Zinc-ribbon; This is a typical zinc-ribbon finger, with each pair of zinc-ligands coming from more-or-less either side of two knuckles. It is found in eukaryotes.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 186495447  1199 GDMQVYFKMLDALLAEEKMPDEYSNKTQVILCNDCGRKGNAPYHWLYHKCTTCGSYNSR 1257
Cdd:pfam14599    1 VDMEAYWRALDAEIAAQPMPEEYANWRVVILCNDCEAKSEVPFHFLGLKCSHCGSYNTR 59

Hemerythrin-like domain; Hemerythrin (Hr) like domains have the same four alpha helix bundle and a similar, but slightly different active site structure than hemerythrin. They are non-heme diiron binding proteins mainly found in bacteria and eukaryotes. Like Hr, they may be involved in oxygen transport or like human FBXL5 (F-box and leucine-rich repeat protein 5), a member of this group, play a role in cellular iron homeostasis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186495447   37 FVYCHKAFRAQLVELRRFATDAAEADsfsGDLAVELSRKFEFLKLVYKYHSAAEDEVIFLALDKRVK--NIVSNYSLEHA 114
Cdd:cd12108     3 LKLEHRAIRRELGRLARLAGALAAGG---PDDARALAERFRFLATELHHHHTAEEELLFPALRERVPlaAVLDALEAEHA 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 186495447  115 GTDDLFTSIfhwLHVLEEEIGSRSDVLREVILCIGTIQSSICQHMLKEERQVFP 168
Cdd:cd12108    80 EIDELLARL---EALLPALLAGDAEDAEELAAALEALRTALREHLDEEEEELFP 130

RING finger, H2 subclass, found in p53-induced RING-H2 protein (Pirh2) and similar proteins; Pirh2, also known as RING finger and CHY zinc finger domain-containing protein 1 (Rchy1), androgen receptor N-terminal-interacting protein, CH-rich-interacting match with PLAG1, RING finger protein 199 (RNF199), or zinc finger protein 363 (ZNF363), is a p53 inducible E3 ubiquitin-protein ligase that functions as a negative regulator of p53. It preferably ubiquitylates the tetrameric form of p53 in vitro and in vivo, suggesting a role of Pirh2 in downregulating the transcriptionally active form of p53 in the cell. Moreover, Pirh2 inhibits the transcriptional activity of p73, a homolog of the tumor suppressor p53, by promoting its ubiquitination. It also monoubiquitinates DNA polymerase eta (PolH) to suppress translesion DNA synthesis. Furthermore, Pirh2 functions as a negative regulator of the cyclin-dependent kinase inhibitor p27(Kip1) function by promoting ubiquitin-dependent proteasomal degradation. Pirh2 enhances androgen receptor (AR) signaling through inhibition of histone deacetylase 1 (HDAC1) and is overexpressed in prostate cancer. It interacts with TIP60 and this association may regulate Pirh2 stability. In addition, the oncoprotein pleomorphic adenoma gene like 2 (PLAGL2) can bind to the Pirh2 dimer and therefore control the stability of Pirh2. Pirh2 contains a total of nine zinc-binding sites with six located at the N-terminal region, two in the C3H2C3-type RING-H2 domain, and one in the C-terminal region. Nine zinc binding sites comprise three different zinc coordination schemes, including RING type cross-brace zinc coordination, C4 zinc finger, and a novel left-handed beta-spiral zinc-binding motif formed by three recurrent CCHC sequence motifs. This subfamily also includes Drosophila melanogaster Deltex, a ubiquitously expressed cytoplasmic ubiquitin E3 ligase that mediates Notch activation in Drosophila. It selectively suppresses T-cell activation through degradation of a key signaling molecule, MAP kinase kinase kinase 1 (MEKK1). It also inhibits Jun-mediated transcription at the stage of Ras-dependent Jun N-terminal protein kinase (JNK) activation. Deltex contains N-terminal two Notch-binding WWE domains that physically interact with the Notch ankyrin domains, a proline-rich motif that shares homology with SH3-binding domains, and a RING finger at the C-terminus.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 186495447 1152 NCPICHEYIFTSSSPVKALPCGHLMHSTCFQEYTCSH-YTCPVCS 1195
Cdd:cd16464     1 NCPVCLEDLFTSREPVHVLPCGHLMHSTCFEEYLKSGnYRCPLCS 45

Zinc-ribbon; This is a typical zinc-ribbon finger, with each pair of zinc-ligands coming from more-or-less either side of two knuckles. It is found in eukaryotes.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 186495447  1199 GDMQVYFKMLDALLAEEKMPDEYSNKTQVILCNDCGRKGNAPYHWLYHKCTTCGSYNSR 1257
Cdd:pfam14599    1 VDMEAYWRALDAEIAAQPMPEEYANWRVVILCNDCEAKSEVPFHFLGLKCSHCGSYNTR 59

Hemerythrin-like domain; Hemerythrin (Hr) like domains have the same four alpha helix bundle and a similar, but slightly different active site structure than hemerythrin. They are non-heme diiron binding proteins mainly found in bacteria and eukaryotes. Like Hr, they may be involved in oxygen transport or like human FBXL5 (F-box and leucine-rich repeat protein 5), a member of this group, play a role in cellular iron homeostasis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186495447   37 FVYCHKAFRAQLVELRRFATDAAEADsfsGDLAVELSRKFEFLKLVYKYHSAAEDEVIFLALDKRVK--NIVSNYSLEHA 114
Cdd:cd12108     3 LKLEHRAIRRELGRLARLAGALAAGG---PDDARALAERFRFLATELHHHHTAEEELLFPALRERVPlaAVLDALEAEHA 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 186495447  115 GTDDLFTSIfhwLHVLEEEIGSRSDVLREVILCIGTIQSSICQHMLKEERQVFP 168
Cdd:cd12108    80 EIDELLARL---EALLPALLAGDAEDAEELAAALEALRTALREHLDEEEEELFP 130

RING finger, H2 subclass, found in p53-induced RING-H2 protein (Pirh2) and similar proteins; Pirh2, also known as RING finger and CHY zinc finger domain-containing protein 1 (Rchy1), androgen receptor N-terminal-interacting protein, CH-rich-interacting match with PLAG1, RING finger protein 199 (RNF199), or zinc finger protein 363 (ZNF363), is a p53 inducible E3 ubiquitin-protein ligase that functions as a negative regulator of p53. It preferably ubiquitylates the tetrameric form of p53 in vitro and in vivo, suggesting a role of Pirh2 in downregulating the transcriptionally active form of p53 in the cell. Moreover, Pirh2 inhibits the transcriptional activity of p73, a homolog of the tumor suppressor p53, by promoting its ubiquitination. It also monoubiquitinates DNA polymerase eta (PolH) to suppress translesion DNA synthesis. Furthermore, Pirh2 functions as a negative regulator of the cyclin-dependent kinase inhibitor p27(Kip1) function by promoting ubiquitin-dependent proteasomal degradation. Pirh2 enhances androgen receptor (AR) signaling through inhibition of histone deacetylase 1 (HDAC1) and is overexpressed in prostate cancer. It interacts with TIP60 and this association may regulate Pirh2 stability. In addition, the oncoprotein pleomorphic adenoma gene like 2 (PLAGL2) can bind to the Pirh2 dimer and therefore control the stability of Pirh2. Pirh2 contains a total of nine zinc-binding sites with six located at the N-terminal region, two in the C3H2C3-type RING-H2 domain, and one in the C-terminal region. Nine zinc binding sites comprise three different zinc coordination schemes, including RING type cross-brace zinc coordination, C4 zinc finger, and a novel left-handed beta-spiral zinc-binding motif formed by three recurrent CCHC sequence motifs. This subfamily also includes Drosophila melanogaster Deltex, a ubiquitously expressed cytoplasmic ubiquitin E3 ligase that mediates Notch activation in Drosophila. It selectively suppresses T-cell activation through degradation of a key signaling molecule, MAP kinase kinase kinase 1 (MEKK1). It also inhibits Jun-mediated transcription at the stage of Ras-dependent Jun N-terminal protein kinase (JNK) activation. Deltex contains N-terminal two Notch-binding WWE domains that physically interact with the Notch ankyrin domains, a proline-rich motif that shares homology with SH3-binding domains, and a RING finger at the C-terminus.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 186495447 1152 NCPICHEYIFTSSSPVKALPCGHLMHSTCFQEYTCSH-YTCPVCS 1195
Cdd:cd16464     1 NCPVCLEDLFTSREPVHVLPCGHLMHSTCFEEYLKSGnYRCPLCS 45

Hemerythrin HHE cation binding domain; Iteration of the HHE family found it to be related to Hemerythrin. It also demonstrated that what has been described as a single domain in fact consists of two cation binding domains. Members of this family occur all across nature and are involved in a variety of processes. For instance, in Nereis diversicolor Swiss:P80255 binds Cadmium so as to protect the organizm from toxicity. However Hemerythrin is classically described as Oxygen-binding through two attached Fe2+ ions. And the bacterial Swiss:Q7WX96 is a regulator of response to NO, which suggests yet another set-up for its metal ligands. In Staphylococcus aureus P72360 has been noted to be important when the organizm switches to living in environments with low oxygen concentrations; perhaps this protein acts as an oxygen store or scavenger. This domain can bind oxygen (Matilla et.al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043)

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186495447    33 PVLFFVYCHKAFRAQLVELRRFATDAAEADsfsgdlAVELSRKFEFLKLVYKYHSAAEDEVIFLALDKRVKNIVSNYSL- 111
Cdd:pfam01814    2 IIELLDAEHRRLRELLALLRALADALGDSH------LRKLAELLDELVDELEAHHAAEEELLFPALERRSPGGEAPIEVl 75

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 186495447   112 --EHAGTDDLFTSIFHWLHvLEEEIGSRSDVLREVIlcigtiqSSICQHMLKEERQVFPLL 170
Cdd:pfam01814   76 rkEHDEIRELLEELEALLK-GAEPGAAFAELLEALA-------EWLREHIAKEEEVLFPLL 128

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
                    ....*....|....*....|....*....|....*....|...
gi 186495447   1153 CPICHEYIFTsssPVKALPCGHLMHSTCFQEYTCSHY-TCPVC 1194
Cdd:smart00184    1 CPICLEEYLK---DPVILPCGHTFCRSCIRKWLESGNnTCPIC 40

Uncharacterized conserved protein, contains Zn-finger domain of CHY type [Function unknown];

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 186495447 1025 CNHYKRNCKLLA---PCCDKLFTCIRCHDEEADHSVDR 1059
Cdd:COG4357    18 CAHYHSELDVIAikfACCGKYYPCYRCHEELADHEAEP 55

Zinc-ribbon; This is a typical zinc-ribbon finger, with each pair of zinc-ligands coming from more-or-less either side of two knuckles. It is found in eukaryotes.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 186495447  1199 GDMQVYFKMLDALLAEEKMPDEYSNKTQVILCNDCGRKGNAPYHWLYHKCTTCGSYNSR 1257
Cdd:pfam14599    1 VDMEAYWRALDAEIAAQPMPEEYANWRVVILCNDCEAKSEVPFHFLGLKCSHCGSYNTR 59

Hemerythrin-like domain; Hemerythrin (Hr) like domains have the same four alpha helix bundle and a similar, but slightly different active site structure than hemerythrin. They are non-heme diiron binding proteins mainly found in bacteria and eukaryotes. Like Hr, they may be involved in oxygen transport or like human FBXL5 (F-box and leucine-rich repeat protein 5), a member of this group, play a role in cellular iron homeostasis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186495447   37 FVYCHKAFRAQLVELRRFATDAAEADsfsGDLAVELSRKFEFLKLVYKYHSAAEDEVIFLALDKRVK--NIVSNYSLEHA 114
Cdd:cd12108     3 LKLEHRAIRRELGRLARLAGALAAGG---PDDARALAERFRFLATELHHHHTAEEELLFPALRERVPlaAVLDALEAEHA 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 186495447  115 GTDDLFTSIfhwLHVLEEEIGSRSDVLREVILCIGTIQSSICQHMLKEERQVFP 168
Cdd:cd12108    80 EIDELLARL---EALLPALLAGDAEDAEELAAALEALRTALREHLDEEEEELFP 130

RING finger, H2 subclass, found in p53-induced RING-H2 protein (Pirh2) and similar proteins; Pirh2, also known as RING finger and CHY zinc finger domain-containing protein 1 (Rchy1), androgen receptor N-terminal-interacting protein, CH-rich-interacting match with PLAG1, RING finger protein 199 (RNF199), or zinc finger protein 363 (ZNF363), is a p53 inducible E3 ubiquitin-protein ligase that functions as a negative regulator of p53. It preferably ubiquitylates the tetrameric form of p53 in vitro and in vivo, suggesting a role of Pirh2 in downregulating the transcriptionally active form of p53 in the cell. Moreover, Pirh2 inhibits the transcriptional activity of p73, a homolog of the tumor suppressor p53, by promoting its ubiquitination. It also monoubiquitinates DNA polymerase eta (PolH) to suppress translesion DNA synthesis. Furthermore, Pirh2 functions as a negative regulator of the cyclin-dependent kinase inhibitor p27(Kip1) function by promoting ubiquitin-dependent proteasomal degradation. Pirh2 enhances androgen receptor (AR) signaling through inhibition of histone deacetylase 1 (HDAC1) and is overexpressed in prostate cancer. It interacts with TIP60 and this association may regulate Pirh2 stability. In addition, the oncoprotein pleomorphic adenoma gene like 2 (PLAGL2) can bind to the Pirh2 dimer and therefore control the stability of Pirh2. Pirh2 contains a total of nine zinc-binding sites with six located at the N-terminal region, two in the C3H2C3-type RING-H2 domain, and one in the C-terminal region. Nine zinc binding sites comprise three different zinc coordination schemes, including RING type cross-brace zinc coordination, C4 zinc finger, and a novel left-handed beta-spiral zinc-binding motif formed by three recurrent CCHC sequence motifs. This subfamily also includes Drosophila melanogaster Deltex, a ubiquitously expressed cytoplasmic ubiquitin E3 ligase that mediates Notch activation in Drosophila. It selectively suppresses T-cell activation through degradation of a key signaling molecule, MAP kinase kinase kinase 1 (MEKK1). It also inhibits Jun-mediated transcription at the stage of Ras-dependent Jun N-terminal protein kinase (JNK) activation. Deltex contains N-terminal two Notch-binding WWE domains that physically interact with the Notch ankyrin domains, a proline-rich motif that shares homology with SH3-binding domains, and a RING finger at the C-terminus.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 186495447 1152 NCPICHEYIFTSSSPVKALPCGHLMHSTCFQEYTCSH-YTCPVCS 1195
Cdd:cd16464     1 NCPVCLEDLFTSREPVHVLPCGHLMHSTCFEEYLKSGnYRCPLCS 45

Ring finger domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 186495447  1151 DNCPICHEYiFTSSSPVKALPCGHLMHSTCFQEYTCSHYTCPVC 1194
Cdd:pfam13639    1 DECPICLEE-FEEGDKVVVLPCGHHFHRECLDKWLRSSNTCPLC 43

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        40
                  ....*....|....*....|....*....|....*....|...
gi 186495447 1153 CPICHEYiFTSSSPVKALPCGHLMHSTCFQEY-TCSHYTCPVC 1194
Cdd:cd16448     1 CVICLEE-FEEGDVVRLLPCGHVFHLACILRWlESGNNTCPLC 42

RING finger, H2 subclass, found in RING finger proteins RNF126, RNF115, and similar proteins; This subfamily includes RING finger proteins RNF126, RNF115, and similar proteins. RNF126 is a Bag6-dependent E3 ubiquitin ligase that is involved in the mislocalized protein (MLP) pathway of quality control. It regulates the retrograde sorting of the cation-independent mannose 6-phosphate receptor (CI-MPR). RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation, and could be a novel therapeutic target in breast and prostate cancers. It is also able to ubiquitylate cytidine deaminase (AID), a poorly soluble protein that is essential for antibody diversification. RNF115, also known as Rab7-interacting ring finger protein (Rabring 7), or zinc finger protein 364 (ZNF364), or breast cancer-associated gene 2 (BCA2), is an E3 ubiquitin-protein ligase that is an endogenous inhibitor of adenosine monophosphate-activated protein kinase (AMPK) activation; this inhibition increases the efficacy of metformin in breast cancer cells. It also functions as a cofactor in the restriction imposed by tetherin on HIV-1, and targets HIV-1 Gag for lysosomal degradation, impairing virus assembly and release, in a tetherin-independent manner. Moreover, RNF115 is a Rab7-binding protein that stimulates c-Myc degradation through mono-ubiquitination of MM-1. It also plays crucial roles as a Rab7 target protein in vesicle traffic to late endosome/lysosome and lysosome biogenesis. RNF115 and RNF126 associate with the epidermal growth factor receptor (EGFR) and promote ubiquitylation of EGFR, suggesting they play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors. Both of them contain an N-terminal BCA2 Zinc-finger domain (BZF), AKT-phosphorylation sites, and a C-terminal C3H2C3-type RING-H2 finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 186495447 1152 NCPICHEyIFTSSSPVKALPCGHLMHSTCFQEYTCSHYTCPVC 1194
Cdd:cd16667     1 ECAVCKE-DFEVGEEVRQLPCKHLFHPDCIVPWLELHNSCPVC 42

Hemerythrin domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186495447   40 CHKAFRAQLVELRRFATDAAEADSFSGDLAVELSRKFEflklVY--KYHSAAEDEVIFLALDKR---VKNIVSNYSLEHA 114
Cdd:COG3945    10 EHRNIRRLLAVLEKLLDRLEEGEEVDFELLRDILDYIR----EFadRCHHPKEEDILFPRLEERggeAAGPIAVLLAEHE 85

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 186495447  115 GTDDLFTSIFHWLH-VLEEEIGSRSDVLREVILCIGTIQssicQHMLKEERQVFPLLIEKFSFREQASL 182
Cdd:COG3945    86 QGRQLTRELEEALEaYLAGDVVARDELAAALRAYIALLR----QHIAKEENVLFPLAERLLSDEDWEEL 150

RING finger, H2 subclass, found in autocrine motility factor receptor (AMFR) and similar proteins; AMFR, also known as AMF receptor, or RING finger protein 45, or ER-protein gp78, is an internalizing cell surface glycoprotein localized in both plasma membrane caveolae and the endoplasmic reticulum (ER). It is involved in the regulation of cellular adhesion, proliferation, motility and apoptosis, as well as in the process of learning and memory. AMFR also functions as a RING finger-dependent ubiquitin protein ligase (E3) implicated in the degradation from the ER. AMFR contains an N-terminal RING-H2 finger and a C-terminal ubiquitin-associated (UBA)-like CUE domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 186495447 1151 DNCPICHEYIFTSsspvKALPCGHLMHSTCFQEYTCSHYTCPVCSKSL 1198
Cdd:cd16455     1 DDCAICWESMQSA----RKLPCGHLFHNSCLRSWLEQDTSCPTCRMSL 44

RING finger, H2 subclass, found in vacuolar protein sorting-associated proteins Vps8, Vps11, Vps18, Vps41, and similar proteins; This subfamily corresponds to a group of vacuolar protein sorting-associated proteins containing a C-terminal C3H2C3-type RING-H2 finger, which includes Vps8, Vps11, Vps18, and Vps41. Vps11 and Vps18 associate with Vps16 and Vps33 to form a Class C Vps core complex that is required for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE)-mediated membrane fusion at the lysosome-like yeast vacuole. The core complex, together with two additional compartment-specific subunits, forms the tethering complexes HOPS (homotypic vacuole fusion and protein sorting) and CORVET (class C core vacuole/endosome transport). CORVET contains the additional Vps3 and Vps8 subunits. It operates at endosomes, controls traffic into late endosomes and interacts with the Rab5/Vps21-GTP form. HOPS contains the additional Vps39 and Vps41 subunits. It operates at the lysosomal vacuole, controls all traffic from late endosomes into the vacuole and interacts with the Rab7/Ypt7-GTP form.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 186495447 1152 NCPICH----EYIFTSSSPVKALPCGHLMHSTCFQEYTCSHYTCPVCS 1195
Cdd:cd16484     1 KCPICTlplkESDVGANSPVVVFFCGHMFHKFCLPELSMTEAACPICL 48

RING finger, H2 subclass, found in DAZ (deleted in azoospermia)-interacting protein 3 (DZIP3) and similar proteins; DZIP3, also known as RNA-binding ubiquitin ligase of 138 kDa (RUL138) or 2A-HUB protein, is an RNA-binding E3 ubiquitin-protein ligase that interacts with coactivator-associated arginine methyltransferase 1 (CARM1) and acts as a transcriptional coactivator of estrogen receptor (ER) alpha. It is also a histone H2A ubiquitin ligase that catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatorial component of the repression machinery required for repressing a specific chemokine gene expression program, critically modulating migratory responses to Toll-like receptors (TLR) activation. DZIP3 contains a C3H2C3-type RING-H2 finger at the C-terminus.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 186495447 1153 CPICHEYiFTSSSPVKALPCGHLMHSTCFQEYTCSHYTCPVC 1194
Cdd:cd16460     3 CVICHEA-FSDGDRLLVLPCAHKFHTQCIGPWLDGQQTCPTC 43

RING finger, H2 subclass, found in RING finger protein 130 (RNF130) and similar proteins; RNF130, also known as Goliath homolog (H-Goliath), is a paralog of RNF128, also known as gene related to anergy in lymphocytes protein (GRAIL). It is a transmembrane E3 ubiquitin-protein ligase expressed in leukocytes. It has a self-ubiquitination property, and controls the development of T cell clonal anergy by ubiquitination. RNF130 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 186495447 1151 DNCPICHEYiFTSSSPVKALPCGHLMHSTCFQEYTCSHYTCPVC 1194
Cdd:cd16803     1 DHCAVCIEG-YKQNDVVRILPCKHVFHKSCVDPWLNEHCTCPMC 43

RING finger, H2 subclass, found in TRAF-interacting protein (TRAIP) and similar proteins; TRAIP, also known as RING finger protein 206 (RNF206) or TRIP, is a ubiquitously expressed nucleolar E3 ubiquitin ligase important for cellular proliferation and differentiation. It is found near mitotic chromosomes and functions as a regulator of the spindle assembly checkpoint. TRAIP interacts with tumor necrosis factor (TNF)-receptor-associated factor (TRAF) proteins and inhibits TNF-alpha-mediated nuclear factor (NF)-kappaB activation. It also interacts with two tumor suppressors CYLD and spleen tyrosine kinase (Syk), and DNA polymerase eta, which facilitates translesional synthesis after DNA damage. TRAIP contains an N-terminal C3H2C2-type RING-H2 finger and an extended coiled-coil domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 186495447 1152 NCPICHEYiFTSSSPVKALPCGHLMHSTCFQEYTCSHYTCPVC 1194
Cdd:cd16480     1 YCTICSDF-FDNSRDVAAIHCGHTFHYDCLLQWFDTSRTCPQC 42

RING finger, H2 subclass, found in 43 kDa receptor-associated protein of the synapse (Rapsyn) and similar proteins; Rapsyn, also known as acetylcholine receptor (AChR)-associated 43 kDa protein or RING finger protein 205 (RNF205), is a 43 kDa postsynaptic protein that plays an essential role in the clustering and maintenance of AChR in the postsynaptic membrane of the motor endplate. AChRs enable the transport of rapsyn from the Golgi complex to the plasma membrane through a molecule-specific interaction. Rapsyn also mediates subsynaptic anchoring of protein kinase A (PKA) type I in close proximity to the postsynaptic membrane, which is essential for synapse maintenance. Its mutations in humans cause endplate AChR deficiency and myasthenic syndrome. Rapsyn contains an N-terminal myristoylation signal required for membrane association, seven tetratricopeptide repeats (TPRs) that subserve rapsyn self-association, a coiled-coil domain responsible for the binding of determinants within the long cytoplasmic loop of each AChR subunit, a C3H2C3-type RING-H2 finger that binds to the cytoplasmic domain of beta-dystroglycan and to S-NRAP and links rapsyn to the subsynaptic cytoskeleton, and a serine phosphorylation site.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 186495447 1152 NCPICHEYIFTSSSPVKALPCGHLMHSTCFQEYTC-SHYTCPVCSK 1196
Cdd:cd16478     3 FCGMCGESIGEKNEQLQALPCSHIFHLKCLQTNLRgGTRGCPNCRR 48

RING finger, H2 subclass, found in Arabidopsis thaliana RING-type E3 ubiquitin transferase BIG BROTHER (BB) and similar proteins; BB (also known as protein ENHANCER OF DA1-1 or EOD1) is an E3 ubiquitin-protein ligase that limits organ size, and possibly seed size, in a dose-dependent manner. It negatively regulates the duration of cell proliferation in leaves and petals independently of the major phytohormones (e.g. auxin, cytokinin, gibberellin, brassinosteroids, ethylene, abscisic acid, jasmonic acid), probably by targeting growth stimulators for degradation. It limits the proliferation of root meristematic cells. BB polyubiquitinates DA1. It is involved in the promotion of leaf senescence, in addition to its function in restricting plant growth. BB-related is an E3 ubiquitin-ligase probably involved in organ size regulation. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

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gi 186495447 1150 EDNCPIC-HEYifTSSSPVKALPCGHLMHSTCFQEYTCSHYTCPVCSKS 1197
Cdd:cd23115     4 NERCVICrLEY--EEGEDLLTLPCKHCYHSECIQQWLQINKVCPVCSAE 50

RING finger, H2 subclass, found in RING finger protein 150 (RNF150) and similar proteins; RNF150 is a RING finger protein and its polymorphisms may be associated with chronic obstructive pulmonary disease (COPD) risk in the Chinese population. Further studies with larger numbers of participants worldwide are needed for validation of the relationships between RNF150 genetic variants and the pathogenesis of COPD. RNF150 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

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gi 186495447 1151 DNCPICHEYiFTSSSPVKALPCGHLMHSTCFQEYTCSHYTCPVCSKSL 1198
Cdd:cd16805     7 DNCAVCIEG-YKPNDVVRILPCRHLFHKSCVDPWLLDHRTCPMCKMNI 53

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.

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gi 186495447  1153 CPICHEYIftsSSPVKALPCGHLMHSTCFQEYT-CSHYTCPVC 1194
Cdd:pfam00097    1 CPICLEEP---KDPVTLLPCGHLFCSKCIRSWLeSGNVTCPLC 40

RING finger, H2 subclass, found in protein E3 ubiquitin-protein ligase Praja-1, Praja-2, and similar proteins; This family includes two highly similar E3 ubiquitin-protein ligases, Praja-1 and Praja-2. Praja-1, also known as RING finger protein 70, is a RING-H2 finger ubiquitin ligase encoded by gene PJA1, a novel human X chromosome gene abundantly expressed in the brain. It has been implicated in bone and liver development, as well as memory formation and X-linked mental retardation (MRX). Praja-1 interacts with and activates the ubiquitin-conjugating enzyme UbcH5B, and shows E2-dependent E3 ubiquitin ligase activity. It is a 3-deazaneplanocin A (DZNep)-induced ubiquitin ligase that directly ubiquitinates individual polycomb repressive complex 2 (PRC2) subunits in a cell free system, which leads to their proteasomal degradation. It also plays an important role in neuronal plasticity, which is the basis for learning and memory. Moreover, Praja-1 ubiquitinates embryonic liver fodrin (ELF) and Smad3, but not Smad4, in a transforming growth factor-beta (TGF-beta)-dependent manner. It controls ELF abundance through ubiquitin-mediated degradation, and further regulates TGF-beta signaling, which plays a key role in the suppression of gastric carcinoma. Praja-1 also regulates the transcription function of the homeodomain protein Dlx5 by controlling the stability of Dlxin-1, via a ubiquitin-dependent degradation pathway. Praja-2, also known as RING finger protein 131, NEURODAP1, or KIAA0438, is an E2-dependent E3 ubiquitin ligase that interacts with and activates the ubiquitin-conjugating enzyme UbcH5B. It functions as an A-kinase anchoring protein (AKAP)-like E3 ubiquitin ligase that plays a critical role in controlling cyclic AMP (cAMP)-dependent PKA activity and pro-survival signaling, and further promotes cell proliferation and growth. Praja-2 is also involved in protein sorting at the postsynaptic density region of axosomatic synapses and possibly plays a role in synaptic communication and plasticity. Together with the AMPK-related kinase SIK2 and the CDK5 activator CDK5R1/p35, it forms a SIK2-p35-PJA2 complex that plays an essential role for glucose homeostasis in pancreatic beta cell functional compensation. Praja-2 ubiquitylates and degrades Mob, a core component of NDR/LATS kinase and a positive regulator of the tumor-suppressor Hippo signaling. Both Praja-1 and Praja-2 contain a potential nuclear localization signal (NLS) and a C-terminal C3H2C3-type RING-H2 motif.

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gi 186495447 1153 CPIC-HEYIftSSSPVKALPCGHLMHSTCFQEYTCSHYTCPVC 1194
Cdd:cd16465     2 CPICcSEYV--KDEIATELPCHHLFHKPCITAWLQKSGTCPVC 42

RING finger, H2 subclass, found in RING finger protein 11 (RNF11) and similar proteins; RNF11 is an E3 ubiquitin-protein ligase that acts both as an adaptor and a modulator of itch-mediated control of ubiquitination events underlying membrane traffic. It acts downstream of an enzymatic cascade for the ubiquitination of specific substrates. It is also a molecular adaptor of homologous to E6-associated protein C-terminus (HECT)-type ligases. RNF11 has been implicated in the regulation of several signaling pathways. It enhances transforming growth factor receptor (TGFR) signaling by both abrogating Smurf2-mediated receptor ubiquitination and by promoting the Smurf2-mediated degradation of AMSH (associated molecule with the SH3 domain of STAM), a de-ubiquitinating enzyme that enhances TGF-beta signaling and epidermal growth factor receptor (EGFR) endosomal recycling. It also acts directly on Smad4 to enhance Smad4 function, and plays a role in prolonged TGF-beta signaling. RNF11 also functions as a critical component of the A20 ubiquitin-editing protein complex that negatively regulates tumor necrosis factor (TNF)-mediated nuclear factor (NF)-kappaB activation. It interacts with Smad anchor for receptor activation (SARA) and the endosomal sorting complex required for transport (ESCRT)-0 complex, thus participating in the regulation of lysosomal degradation of EGFR. RNF11 acts as a novel GGA cargo actively participating in regulating the ubiquitination of the GGA protein family. RNF11 functions together with TAX1BP1 to target TANK-binding kinase 1 (TBK1)/IkappaB kinase IKKi, and further restricts antiviral signaling and type I interferon (IFN)-beta production. RNF11 contains an N-terminal PPPY motif that binds WW domain-containing proteins such as AIP4/itch, Nedd4 and Smurf1/2 (SMAD-specific E3 ubiquitin-protein ligase 1/2), and a C-terminal C3H2C3-type RING-H2 finger that functions as a scaffold for the coordinated transfer of ubiquitin to substrate proteins together with the E2 enzymes UbcH527 and Ubc13.

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gi 186495447 1152 NCPIC-HEYIFTSssPVKALPCGHLMHSTCFQEYTCSHYTCPVC 1194
Cdd:cd16468     1 ECVICmADFVVGD--PIRYLPCMHIYHVDCIDDWLMRSFTCPSC 42

RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; RNF213, also known as ALK lymphoma oligomerization partner on chromosome 17 or Moyamoya steno-occlusive disease-associated AAA+ and RING finger protein (mysterin), is an intracellular soluble protein that functions as an E3 ubiquitin-protein ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. It plays a unique role in endothelial cells for proper gene expression in response to inflammatory signals from the environment. Mutations in RNF213 may be associated with Moyamoya disease (MMD), an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. It also acts as a nuclear marker for acanthomorph phylogeny. RNF213 contains two tandem enzymatically active AAA+ ATPase modules and a C3HC4-type RING-HC finger. It can form a huge ring-shaped oligomeric complex.

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gi 186495447 1152 NCPICHEyifTSSSPVKaLPCGHLMHSTCFQEYTCSHYTCPVCSKSLGD 1200
Cdd:cd16561     4 ECSICLE---DLNDPVK-LPCDHVFCEECIRQWLPGQMSCPLCRTELPD 48

RING finger, H2 subclass, found in RING finger protein 167 (RNF167) and similar proteins; RNF167, also known as RING105, is an endosomal/lysosomal E3 ubiquitin-protein ligase involved in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) ubiquitination. It ubiquitinates AMPA-type glutamate receptor subunit GluA2 and regulates its surface expression, and thus acts as a selective regulator of AMPAR-mediated neurotransmission. It acts as an endosomal membrane protein which ubiquitylates vesicle-associated membrane protein 3 (VAMP3) and regulates endosomal trafficking. Moreover, RNF167 plays a role in the regulation of TSSC5 (tumor-suppressing subchromosomal transferable fragment cDNA, also known as ORCTL2/IMPT1/BWR1A/SLC22A1L), which can function in concert with the ubiquitin-conjugating enzyme UbcH6. RNF167 is widely conserved in metazoans and contains an N-terminal signal peptide, a protease-associated (PA) domain, two transmembrane domains (TM1 and TM2), and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

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gi 186495447 1151 DNCPICHEYiFTSSSPVKALPCGHLMHSTCFQEY-TCSHYTCPVCSK 1196
Cdd:cd16797     1 DVCAICLDE-YEEGDKLRVLPCSHAYHSKCVDPWlTQTKKTCPVCKQ 46

RING finger, H2 subclass, found in Arabidopsis thaliana protein ABA INSENSITIVE RING PROTEIN 1 (AIRP1) and similar proteins; This subfamily includes Arabidopsis thaliana AIRP1 and RING-H2 finger B1a (RHB1A). AIRP1, also known as RING-type E3 ubiquitin transferase AIRP1, possesses E3 ubiquitin-protein ligase activity in vitro when associated with the E2 enzyme UBC8. It plays combinatory roles with AIRP2 in the positive regulation of the abscisic acid-mediated drought stress response. RHB1A is a probable E3 ubiquitin-protein ligase. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

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gi 186495447 1150 EDNCPICHEYiFTSSSPVKALPCGHLMHSTCFQEYTCSHYTCPVCSKSL 1198
Cdd:cd23116     2 EDVCPTCLEG-YTEENPKLLTKCGHHFHLACIYEWMERSERCPVCDKEM 49

RING finger, HC subclass, found in seven in absentia homolog 2 (SIAH2) and similar proteins; SIAH2 is an E3 ubiquitin-protein ligase that contributes to proteasome-mediated degradation of multiple targets in numerous cellular processes. It targets the ubiquitylation and degradation of tumor necrosis factor receptor-associated factor 2 (TRAF2) under stress conditions, which is required for the cell to commit to undergoing apoptosis. It is, therefore, a key regulator of TRAF2-dependent signaling in response to tumor necrosis factor-alpha (TNF-alpha) treatment and UV irradiation. SIAH2 modulates the polyubiquitination of G protein pathway suppressor 2 (GPS2), and targets it for proteasomal degradation. It is also a regulator of NF-E2-related factor 2 (Nrf2), a key regulator of cellular oxidative response, and contributes to the degradation of Nrf2 irrespective of its phosphorylation status. Moreover, SIAH2 contributes to castration-resistant prostate cancer (CRPC) by regulation of androgen receptor (AR) transcriptional activity. It enhances AR transcriptional activity and prostate cancer cell growth. Its stability can be regulated by AKR1C3. SIAH2 also inhibits tyrosine kinase-2 (TYK2)-STAT3 signaling in lung carcinoma cells. Furthermore, SIAH2 regulates obesity-induced adipose tissue inflammation by altering peroxisome proliferator-activated receptor gamma (PPAR gamma) protein levels and selectively regulating PPAR gamma activity. It also functions as a regulator of the nuclear hormone receptor RevErbalpha (Nr1d1) stability and rhythmicity, and overall circadian oscillator function. In addition, SIAH2 is an essential component of the hypoxia response Hippo signaling pathway and has been implicated in normal development and tumorigenesis. It modulates the hypoxia pathway upstream of hypoxia-induced transcription factor subunit HIF-1alpha, and therefore may play an important role in angiogenesis in response to hypoxic stress in endothelial cells. It also stimulates transcriptional coactivator YAP1 by destabilizing serine/threonine-protein kinase LATS2, a critical component of the Hippo pathway, in response to hypoxia. Meanwhile, SIAH2 is involved in regulation of tight junction integrity and cell polarity under hypoxia, through its regulation of apoptosis-stimulating proteins of p53 subunit 2 (ASPP2) stability. SIAH2 contains an N-terminal C3HC4-type RING-HC finger, two zinc-finger subdomains, and a C-terminal tumor necrosis factor (TNF) receptor associated factor (TRAF)-like substrate-binding domain (SBD) responsible for dimer formation.

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gi 186495447 1153 CPICHEYIFtssSPVKALPCGHLMHSTCFQEYTCshytCPVCSKSLGD 1200
Cdd:cd16752     6 CPVCFDYVL---PPILQCQAGHLVCNQCRQKLSC----CPTCRGPLTP 46

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).

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gi 186495447 1153 CPICHEyifTSSSPVKALPCGHLMHSTCFQE-YTCSHYTCPVCSKSLG 1199
Cdd:cd16544     5 CPVCQE---VLKDPVELPPCRHIFCKACILLaLRSSGARCPLCRGPVG 49

RING finger, H2 subclass, found in RING finger protein 165 (RNF165) and similar proteins; RNF165, also known as Arkadia-like 2, Arkadia2, or Ark2C, is an E3 ubiquitin ligase with homology to the C-terminal half of RNF111. It is expressed specifically in the nervous system, and can serve to amplify neuronal responses to specific signals. It acts as a positive regulator of bone morphogenetic protein (BMP)-Smad signaling that is involved in motor neuron (MN) axon elongation. RNF165 contains two serine rich domains, a nuclear localization signal, an NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is responsible for the enhancement of BMP-Smad1/5/8 signaling in the spinal cord.

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gi 186495447 1146 EKCLEDNCPICHEyIFTSSSPVKALPCGHLMHSTCFQEYTCSHYTCPVC 1194
Cdd:cd16682     3 ESDTDEKCTICLS-MLEDGEDVRRLPCMHLFHQLCVDQWLAMSKKCPIC 50

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.

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gi 186495447 1153 CPICHEYIftssSPVKALPCGHLMHSTCFQEYTCS-HYTCPVC 1194
Cdd:cd16449     3 CPICLERL----KDPVLLPCGHVFCRECIRRLLESgSIKCPIC 41

RING finger, H2 subclass, found in RING finger protein 215 (RNF215) and similar proteins; This family includes uncharacterized protein RNF215 and similar proteins. Although its biological function remains unclear, RNF215 shares high sequence similarity with PA-TM-RING ubiquitin ligases, which have been characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger.

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gi 186495447 1151 DNCPICHEYiFTSSSPVKALPCGHLMHSTCFQEYTCSHYTCPVCSKSL 1198
Cdd:cd16670     1 ESCAVCLDQ-FYKNQCLRVLPCLHEFHRDCVDPWLLLQQTCPLCKRNI 47

RING finger, H2 subclass, found in RING finger proteins RNF24, RNF122, and similar proteins; This subfamily includes RNF24, RNF122, and similar proteins. RNF24 is an intrinsic membrane protein localized in the Golgi apparatus. It specifically interacts with the ankyrin-repeats domains (ARDs) of TRPC1, -3, -4, -5, -6, and -7, and affects TRPC intracellular trafficking without affecting their activity. RNF122 is a RING finger protein associated with HEK 293T cell viability. It is localized to the endoplasmic reticulum (ER) and the Golgi apparatus, and overexpressed in anaplastic thyroid cancer cells. RNF122 functions as an E3 ubiquitin ligase that can ubiquitinate itself and undergo degradation through its RING finger in a proteasome-dependent manner. Both RNF24 and RNF122 contain an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.

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gi 186495447 1151 DNCPIC-HEYIFTSSspVKALPCGHLMHSTCFQEYTCSHYTCPVCSKSL 1198
Cdd:cd16469     1 DTCAVClEEFKLKEE--LGVCPCGHAFHTKCLKKWLEVRNSCPICKSPV 47