p28-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 54035497  179 ECRFGDACVYLHGDMCEICRLQVLHPFDPEQRKAHEKMCMSTFEHEMEKafafqasqdKVCSICMEVILEKaSASERRFG 258
Cdd:PHA03096 130 NCYKGKYCEYLHGDICDICEKYLLHPTDIKQRYNEQKTCLSYQLRLLLS---------KICGICLENIKAK-YIIKKYYG 199

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 54035497  259 ILSNCSHTYCLSCIRQW---RCAKQFENpiikSCPECRVISEFV----------IPSVYWVEDQNKKNELIEAFKQGMGK 325
Cdd:PHA03096 200 ILSEIKHEFNIFCIKIWmteSLYKETEP----ENRRLNTVIVFIekinedlknnIPSRYWIDDKYDKNLLSFRYKKMHIR 275

                 ...
gi 54035497  326 KAC 328
Cdd:PHA03096 276 KVC 278

Zinc-finger containing family; zf-CCCH_3 family is found in eukaryotes, and is typically between 155 and 169 amino acids in length.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 54035497     1 MSTKQVTCRYFMHGVCREGSQCLFSHDLANSKPSTICKYYQKGYCaYGARCRYDH 55
Cdd:pfam15663   1 MENKGDDCYFFYYSTCTKGDSCPFRHCEAALGNETVCTLWQEGRC-FRPVCRFRH 54

p28-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 54035497  179 ECRFGDACVYLHGDMCEICRLQVLHPFDPEQRKAHEKMCMSTFEHEMEKafafqasqdKVCSICMEVILEKaSASERRFG 258
Cdd:PHA03096 130 NCYKGKYCEYLHGDICDICEKYLLHPTDIKQRYNEQKTCLSYQLRLLLS---------KICGICLENIKAK-YIIKKYYG 199

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 54035497  259 ILSNCSHTYCLSCIRQW---RCAKQFENpiikSCPECRVISEFV----------IPSVYWVEDQNKKNELIEAFKQGMGK 325
Cdd:PHA03096 200 ILSEIKHEFNIFCIKIWmteSLYKETEP----ENRRLNTVIVFIekinedlknnIPSRYWIDDKYDKNLLSFRYKKMHIR 275

                 ...
gi 54035497  326 KAC 328
Cdd:PHA03096 276 KVC 278

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 54035497 227 KAFAFQASQDKVCSICMEVIlEKASASErrfgilsnCSHTYCLSCIRQWRCAKQFENpiiksCPECR 293
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 54035497    239 CSICMEVILEKAsaserrfgILSNCSHTYCLSCIRQWRCAKQfenpiiKSCPEC 292
Cdd:smart00184   1 CPICLEEYLKDP--------VILPCGHTFCRSCIRKWLESGN------NTCPIC 40

Zinc-finger containing family; zf-CCCH_3 family is found in eukaryotes, and is typically between 155 and 169 amino acids in length.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 54035497     1 MSTKQVTCRYFMHGVCREGSQCLFSHDLANSKPSTICKYYQKGYCaYGARCRYDH 55
Cdd:pfam15663   1 MENKGDDCYFFYYSTCTKGDSCPFRHCEAALGNETVCTLWQEGRC-FRPVCRFRH 54

Cleavage and polyadenylation specificity factor (CPSF) Clipper subunit and related makorin family Zn-finger proteins [General function prediction only];

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 54035497   6 VTCRYFMHGVCREGSQCLFSHDLANSKPSTI-CKYYQ-KGYCAYGARCRYDH 55
Cdd:COG5084 105 VVCKFFLRGLCKSGFSCEFLHEYDLRSSQGPpCRSFSlKGSCSSGPSCGYSH 156

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 54035497 236 DKVCSICMEVILEKASASERRFGILSNCSHTYCLSCIRQWRCAKQFENPIIKSCPECRVIS 296
Cdd:cd16730   1 DKVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECRITS 61

RING finger, HC subclass, found in the makorin (MKRN) proteins; The MKRN protein subfamily includes ribonucleoproteins that are characterized by a variety of zinc-finger motifs, including typical arrays of one to four C3H1-type zinc fingers and a C3HC4-type RING-HC finger. Another motif rich in Cys and His residues (CH), with so far unknown function, is also generally present in MKRN proteins. MKRN proteins may have E3 ubiquitin ligase activity.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 54035497 237 KVCSICMEVILEKasasERRFGILSNCSHTYCLSCIRQWRCAKQFENPIIKSCPECR 293
Cdd:cd16521   1 IECGICMEVVLEK----ERRFGILSNCNHVFCLECIREWRSSKDFENSIVRSCPICR 53

N1R/p28-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 54035497  217 CMSTFEHEMEKAFafQASQDKVCSICMEVILEKASASeRRFGILSNCSHTYCLSCIRQWRCAKqfenpiiKSCPECRVIS 296
Cdd:PHA02929 157 TIPSVLSEYEKLY--NRSKDKECAICMEKVYDKEIKN-MYFGILSNCNHVFCIECIDIWKKEK-------NTCPVCRTPF 226

                 ....*.
gi 54035497  297 EFVIPS 302
Cdd:PHA02929 227 ISVIKS 232

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 54035497 227 KAFAFQASQDKVCSICMEVIlEKASASErrfgilsnCSHTYCLSCIRQWRCAKQFENpiiksCPECR 293
Cdd:COG5574 206 NGLPFIPLADYKCFLCLEEP-EVPSCTP--------CGHLFCLSCLLISWTKKKYEF-----CPLCR 258

RING finger, HC subclass, found in topoisomerase I-binding arginine/serine-rich protein (Topors) and similar proteins; Topors, also known as topoisomerase I-binding RING finger protein, tumor suppressor p53- binding protein 3, or p53-binding protein 3 (p53BP3), is a ubiquitously expressed nuclear E3 ubiquitin-protein ligase that can ligate both ubiquitin and small ubiquitin-like modifier (SUMO) to substrate proteins in the nucleus. It contains an N-terminal C3HC4-type RING-HC finger which ligates ubiquitin to its target proteins including DNA topoisomerase I, p53, NKX3.1, H2AX, and the AAV-2 Rep78/68 proteins. As a RING-dependent E3 ubiquitin ligase, Topors works with the E2 enzymes UbcH5a, UbcH5c, and UbcH6, but not with UbcH7, CDC34, or UbcH2b. Topors acts as a tumor suppressor in various malignancies. It regulates p53 modification, suggesting it may be responsible for astrocyte elevated gene-1 (AEG-1, also known as metadherin, or LYRIC) ubiquitin modification. Plk1-mediated phosphorylation of Topors inhibits Topors-mediated sumoylation of p53, whereas p53 ubiquitination is enhanced, leading to p53 degradation. It also functions as a negative regulator of the prostate tumor suppressor NKX3.1. Moreover, Topors is associated with promyelocytic leukemia nuclear bodies, and may be involved in the cellular response to camptothecin. It also plays a key role in the turnover of H2AX protein, discriminating the type of DNA damaging stress. Furthermore, Topors is a cilia-centrosomal protein associated with autosomal dominant retinal degeneration. Mutations in TOPORS cause autosomal dominant retinitis pigmentosa (adRP).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 54035497 236 DKVCSICMEVIlekasasERRFGILSNCSHTYCLSCIRQWrcAKQfENpiikSCPECR 293
Cdd:cd16574   1 DSSCPICLDRF-------ENEKAFLDGCFHAFCFTCILEW--SKV-KN----ECPLCK 44

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 54035497 239 CSICMEVILEKASAserrfgilsNCSHTYCLSCIRQWRCAKqfenpiiKSCPECR 293
Cdd:cd16535   4 CSICSELFIEAVTL---------NCSHSFCSYCITEWMKRK-------KECPICR 42

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 54035497 238 VCSICMEvilekasaseRRFGILSNCSHTYCLSCIRQWRCAKqfenpiiKSCPECR 293
Cdd:cd16545   2 ECCICMD----------RKADLILPCAHSYCQKCIDKWSDRH-------RTCPICR 40

Zinc-finger containing family; zf-CCCH_3 family is found in eukaryotes, and is typically between 155 and 169 amino acids in length.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 54035497     1 MSTKQVTCRYFMHGVCREGSQCLFSHDLANSKPSTICKYYQKGYCaYGARCRYDH 55
Cdd:pfam15663   1 MENKGDDCYFFYYSTCTKGDSCPFRHCEAALGNETVCTLWQEGRC-FRPVCRFRH 54

H2 subclass of RING (RING-H2) fingers and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serves as a scaffold for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 54035497 239 CSICMEVILEKasaserRFGILSNCSHTYCLSCIRQWrcakqfENPIIKSCPECR 293
Cdd:cd16448   1 CVICLEEFEEG------DVVRLLPCGHVFHLACILRW------LESGNNTCPLCR 43

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 54035497 239 CSICMEVILEKASAserrfgilsNCSHTYCLSCIRQWRCAKQFENPIIK--SCPECR 293
Cdd:cd16600   8 CSICLQLMTEPVSI---------NCGHSYCKRCIVSFLENQSQLEPGLEtfSCPQCR 55

Cleavage and polyadenylation specificity factor (CPSF) Clipper subunit and related makorin family Zn-finger proteins [General function prediction only];

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 54035497   6 VTCRYFMHGVCREGSQCLFSHDLANSKPSTI-CKYYQ-KGYCAYGARCRYDH 55
Cdd:COG5084 105 VVCKFFLRGLCKSGFSCEFLHEYDLRSSQGPpCRSFSlKGSCSSGPSCGYSH 156

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 54035497 239 CSICMEvilekasasERRFGILSNCSHTYCLSCIRQWRCAKQfenpiiKSCPEC 292
Cdd:cd16449   3 CPICLE---------RLKDPVLLPCGHVFCRECIRRLLESGS------IKCPIC 41

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 54035497 236 DKVCSICMEvilekasasERRFGILSNCSHTYCLSCIRQWRCAKQfenpiikSCPECRV 294
Cdd:cd16561   2 EQECSICLE---------DLNDPVKLPCDHVFCEECIRQWLPGQM-------SCPLCRT 44