p28-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45645205  178 ECRFGDACVYLHGEVCEICRLQVLHPFDPEQRKAHEKICMLTFEHEMEKafafqasqdKVCSICMEVILEKaSASERRFG 257
Cdd:PHA03096 130 NCYKGKYCEYLHGDICDICEKYLLHPTDIKQRYNEQKTCLSYQLRLLLS---------KICGICLENIKAK-YIIKKYYG 199

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45645205  258 ILSNCNHTYCLSCIRQW---RCAKQFENpiikSCPECRVISEFV----------IPSVYWVEDQNKKNELIEAFKQGMGK 324
Cdd:PHA03096 200 ILSEIKHEFNIFCIKIWmteSLYKETEP----ENRRLNTVIVFIekinedlknnIPSRYWIDDKYDKNLLSFRYKKMHIR 275

                 ...
gi 45645205  325 KAC 327
Cdd:PHA03096 276 KVC 278

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 45645205   6 ITCRYFMHGVCREGSQCLFSHDLANSKPSTI-CKYYQ-KGYCAYGTRCRYDHTRPSAAAG 63
Cdd:COG5084 105 VVCKFFLRGLCKSGFSCEFLHEYDLRSSQGPpCRSFSlKGSCSSGPSCGYSHIDPDSFAG 164

p28-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45645205  178 ECRFGDACVYLHGEVCEICRLQVLHPFDPEQRKAHEKICMLTFEHEMEKafafqasqdKVCSICMEVILEKaSASERRFG 257
Cdd:PHA03096 130 NCYKGKYCEYLHGDICDICEKYLLHPTDIKQRYNEQKTCLSYQLRLLLS---------KICGICLENIKAK-YIIKKYYG 199

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45645205  258 ILSNCNHTYCLSCIRQW---RCAKQFENpiikSCPECRVISEFV----------IPSVYWVEDQNKKNELIEAFKQGMGK 324
Cdd:PHA03096 200 ILSEIKHEFNIFCIKIWmteSLYKETEP----ENRRLNTVIVFIekinedlknnIPSRYWIDDKYDKNLLSFRYKKMHIR 275

                 ...
gi 45645205  325 KAC 327
Cdd:PHA03096 276 KVC 278

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 45645205 226 KAFAFQASQDKVCSICMEVIlEKASASErrfgilsnCNHTYCLSCIRQWRCAKQFENpiiksCPECR 292
Cdd:COG5574 206 NGLPFIPLADYKCFLCLEEP-EVPSCTP--------CGHLFCLSCLLISWTKKKYEF-----CPLCR 258

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 45645205    37 CKYYQKGYCAYGTRCRYDH 55
Cdd:pfam18345   1 CKFFLKGRCRYGDKCRFAH 19

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 45645205     1 MSTKQITCRYFMHGVCREGSQCLFSHDLANSKPSTICKYYQKGYCaYGTRCRYDHTR 57
Cdd:pfam15663   1 MENKGDDCYFFYYSTCTKGDSCPFRHCEAALGNETVCTLWQEGRC-FRPVCRFRHME 56

zinc finger;

                           10        20
                   ....*....|....*....|....*..
gi 45645205      2 STKQITCRYFMHGVCREGSQCLFSHDL 28
Cdd:smart00356   1 KYKTELCKFFKRGYCPRGDRCKFAHPL 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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 45645205 235 DKVCSICMEVILEKASASERRFGILSNCNHTYCLSCIRQWRCAKQFENPIIKSCPECRVIS 295
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 45645205 235 DKVCSICMEVILEKASASERRFGILSNCNHTYCLSCIRQWRCAKQFENPIIKSCPECRVIS 295
Cdd:cd16732   1 DVACGICMDKVYEKAHAKERVFGILPNCNHAFCVGCIKKWRKSKDFQNEVIKACPQCRVKS 61

N1R/p28-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45645205  214 KICMLTFEHEMEKAFafQASQDKVCSICMEVILEKASASeRRFGILSNCNHTYCLSCIRQWRCAKqfenpiiKSCPECRV 293
Cdd:PHA02929 155 LKTIPSVLSEYEKLY--NRSKDKECAICMEKVYDKEIKN-MYFGILSNCNHVFCIECIDIWKKEK-------NTCPVCRT 224

                 ....*...
gi 45645205  294 ISEFVIPS 301
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 45645205 237 VCSICMEVILEkasaserrfGILSNCNHTYCLSCIRQWrcakqFENPIIKSCPECRVI 294
Cdd:cd16568   6 ECIICHEYLYE---------PMVTTCGHTYCYTCLNTW-----FKSNRSLSCPDCRTK 49

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 45645205    238 CSICMEVILEKAsaserrfgILSNCNHTYCLSCIRQWRCAKQfenpiiKSCPEC 291
Cdd:smart00184   1 CPICLEEYLKDP--------VILPCGHTFCRSCIRKWLESGN------NTCPIC 40

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 45645205    37 CKYYQKGYCAYGTRCRYDH 55
Cdd:pfam18345   1 CKFFLKGRCRYGDKCRFAH 19

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 45645205 238 CSICMEVILEKASAserrfgilsNCNHTYCLSCIRQWRCAKqfenpiiKSCPECR 292
Cdd:cd16535   4 CSICSELFIEAVTL---------NCSHSFCSYCITEWMKRK-------KECPICR 42

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 45645205     1 MSTKQITCRYFMHGVCREGSQCLFSHDLANSKPSTICKYYQKGYCaYGTRCRYDHTR 57
Cdd:pfam15663   1 MENKGDDCYFFYYSTCTKGDSCPFRHCEAALGNETVCTLWQEGRC-FRPVCRFRHME 56

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 45645205 238 CSICMEVILEKasaserRFGILSNCNHTYCLSCIRQWrcakqfENPIIKSCPECR 292
Cdd:cd16448   1 CVICLEEFEEG------DVVRLLPCGHVFHLACILRW------LESGNNTCPLCR 43

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 45645205 238 CSICMEvilekasasERRFGILSNCNHTYCLSCIRQWRCAKQfenpiiKSCPEC 291
Cdd:cd16449   3 CPICLE---------RLKDPVLLPCGHVFCRECIRRLLESGS------IKCPIC 41

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 45645205     6 ITCRYFMHGVCREGSQCLFSHD 27
Cdd:pfam18044   1 RLCRYFQKGGCRYGDNCRFSHD 22

zinc finger;

                           10        20
                   ....*....|....*....|....*..
gi 45645205      2 STKQITCRYFMHGVCREGSQCLFSHDL 28
Cdd:smart00356   1 KYKTELCKFFKRGYCPRGDRCKFAHPL 27

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 45645205     8 CRYFMHGVCREGSQCLFSH 26
Cdd:pfam18345   1 CKFFLKGRCRYGDKCRFAH 19