RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 2(RNFT2); RNFT2, also known as transmembrane protein 118 (TMEM118), is a multi-pass membrane protein containing a C3HC4-type RING-HC finger. Its biological role remains unclear.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568937242 371 GVRATGQQCTEAGAVCAICQAEFRDPMILLCQHVFCEECLCLWLDRERTCPLCRSVAVDTLRCWKDG 437
Cdd:cd16742    1 GVRATSQQCSEAGDICAICQAEFREPLILICQHVFCEECLCLWFDRERTCPLCRSVVVETLRCWKDG 67

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 2(RNFT2); RNFT2, also known as transmembrane protein 118 (TMEM118), is a multi-pass membrane protein containing a C3HC4-type RING-HC finger. Its biological role remains unclear.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568937242 371 GVRATGQQCTEAGAVCAICQAEFRDPMILLCQHVFCEECLCLWLDRERTCPLCRSVAVDTLRCWKDG 437
Cdd:cd16742    1 GVRATSQQCSEAGDICAICQAEFREPLILICQHVFCEECLCLWFDRERTCPLCRSVVVETLRCWKDG 67

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 568937242   386 CAICQAEF-RDPMILLCQHVFCEECLCLWLDRE-RTCPLC 423
Cdd:smart00184   1 CPICLEEYlKDPVILPCGHTFCRSCIRKWLESGnNTCPIC 40

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568937242 372 VRATGQQCTEAGAVCAICQAEF-------------RDPMILLCQHVFCEECLCLWLDRERTCPLCRS 425
Cdd:COG5243  276 PTATEEQLTNSDRTCTICMDEMfhpdheplprgldMTPKRLPCGHILHLHCLKNWLERQQTCPICRR 342

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 2(RNFT2); RNFT2, also known as transmembrane protein 118 (TMEM118), is a multi-pass membrane protein containing a C3HC4-type RING-HC finger. Its biological role remains unclear.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568937242 371 GVRATGQQCTEAGAVCAICQAEFRDPMILLCQHVFCEECLCLWLDRERTCPLCRSVAVDTLRCWKDG 437
Cdd:cd16742    1 GVRATSQQCSEAGDICAICQAEFREPLILICQHVFCEECLCLWFDRERTCPLCRSVVVETLRCWKDG 67

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein RNFT1, RNFT2, and similar proteins; Both RNFT1 and RNFT2 are multi-pass membrane proteins containing a C3HC4-type RING-HC finger. Their biological roles remain unclear.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 568937242 384 AVCAICQAEFRDPMILLCQHVFCEECLCLWLDRERTCPLCR 424
Cdd:cd16532    1 DICPICQDEFKDPVVLRCKHIFCEDCVSEWFERERTCPLCR 41

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 568937242  386 CAICQAEF---RDPMILLCQHVFCEECLCLWLDRERTCPLCR 424
Cdd:pfam13639   3 CPICLEEFeegDKVVVLPCGHHFHRECLDKWLRSSNTCPLCR 44

HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle, and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 568937242 386 CAICQAEFRDPMILLCQHVFCEECLCLWL-DRERTCPLC 423
Cdd:cd16449    3 CPICLERLKDPVLLPCGHVFCRECIRRLLeSGSIKCPIC 41

RING finger, H2 subclass, found in the PA-TM-RING ubiquitin ligase family; The PA-TM-RING family represents a group of transmembrane-type E3 ubiquitin ligases, which has been characterized by an N-terminal transient signal peptide, a PA (protease-associated) domain, a TM (transmembrane) domain, as well as a C-terminal C3H2C3-type RING-H2 finger domain. It includes RNF13, RNF167, ZNRF4 (zinc and RING finger 4), GRAIL (gene related to anergy in lymphocytes)/RNF128, RNF130, RNF133, RNF148, RNF149 and RNF150 (which are more closely related), as well as RNF43 and ZNRF3, which have substantially longer C-terminal tail extensions compared with the others. PA-TM-RING proteins are expressed at low levels in all mammalian tissues and species, but they are not present in yeast. They play a common regulatory role in intracellular trafficking/sorting, suggesting that abrogation of their function may result in dysregulation of cellular signaling events in cancer.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 568937242 385 VCAICQAEFRDP---MILLCQHVFCEECLCLWLDRERTCPLCR 424
Cdd:cd16454    1 TCAICLEEFKEGekvRVLPCNHLFHKDCIDPWLEQHNTCPLCR 43

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 568937242 386 CAICQAEFRDPMILLCQHVFCEECLCLWLDRER---TCPLCRSV 426
Cdd:cd16611    7 CPLCLDFFRDPVMLSCGHNFCQSCITGFWELQAedtTCPECREL 50

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 568937242  385 VCAICQAEFRDP-MILLCQHVFCEECLCLWLDRERTCPLC 423
Cdd:pfam13923   1 MCPICMDMLKDPsTTTPCGHVFCQDCILRALRAGNECPLC 40

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 568937242   386 CAICQAEF-RDPMILLCQHVFCEECLCLWLDRE-RTCPLC 423
Cdd:smart00184   1 CPICLEEYlKDPVILPCGHTFCRSCIRKWLESGnNTCPIC 40

RING finger, HC subclass, found in yeast Bre1 and its homologs from eukaryotes; Bre1 is an E3 ubiquitin-protein ligase that catalyzes monoubiquitination of histone H2B in concert with the E2 ubiquitin-conjugating enzyme, Rad6. The Rad6-Bre1-mediated histone H2B ubiquitylation modulates the formation of double-strand breaks (DSBs) during meiosis in yeast. it is also required, indirectly, for the methylation of histone 3 on lysine 4 (H3K4) and 79. RNF20, also known as BRE1A and RNF40, also known as BRE1B, are the mammalian homologs of Bre1. They work together to form a heterodimeric Bre1 complex that facilitate the K120 monoubiquitination of histone H2B (H2Bub1), a DNA damage-induced histone modification that is crucial for recruitment of the chromatin remodeler SNF2h to DNA double-strand break (DSB) damage sites. Moreover, the Bre1 complex acts as a tumor suppressor, augmenting expression of select tumor suppressor genes and suppressing select oncogenes. Deficiency in the mammalian histone H2B ubiquitin ligase Bre1 leads to replication stress and chromosomal instability. All subfamily members contain a C3HC4-type RING-HC finger at its C-terminus.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 568937242 386 CAICQAEFRDPMILLCQHVFCEECLCLWLD-RERTCPLC 423
Cdd:cd16499    9 CSVCNDRFKDVIITKCGHVFCNECVQKRLEtRQRKCPGC 47

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 568937242  386 CAICQAEFRDPMILL-CQHVFCEECLCLWLDRE-RTCPLC 423
Cdd:pfam00097   1 CPICLEEPKDPVTLLpCGHLFCSKCIRSWLESGnVTCPLC 40

RING finger, HC subclass, found in RING finger protein 141 (RNF141) and similar proteins; RNF141, also known as zinc finger protein 230 (ZNF230), is a RING finger protein present primarily in the nuclei of spermatogonia, the acrosome, and the tail of spermatozoa. It may have a broad function during early development of vertebrates. It plays an important role in spermatogenesis, including spermatogenic cell proliferation and sperm maturation, as well as motility and fertilization. It also exhibits DNA binding activity. RNF141/ZNF230 gene mutations may be associated with azoospermia. RNF141 contains a C3HC4-type RING finger domain that may function as an activator module in transcription.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 568937242 385 VCAICQaEFRDPMILLCQHVFCEECLCLWLDRERTCPLCR 424
Cdd:cd16545    2 ECCICM-DRKADLILPCAHSYCQKCIDKWSDRHRTCPICR 40

RING finger, HC subclass, found in tripartite motif-containing protein TRIM65 and similar proteins; TRIM65 is an E3 ubiquitin-protein ligase that interacts with the innate immune receptor MDA5, enhancing its ability to stimulate interferon-beta signaling. It functions as a potential oncogenic protein that negatively regulates p53 through ubiquitination, providing insight into the development of novel approaches targeting TRIM65 for non-small cell lung carcinoma (NSCLC) treatment, and also overcoming chemotherapy resistance. Moreover, TRIM65 negatively regulates microRNA-driven suppression of mRNA translation by targeting TNRC6 proteins for ubiquitination and degradation. TRIM65 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 568937242 386 CAICQAEFRDPMILLCQHVFCEECLCLWLDR----ERTCPLCRS 425
Cdd:cd16609    6 CSICLGLYQDPVTLPCQHSFCRACIEDHWRQkdegSFSCPECRA 49

RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 568937242 386 CAICQAEFRDPMILLCQHVFCEECLCLWLDR--ERTCPLCR-SVAVDTLR 432
Cdd:cd16599    7 CPICYEPFREAVTLRCGHNFCKGCVSRSWERqpRAPCPVCKeASSSDDLR 56

first RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, proteins with double RING-H2 fingers may act as scaffolds for binding several proteins that function in the same pathway. This model corresponds to the first RING-H2 finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 568937242 385 VCAICQAEFR-DPMILL-CQHVFCEECLCLW--LDRERTCPLCR 424
Cdd:cd16677    1 PCPICLEDFGlQQQVLLsCSHVFHRACLESFerFSGKKTCPMCR 44

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 568937242 386 CAICQAEFR--DPM-ILLCQHVFCEECLCLWLDRERTCPLC 423
Cdd:cd16468    2 CVICMADFVvgDPIrYLPCMHIYHVDCIDDWLMRSFTCPSC 42

RING finger, HC subclass, found in tripartite motif-containing proteins, TRIM7, TRIM11 and TRIM27, and similar proteins; TRIM7, TRIM11 and TRIM27, closely related tripartite motif-containing proteins, belong to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM7, also known as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90), is an E3 ubiquitin-protein ligase that mediates c-Jun/AP-1 activation by Ras signalling. Its phosphorylation and activation by MSK1 in response to direct activation by the Ras-Raf-MEK-ERK pathway can stimulate TRIM7 E3 ubiquitin ligase activity in mediating Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilization. Moreover, TRIM7 binds and activates glycogenin, the self-glucosylating initiator of glycogen biosynthesis. TRIM11, also known as protein BIA1, or RING finger protein 92 (RNF92), is an E3 ubiquitin-protein ligase involved in the development of the central nervous system. It is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 acts as a potential therapeutic target for congenital central hypoventilation syndrome (CCHS) by mediating the degradation of CCHS-associated polyalanine-expanded Phox2b. TRIM11 modulates the function of neurogenic transcription factor Pax6 through the ubiquitin-proteosome system, and thus plays an essential role for Pax6-dependent neurogenesis. It also binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105), humanin, a neuroprotective peptide against Alzheimer's disease-relevant insults, and further regulates ARC105 function in transforming growth factor beta (TGFbeta) signaling. Moreover, TRIM11 negatively regulates retinoic acid-inducible gene-I (RIG-I)-mediated interferon-beta (IFNbeta) production and antiviral activity by targeting TANK-binding kinase-1 (TBK1). It may contribute to the endogenous restriction of retroviruses in cells. It enhances N-tropic murine leukemia virus (N-MLV) entry by interfering with Ref1 restriction. It also suppresses the early steps of human immunodeficiency virus HIV-1 transduction, resulting in decreased reverse transcripts. TRIM27, also known as RING finger protein 76 (RNF76), RET finger protein (RFP), or zinc finger protein RFP, is a nuclear E3 ubiquitin-protein ligase that is highly expressed in testis and in various tumor cell lines. Expression of TRIM27 is associated with prognosis of colon and endometrial cancers. TRIM27 was first identified as a fusion partner of the RET receptor tyrosine kinase. It functions as a transcriptional repressor and associates with several proteins involved in transcriptional activity, such as enhancer of polycomb 1 (Epc1), a member of the Polycomb group proteins, and Mi-2beta, a main component of the nucleosome remodeling and deacetylase (NuRD) complex, and the cell cycle regulator retinoblastoma protein (RB1). It also interacts with HDAC1, leading to downregulation of thioredoxin binding protein 2 (TBP-2), which inhibits the function of thioredoxin. Moreover, TRIM27 mediates Pax7-induced ubiquitination of MyoD in skeletal muscle atrophy. In addition, it inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. TRIM27 promotes a non-canonical polyubiquitination of PTEN, a lipid phosphatase that catalyzes PtdIns(3,4,5)P3 (PIP3) to PtdIns(4,5)P2 (PIP2). It is an IKKepsilon-interacting protein that regulates IkappaB kinase (IKK) function and negatively regulates signaling involved in the antiviral response and inflammation. TRIM27 also forms a protein complex with MBD4 or MBD2 or MBD3, and thus plays an important role in the enhancement of transcriptional repression through MBD proteins in tumorigenesis, spermatogenesis, and embryogenesis. It is a component of an estrogen receptor 1 (ESR1) regulatory complex that is involved in estrogen receptor-mediated transcription in MCF-7 cells.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 568937242 384 AVCAICQAEFRDPMILLCQHVFCEECL--ClWLDRER--TCPLCR 424
Cdd:cd16594    6 LTCPICLDYFTDPVTLDCGHSFCRACIarC-WEEPETsaSCPQCR 49

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 568937242 384 AVCAICQAEFRDP---MILLCQHVFCEECLCLWLDRERTCPLCRS 425
Cdd:cd16469    1 DTCAVCLEEFKLKeelGVCPCGHAFHTKCLKKWLEVRNSCPICKS 45

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
                 ....*....|....*....|....*....|....*....|...
gi 568937242 386 CAICQAEFRDP---MILLCQHVFCEECLCLWLDRER-TCPLCR 424
Cdd:cd16473    7 CAICLENYQNGdllRGLPCGHVFHQNCIDVWLERDNhCCPVCR 49

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 568937242  386 CAICQAEFRDPMILLCQH-VFCEECLCLWLDRERTCPLCRS 425
Cdd:pfam13920   5 CVICLDRPRNVVLLPCGHlCLCEECAERLLRKKKKCPICRQ 45

RING finger, HC subclass, found in Ret finger protein-like 4B (RFPL4B) and similar proteins; RFPL4B, also called RING finger protein 211 (RNF211), is an uncharacterized RING finger protein containing a typical C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 568937242 381 EAGAVCAICQAEFRDPMILLCQHVFCEECLCLWL----DRERTCPLCRSV 426
Cdd:cd16623    6 EMEATCPICLDFFSHPISLSCAHIFCFDCIQKWMtkreDSILTCPLCRKE 55

RING finger, HC subclass, found in Mus musculus tripartite motif-containing protein 43 (TRIM43) and similar propteins; This subfamily includes TRIM43A, TRIM43B and TRIM43C, which are expressed specifically in mouse preimplantation embryos. They contain a typical C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 568937242 386 CAICQAEFRDPMILLCQHVFCEECLCLWLDR---ERTCPLCRSV 426
Cdd:cd23133    6 CSICQGIFMNPVYLRCGHKFCEACLLLFQEDikfPAYCPMCRQP 49

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        30        40
                 ....*....|....*....|....*....|....*....|..
gi 568937242 386 CAICQAEFRDP---MILLCQHVFCEECLCLWLDRERTCPLCR 424
Cdd:cd16669    2 CPICLLEFEEGetvKQLPCKHSFHSDCILPWLGKTNSCPLCR 43

RING finger, HC subclass, found in RING finger protein 39 (RNF39) and similar proteins; RNF39, also called protein HZFw, may play a role in prolonged long term-potentiation (LTP) maintenance. It is involved in the etiology of Behcet's disease (BD). It may also be involved in HIV-1 replication. RNF39 acts as an E3 ubiquitin ligase that inhibits retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) pathways by mediating K48-linked ubiquitination and proteasomal degradation of DDX3X (DEAD-box RNA helicase 3, X-linked). RNF39 contains a typical C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 568937242 384 AVCAICQAEFRDPMILLCQHVFCEECLCLWLDRERT---------CPLCR 424
Cdd:cd16592    5 TTCPICLGYFKDPVILDCEHSFCRACIARHWGQEAMegngaegvfCPQCG 54

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 568937242 380 TEAGAVCAICQAEF---------RDPMILLCQHVFCEECLCLWLDRERTCPLCRS 425
Cdd:cd23117    1 ENGSVDCVICMSDIelpstnsvrRDYMVTPCNHIFHTNCLERWMDIKLECPTCRR 55

Modified RING finger, HC subclass (C3HC3D-type), found in PHD and RING finger domain-containing protein 1 (PHRF1) and similar proteins; PHRF1, also known as KIAA1542, or CTD-binding SR-like protein rA9, is a ubiquitin ligase which induces the ubiquitination of TGIF (TG-interacting factor) at lysine 130. It acts as a tumor suppressor that promotes the transforming growth factor (TGF)-beta cytostatic program through selective release of TGIF-driven promyelocytic leukemia protein (PML) inactivation. PHRF1 contains a plant homeodomain (PHD) finger and a modified C3HC3D-type RING-HC finger.

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                 ....*....|....*....|....*....|....*....|....*....|
gi 568937242 380 TEAGAVCAICQAEFRDPMILL---CQHVFCEECLCLWLDRERTCPLCRSV 426
Cdd:cd16635    1 DDESESCPICLNTFRDQAVGTpesCDHIFCLDCILEWSKNANTCPVDRIV 50

RING finger, HC subclass, found in Caenorhabditis elegans RING finger protein NHL-1 and similar proteins; NHL-1 functions as an E3 ubiquitin-protein ligase in the presence of both UBC-13 and UBC-1 within the ubiquitin pathway of Caenorhabditis elegans. It acts in chemosensory neurons to promote stress resistance in distal tissues by the transcription factor DAF-16 activation but is dispensable for the activation of heat shock factor 1 (HSF-1). NHL-1 belongs to the TRIM (tripartite motif)-NHL family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil domain, as well as an NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain.

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                 ....*....|....*....|....*....|....*....|....*.
gi 568937242 386 CAICQAEFRDPMILLCQHVFCEEcLCL-----WLDRERTCPLCRSV 426
Cdd:cd16524    8 CPICLDRYRRPKLLPCQHTFCLS-PCLeglvdYVTRKLKCPECRAE 52

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.

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                 ....*....|....*....|....*....|....*....|..
gi 568937242 386 CAICQAEFR---DPMILLCQHVFCEECLCLWLDRERTCPLCR 424
Cdd:cd16667    2 CAVCKEDFEvgeEVRQLPCKHLFHPDCIVPWLELHNSCPVCR 43

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM41, TRIM52 and similar proteins; TRIM41 and TRIM52, two closely related tripartite motif-containing proteins, have dramatically expanded RING domains compared with the rest of the TRIM family proteins. TRIM41 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. In contrast, TRIM52 lacks the putative viral recognition SPRY/B30.2 domain, and thus has been classified to the C-V subclass of the TRIM family that contains only RBCC domains. TRIM41, also known as RING finger-interacting protein with C kinase (RINCK), is an E3 ubiquitin-protein ligase that promotes the ubiquitination of protein kinase C (PKC) isozymes in cells. It specifically recognizes the C1 domain of PKC isozymes. It controls the amplitude of PKC signaling by controlling the amount of PKC in the cell. TRIM52, also known as RING finger protein 102 (RNF102), is encoded by a novel, noncanonical antiviral TRIM52 gene in primate genomes with unique specificity determined by the rapidly evolving RING domain.

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gi 568937242 384 AVCAICQAEFRDPMILLCQHVFCEECLC-LWldrERTCPLCR 424
Cdd:cd16602    4 AVCAICLDYFKDPVSIGCGHNFCRVCVTqLW---GFTCPQCR 42

RING finger, HC subclass, found in RING finger protein 5 (RNF5) and similar proteins; RNF5, also known as protein G16 or Ram1, is an E3 ubiquitin-protein ligase anchored to the outer membrane of the endoplasmic reticulum (ER). It acts at early stages of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) biosynthesis and functions as a target for therapeutic modalities to antagonize mutant CFTR proteins in CF patients carrying the F508del allele. It also regulates the turnover of specific G protein-coupled receptors by ubiquitinating JNK-associated membrane protein (JAMP) and preventing proteasome recruitment. RNF5 limits basal levels of autophagy and influences susceptibility to bacterial infection through the regulation of ATG4B stability. It is also involved in the degradation of Pendrin, a transmembrane chloride/anion exchanger highly expressed in thyroid, kidney, and inner ear. RNF5 plays an important role in cell adhesion and migration. It can modulate cell migration by ubiquitinating paxillin. Furthermore, RNF5 interacts with virus-induced signaling adaptor (VISA) at mitochondria in a viral infection-dependent manner, and further targets VISA at K362 and K461 for K48-linked ubiquitination and degradation after viral infection. It also negatively regulates virus-triggered signaling by targeting MITA, also known as STING, for ubiquitination and degradation at the mitochondria. In addition, RNF5 determines breast cancer response to ER stress-inducing chemotherapies through the regulation of the L-glutamine carrier proteins SLC1A5 and SLC38A2 (SLC1A5/38A2). It also has been implicated in muscle organization and in recognition and processing of misfolded proteins. RNF5 contains a C3HC4-type RING-HC finger.

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gi 568937242 386 CAICQAEFRDPMILLCQHVFCEECLCLWLD---RERTCPLCRS 425
Cdd:cd16743    3 CNICLETARDAVVSLCGHLFCWPCLHQWLEtrpERQECPVCKA 45

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.

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gi 568937242 385 VCAICQAEF--RDPM-ILLCQHVFCEECLCLWLDRERTCPLC 423
Cdd:cd16675    2 ICAVCLEEFkpKDELgICPCKHAFHRKCLIKWLEVRKVCPLC 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.

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gi 568937242 386 CAICQAEFRDP---MILLCQHVFCEECLCLWL-DRERTCPLCR 424
Cdd:cd16448    1 CVICLEEFEEGdvvRLLPCGHVFHLACILRWLeSGNNTCPLCR 43

zinc-RING finger domain;

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gi 568937242  386 CAICQAEF---RDPMILLCQHVFCEECLCLwLDRERTCPLCRS 425
Cdd:pfam14634   2 CNKCFKELsktRPFYLTSCGHIFCEECLTR-LLQERQCPICKK 43

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

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gi 568937242 372 VRATGQQCTEAGAVCAICQAEF-------------RDPMILLCQHVFCEECLCLWLDRERTCPLCRS 425
Cdd:COG5243  276 PTATEEQLTNSDRTCTICMDEMfhpdheplprgldMTPKRLPCGHILHLHCLKNWLERQQTCPICRR 342

RING finger, HC subclass, found in RING finger protein RNF5, RNF185 and similar proteins; RNF5 and RNF185 are E3 ubiquitin-protein ligases that are anchored to the outer membrane of the endoplasmic reticulum (ER). RNF5 acts at early stages of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) biosynthesis, and functions as a target for therapeutic modalities to antagonize mutant CFTR proteins in CF patients carrying the F508del allele. RNF185 controls the degradation of CFTR and CFTR F508del allele in a RING- and proteasome-dependent manner, but does not control that of other classical endoplasmic reticulum-associated degradation (ERAD) model substrates. Moreover, both RNF5 and RNF185 play important roles in cell adhesion and migration through the modulation of cell migration by ubiquitinating paxillin. Arabidopsis thaliana RING membrane-anchor proteins (AtRMAs) are also included in this family. They possess E3 ubiquitin-protein ligase activity and may play a role in the growth and development of Arabidopsis. All members of this family contain a C3HC4-type RING-HC finger.

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gi 568937242 386 CAICQAEFRDPMILLCQHVFCEECLCLWLDRE---RTCPLCR 424
Cdd:cd16534    3 CNICLDTASDPVVTMCGHLFCWPCLYQWLETRpdrQTCPVCK 44

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.

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gi 568937242 386 CAICQAEFRDP----MILLCQHVFCEECLCLWLDRERTCPLCR 424
Cdd:cd16461    2 CAICLSDYENGeelrRLPECKHAFHKECIDEWLKSNSTCPLCR 44

RING finger, HC subclass, found in tripartite motif-containing protein 62 (TRIM62) and similar proteins; TRIM62, also known as Ductal Epithelium Associated Ring Chromosome 1 (DEAR1), is a cytoplasmic E3 ubiquitin-protein ligase that was identified as a dominant regulator of acinar morphogenesis in the mammary gland. It is implicated in the inflammatory response of immune cells by regulating the Toll-like receptor 4 (TLR4) signaling pathway, leading to increased activity of the activator protein 1 (AP-1) transcription factor in primary macrophages. It is also involved in muscular protein homeostasis, especially during inflammation-induced atrophy, and may play a role in the pathogenesis of ICU-acquired weakness (ICUAW) by activating and maintaining inflammation in myocytes. Moreover, TRIM62 facilitates K27-linked poly-ubiquitination of CARD9 and also regulates CARD9-mediated anti-fungal immunity and intestinal inflammation. It also functions as a chromosome 1p35 tumor suppressor and negatively regulates transforming growth factor beta (TGFbeta)-driven epithelial-mesenchymal transition (EMT) by binding to and promoting the ubiquitination of SMAD3, a major effector of TGFbeta-mediated EMT. TRIM62 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

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gi 568937242 386 CAICQAEFRDPMILLCQHVFCEECLCLWLDRERT--CPLCRSV 426
Cdd:cd16608    9 CSICLSIYQDPVSLGCEHYFCRQCITEHWSRSEHrdCPECRRT 51

Modified RING finger, HC subclass (C3HC3D-type), found in neuregulin receptor degradation protein-1 (Nrdp1) and similar proteins; Nrdp1 (referred to as FLRF in mice), also known as RING finger protein 41 (RNF41), is an E3 ubiquitin-protein ligase that plays a critical role in the regulation of cell growth and apoptosis, inflammation and production of reactive oxygen species (ROS), as well as in doxorubicin (DOX)-induced cardiac injury. It promotes the degradation of the epidermal growth factor receptor (EGFR/ErbB) family member, ErbB3, which is independent of growth factor stimulation. It also promotes M2 macrophage polarization by ubiquitinating and activating transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) via Lys-63-linked ubiquitination. Moreover, Nrdp1 interacts with and modulates the activity of Parkin, a causative protein for early onset recessive juvenile parkinsonism (AR-JP). It also interacts with ubiquitin-specific protease 8 (USP8), which is involved in trafficking of various transmembrane proteins. Furthermore, Nrdp1 inhibits basal lysosomal degradation and enhances ectodomain shedding of JAK2-associated cytokine receptors. Its phosphorylation by the kinase Par-1b (also known as MARK2) is required for epithelial cell polarity. Nrdp1 contains an N-terminal modified C3HC3D-type RING-HC finger required for enhancing ErbB3 degradation, a B-box, a coiled-coil domain responsible for Nrdp1 oligomerization, and a C-terminal ErbB3-binding domain.

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gi 568937242 385 VCAICQAEFRDPM-ILLCQHVFCEECLCLWLDRERTCPLCR 424
Cdd:cd16634    3 ICPICSGVLEEPLqAPHCEHAFCNACITEWLSRQQTCPVDR 43

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.

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gi 568937242 386 CAICQAEFRDPMI---LLCQHVFCEECLCLWLDRERTCPLCR 424
Cdd:cd16474    3 CTICLSDFEEGEDvrrLPCMHLFHQECVDQWLSTNKRCPICR 44

RING finger, HC subclass, found in Casitas B-lineage lymphoma (Cbl) proteins; The Cbl adaptor protein family contains a small class of RING-type E3 ubiquitin ligases with oncogenic activity, which is represented by three mammalian members, c-Cbl, Cbl-b and Cbl-c, as well as two invertebrate Cbl-family proteins, D-Cbl in Drosophila and Sli-1 in C. elegans. Cbl proteins function as potent negative regulators of various signaling cascades in a wide range of cell types. They play roles in ubiquitinating activated tyrosine kinases and targeting them for degradation. D-Cbl associates with the Drosophila epidermal growth factor receptor (EGFR) and overexpression of D-Cbl in the eye of Drosophila embryos inhibits EGFR-dependent photoreceptor cell development. Sli-1 is a negative regulator of the Let-23 receptor tyrosine kinase, an EGFR homolog, in vulva development. Cbl proteins in this subfamily consist of a highly conserved N-terminal half that includes a tyrosine-kinase-binding domain (TKB, also known as the phosphotyrosine binding PTB domain, composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain) and a C3HC4-type RING-HC finger, both of which are required for Cbl-mediated downregulation of RTKs, and a divergent C-terminal region.

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gi 568937242 385 VCAICQAEFRDPMILLCQHVFCEECLCLWLDRER-TCPLCR 424
Cdd:cd16502    3 LCKICAENDKDVRIEPCGHLLCTPCLTSWQDSDGqTCPFCR 43

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 568937242 386 CAICQAEFRDP---MILLCQHVFCEECLCLWLDRERTCPLCRS 425
Cdd:cd23115    7 CVICRLEYEEGedlLTLPCKHCYHSECIQQWLQINKVCPVCSA 49

RING finger, HC subclass, found in ligand of Numb protein LNX3, LNX4, and similar proteins; The ligand of Numb protein X (LNX) family, also known as PDZ and RING (PDZRN) family, includes LNX1-5, which can interact with Numb, a key regulator of neurogenesis and neuronal differentiation. LNX5 (also known as PDZK4, or PDZRN4L) shows high sequence homology to LNX3 and LNX4, but it lacks the RING domain. LNX1-4 proteins function as E3 ubiquitin ligases and have a unique domain architecture consisting of an N-terminal RING-HC finger for E3 ubiquitin ligase activity and either two or four PDZ domains necessary for the substrate-binding. This family corresponds to LNX3/LNX4-like proteins, which contains a C3HC4-type RING-HC finger and two PDZ domains.

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gi 568937242 386 CAICQAEFRDPMILLCQHVFCEECLCLWLDRERTCPL 422
Cdd:cd16512    3 CKLCLGVLEEPLATPCGHVFCAGCVLPWVVRNGSCPL 39

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 568937242 385 VCAICQAEFRDP---MILLCQHVFCEECLCLWLDRER-TCPLCR 424
Cdd:cd16797    2 VCAICLDEYEEGdklRVLPCSHAYHSKCVDPWLTQTKkTCPVCK 45

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.

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gi 568937242 386 CAICQAEFRDPMILLCQHVFCEECLCLWLDRERTCPLCR 424
Cdd:cd16455    3 CAICWESMQSARKLPCGHLFHNSCLRSWLEQDTSCPTCR 41

RING finger, HC subclass, found in Saccharomyces cerevisiae DNA repair protein RAD16, Schizosaccharomyces pombe rhp16, and similar proteins; Budding yeast RAD16, also known as ATP-dependent helicase RAD16, is encoded by a yeast excision repair gene homologous to the recombinational repair gene RAD54 and to the SNF2 gene involved in transcriptional activation. It is a component of the global genome repair (GGR) complex that promotes global genome nucleotide excision repair (GG-NER) by removing DNA damage from non-transcribing DNA. RAD16 is involved in differential repair of DNA after UV damage, and repairs preferentially the MAT-alpha locus compared with the HML-alpha locus. Fission yeast rhp16, also known as ATP-dependent helicase rhp16, is a RAD16 homolog. It is involved in GGR via nucleotide excision repair (NER), in conjunction with rhp7, after UV irradiation. Both RAD16 and rhp16 contain a C3HC4-type RING-HC finger, as well as a DEAD-like helicase domain and a helicase superfamily C-terminal domain.

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gi 568937242 385 VCAICQAEFRDPMILLCQHVFCEECLCLWLD----RERTCPLC 423
Cdd:cd16567    2 VCGICHEEAEDPVVARCHHVFCRACVKEYIEsapgGKVTCPTC 44

RING finger, HC subclass, found in RING finger protein 125 (RNF125); RNF125, also known as T-cell RING activation protein 1 (TRAC-1), is an E3 ubiquitin-protein ligase that is predominantly expressed in lymphoid cells, and functions as a positive regulator of T cell activation. It also down-modulates HIV replication and inhibits pathogen-induced cytokine production. It negatively regulates type I interferon signaling, which conjugates Lys(48)-linked ubiquitination to retinoic acid-inducible gene-I (RIG-I) and subsequently leads to the proteasome-dependent degradation of RIG-I. Further, RNF125 conjugates ubiquitin to melanoma differentiation-associated gene 5 (MDA5), a family protein of RIG-I. It thus acts as a negative regulator of RIG-I signaling, and is a direct target of miR-15b in the context of Japanese encephalitis virus (JEV) infection. Moreover, RNF125 binds to and ubiquitinates JAK1, prompting its degradation and inhibition of receptor tyrosine kinase (RTK) expression. It also negatively regulates p53 function through physical interaction and ubiquitin-mediated proteasome degradation. Mutations in RNF125 may lead to overgrowth syndromes (OGS). RNF125, together with three closely related proteins: RNF114, RNF138 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). The UIM of RNF125 binds K48-linked poly-ubiquitin chains and is, together with the RING domain, required for auto-ubiquitination.

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gi 568937242 386 CAICQAEFRDPMILLCQHVFCEECLCLWLDRER-TCPLCRS 425
Cdd:cd16542    4 CAVCLEVLHQPVRTRCGHVFCRPCIATSLRNNTwTCPYCRA 44

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 568937242 386 CAICQAEF--RDPM-ILLCQHVFCEECLCLWLDRERTCPLC 423
Cdd:cd16676    3 CAVCLEDFktKDELgVLPCQHAFHRKCLVKWLEIRCVCPMC 43

RING finger, H2 subclass, found in RING finger proteins RNF38, RNF44, and similar proteins; This subfamily includes RING finger proteins RNF38, RNF44, and similar proteins. RNF38 is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 is an uncharacterized RING finger protein that shows high sequence similarity to RNF38. Both RNF38 and RNF44 contain a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C3-type RING-H2 finger. In addition, RNF38 harbors two potential nuclear localization signals.