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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063741983 1651 TGKMASLAGAIYGLMLRVLPAYVREWFSEMRDRSASSLIEAFTRTWCSPSLIKNEL----SQIKKADFNDES-FSVSISK 1725
Cdd:COG5219   1308 TDRIRCLAIHIYYQFFEKMVGEKEEWWVFLKDRGLQRSLEAFVFPNISPSLIKMEVddldSFILKEASRTIAdVTVKANK 1387

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063741983 1726 AANEVVATYTKDETGMDLVIRLPVSYPLKPVDVNCAKSIGISEAKQRKWLMSMQMFVRHQNGALAEAIRIWKRNSDKEFE 1805
Cdd:COG5219   1388 LTNEIGITYTADGTKLEALIKIPSGYPLKNVQVEGIKRVGTSEIGWKSWINLRQNEMIKKNGSFMDLLGLWKKNIDEKFS 1467

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1063741983 1806 GVEDCPICYSVIHIGNHSLPRRACVTCKYKFHKACLDKWFYTSNKKLCPLCQS 1858
Cdd:COG5219   1468 GHEECAICYSVLDMVDRSLPSKRCATCKNKFHTRCLYKWFASSARSNCPLCRS 1520

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063741983 1651 TGKMASLAGAIYGLMLRVLPAYVREWFSEMRDRSASSLIEAFTRTWCSPSLIKNEL----SQIKKADFNDES-FSVSISK 1725
Cdd:COG5219   1308 TDRIRCLAIHIYYQFFEKMVGEKEEWWVFLKDRGLQRSLEAFVFPNISPSLIKMEVddldSFILKEASRTIAdVTVKANK 1387

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063741983 1726 AANEVVATYTKDETGMDLVIRLPVSYPLKPVDVNCAKSIGISEAKQRKWLMSMQMFVRHQNGALAEAIRIWKRNSDKEFE 1805
Cdd:COG5219   1388 LTNEIGITYTADGTKLEALIKIPSGYPLKNVQVEGIKRVGTSEIGWKSWINLRQNEMIKKNGSFMDLLGLWKKNIDEKFS 1467

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1063741983 1806 GVEDCPICYSVIHIGNHSLPRRACVTCKYKFHKACLDKWFYTSNKKLCPLCQS 1858
Cdd:COG5219   1468 GHEECAICYSVLDMVDRSLPSKRCATCKNKFHTRCLYKWFASSARSNCPLCRS 1520

Ring finger domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1063741983 1809 DCPICYSVIHIGNHSLprraCVTCKYKFHKACLDKWFYTSNKklCPLC 1856
Cdd:pfam13639    2 ECPICLEEFEEGDKVV----VLPCGHHFHRECLDKWLRSSNT--CPLC 43

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063741983   59 LDSEVAQHLQRLSRKDPTTKIKALASLSELVKQKQGKELLpIIPQWTFEYKKLILDYSRDVRRATHDVMTNVVTGAGRDI 138
Cdd:COG5219     42 LDAEMIVIVKNLQKRDIVTKCRALQDLIQWNDPSQFDNEQ-FLNALAVLFPRLSIEVEMNPRLEGLQFDSRLYEILSKKI 120

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063741983  139 APHLKSIMGPWWFSQFDLASEVSQAAKSSFQAAFpAQEKRLH-----ALNLCSAEIFAYLEENLkltpQNLSDKSLASDE 213
Cdd:COG5219    121 GKRLKKTILRGLLGLKDVDDTVSVEANIDTLLEI-VEDKWPTiwksfNLQIKNLVIDVLYHELL----SSVEDRRKFSKE 195

                          170       180
                   ....*....|....*....|
gi 1063741983  214 LEE-MYQQMISSSLVGLATL 232
Cdd:COG5219    196 ESEwLYGRVENSEYLVLRKL 215

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063741983 1651 TGKMASLAGAIYGLMLRVLPAYVREWFSEMRDRSASSLIEAFTRTWCSPSLIKNEL----SQIKKADFNDES-FSVSISK 1725
Cdd:COG5219   1308 TDRIRCLAIHIYYQFFEKMVGEKEEWWVFLKDRGLQRSLEAFVFPNISPSLIKMEVddldSFILKEASRTIAdVTVKANK 1387

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063741983 1726 AANEVVATYTKDETGMDLVIRLPVSYPLKPVDVNCAKSIGISEAKQRKWLMSMQMFVRHQNGALAEAIRIWKRNSDKEFE 1805
Cdd:COG5219   1388 LTNEIGITYTADGTKLEALIKIPSGYPLKNVQVEGIKRVGTSEIGWKSWINLRQNEMIKKNGSFMDLLGLWKKNIDEKFS 1467

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1063741983 1806 GVEDCPICYSVIHIGNHSLPRRACVTCKYKFHKACLDKWFYTSNKKLCPLCQS 1858
Cdd:COG5219   1468 GHEECAICYSVLDMVDRSLPSKRCATCKNKFHTRCLYKWFASSARSNCPLCRS 1520

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 1063741983 1810 CPICYSVIHIGNHslprRACVTCKYKFHKACLDKWFYTSNKKlCPLCQ 1857
Cdd:cd16448      1 CVICLEEFEEGDV----VRLLPCGHVFHLACILRWLESGNNT-CPLCR 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 1063741983 1805 EGVEDCPICYSVIHIGNHSLPRRAC-VT-CKYKFHKACLDKWFYTsnKKLCPLCQSP 1859
Cdd:cd23117      2 NGSVDCVICMSDIELPSTNSVRRDYmVTpCNHIFHTNCLERWMDI--KLECPTCRRP 56

Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins; RFWD3, also known as RING finger protein 201 (RNF201) or FLJ10520, is an E3 ubiquitin-protein ligase that forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and acts as a positive regulator of p53 stability in response to DNA damage. It is phosphorylated by checkpoint kinase ATM/ATR and the phosphorylation mutant fails to stimulate p53 ubiquitination. RFWD3 also functions as a novel replication protein A (RPA)-associated protein involved in DNA replication checkpoint control. RFWD3 contains an N-terminal SQ-rich region followed by a RING finger domain that exhibits robust E3 ubiquitin ligase activity toward p53, a coiled-coil domain and three WD40 repeats in the C-terminus, the latter two of which may be responsible for protein-protein interaction. The RING finger in this family is a modified C3HGC3-type RING finger, but not a canonical C3H2C3-type RING-H2 finger or C3HC4-type RING-HC finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1063741983 1810 CPICYSVIHI-GNHslpRRACVTCKYKFHKACLDKWFYTSNKKlCPLCQSPC 1860
Cdd:cd16450      5 CPICFEPWTSsGEH---RLVSLKCGHLFGYSCIEKWLKGKGKK-CPQCNKKA 52

The RING-variant domain is a C4HC3 zinc-finger like motif found in a number of cellular and viral proteins; Some of these proteins have been shown both in vivo and in vitro to have ubiquitin E3 ligase activity. The RING-variant domain is reminiscent of both the RING and the PHD domains and may represent an evolutionary intermediate. To describe this domain the term PHD/LAP domain has been used in the past. Extended description: The RING-variant (RINGv) domain contains a C4HC3 zinc-finger-like motif similar to the PHD domain, while some of the spacing between the Cys/His residues follow a pattern somewhat closer to that found in the RING domain. The RINGv domain, similar to the RING, PHD and LIM domains, is thought to bind two zinc ions co-ordinated by the highly conserved Cys and His residues. RING variant domain: C-x (2) -C-x(10-45)-C-x (1) -C-x (7) -H-x(2)-C-x(11-25)-C-x(2)-C As opposed to a PHD: C-x(1-2) -C-x (7-13)-C-x(2-4)-C-x(4-5)-H-x(2)-C-x(10-21)-C-x(2)-C Classical RING domain: C-x (2) -C-x (9-39)-C-x(1-3)-H-x(2-3)-C-x(2)-C-x(4-48) -C-x(2)-C

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 1063741983  1809 DCPICYSVIHIGNHSLprRACVtCK--YKF-HKACLDKWFYTSNKKLCPLCQ 1857
Cdd:smart00744    1 ICRICHDEGDEGDPLV--SPCR-CKgsLKYvHQECLERWINESGNKTCEICK 49

RING finger, H2 subclass, found in rice E3 ubiquitin-protein ligase EL5 and similar proteins; EL5, also known as protein ELICITOR 5, is an E3 ubiquitin-protein ligase containing an N-terminal transmembrane domain and a C3H2C3-type RING-H2 finger that is a binding site for ubiquitin-conjugating enzyme (E2). It can be rapidly induced by N-acetylchitooligosaccharide elicitor. EL5 catalyzes polyubiquitination via the Lys48 residue of ubiquitin, and thus plays a crucial role as a membrane-anchored E3 in the maintenance of cell viability after the initiation of root primordial formation in rice. It also acts as an anti-cell death enzyme that might be responsible for mediating the degradation of cytotoxic proteins produced in root cells after the actions of phytohormones. Moreover, EL5 interacts with UBC5b, a rice ubiquitin carrier protein, through its RING-H2 finger. EL5 is an unstable protein, and its degradation is regulated by the C3H2C3-type RING-H2 finger in a proteasome-independent manner.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1063741983 1809 DCPICYSVIHIGNHS--LPRracvtCKYKFHKACLDKWFYTSNKklCPLC 1856
Cdd:cd16461      1 ECAICLSDYENGEELrrLPE-----CKHAFHKECIDEWLKSNST--CPLC 43

RING finger, H2 subclass, found in RING finger protein 111 (RNF111) and similar proteins; RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It acts as an amplifier of Nodal signals, and enhances the dorsalizing activity of limiting amounts of Xnr1, a Nodal homolog, and requires Nodal signaling for its function. The loss of RNF111 results in early embryonic lethality, with defects attributed to compromised Nodal signaling. RNF111 also regulates tumor metastasis by modulation of the TGF-beta pathway. Its ubiquitination can be modulated by the four and a half LIM-only protein 2 (FHL2) that activates TGF-beta signal transduction. Furthermore, RNF111 interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. In addition, RNF111 has been identified as a small ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting motifs (SIMs) that together form a SUMO-binding domain (SBD). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). The N-terminal half of RNF111 harbors three SIMs. Its C-terminal half show high sequence similarity with RING finger protein 165 (RNF165), where it contains two serine rich domains, two nuclear localization signals, an NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is required for polyubiqutination and proteasome-dependent degradation of phosphorylated forms of Smad2/3 and three major negative regulators of TGF-beta signaling, Smad7, SnoN and c-Ski.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1063741983 1808 EDCPICYSVIHIGNHSlpRRacVTCKYKFHKACLDKWFYTsNKKlCPLCQ 1857
Cdd:cd16681     11 EKCTICLSILEEGEDV--RR--LPCMHLFHQVCVDQWLIT-NKK-CPICR 54

RING finger, H2 subclass, found in Saccharomyces cerevisiae alcohol-sensitive RING finger protein 1 (ASR1) and similar proteins; ASR1 is required for tolerance to alcohol. It signals alcohol stress to the nucleus. ASR1 contains a C3H2C3-type RING-H2 finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1063741983 1808 EDCPICYSVIHIGNhslprrACVT-CKYKFHKACLDKWFYTSNKKLCPLCQ 1857
Cdd:cd23120      2 EECPICLEEMNSGT------GYLAdCGHEFHLTCIREWHNKSGNLDCPICR 46

RING finger, H2 subclass, found in RING finger proteins RNF111, RNF165, and similar proteins; The family includes RING finger proteins RNF111, RNF165, and similar proteins. RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It also interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. The N-terminal half of RNF111 harbors three SUMO-interacting motifs (SIMs). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). 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. Both RNF165 and RNF111 contain a C-terminal C3H2C3-type RING-H2 finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1063741983 1808 EDCPICYSVIHIGN--HSLPrracvtCKYKFHKACLDKWFyTSNKKlCPLCQ 1857
Cdd:cd16474      1 EKCTICLSDFEEGEdvRRLP------CMHLFHQECVDQWL-STNKR-CPICR 44

Modified RING finger, H2 subclass (C3H2C2D-type), found in zinc finger SWIM domain-containing protein 2 (ZSWIM2) and similar proteins; ZSWIM2, also known as MEKK1-related protein X (MEX) or ZZ-type zinc finger-containing protein 2, is a testis-specific E3 ubiquitin ligase that promotes death receptor-induced apoptosis through Fas, death receptor (DR) 3 and DR4 signaling. ZSWIM2 is self-ubiquitinated and targeted for degradation through the proteasome pathway. It acts as an E3 ubiquitin ligase, through the E2, Ub-conjugating enzymes UbcH5a, UbcH5c, or UbcH6. ZSWIM2 contains four putative zinc-binding domains including an N-terminal SWIM (SWI2/SNF2 and MuDR) domain critical for its ubiquitination, and two modified RING-H2 fingers separated by a ZZ zinc finger domain, which was required for interaction with UbcH5a and its self-association. This model corresponds to the second RING-H2 finger, which is not a canonical C3H2C3-type, but a modified C3H2C2D-type.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1063741983 1810 CPICYSVIHIGNH--SLPrracvtCKYKFHKACLDKWFYTSNKKlCPLC 1856
Cdd:cd16486      2 CRICLKAFQLGQHvrTLP------CRHKFHRDCIDNWLLHSRNS-CPID 43

RING finger, H2 subclass, found in RING finger protein 24 (RNF24) 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. RNF24 contains an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.

                           10        20
                   ....*....|....*....|....*...
gi 1063741983 1832 CKYKFHKACLDKWFYTsnKKLCPLCQSP 1859
Cdd:cd16675     21 CKHAFHRKCLIKWLEV--RKVCPLCNMP 46

RING finger, H2 subclass, found in RING finger protein 103 (RNF103) and similar proteins; RNF103, also known as KF-1 or zinc finger protein 103 homolog (Zfp-103), is an endoplasmic reticulum (ER)-resident E3 ubiquitin-protein ligase that is widely expressed in many different organs, including brain, heart, kidney, spleen, and lung. It is involved in the ER-associated degradation (ERAD) pathway by interacting with components of the ERAD pathway, including Derlin-1 and VCP. RNF103 contains several hydrophobic regions at its N-terminal and middle regions, as well as a C-terminal C3H2C3-type RING-H2 finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1063741983 1808 EDCPICYS-----VIHIGnhsLPrracvtCKYKFHKACLDKWFYTSNKKlCPLCQSP 1859
Cdd:cd16473      5 EECAICLEnyqngDLLRG---LP------CGHVFHQNCIDVWLERDNHC-CPVCRWP 51

RING finger, H2 subclass, found in RING finger protein 145 (RNF145) and similar proteins; RNF145 is an uncharacterized RING finger protein encoded by the RNF145 gene, which is expressed in T lymphocytes, and its expression is altered in acute myelomonocytic and acute promyelocytic leukemias. Although its biological function remains unclear, RNF145 shows high sequence similarity with RNF139, an endoplasmic reticulum (ER)-resident multi-transmembrane protein that functions as a potent growth suppressor in mammalian cells, inducing G2/M arrest, decreased DNA synthesis and increased apoptosis. Like RNF139, RNF145 contains a C3H2C3-type RING-H2 finger with possible E3-ubiquitin ligase activity.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1063741983 1810 CPICYSVIHignhslprRACVT-CKYKFHKACLDKWFYTsnKKLCPLCQ 1857
Cdd:cd16684      5 CSICYQDMK--------SAVITpCSHFFHAGCLKKWLYV--QETCPLCH 43

RING finger, HC subclass, found in bifunctional apoptosis regulator (BAR); BAR, also known as RING finger protein 47, was originally identified as an inhibitor of Bax-induced apoptosis. It participates in the block of apoptosis induced by TNF-family death receptors (extrinsic pathway) and mitochondria-dependent apoptosis (intrinsic pathway). BAR is predominantly expressed by neurons in the central nervous system and is involved in the regulation of neuronal survival. It is an endoplasmic reticulum (ER)-associated RING-type E3 ubiquitin ligase that interacts with BI-1 protein and post-translationally regulates its stability, as well as functioning in ER stress. BAR contains an N-terminal C3HC4-type RING-HC finger, a SAM domain, a coiled-coil domain, and a C-terminal transmembrane (TM) domain. This model corresponds to the RING-HC finger responsible for the binding of ubiquitin conjugating enzymes (E2s).

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1063741983 1810 CPICYSVihignhsLPRRACVTCKYKFHKACLDKWFYTSNKKLCPLCQ 1857
Cdd:cd16497      4 CHCCYDL-------LVNPTTLNCGHSFCRHCLALWWKSSKKTECPECR 44

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
                   ....*....|....*....|....*....
gi 1063741983 1828 ACVTCKYKFHKACLDKWFYTSnkKLCPLC 1856
Cdd:cd16480     16 AAIHCGHTFHYDCLLQWFDTS--RTCPQC 42

RING finger, HC subclass, found in Equid alphaherpesvirus 1 (Equine herpesvirus 1/EHV-1) regulatory protein and similar proteins; EHV-1 regulatory protein belongs to the Vmw110 (IPC0) protein family. It contains a typical C3HC4-type RING-HC finger and binds zinc stably.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1063741983 1808 EDCPICYSVIHIGNHSLPrracvtCKYKFHKACLDKWFYTSNKklCPLCQSP 1859
Cdd:cd23130      1 DVCPICLDDPEDEAITLP------CLHQFCYTCILRWLQTSPT--CPLCKTP 44

RING-CH finger, H2 subclass (C4HC3-type), found in zinc finger SWIM domain-containing protein 2 (ZSWIM2) and similar proteins; ZSWIM2, also known as MEKK1-related protein X (MEX) or ZZ-type zinc finger-containing protein 2, is a testis-specific E3 ubiquitin ligase that promotes death receptor-induced apoptosis through Fas, death receptor (DR) 3, and DR4 signaling. ZSWIM2 is self-ubiquitinated and targeted for degradation through the proteasome pathway. It also acts as an E3 ubiquitin ligase, through the E2, Ub-conjugating enzymes UbcH5a, UbcH5c, or UbcH6. ZSWIM2 contains four putative zinc-binding domains including an N-terminal SWIM (SWI2/SNF2 and MuDR) domain critical for its ubiquitination and two RING fingers separated by a ZZ zinc finger domain, which was required for interaction with UbcH5a and its self-association. This model corresponds to the first RING finger, which is a C4HC3-type RING-CH finger, also known as vRING or RINGv, rather than the canonical C3H2C3-type RING-H2 finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1063741983 1808 EDCPICYSVIHIGNHSLPRraC-VTCKYKFHKACLDKWF---YTSNKKL-CPLCQSP 1859
Cdd:cd16494      2 DDCPICYEEMLEKGEPLTY--CrFGCGNNVHIHCMKVWAehqRQSDEPVtCPLCRSD 56

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6 and similar proteins; RNF6 is an androgen receptor (AR)-associated protein that induces AR ubiquitination and promotes AR transcriptional activity. RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity by modulating cofactor recruitment. RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. Moreover, RNF6 regulates local serine/threonine kinase LIM kinase 1 (LIMK1) levels in axonal growth cones. RNF6-induced LIMK1 polyubiquitination is mediated via K48 of ubiquitin and leads to proteasomal degradation of the kinase. RNF6 also binds and upregulates the Inha promoter, and functions as a transcription regulatory protein in the mouse sertoli cell. RNF6 also acts as a potential tumor suppressor gene involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). RNF6 contains an N-terminal coiled-coil domain, a Lys-X-X-Leu/Ile-X-X-Leu/Ile (KIL) motif, and a C-terminal C3H2C3-type RING-H2 finger which is responsible for its ubiquitin ligase activity. The KIL motif is present in a subset of RING-H2 proteins from organisms as evolutionarily diverse as human, mouse, chicken, Drosophila, Caenorhabditis elegans, and Arabidopsis thaliana.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1063741983 1810 CPICYSVIHIGN--HSLPrracvtCKYKFHKACLDKWFytSNKKLCPLCQSP 1859
Cdd:cd16673      3 CSVCINEYATGNklRRLP------CAHEFHIHCIDRWL--SENSTCPICRQP 46

Modified RING finger, HC subclass (C4C4-type), found in tripartite motif-containing protein 37 (TRIM37) and similar proteins; TRIM37, also known as mulibrey nanism protein, or MUL, is a peroxisomal E3 ubiquitin-protein ligase that is involved in the tumorigenesis of several cancer types, including pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), breast cancer, and sporadic fibrothecoma. It mono-ubiquitinates histone H2A, a chromatin modification associated with transcriptional repression. Moreover, TRIM37 possesses anti-HIV-1 activity, and interferes with viral DNA synthesis. Mutations in the human TRIM37 gene (also known as MUL) cause Mulibrey (muscle-liver-brain-eye) nanism, a rare growth disorder of prenatal onset characterized by dysmorphic features, pericardial constriction, and hepatomegaly. TRIM37 belongs to the C-VIII 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 C4C4-type RING finger, whose overall folding is similar to that of the typical C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a MATH (meprin and TRAF-C homology) domain positioned C-terminal to the RBCC domain. Its MATH domain has been shown to interact with the TRAF (TNF-Receptor-Associated Factor) domain of six known TRAFs in vitro.

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gi 1063741983 1809 DCPICYSVIhIGNHSLPRracvtCKYKFHKACLDKWfYTSNKKLCPLCQ 1857
Cdd:cd16619      2 RCFICMEKL-RDPRLCPH-----CSKLFCKGCIRRW-LSEQRSSCPHCR 43

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH2 (MARCH2); MARCH2, also known as membrane-associated RING finger protein 2, membrane-associated RING-CH protein II (MARCH-II), or RING finger protein 172 (RNF172), is a Golgi-localized, membrane-associated E3 ubiquitin-protein ligase that is involved in endosomal trafficking through the binding of syntaxin 6 (STX6). It is involved in the cystic fibrosis transmembrane conductance regulator (CFTR)-associated ligand (CAL)-mediated ubiquitination and lysosomal degradation of mature CFTR through the association with adaptor proteins CAL and STX6. It also reduces the surface expression of CD86 and the transferrin receptor TFRC and regulates cell surface carvedilol-bound beta2-adrenergic receptor (beta2AR) expression. Moreover, MARCH2 interacts with and ubiquitinates PDZ domains polarity determining scaffold protein DLG1 through its PDZ-binding motif, suggesting it may function as a molecular bridge with ubiquitin ligase activity connecting endocytic tumor suppressor proteins such as syntaxins to DLG1. MARCH2 contains a C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, in the N-terminal cytoplasmic region, two transmembrane domains in the middle region, and a PDZ-binding motif at the C-terminus.

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gi 1063741983 1811 PICySVIHIGNHS---LPRRACVTCKYKFHKACLDKWFYTSNKKLCPLCQS 1858
Cdd:cd16808      1 PIC-RICHEGGNGeslLSPCDCTGTLGTVHKSCLEKWLSSSNTSYCELCHT 50

RING-CH finger, H2 subclass (C4HC3-type), found in Fanconi anemia group L protein (FANCL) and similar proteins; FANCL, also known as fanconi anemia-associated polypeptide of 43 kDa (FAAP43) or PHF9, is a monomeric RING E3 ubiquitin-protein ligase that monoubiquitinates FANCD2 and FANCI. The monoubiquitinated FANCD2-FANCI heterodimer complex in turn recruits key proteins involved in homologous recombination and DNA repair. FANCL is also one of seven components in Fanconi anemia (FA) nuclear core complex, which provides the essential E3 ligase function for spatially defined FANCD2 ubiquitination and FA pathway activation. In the FA core complex, FANCL associates with FANCB and FAAP100 to constitute a catalytic subcomplex that functions as the monoubiquitination module. FANCL specifically interacts with the E2 ubiquitin-conjugating (UBC) enzyme Ube2T to make an E3-E2 pair, which is the catalytic center of the Fanconi Anemia (FA) pathway required for DNA interstrand crosslink repair. Moreover, FANCL has a noncanonical function to regulate the Wnt/beta-catenin signaling, a pathway involved in hematopoietic stem cell self-renewal. It functionally enhances beta-catenin activity by ubiquitinating beta-catenin, with atypical ubiquitin chains (K11 linked). FANCL contains an N-terminal E2-like fold (ELF) domain, a novel double-RWD (DRWD) domain with a clear hydrophobic core, and a C-terminal C4HC3-type RING-CH finger. The DRWD domain is required for substrate binding. The RING-CH finger, also known as vRING or RINGv, is predicted to facilitate E2 binding. It has an unusual arrangement of zinc-coordinating residues. Its cysteines and histidines are arranged in the sequence as C4HC3-type, rather than the C3H2C3-type in canonical RING-H2 finger.

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gi 1063741983 1809 DCPICYSviHIGNHSLPRRAC--VTCKYKFHKACLDKWF 1845
Cdd:cd16490      1 ECGICYA--YRLDGEVPDQVCdnARCGQPFHQSCLYEWL 37

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Deltex3 (DTX3), Deltex-3-like (DTX3L) and similar proteins; This subfamily contains Deltex3 (DTX3) and Deltex-3-like (DTX3L), both of which are E3 ubiquitin-protein ligases belonging to the Deltex (DTX) family. DTX3, also known as RING finger protein 154 (RNF154), has a biological function that remains unclear. DTX3L, also known as B-lymphoma- and BAL-associated protein (BBAP) or Rhysin-2 (Rhysin2), regulates endosomal sorting of the G protein-coupled receptor CXCR4 from endosomes to lysosomes. It also regulates subcellular localization of its partner protein, B aggressive lymphoma (BAL), by a dynamic nucleocytoplasmic trafficking mechanism. In contrast to other DTXs, both DTX3 and DTX3L contain a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain. DTX3L can associate with DTX1 through its unique N termini and further enhance self-ubiquitination.

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gi 1063741983 1808 EDCPICYSVIHignhslPRRACVTCKYKFHKACLDKWFytSNKKLCPLCQ 1857
Cdd:cd16506      1 DTCPICLDEIQ------NKKTLEKCKHSFCEDCIDRAL--QVKPVCPVCG 42

RING finger, H2 subclass, found in RING finger protein 122 (RNF122) and similar proteins; 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. It interacts with calcium-modulating cyclophilin ligand (CAML), which is not a substrate, but a stabilizer of RNF122. RNF122 contains an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.

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gi 1063741983 1832 CKYKFHKACLDKWFYTsnKKLCPLCQSP 1859
Cdd:cd16676     21 CQHAFHRKCLVKWLEI--RCVCPMCNKP 46