p28-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952709570 167 ECRFGDACVYLHGEVCEICRLRVLHPFDPEQRKAHEKICMSTFEHEMEKafafqasqdKVCSICMEVVLEKaSASERRFG 246
Cdd:PHA03096  130 NCYKGKYCEYLHGDICDICEKYLLHPTDIKQRYNEQKTCLSYQLRLLLS---------KICGICLENIKAK-YIIKKYYG 199

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952709570 247 ILSNCNHTYCLSCIRQW---RCAKQFENpiikSCPECRVISEFV----------IPSVYWVEDQNKKNELIEAFKQGMGK 313
Cdd:PHA03096  200 ILSEIKHEFNIFCIKIWmteSLYKETEP----ENRRLNTVIVFIekinedlknnIPSRYWIDDKYDKNLLSFRYKKMHIR 275

                  ...
gi 1952709570 314 KAC 316
Cdd:PHA03096  276 KVC 278

p28-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952709570 167 ECRFGDACVYLHGEVCEICRLRVLHPFDPEQRKAHEKICMSTFEHEMEKafafqasqdKVCSICMEVVLEKaSASERRFG 246
Cdd:PHA03096  130 NCYKGKYCEYLHGDICDICEKYLLHPTDIKQRYNEQKTCLSYQLRLLLS---------KICGICLENIKAK-YIIKKYYG 199

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952709570 247 ILSNCNHTYCLSCIRQW---RCAKQFENpiikSCPECRVISEFV----------IPSVYWVEDQNKKNELIEAFKQGMGK 313
Cdd:PHA03096  200 ILSEIKHEFNIFCIKIWmteSLYKETEP----ENRRLNTVIVFIekinedlknnIPSRYWIDDKYDKNLLSFRYKKMHIR 275

                  ...
gi 1952709570 314 KAC 316
Cdd:PHA03096  276 KVC 278

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1952709570 215 KAFAFQASQDKVCSICMEVVlEKASASErrfgilsnCNHTYCLSCIRQWRCAKQFENpiiksCPECR 281
Cdd:COG5574   206 NGLPFIPLADYKCFLCLEEP-EVPSCTP--------CGHLFCLSCLLISWTKKKYEF-----CPLCR 258

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        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1952709570  227 CSICMEVVLEKAsaserrfgILSNCNHTYCLSCIRQWRCAKQfenpiiKSCPEC 280
Cdd:smart00184   1 CPICLEEYLKDP--------VILPCGHTFCRSCIRKWLESGN------NTCPIC 40

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1952709570 224 DKVCSICMEVVLEKASASERRFGILSNCNHTYCLSCIRQWRCAKQFENPIIKSCPECRVIS 284
Cdd:cd16730     1 DKVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECRITS 61

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1952709570 224 DKVCSICMEVVLEKASASERRFGILSNCNHTYCLSCIRQWRCAKQFENPIIKSCPECRVIS 284
Cdd:cd16732     1 DVACGICMDKVYEKAHAKERVFGILPNCNHAFCVGCIKKWRKSKDFQNEVIKACPQCRVKS 61

N1R/p28-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952709570 203 KICMSTFEHEMEKAFafQASQDKVCSICMEVVLEKASASeRRFGILSNCNHTYCLSCIRQWRCAKqfenpiiKSCPECRV 282
Cdd:PHA02929  155 LKTIPSVLSEYEKLY--NRSKDKECAICMEKVYDKEIKN-MYFGILSNCNHVFCIECIDIWKKEK-------NTCPVCRT 224

                  ....*...
gi 1952709570 283 ISEFVIPS 290
Cdd:PHA02929  225 PFISVIKS 232

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        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1952709570 226 VCSICMEVVLEkasaserrfGILSNCNHTYCLSCIRQWrcakqFENPIIKSCPECRVI 283
Cdd:cd16568     6 ECIICHEYLYE---------PMVTTCGHTYCYTCLNTW-----FKSNRSLSCPDCRTK 49

Zinc finger domain; This is a zinc finger domain found in Zinc finger CCCH-type with G patch domain-containing proteins such as ZIP. Functional studies indicate that ZIP specifically targets EGFR and represses its transcription, and that the zinc finger and the coiled-coil domains are central to that process.

                          10
                  ....*....|....*....
gi 1952709570  26 CKYYQKGYCAYGTRCRYDH 44
Cdd:pfam18345   1 CKFFLKGRCRYGDKCRFAH 19

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1952709570 226 VCSICMEvvlekasaseRRFGILSNCNHTYCLSCIRQWRCAKqfenpiiKSCPECR 281
Cdd:cd16545     2 ECCICMD----------RKADLILPCAHSYCQKCIDKWSDRH-------RTCPICR 40

RING finger, HC subclass, found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is a telomere-associated E3 ubiquitin-protein ligase that plays an important role in DNA double-strand break (DSB) repair via histone ubiquitination. It is localized in the nucleus and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless). It recruits UBC13 for lysine 63-based self polyubiquitylation. Its deficiency causes neuronal pathology and cognitive decline, and its loss results in neuron degeneration. RNF8, together with RNF168, catalyzes a series of ubiquitylation events on substrates such as H2A and H2AX, with the H2AK13/15 ubiquitylation being particularly important for recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of DSBs. RNF8 mediates the ubiquitination of gammaH2AX, and recruits 53BP1 and BRCA1 to DNA damage sites which promotes DNA damage response (DDR) and inhibits chromosomal instability. Moreover, RNF8 interacts with retinoid X receptor alpha (RXR alpha) and enhances its transcription-stimulating activity. It also regulates the rate of exit from mitosis and cytokinesis. RNF8 contains an N-terminal forkhead-associated (FHA) domain and a C-terminal C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1952709570 227 CSICMEVVLEKASAserrfgilsNCNHTYCLSCIRQWRCAKqfenpiiKSCPECR 281
Cdd:cd16535     4 CSICSELFIEAVTL---------NCSHSFCSYCITEWMKRK-------KECPICR 42

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1952709570 224 DKVCSICMEvvlekasasERRFGILSNCNHTYCLSCIRQWRCAKQfenpiikSCPECRV 282
Cdd:cd16561     2 EQECSICLE---------DLNDPVKLPCDHVFCEECIRQWLPGQM-------SCPLCRT 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        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1952709570 227 CSICMEvvlekasasERRFGILSNCNHTYCLSCIRQWRCAKQfenpiiKSCPEC 280
Cdd:cd16449     3 CPICLE---------RLKDPVLLPCGHVFCRECIRRLLESGS------IKCPIC 41

RING finger, HC subclass, found in tripartite motif-containing protein 38 (TRIM38) and similar proteins; TRIM38, also known as RING finger protein 15 (RNF15) or zinc finger protein RoRet, is an E3 ubiquitin-protein ligase that promotes K63- and K48-linked ubiquitination of cellular proteins and also catalyzes self-ubiquitination. It negatively regulates Tumor necrosis factor alpha (TNF-alpha)- and interleukin-1beta-triggered Nuclear factor-kappaB (NF-kappaB) activation by mediating lysosomal-dependent degradation of transforming growth factor beta (TGFbeta)-activated kinase 1 (TAK1)-binding protein (TAB)2/3, two critical components of the TAK1 kinase complex. It also inhibits TLR3/4-mediated activation of NF-kappaB and interferon regulatory factor 3 (IRF3) by mediating ubiquitin-proteasomal degradation of TNF receptor-associated factor 6 (Traf6) and NAK-associated protein 1 (Nap1), respectively. Moreover, TRIM38 negatively regulates TLR3-mediated interferon beta (IFN-beta) signaling by targeting ubiquitin-proteasomal degradation of TIR domain-containing adaptor inducing IFN-beta (TRIF). It functions as a valid target for autoantibodies in primary Sjogren's Syndrome. TRIM38 belongs 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, a B-box, and two coiled coil domains, 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 1952709570 227 CSICMEVVLEKASAserrfgilsNCNHTYCLSCIRQWRCAKQFENPIIK--SCPECR 281
Cdd:cd16600     8 CSICLQLMTEPVSI---------NCGHSYCKRCIVSFLENQSQLEPGLEtfSCPQCR 55