RING finger (Really Interesting New Gene) domain and U-box domain superfamily; 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). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are 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 enable efficient transfer of ubiquitin from E2 to the substrates.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1034595648 189 KQCVACRERAHGAVLRPCQHHILCEPCAATAPECPYCKGQPLQW 232
Cdd:cd16772     1 KKCIVCQERDRSIVLQPCQHYVLCEHCAASKPECPYCKTKILKW 44

RING finger, HC subclass, found in RING finger protein unkempt-like (UNKL) and similar proteins; UNKL, also known as zinc finger CCCH domain-containing protein 5-like, is a putative E3 ubiquitin-protein ligase that may participate in a protein complex showing an E3 ligase activity regulated by RAC1. It shows high sequence similarity with RING finger protein unkempt (UNK), which is a metazoan-specific zinc finger protein enriched in embryonic brains, and may play a broad regulatory role during the formation of the central nervous system (CNS). UNKL contains several CCCH-type zinc fingers at the N-terminus, and a C3HC4-type RING-HC finger at its C-terminus.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1034595648 189 KQCVACRERAHGAVLRPCQHHILCEPCAATAPECPYCKGQPLQW 232
Cdd:cd16772     1 KKCIVCQERDRSIVLQPCQHYVLCEHCAASKPECPYCKTKILKW 44

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034595648   68 ELARVRRQLDEAKRKIRQWEESWQQVKQVCDAWQREAQEAKERARVADS---DRQLALQKKEEVEAQV-KQLQEELEGL 142
Cdd:COG4913    700 ELEELEEELDELKGEIGRLEKELEQAEEELDELQDRLEAAEDLARLELRallEERFAAALGDAVERELrENLEERIDAL 778

flagellar assembly protein H; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034595648  68 ELARVRRQLDEAKRKIRQWEESWQQVKQVCDAWQREAQEAKERARVADSD---------RQLALQKKEEVEAQVKQLQEE 138
Cdd:PRK06669   21 EIQKYRFKVLSIKEKERLREEEEEQVEQLREEANDEAKEIIEEAEEDAFEiveaaeeeaKEELLKKTDEASSIIEKLQMQ 100

                  ..
gi 1034595648 139 LE 140
Cdd:PRK06669  101 IE 102

RING finger, HC subclass, found in RING finger protein unkempt-like (UNKL) and similar proteins; UNKL, also known as zinc finger CCCH domain-containing protein 5-like, is a putative E3 ubiquitin-protein ligase that may participate in a protein complex showing an E3 ligase activity regulated by RAC1. It shows high sequence similarity with RING finger protein unkempt (UNK), which is a metazoan-specific zinc finger protein enriched in embryonic brains, and may play a broad regulatory role during the formation of the central nervous system (CNS). UNKL contains several CCCH-type zinc fingers at the N-terminus, and a C3HC4-type RING-HC finger at its C-terminus.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1034595648 189 KQCVACRERAHGAVLRPCQHHILCEPCAATAPECPYCKGQPLQW 232
Cdd:cd16772     1 KKCIVCQERDRSIVLQPCQHYVLCEHCAASKPECPYCKTKILKW 44

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1034595648 189 KQCVACRERAHGAVLRPCQHHILCEPCA----ATAPECPYCK 226
Cdd:pfam13920   3 LLCVICLDRPRNVVLLPCGHLCLCEECAerllRKKKKCPICR 44

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034595648   68 ELARVRRQLDEAKRKIRQWEESWQQVKQVCDAWQREAQEAKERARVADS---DRQLALQKKEEVEAQV-KQLQEELEGL 142
Cdd:COG4913    700 ELEELEEELDELKGEIGRLEKELEQAEEELDELQDRLEAAEDLARLELRallEERFAAALGDAVERELrENLEERIDAL 778

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034595648  68 ELARVRRQLDEAKRKIRQWEE---SWQQVKQVCDAWQREAQEAKERARVADSDR-QLALQKKEEVEAQVKQLQEELEGL 142
Cdd:COG4717   140 ELAELPERLEELEERLEELREleeELEELEAELAELQEELEELLEQLSLATEEElQDLAEELEELQQRLAELEEELEEA 218

RING finger, HC subclass, found in RING finger protein unkempt (UNK) and similar proteins; UNK, also known as zinc finger CCCH domain-containing protein 5, is a metazoan-specific zinc finger protein enriched in embryonic brains. It may play a broad regulatory role during the formation of the central nervous system (CNS). It is a sequence-specific RNA-binding protein required for early neuronal morphology. UNK is a neurogenic component of the mTOR pathway, and functions as a negative regulator of the timing of photoreceptor differentiation. It also specifically binds to Brg/Brm-associated factor BAF60b and promotes its ubiquitination in a Rac1-dependent manner. UNK contains six tandem CCCH-type zinc fingers at the N-terminus, and a C3HC4-type RING-HC finger at its C-terminus.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1034595648 191 CVACRERahGAVLRPCQHHILCEPCaATAPECPYC 225
Cdd:cd16771     5 CLKCQEL--KRVTLPCQHALLCETC-ATSEECPIC 36

Uncharacterized protein, contains DUF3084 domain [Function unknown];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034595648  68 ELARVRRQLDEAKRKIRQWEESWQQVKQVCDAWQREAQEAKERARVADSDRQLALQKKEEVEAQVKQLQEELEGL 142
Cdd:COG4372    67 ELEQARSELEQLEEELEELNEQLQAAQAELAQAQEELESLQEEAEELQEELEELQKERQDLEQQRKQLEAQIAEL 141

RING finger, HC subclass, found in RNA-binding protein MEX3A; MEX3A, also known as RING finger and KH domain-containing protein 4 (RKHD4), is an RNA-binding phosphoprotein that localizes in P-bodies and stress granules, which are two structures involved in the storage and turnover of mRNAs. It has been implicated in the regulation of tumorigenesis. It controls the polarity and stemness of intestinal epithelial cells through the post-transcriptional regulation of the homeobox transcription factor CDX2, which plays a crucial role in intestinal cell fate specification, both during normal development and in tumorigenic processes involving intestinal reprogramming. Moreover, it exhibits a transforming activity when overexpressed in gastric epithelial cells. MEX3A contains two K homology (KH) domains that provide RNA-binding capacity, and a C-terminal C3HC4-type RING-HC finger. Like other MEX-3 family proteins, MEX3A shuttles between the nucleus and the cytoplasm via the CRM1-dependent export pathway.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1034595648 188 AKQCVACRERAHGAVLRPCQHHILCEPCAA-----TAPECPYC 225
Cdd:cd16720     2 GRDCMVCFESEVTAALVPCGHNLFCMECAVricerNEPECPVC 44

Modified RING finger, HC subclass (C3HC5-type), found in RING finger proteins, RNF26, RNF197 (CGRRF1), RNF156 (MGRN1), RNF157 and similar proteins; This subfamily corresponds to a group of RING finger proteins containing a modified C3HC5-type RING-HC finger, which is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain. Cell growth regulator with RING finger domain protein 1 (CGRRF1), also known as cell growth regulatory gene 19 protein (CGR19) or RING finger protein 197 (RNF197), functions as a novel biomarker to monitor endometrial sensitivity and response to insulin-sensitizing drugs, such as metformin, in the context of obesity. RNF26 is an E3 ubiquitin ligase that temporally regulates virus-triggered type I interferon induction by increasing the stability of Mediator of IRF3 activation, MITA, also known as STING, through K11-linked polyubiquitination after viral infection and promoting degradation of IRF3, another important component required for virus-triggered interferon induction. Mahogunin ring finger-1 (MGRN1), also known as RING finger protein 156 (RNF156), is a cytosolic E3 ubiquitin-protein ligase that inhibits signaling through the G protein-coupled melanocortin receptors-1 (MC1R), -2 (MC2R) and -4 (MC4R) via ubiquitylation-dependent and -independent processes. It suppresses chaperone-associated misfolded protein aggregation and toxicity. RNF157 is a cytoplasmic E3 ubiquitin ligase predominantly expressed in the brain. It is a homolog of the E3 ligase MGRN1. In cultured neurons, it promotes neuronal survival in an E3 ligase-dependent manner. In contrast, it supports growth and maintenance of dendrites independent of its E3 ligase activity. RNF157 interacts with and ubiquitinates the adaptor protein APBB1 (amyloid beta precursor protein-binding, family B, member 1 or Fe65), which regulates neuronal survival, but not dendritic growth downstream of RNF157. The nuclear localization of APBB1 together with its interaction partner RNA-binding protein SART3 (squamous cell carcinoma antigen recognized by T cells 3 or Tip110) is crucial to trigger apoptosis.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034595648 189 KQCVACRERAHGAVLRPCQHHILCEPCAATA--PECPYCK 226
Cdd:cd16649     1 GLCVVCLENPASVLLLPCRHLCLCEVCAKGLrgKTCPICR 40

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034595648   69 LARVRRQLDEAKRKIRQWEESWQQVKQVCDAWQREAQEAKERARVADSDRQLAlqkkeEVEAQVKQLQEELEGL 142
Cdd:COG4913    612 LAALEAELAELEEELAEAEERLEALEAELDALQERREALQRLAEYSWDEIDVA-----SAEREIAELEAELERL 680

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034595648   68 ELARVRRQLDEAKRKIRQ----------WEESWQQ------VKQVCDAW--QREAQEAKERARVADSDRQLALQKKEEVE 129
Cdd:COG4913    236 DLERAHEALEDAREQIELlepirelaerYAAARERlaeleyLRAALRLWfaQRRLELLEAELEELRAELARLEAELERLE 315

                           90
                   ....*....|...
gi 1034595648  130 AQVKQLQEELEGL 142
Cdd:COG4913    316 ARLDALREELDEL 328

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034595648   68 ELARVRRQLDEAKRKIRQWEESWQQVKQVC-----------DAWQREAQEAKERARVADSDRQL-------ALQKKEEVE 129
Cdd:COG4913    339 RLEQLEREIERLERELEERERRRARLEALLaalglplpasaEEFAALRAEAAALLEALEEELEAleealaeAEAALRDLR 418

                           90
                   ....*....|...
gi 1034595648  130 AQVKQLQEELEGL 142
Cdd:COG4913    419 RELRELEAEIASL 431

Modified RING finger, HC subclass (C3HC5-type), found in cell growth regulator with RING finger domain protein 1 (CGRRF1) and similar proteins; CGRRF1, also known as cell growth regulatory gene 19 protein (CGR19) or RING finger protein 197 (RNF197), functions as a novel biomarker to monitor endometrial sensitivity and response to insulin-sensitizing drugs, such as metformin, in the context of obesity. CGRRF1 contains a C-terminal modified C3HC5-type RING-HC finger, which is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1034595648 189 KQCVACRERAHGAVLRPCQHHILCEPCAATAPECPYCK 226
Cdd:cd16787     1 KDCVVCQNAPVNRVLLPCRHACVCDECFKRLQRCPMCR 38

flagellar assembly protein H; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034595648  68 ELARVRRQLDEAKRKIRQWEESWQQVKQVCDAWQREAQEAKERARVADSD---------RQLALQKKEEVEAQVKQLQEE 138
Cdd:PRK06669   21 EIQKYRFKVLSIKEKERLREEEEEQVEQLREEANDEAKEIIEEAEEDAFEiveaaeeeaKEELLKKTDEASSIIEKLQMQ 100

                  ..
gi 1034595648 139 LE 140
Cdd:PRK06669  101 IE 102

type I restriction enzyme EcoKI subunit R; Provisional

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034595648   68 ELARVRRQLDEAKRKIRQWEESWQQVKQVCDAWQREAQEAKErarvadsdrqlalqKKEEVEAQVKQLQEE 138
Cdd:PRK11448   150 EVLTLKQQLELQAREKAQSQALAEAQQQELVALEGLAAELEE--------------KQQELEAQLEQLQEK 206

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034595648   68 ELARVRRQLDEAKRKIRQWEESWQQVKQvcDAWQREAQEAKERARVadsdrQLALQKKEEVEAQVKQLQEELEGLG 143
Cdd:TIGR02168  359 ELEELEAELEELESRLEELEEQLETLRS--KVAQLELQIASLNNEI-----ERLEARLERLEDRRERLQQEIEELL 427

RING finger, HC subclass, found in caspases-8 and -10-associated RING finger protein CARP-1, CARP-2 and similar proteins; The CARP subfamily includes CARP-1 and CARP-2 proteins, both of which are E3 ubiquitin ligases that ubiquitinate apical caspases and target them for proteasome-mediated degradation. As a novel group of caspase regulators with a FYVE-type zinc finger domain, they do not localize to membranes in the cell and are involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8, and caspase 10. Moreover, they stabilize MDM2 by inhibiting MDM2 self-ubiquitination, as well as by targeting 14-3-3sigma for degradation. They work together with MDM2 to enhance p53 degradation, thereby inhibiting p53-mediated cell death. CARPs contain an N-terminal FYVE-like domain that can serve as a membrane-targeting or endosome localizing signal and a C-terminal C3HC4-type RING-HC finger domain.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1034595648 191 CVACRERAHGAVLRPCQHHILCEPCAATAPECPYCK 226
Cdd:cd16500     3 CKICMDAAIDCVLLECGHMVTCTDCGKKLSECPICR 38

RING finger, HC subclass, found in ubiquitin-like PHD and RING finger domain-containing proteins, UHRF1 and UHRF2, and similar proteins; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of transcription factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation, but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) by interacting with the HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1034595648 190 QCVACRERAHGAVLRPCQHHIlCEPC-----AATAPECPYCK 226
Cdd:cd16613     2 TCICCQELVYKPITTPCKHNI-CKSClqrsfKAEVYTCPACR 42