulator of cullins 2 (ROC2), or sensitive to apoptosis gene protein (SAG), is an E3 ubiquitin-protein ligase that protects cells from apoptosis, confers radioresistance, and plays an essential and non-redundant role in embryogenesis and vasculogenesis. It promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1alpha, IkappaBalpha, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes. RBX2 is necessary for ubiquitin ligation activity of the multimeric cullin (Cul)-RING E3 ligases (CRLs). RBX2-containing CRLs are involved in the NEDD8 pathway and RBX2 specifically regulates NEDD8ylation of Cul5. It can bind and activate the HIV-1 Vif-Cullin5 E3 ligase complex in vitro. It is also a substrate of NEDD4-1 E3 ubiquitin ligase and mediates NEDD4-1 induced chemosensitization. The inactivation of RBX2 E3 ubiquitin ligase activity triggers senescence and inhibits Kras-induced immortalization. Endothelial deletion of RBX2 causes embryonic lethality and blocks tumor angiogenesis, and may have potential use in anti-angiogenesis therapy of human cancers. Moreover, as a component of the Cullin 5-RING E3 ubiquitin ligase (CRL5) complex, RBX2 regulates neuronal migration through different CRL5 adaptors, such as SOCS7. RBX2 also functions as a redox inducible antioxidant protein that scavenges oxygen radicals by forming inter- and intra-molecular disulfide bonds when acting alone. It contains a C-terminal C3H2C3-type RING-H2 finger that is essential for its ligase activity.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 157820759  47 CDTCAICRVQVMDACLRCQAENKQEDCVVVWGECNHSFHNCCMSLWVKQNNRCPLCQQDW 106
Cdd:cd16466    1 CDTCAICRVQVMDACLRCQAENKQEDCVVVWGECNHSFHNCCMSLWVKQNNRCPLCQQDW 60

RING-H2 zinc finger domain; There are 8 cysteine/ histidine residues which are proposed to be the conserved residues involved in zinc binding. The protein, of which this domain is the conserved region, participates in diverse functions relevant to chromosome metabolism and cell cycle control.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 157820759   48 DTCAICRVQVMDACLRCQAENKqEDCVVVWGECNHSFHNCCMSLWVKQNNRCPLCQ 103
Cdd:pfam12678   1 DTCAICRNPFMEPCPECQAPGD-DECPVVWGECGHAFHLHCISRWLKTNNTCPLCR 55

Anaphase-promoting complex subunit 11 RING-H2 finger; Apc11 is one of the subunits of the anaphase-promoting complex or cyclosome. The APC subunits are cullin family proteins with ubiquitin ligase activity. Polyubiquitination marks proteins for degradation by the 26S proteasome and is carried out by a cascade of enzymes that includes ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). Apc11 acts as an E3 enzyme and is responsible for recruiting E2s to the APC and for mediating the subsequent transfer of ubiquitin to APC substrates in vivo. In Saccharomyces cerevisiae this RING-H2 finger protein defines the minimal ubiquitin ligase activity of the APC, and the integrity of the RING-H2 finger is essential for budding yeast cell viability.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157820759   32 LKKWNAVAMWSWDV-ECDTCAICRVQVMDACLRCQAENkqEDCVVVWGECNHSFHNCCMSLWVKQNN---RCPLCQQDWV 107
Cdd:pfam12861   5 IKEWNAVATWLWDVpSDDVCGICRVSFDGTCPDCKFPG--DDCPLVWGKCSHNFHMHCILKWLHTETskgLCPMCRQTFK 82

                  ..
gi 157820759  108 VQ 109
Cdd:pfam12861  83 FA 84

H2 subclass of RING (RING-H2) fingers 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 different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger 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 serves as a scaffold 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
                 ....*....|....*....|....*....|....*
gi 157820759  70 QEDCVVVWGECNHSFHNCCMSLWVK-QNNRCPLCQ 103
Cdd:cd16448    9 EEGDVVRLLPCGHVFHLACILRWLEsGNNTCPLCR 43

RING finger, H2 subclass, found in RING finger protein 44 (RNF44) and similar proteins; RNF44 is an uncharacterized RING finger protein that shows high sequence similarity with RNF38, which is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 contains a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C2-type RING-H2 finger.

                         10        20
                 ....*....|....*....|....*.
gi 157820759  80 CNHSFHNCCMSLWVKQNNRCPLCQQD 105
Cdd:cd16680   28 CNHEFHTKCVDKWLKTNRTCPICRAD 53

RING finger, H2 subclass, found in RING finger protein 181 (RNF181) and similar proteins; RNF181, also known as HSPC238, is a platelet E3 ubiquitin-protein ligase containing a C3H2C3-type RING-H2 finger. It interacts with the KVGFFKR motif of platelet integrin alpha(IIb)beta3, suggesting a role for RNF181-mediated ubiquitination in integrin and platelet signaling. It also suppresses the tumorigenesis of hepatocellular carcinoma (HCC) through the inhibition of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in the liver.

                         10        20
                 ....*....|....*....|...
gi 157820759  80 CNHSFHNCCMSLWVKQNNRCPLC 102
Cdd:cd16669   20 CKHSFHSDCILPWLGKTNSCPLC 42

N1R/p28-like protein; Provisional

                         10        20
                 ....*....|....*....|....
gi 157820759  80 CNHSFHNCCMSLWVKQNNRCPLCQ 103
Cdd:PHA02929 200 CNHVFCIECIDIWKKEKNTCPVCR 223

RING finger, H2 subclass, found in Arabidopsis thaliana RING-H2 finger A1a (RHA1A), A1b (RHA1B) and similar proteins; This subfamily includes Arabidopsis thaliana RHA1A, RHA1B and XERICO. RHA1A is a probable E3 ubiquitin-protein ligase that may possess E3 ubiquitin ligase activity in vitro. RHA1B possesses E3 ubiquitin-protein ligase activity when associated with the E2 enzyme UBC8 in vitro. XERICO functions on abscisic acid homeostasis at post-translational level, probably through ubiquitin/proteasome-dependent substrate-specific degradation. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 157820759  59 DACLRCQAENKQEDCVVVWGECNHSFHNCCMSLWVKQNN-RCPLCQQDW 106
Cdd:cd23121    2 DCCAICLSDFNSDEKLRQLPKCGHIFHHHCLDRWIRYNKiTCPLCRADL 50

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 157820759  49 TCAICRVQVMDACLRCQAENKQEDCVVVwgECNHSFHNCCMSLWVKQNNRCPLCQ 103
Cdd:COG5243  289 TCTICMDEMFHPDHEPLPRGLDMTPKRL--PCGHILHLHCLKNWLERQQTCPICR 341

RING finger, H2 subclass, found in RING finger protein 38 (RNF38) and similar proteins; RNF38 is a nuclear E3 ubiquitin protein ligase that is widely expressed throughout the human body, and is especially highly expressed in the heart, brain, placenta and the testis. It recognizes p53 as a substrate for ubiquitination, and thus plays a role in regulating p53. The overexpression of RNF38 increases p53 ubiquitination and alters p53 localization. It is also capable of autoubiquitination. RNF38 expression is negatively regulated by the serotonergic system. Induction of RNF38 may be involved in the anxiety-like behavior or non-cell autonomy in Oryzias latipes by the decline of serotonin (5-HT) levels. RNF38 contains a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), a C3H2C3-type RING-H2 finger, as well as two potential nuclear localization signals.

                         10        20
                 ....*....|....*....|....*.
gi 157820759  80 CNHSFHNCCMSLWVKQNNRCPLCQQD 105
Cdd:cd16679   41 CNHEFHAKCVDKWLKANRTCPICRAD 66