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        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2288874410 214 DMVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIK 265
Cdd:cd16730     1 DKVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIK 52

zinc finger;

                           10        20
                   ....*....|....*....|...
gi 2288874410   24 VVCKYFQRGYCVYGDRCRYEHSK 46
Cdd:smart00356   5 ELCKFFKRGYCPRGDRCKFAHPL 27

RING finger, HC subclass, found in makorin-1 (MKRN1), makorin-3 (MKRN3), and similar proteins; MKRN1, also known as makorin RING finger protein 1 or RING finger protein 61 (RNF61), is an E3 ubiquitin-protein ligase targeting the telomerase catalytic subunit (TERT) for proteasome processing. It regulates the ubiquitination and degradation of peroxisome-proliferator-activated receptor gamma (PPARgamma), a nuclear receptor that is linked to obesity and metabolic diseases. It also mediates the posttranslational regulation of p14ARF, and thus potentially regulates cellular senescence and tumorigenesis in gastric cancer. Moreover, MKRN1 functions as a differentially negative regulator of p53 and p21, and controls cell cycle arrest and apoptosis. It induces degradation of West Nile virus (WNV) capsid protein to protect cells from WNV. It is a RNA-binding protein involved in the modulation of cellular stress and apoptosis. It predominantly associates with proteins involved in mRNA metabolism including regulators of mRNA turnover, transport, and/or translation, and acts as a component of a ribonucleoprotein complex in embryonic stem cells (ESCs) that is recruited to stress granules upon exposure to environmental stress. MKRN1 interacts with poly(A)-binding protein (PABP), a key component of different ribonucleoprotein complexes, in an RNA-independent manner, and stimulates translation in nerve cells. In addition, MKRN1 is a novel SEREX (serological identification of antigens by recombinant cDNA expression cloning) antigen of esophageal squamous cell carcinoma (SCC). It may be involved in carcinogenesis of the well-differentiated type of tumors possibly via ubiquitination of filamin A interacting protein 1 (L-FILIP). Human MKRN1 contains three N-terminal C3H1-type zinc fingers, a motif rich in Cys and His residues (CH), a C3HC4-type RING-HC finger, and another C3H1-type zinc finger at the C-terminus. MKRN3, also known as makorin RING finger protein 3, RING finger protein 63 (RNF63), or zinc finger protein 127 (ZNF127), is a therian mammal-specific retrocopy of MKRN1. It acts as a putative E3 ubiquitin-protein ligase involved in ubiquitination and cell signaling. MKRN3 shows a potential inhibitory effect on hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Its defects represent the most frequent known genetic cause of familial central precocious puberty (CPP). In contrast to human MKRN1, human MKRN3 lacks the second C3H1-type zinc finger at the N-terminal region. The RING-HC finger of mammalian MKRN4 shows high sequence similarity with that of MKRN3, and is also included in this model.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2288874410 214 DMVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIK 265
Cdd:cd16730     1 DKVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIK 52

N1R/p28-like protein; Provisional

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2288874410 211 RSKDMVCGICMEVVYEKaNPSERRFGILSNCNHTYCLKCIRKWRSAK 257
Cdd:PHA02929  171 RSKDKECAICMEKVYDK-EIKNMYFGILSNCNHVFCIECIDIWKKEK 216

zinc finger;

                           10        20
                   ....*....|....*....|...
gi 2288874410   24 VVCKYFQRGYCVYGDRCRYEHSK 46
Cdd:smart00356   5 ELCKFFKRGYCPRGDRCKFAHPL 27

Uncharacterized conserved protein, contains RING and CCCH-type Zn-fingers [General function prediction only];

                          10        20
                  ....*....|....*....|....
gi 2288874410  24 VVCK-YFQRGYCVYGDRCRYEHSK 46
Cdd:COG5152   142 DVCKdYKETGYCGYGDSCKFLHDR 165

RING finger, HC subclass, found in makorin-1 (MKRN1), makorin-3 (MKRN3), and similar proteins; MKRN1, also known as makorin RING finger protein 1 or RING finger protein 61 (RNF61), is an E3 ubiquitin-protein ligase targeting the telomerase catalytic subunit (TERT) for proteasome processing. It regulates the ubiquitination and degradation of peroxisome-proliferator-activated receptor gamma (PPARgamma), a nuclear receptor that is linked to obesity and metabolic diseases. It also mediates the posttranslational regulation of p14ARF, and thus potentially regulates cellular senescence and tumorigenesis in gastric cancer. Moreover, MKRN1 functions as a differentially negative regulator of p53 and p21, and controls cell cycle arrest and apoptosis. It induces degradation of West Nile virus (WNV) capsid protein to protect cells from WNV. It is a RNA-binding protein involved in the modulation of cellular stress and apoptosis. It predominantly associates with proteins involved in mRNA metabolism including regulators of mRNA turnover, transport, and/or translation, and acts as a component of a ribonucleoprotein complex in embryonic stem cells (ESCs) that is recruited to stress granules upon exposure to environmental stress. MKRN1 interacts with poly(A)-binding protein (PABP), a key component of different ribonucleoprotein complexes, in an RNA-independent manner, and stimulates translation in nerve cells. In addition, MKRN1 is a novel SEREX (serological identification of antigens by recombinant cDNA expression cloning) antigen of esophageal squamous cell carcinoma (SCC). It may be involved in carcinogenesis of the well-differentiated type of tumors possibly via ubiquitination of filamin A interacting protein 1 (L-FILIP). Human MKRN1 contains three N-terminal C3H1-type zinc fingers, a motif rich in Cys and His residues (CH), a C3HC4-type RING-HC finger, and another C3H1-type zinc finger at the C-terminus. MKRN3, also known as makorin RING finger protein 3, RING finger protein 63 (RNF63), or zinc finger protein 127 (ZNF127), is a therian mammal-specific retrocopy of MKRN1. It acts as a putative E3 ubiquitin-protein ligase involved in ubiquitination and cell signaling. MKRN3 shows a potential inhibitory effect on hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Its defects represent the most frequent known genetic cause of familial central precocious puberty (CPP). In contrast to human MKRN1, human MKRN3 lacks the second C3H1-type zinc finger at the N-terminal region. The RING-HC finger of mammalian MKRN4 shows high sequence similarity with that of MKRN3, and is also included in this model.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2288874410 214 DMVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIK 265
Cdd:cd16730     1 DKVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIK 52

RING finger, HC subclass, found in makorin-4 (MKRN4) and similar proteins; MKRN4, also known as makorin RING finger protein pseudogene 4, makorin RING finger protein pseudogene 5, RING finger protein 64 (RNF64), zinc finger protein 127-Xp (ZNF127-Xp), or zinc finger protein 127-like 1, is a new divergent member of the makorin protein family in vertebrates. It may have an ancestral gonad-specific function and maternal embryonic expression before duplication in vertebrates. MKRN4 contains typical arrays of one to four C3H1-type zinc fingers, a motif rich in Cys and His residues (CH) and a C3HC4-type RING-HC finger. The RING-HC finger of mammalian MKRN4 shows high sequence similarity with that of MKRN3, and is not included in this model.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2288874410 214 DMVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIK 265
Cdd:cd16732     1 DVACGICMDKVYEKAHAKERVFGILPNCNHAFCVGCIKKWRKSKDFQNEVIK 52

p28-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2288874410 157 ECRYGENCVYLHGDSCDMCGLQVLHPVDAAQRSQHIKSCIEAheKDMELSFAvqrskdmVCGICMEVVYEKaNPSERRFG 236
Cdd:PHA03096  130 NCYKGKYCEYLHGDICDICEKYLLHPTDIKQRYNEQKTCLSY--QLRLLLSK-------ICGICLENIKAK-YIIKKYYG 199

                          90       100
                  ....*....|....*....|....*...
gi 2288874410 237 ILSNCNHTYCLKCIRKW---RSAKQFES 261
Cdd:PHA03096  200 ILSEIKHEFNIFCIKIWmteSLYKETEP 227

zinc finger-like protein; Provisional

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2288874410 212 SKDMVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQ 258
Cdd:PHA02926  168 SKEKECGICYEVVYSKRLENDRYFGLLDSCNHIFCITCINIWHRTRR 214

zinc finger;

                           10        20
                   ....*....|....*....|...
gi 2288874410   24 VVCKYFQRGYCVYGDRCRYEHSK 46
Cdd:smart00356   5 ELCKFFKRGYCPRGDRCKFAHPL 27

CCCH-type zinc finger; This short zinc binding domain has the pattern of three cysteines and one histidine to coordinate the zinc ion. This domain is found in a wide variety of proteins such as E3 ligases.

                          10        20
                  ....*....|....*....|.
gi 2288874410  24 VVCKYFQRGYCVYGDRCRYEH 44
Cdd:pfam18044   1 RLCRYFQKGGCRYGDNCRFSH 21

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
                  ....*....|....*....|....*....|....*...
gi 2288874410 216 VCGICMEvvyekanpseRRFGILSNCNHTYCLKCIRKW 253
Cdd:cd16545     2 ECCICMD----------RKADLILPCAHSYCQKCIDKW 29

RING finger, HC subclass, found in Saccharomyces cerevisiae POB3/SPT16 histone-associated protein 1 (ScPSH1) and similar proteins; ScPSH1 is a Cse4-specific E3 ubiquitin ligase that interacts with the kinetochore protein Pat1 and targets the degradation of budding yeast centromeric histone H3 variant, CENP-ACse4, which is essential for faithful chromosome segregation. ScPSH1 contains a C3HC4-type RING-HC finger and a DNA directed RNA polymerase domain.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 2288874410 216 VCGICMEVVYEkanpserrfGILSNCNHTYCLKCIRKW 253
Cdd:cd16568     6 ECIICHEYLYE---------PMVTTCGHTYCYTCLNTW 34