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Conserved domains on  [gi|223468620|ref|NP_038474|]
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E3 ubiquitin-protein ligase makorin-1 isoform 1 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
MKRN1_C pfam15815
E3 ubiquitin-protein ligase makorin, C-terminal; MKRN1_C is the very C-terminus of E3 ...
 392-482 3.61e-42

E3 ubiquitin-protein ligase makorin, C-terminal; MKRN1_C is the very C-terminus of E3 ubiquitin-protein ligase makorin-1, or MKRN1, a family of eukaryotic putative ribonucleoproteins with a distinctive array of zinc-finger motifs. MKRN1 plays an important role in modulating the homeostasis of telomere-length through a dynamic balance involving the stability of the protein hTERT. MKRN1 has been shown to be a a transcriptional co-regulator and an E3 ligase. It functions simultaneously as a differentially negative regulator of p53 and p21, preferentially leading cells to p53-dependent apoptosis by suppressing p21. The exact function of the C-terminal region has not been determined.


:

Pssm-ID: 464890  Cd Length: 87  Bit Score: 144.78  E-value: 3.61e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223468620  392 YPDGRREEPQRQKVGTSSRYRAQRRNHfwelIEERENSNPFDNDEEEVVTFELGEMLLMLLAAGGDDELTDSEDEWDLFH 471
Cdd:pfam15815   1 YPDGRGEEPQRQGGGSSSRYWHQRREP----VQVREGSMPFKNDKKELVTLELAELLLKLLLALRDDELTDSEDEWDLLH 76

                          90
                  ....*....|.
gi 223468620  472 DELEDFYDLDL 482
Cdd:pfam15815  77 YELEEYFDLDL 87
RING-HC_MKRN1_3 cd16730
RING finger, HC subclass, found in makorin-1 (MKRN1), makorin-3 (MKRN3), and similar proteins; ...
 278-338 3.97e-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.


:

Pssm-ID: 319644 [Multi-domain]  Cd Length: 61  Bit Score: 138.40  E-value: 3.97e-40
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 223468620 278 DMVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECRITS 338
Cdd:cd16730    1 DKVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECRITS 61
PHA03096 super family cl33708
p28-like protein; Provisional
 221-370 2.45e-21

p28-like protein; Provisional


The actual alignment was detected with superfamily member PHA03096:

Pssm-ID: 222981 [Multi-domain]  Cd Length: 284  Bit Score: 93.72  E-value: 2.45e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223468620 221 ECRYGENCVYLHGDSCDMCGLQVLHPMDAAQRSQHIKSCIEAheKDMELSFAvqrskdmVCGICMEVVYEKaNPSERRFG 300
Cdd:PHA03096 130 NCYKGKYCEYLHGDICDICEKYLLHPTDIKQRYNEQKTCLSY--QLRLLLSK-------ICGICLENIKAK-YIIKKYYG 199

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223468620 301 ILSNCNHTYCLKCIRKWRSAKQfESKIIKSCPECRITSNFV----------IPSEYWVEEKEEKQKLILKYKEAMSNKAC 370
Cdd:PHA03096 200 ILSEIKHEFNIFCIKIWMTESL-YKETEPENRRLNTVIVFIekinedlknnIPSRYWIDDKYDKNLLSFRYKKMHIRKVC 278
zf-CCCH_4 pfam18044
CCCH-type zinc finger; This short zinc binding domain has the pattern of three cysteines and ...
 59-80 2.46e-05

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.


:

Pssm-ID: 465626  Cd Length: 22  Bit Score: 41.03  E-value: 2.46e-05
                          10        20
                  ....*....|....*....|..
gi 223468620   59 VTCRYFMHGVCKEGDNCRYSHD 80
Cdd:pfam18044   1 RLCRYFQKGGCRYGDNCRFSHD 22
zf_CCCH_4 pfam18345
Zinc finger domain; This is a zinc finger domain found in Zinc finger CCCH-type with G patch ...
 90-108 4.35e-05

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.


:

Pssm-ID: 465719 [Multi-domain]  Cd Length: 19  Bit Score: 40.09  E-value: 4.35e-05
                          10
                  ....*....|....*....
gi 223468620   90 CKYFQRGYCIYGDRCRYEH 108
Cdd:pfam18345   1 CKFFLKGRCRYGDKCRFAH 19
 
Name Accession Description Interval E-value
MKRN1_C pfam15815
E3 ubiquitin-protein ligase makorin, C-terminal; MKRN1_C is the very C-terminus of E3 ...
 392-482 3.61e-42

E3 ubiquitin-protein ligase makorin, C-terminal; MKRN1_C is the very C-terminus of E3 ubiquitin-protein ligase makorin-1, or MKRN1, a family of eukaryotic putative ribonucleoproteins with a distinctive array of zinc-finger motifs. MKRN1 plays an important role in modulating the homeostasis of telomere-length through a dynamic balance involving the stability of the protein hTERT. MKRN1 has been shown to be a a transcriptional co-regulator and an E3 ligase. It functions simultaneously as a differentially negative regulator of p53 and p21, preferentially leading cells to p53-dependent apoptosis by suppressing p21. The exact function of the C-terminal region has not been determined.


Pssm-ID: 464890  Cd Length: 87  Bit Score: 144.78  E-value: 3.61e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223468620  392 YPDGRREEPQRQKVGTSSRYRAQRRNHfwelIEERENSNPFDNDEEEVVTFELGEMLLMLLAAGGDDELTDSEDEWDLFH 471
Cdd:pfam15815   1 YPDGRGEEPQRQGGGSSSRYWHQRREP----VQVREGSMPFKNDKKELVTLELAELLLKLLLALRDDELTDSEDEWDLLH 76

                          90
                  ....*....|.
gi 223468620  472 DELEDFYDLDL 482
Cdd:pfam15815  77 YELEEYFDLDL 87
RING-HC_MKRN1_3 cd16730
RING finger, HC subclass, found in makorin-1 (MKRN1), makorin-3 (MKRN3), and similar proteins; ...
 278-338 3.97e-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.


Pssm-ID: 319644 [Multi-domain]  Cd Length: 61  Bit Score: 138.40  E-value: 3.97e-40
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 223468620 278 DMVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECRITS 338
Cdd:cd16730    1 DKVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECRITS 61
PHA03096 PHA03096
p28-like protein; Provisional
 221-370 2.45e-21

p28-like protein; Provisional


Pssm-ID: 222981 [Multi-domain]  Cd Length: 284  Bit Score: 93.72  E-value: 2.45e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223468620 221 ECRYGENCVYLHGDSCDMCGLQVLHPMDAAQRSQHIKSCIEAheKDMELSFAvqrskdmVCGICMEVVYEKaNPSERRFG 300
Cdd:PHA03096 130 NCYKGKYCEYLHGDICDICEKYLLHPTDIKQRYNEQKTCLSY--QLRLLLSK-------ICGICLENIKAK-YIIKKYYG 199

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223468620 301 ILSNCNHTYCLKCIRKWRSAKQfESKIIKSCPECRITSNFV----------IPSEYWVEEKEEKQKLILKYKEAMSNKAC 370
Cdd:PHA03096 200 ILSEIKHEFNIFCIKIWMTESL-YKETEPENRRLNTVIVFIekinedlknnIPSRYWIDDKYDKNLLSFRYKKMHIRKVC 278
PHA02929 PHA02929
N1R/p28-like protein; Provisional
 275-350 1.04e-15

N1R/p28-like protein; Provisional


Pssm-ID: 222944 [Multi-domain]  Cd Length: 238  Bit Score: 76.36  E-value: 1.04e-15
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 223468620 275 RSKDMVCGICMEVVYEKaNPSERRFGILSNCNHTYCLKCIRKWRSAKqfeskiiKSCPECRITSNFVIPSEYWVEE 350
Cdd:PHA02929 171 RSKDKECAICMEKVYDK-EIKNMYFGILSNCNHVFCIECIDIWKKEK-------NTCPVCRTPFISVIKSRFFTKG 238
zf-CCCH_4 pfam18044
CCCH-type zinc finger; This short zinc binding domain has the pattern of three cysteines and ...
 59-80 2.46e-05

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.


Pssm-ID: 465626  Cd Length: 22  Bit Score: 41.03  E-value: 2.46e-05
                          10        20
                  ....*....|....*....|..
gi 223468620   59 VTCRYFMHGVCKEGDNCRYSHD 80
Cdd:pfam18044   1 RLCRYFQKGGCRYGDNCRFSHD 22
zf_CCCH_4 pfam18345
Zinc finger domain; This is a zinc finger domain found in Zinc finger CCCH-type with G patch ...
 90-108 4.35e-05

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.


Pssm-ID: 465719 [Multi-domain]  Cd Length: 19  Bit Score: 40.09  E-value: 4.35e-05
                          10
                  ....*....|....*....
gi 223468620   90 CKYFQRGYCIYGDRCRYEH 108
Cdd:pfam18345   1 CKFFLKGRCRYGDKCRFAH 19
ZnF_C3H1 smart00356
zinc finger;
88-110 5.44e-05

zinc finger;


Pssm-ID: 214632 [Multi-domain]  Cd Length: 27  Bit Score: 39.92  E-value: 5.44e-05
                           10        20
                   ....*....|....*....|...
gi 223468620    88 VVCKYFQRGYCIYGDRCRYEHSK 110
Cdd:smart00356   5 ELCKFFKRGYCPRGDRCKFAHPL 27
COG5152 COG5152
Uncharacterized conserved protein, contains RING and CCCH-type Zn-fingers [General function ...
 205-318 1.50e-04

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


Pssm-ID: 227481 [Multi-domain]  Cd Length: 259  Bit Score: 43.53  E-value: 1.50e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223468620 205 TAVETKKQLC-PYAAVGECRYGENCVYLHGDSCDMCGLQVLHPMDAAQRSQHIKScieahEKDMELSFavqrskdmVCGI 283
Cdd:COG5152  135 EVIDTQPDVCkDYKETGYCGYGDSCKFLHDRSDFKTGWKLNQEWNAEYEEAPVIS-----GPGEKIPF--------LCGI 201

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 223468620 284 CMEVVYEKanpserrfgILSNCNHTYCLKC-IRKWR 318
Cdd:COG5152  202 CKKDYESP---------VVTECGHSFCSLCaIRKYQ 228
RING smart00184
Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ...
 281-334 1.71e-04

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)


Pssm-ID: 214546 [Multi-domain]  Cd Length: 40  Bit Score: 39.03  E-value: 1.71e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 223468620   281 CGICMEVVYEKAnpserrfgILSNCNHTYCLKCIRKWRSAKQfeskiiKSCPEC 334
Cdd:smart00184   1 CPICLEEYLKDP--------VILPCGHTFCRSCIRKWLESGN------NTCPIC 40
ZnF_C3H1 smart00356
zinc finger;
55-81 2.19e-04

zinc finger;


Pssm-ID: 214632 [Multi-domain]  Cd Length: 27  Bit Score: 38.38  E-value: 2.19e-04
                           10        20
                   ....*....|....*....|....*..
gi 223468620    55 WTKQVTCRYFMHGVCKEGDNCRYSHDL 81
Cdd:smart00356   1 KYKTELCKFFKRGYCPRGDRCKFAHPL 27
 
Name Accession Description Interval E-value
MKRN1_C pfam15815
E3 ubiquitin-protein ligase makorin, C-terminal; MKRN1_C is the very C-terminus of E3 ...
 392-482 3.61e-42

E3 ubiquitin-protein ligase makorin, C-terminal; MKRN1_C is the very C-terminus of E3 ubiquitin-protein ligase makorin-1, or MKRN1, a family of eukaryotic putative ribonucleoproteins with a distinctive array of zinc-finger motifs. MKRN1 plays an important role in modulating the homeostasis of telomere-length through a dynamic balance involving the stability of the protein hTERT. MKRN1 has been shown to be a a transcriptional co-regulator and an E3 ligase. It functions simultaneously as a differentially negative regulator of p53 and p21, preferentially leading cells to p53-dependent apoptosis by suppressing p21. The exact function of the C-terminal region has not been determined.


Pssm-ID: 464890  Cd Length: 87  Bit Score: 144.78  E-value: 3.61e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223468620  392 YPDGRREEPQRQKVGTSSRYRAQRRNHfwelIEERENSNPFDNDEEEVVTFELGEMLLMLLAAGGDDELTDSEDEWDLFH 471
Cdd:pfam15815   1 YPDGRGEEPQRQGGGSSSRYWHQRREP----VQVREGSMPFKNDKKELVTLELAELLLKLLLALRDDELTDSEDEWDLLH 76

                          90
                  ....*....|.
gi 223468620  472 DELEDFYDLDL 482
Cdd:pfam15815  77 YELEEYFDLDL 87
RING-HC_MKRN1_3 cd16730
RING finger, HC subclass, found in makorin-1 (MKRN1), makorin-3 (MKRN3), and similar proteins; ...
 278-338 3.97e-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.


Pssm-ID: 319644 [Multi-domain]  Cd Length: 61  Bit Score: 138.40  E-value: 3.97e-40
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 223468620 278 DMVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECRITS 338
Cdd:cd16730    1 DKVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECRITS 61
RING-HC_MKRN2 cd16731
RING finger, HC subclass, found in makorin-2 (MKRN2) and similar proteins; MKRN2, also known ...
 278-335 5.51e-30

RING finger, HC subclass, found in makorin-2 (MKRN2) and similar proteins; MKRN2, also known as makorin RING finger protein 2, RING finger protein 62 (RNF62), or HSPC070, is a putative ribonucleoprotein that acts as a neurogenesis inhibitor acting upstream of glycogen synthase kinase-3beta (GSK-3beta) in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. It also functions in promoting cell proliferation of primary CD34+ progenitor cells and K562 cells, indicating its possible involvement in normal and malignant hematopoiesis. Mammalian MKRN2 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. The third C3H1-type zinc finger, the CH motif, as well as the RING zinc finger are necessary for its anti-neurogenic activity.


Pssm-ID: 319645 [Multi-domain]  Cd Length: 58  Bit Score: 111.15  E-value: 5.51e-30
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 223468620 278 DMVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECR 335
Cdd:cd16731    1 DKVCSICMEVVYEKASASERRFGILSNCNHTYCLSCIRQWRCAKQFENPIIKSCPECR 58
RING-HC_MKRN4 cd16732
RING finger, HC subclass, found in makorin-4 (MKRN4) and similar proteins; MKRN4, also known ...
 278-338 4.41e-29

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.


Pssm-ID: 438390 [Multi-domain]  Cd Length: 61  Bit Score: 108.74  E-value: 4.41e-29
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 223468620 278 DMVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECRITS 338
Cdd:cd16732    1 DVACGICMDKVYEKAHAKERVFGILPNCNHAFCVGCIKKWRKSKDFQNEVIKACPQCRVKS 61
RING-HC_MKRN cd16521
RING finger, HC subclass, found in the makorin (MKRN) proteins; The MKRN protein subfamily ...
 279-335 1.68e-25

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.


Pssm-ID: 438184 [Multi-domain]  Cd Length: 53  Bit Score: 98.50  E-value: 1.68e-25
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 223468620 279 MVCGICMEVVYEKanpsERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECR 335
Cdd:cd16521    1 IECGICMEVVLEK----ERRFGILSNCNHVFCLECIREWRSSKDFENSIVRSCPICR 53
PHA03096 PHA03096
p28-like protein; Provisional
 221-370 2.45e-21

p28-like protein; Provisional


Pssm-ID: 222981 [Multi-domain]  Cd Length: 284  Bit Score: 93.72  E-value: 2.45e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223468620 221 ECRYGENCVYLHGDSCDMCGLQVLHPMDAAQRSQHIKSCIEAheKDMELSFAvqrskdmVCGICMEVVYEKaNPSERRFG 300
Cdd:PHA03096 130 NCYKGKYCEYLHGDICDICEKYLLHPTDIKQRYNEQKTCLSY--QLRLLLSK-------ICGICLENIKAK-YIIKKYYG 199

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223468620 301 ILSNCNHTYCLKCIRKWRSAKQfESKIIKSCPECRITSNFV----------IPSEYWVEEKEEKQKLILKYKEAMSNKAC 370
Cdd:PHA03096 200 ILSEIKHEFNIFCIKIWMTESL-YKETEPENRRLNTVIVFIekinedlknnIPSRYWIDDKYDKNLLSFRYKKMHIRKVC 278
PHA02929 PHA02929
N1R/p28-like protein; Provisional
 275-350 1.04e-15

N1R/p28-like protein; Provisional


Pssm-ID: 222944 [Multi-domain]  Cd Length: 238  Bit Score: 76.36  E-value: 1.04e-15
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 223468620 275 RSKDMVCGICMEVVYEKaNPSERRFGILSNCNHTYCLKCIRKWRSAKqfeskiiKSCPECRITSNFVIPSEYWVEE 350
Cdd:PHA02929 171 RSKDKECAICMEKVYDK-EIKNMYFGILSNCNHVFCIECIDIWKKEK-------NTCPVCRTPFISVIKSRFFTKG 238
PHA02926 PHA02926
zinc finger-like protein; Provisional
 276-347 4.10e-11

zinc finger-like protein; Provisional


Pssm-ID: 165237 [Multi-domain]  Cd Length: 242  Bit Score: 63.16  E-value: 4.10e-11
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 223468620 276 SKDMVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQfESKIIKSCPECRITSNFVIPSEYW 347
Cdd:PHA02926 168 SKEKECGICYEVVYSKRLENDRYFGLLDSCNHIFCITCINIWHRTRR-ETGASDNCPICRTRFRNITMSKFY 238
RING-HC_ScPSH1-like cd16568
RING finger, HC subclass, found in Saccharomyces cerevisiae POB3/SPT16 histone-associated ...
 280-335 2.86e-06

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.


Pssm-ID: 438230 [Multi-domain]  Cd Length: 54  Bit Score: 44.28  E-value: 2.86e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 223468620 280 VCGICMEVVYEkanpserrfGILSNCNHTYCLKCIRKWrsakqFESKIIKSCPECR 335
Cdd:cd16568    6 ECIICHEYLYE---------PMVTTCGHTYCYTCLNTW-----FKSNRSLSCPDCR 47
zf-CCCH_4 pfam18044
CCCH-type zinc finger; This short zinc binding domain has the pattern of three cysteines and ...
 59-80 2.46e-05

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.


Pssm-ID: 465626  Cd Length: 22  Bit Score: 41.03  E-value: 2.46e-05
                          10        20
                  ....*....|....*....|..
gi 223468620   59 VTCRYFMHGVCKEGDNCRYSHD 80
Cdd:pfam18044   1 RLCRYFQKGGCRYGDNCRFSHD 22
RING-HC_Topors cd16574
RING finger, HC subclass, found in topoisomerase I-binding arginine/serine-rich protein ...
 278-335 4.22e-05

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).


Pssm-ID: 438236 [Multi-domain]  Cd Length: 47  Bit Score: 40.73  E-value: 4.22e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 223468620 278 DMVCGICMEVVyekanpsERRFGILSNCNHTYCLKCIRKWrsakqfeSKIIKSCPECR 335
Cdd:cd16574    1 DSSCPICLDRF-------ENEKAFLDGCFHAFCFTCILEW-------SKVKNECPLCK 44
zf_CCCH_4 pfam18345
Zinc finger domain; This is a zinc finger domain found in Zinc finger CCCH-type with G patch ...
 90-108 4.35e-05

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.


Pssm-ID: 465719 [Multi-domain]  Cd Length: 19  Bit Score: 40.09  E-value: 4.35e-05
                          10
                  ....*....|....*....
gi 223468620   90 CKYFQRGYCIYGDRCRYEH 108
Cdd:pfam18345   1 CKFFLKGRCRYGDKCRFAH 19
ZnF_C3H1 smart00356
zinc finger;
88-110 5.44e-05

zinc finger;


Pssm-ID: 214632 [Multi-domain]  Cd Length: 27  Bit Score: 39.92  E-value: 5.44e-05
                           10        20
                   ....*....|....*....|...
gi 223468620    88 VVCKYFQRGYCIYGDRCRYEHSK 110
Cdd:smart00356   5 ELCKFFKRGYCPRGDRCKFAHPL 27
COG5152 COG5152
Uncharacterized conserved protein, contains RING and CCCH-type Zn-fingers [General function ...
 205-318 1.50e-04

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


Pssm-ID: 227481 [Multi-domain]  Cd Length: 259  Bit Score: 43.53  E-value: 1.50e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223468620 205 TAVETKKQLC-PYAAVGECRYGENCVYLHGDSCDMCGLQVLHPMDAAQRSQHIKScieahEKDMELSFavqrskdmVCGI 283
Cdd:COG5152  135 EVIDTQPDVCkDYKETGYCGYGDSCKFLHDRSDFKTGWKLNQEWNAEYEEAPVIS-----GPGEKIPF--------LCGI 201

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 223468620 284 CMEVVYEKanpserrfgILSNCNHTYCLKC-IRKWR 318
Cdd:COG5152  202 CKKDYESP---------VVTECGHSFCSLCaIRKYQ 228
RING smart00184
Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ...
 281-334 1.71e-04

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)


Pssm-ID: 214546 [Multi-domain]  Cd Length: 40  Bit Score: 39.03  E-value: 1.71e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 223468620   281 CGICMEVVYEKAnpserrfgILSNCNHTYCLKCIRKWRSAKQfeskiiKSCPEC 334
Cdd:smart00184   1 CPICLEEYLKDP--------VILPCGHTFCRSCIRKWLESGN------NTCPIC 40
RING-HC_RNF141 cd16545
RING finger, HC subclass, found in RING finger protein 141 (RNF141) and similar proteins; ...
 280-335 2.00e-04

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.


Pssm-ID: 438207 [Multi-domain]  Cd Length: 40  Bit Score: 38.61  E-value: 2.00e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 223468620 280 VCGICMEvvyekanpseRRFGILSNCNHTYCLKCIRKWRSAKqfeskiiKSCPECR 335
Cdd:cd16545    2 ECCICMD----------RKADLILPCAHSYCQKCIDKWSDRH-------RTCPICR 40
ZnF_C3H1 smart00356
zinc finger;
55-81 2.19e-04

zinc finger;


Pssm-ID: 214632 [Multi-domain]  Cd Length: 27  Bit Score: 38.38  E-value: 2.19e-04
                           10        20
                   ....*....|....*....|....*..
gi 223468620    55 WTKQVTCRYFMHGVCKEGDNCRYSHDL 81
Cdd:smart00356   1 KYKTELCKFFKRGYCPRGDRCKFAHPL 27
zf_CCCH_4 pfam18345
Zinc finger domain; This is a zinc finger domain found in Zinc finger CCCH-type with G patch ...
 61-79 3.82e-04

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.


Pssm-ID: 465719 [Multi-domain]  Cd Length: 19  Bit Score: 37.40  E-value: 3.82e-04
                          10
                  ....*....|....*....
gi 223468620   61 CRYFMHGVCKEGDNCRYSH 79
Cdd:pfam18345   1 CKFFLKGRCRYGDKCRFAH 19
RING-HC_CHFR cd16503
RING finger, HC subclass, found in checkpoint with forkhead and RING finger domains protein ...
 278-337 1.11e-03

RING finger, HC subclass, found in checkpoint with forkhead and RING finger domains protein (CHFR); CHFR, also known as RING finger protein 196 (RNF196), is a checkpoint protein that delays entry into mitosis in response to stress. It functions as an E3 ubiquitin ligase that ubiquitinates and degrades its target proteins, such as Aurora-A, Plk1, Kif22, and PARP-1, which are critical for proper mitotic transitions. It also plays an important role in cell cycle progression and tumor suppression, and is negatively regulated by SUMOylation-mediated proteasomal ubiquitylation. Moreover, CHFR is involved in the early stage of the DNA damage response, which mediates the crosstalk between ubiquitination and poly-ADP-ribosylation. CHFR contains a fork head associated (FHA) domain and a C3HC4-type RING-HC finger.


Pssm-ID: 438166 [Multi-domain]  Cd Length: 55  Bit Score: 36.96  E-value: 1.11e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 223468620 278 DMVCGICMEVVYE--KANPserrfgilsnCNHTYCLKCIRKWRSAKQFEskiiksCPECRIT 337
Cdd:cd16503    2 NLTCSICQDLLHDcvSLQP----------CMHNFCAACYSDWMERSNTE------CPTCRAT 47
zf-CCCH_4 pfam18044
CCCH-type zinc finger; This short zinc binding domain has the pattern of three cysteines and ...
 88-108 1.15e-03

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.


Pssm-ID: 465626  Cd Length: 22  Bit Score: 36.41  E-value: 1.15e-03
                          10        20
                  ....*....|....*....|.
gi 223468620   88 VVCKYFQRGYCIYGDRCRYEH 108
Cdd:pfam18044   1 RLCRYFQKGGCRYGDNCRFSH 21
zf-CCCH pfam00642
Zinc finger C-x8-C-x5-C-x3-H type (and similar);
88-110 2.24e-03

Zinc finger C-x8-C-x5-C-x3-H type (and similar);


Pssm-ID: 459885 [Multi-domain]  Cd Length: 27  Bit Score: 35.63  E-value: 2.24e-03
                          10        20
                  ....*....|....*....|....
gi 223468620   88 VVCKYFQR-GYCIYGDRCRYEHSK 110
Cdd:pfam00642   4 ELCRFFLRtGYCKYGDRCKFAHGQ 27
RING-HC_RNF170 cd16553
RING finger, HC subclass, found in RING finger protein 170 (RNF170) and similar proteins; ...
 278-343 2.72e-03

RING finger, HC subclass, found in RING finger protein 170 (RNF170) and similar proteins; RNF170, also known as putative LAG1-interacting protein, is an endoplasmic reticulum (ER) membrane-bound E3 ubiquitin-protein ligase that mediates ubiquitination-dependent degradation of type-I inositol 1,4,5-trisphosphate (IP3) receptors (ITPR1) via the endoplasmic-reticulum-associated protein degradation (ERAD) pathway. A point mutation (arginine to cysteine at position 199) in the RNF170 gene is linked with autosomal-dominant sensory ataxia (ADSA), a disease characterized by neurodegeneration in the posterior columns of the spinal cord. RNF170 contains a C3HC4-type RING-HC finger.


Pssm-ID: 438215 [Multi-domain]  Cd Length: 57  Bit Score: 36.11  E-value: 2.72e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 223468620 278 DMVCGICMevvyekanpSERRFGILSNCNHTYCLKCIRK-WRSAKQFESkiiKSCPECRITSNFVIP 343
Cdd:cd16553    1 DMECPICL---------QDARFPVETNCGHLFCGPCIITyWRHGSWLGA---VSCPVCRQTVTLLLP 55
RING-HC cd16449
HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type ...
 281-334 2.87e-03

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.


Pssm-ID: 438113 [Multi-domain]  Cd Length: 41  Bit Score: 35.54  E-value: 2.87e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 223468620 281 CGICMEvvyekanpsERRFGILSNCNHTYCLKCIRKWRSAKQfeskiiKSCPEC 334
Cdd:cd16449    3 CPICLE---------RLKDPVLLPCGHVFCRECIRRLLESGS------IKCPIC 41
mRING-HC-C3HC3D_PHRF1 cd16635
Modified RING finger, HC subclass (C3HC3D-type), found in PHD and RING finger ...
 281-337 5.10e-03

Modified RING finger, HC subclass (C3HC3D-type), found in PHD and RING finger domain-containing protein 1 (PHRF1) and similar proteins; PHRF1, also known as KIAA1542, or CTD-binding SR-like protein rA9, is a ubiquitin ligase which induces the ubiquitination of TGIF (TG-interacting factor) at lysine 130. It acts as a tumor suppressor that promotes the transforming growth factor (TGF)-beta cytostatic program through selective release of TGIF-driven promyelocytic leukemia protein (PML) inactivation. PHRF1 contains a plant homeodomain (PHD) finger and a modified C3HC3D-type RING-HC finger.


Pssm-ID: 438297 [Multi-domain]  Cd Length: 51  Bit Score: 35.09  E-value: 5.10e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 223468620 281 CGICMEVVYEKAnpserrFGILSNCNHTYCLKCIRKWrsakqfeSKIIKSCPECRIT 337
Cdd:cd16635    7 CPICLNTFRDQA------VGTPESCDHIFCLDCILEW-------SKNANTCPVDRIV 50
RING-HC_RNF8 cd16535
RING finger, HC subclass, found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is ...
 278-338 6.14e-03

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.


Pssm-ID: 438197 [Multi-domain]  Cd Length: 64  Bit Score: 35.45  E-value: 6.14e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 223468620 278 DMVCGICMEVVYEkanpserrfGILSNCNHTYCLKCIRKWRSAKqfeskiiKSCPECR--ITS 338
Cdd:cd16535    1 ELQCSICSELFIE---------AVTLNCSHSFCSYCITEWMKRK-------KECPICRkpITS 47
RING-HC_RBR_RNF19 cd16629
RING finger, HC subclass, found in the family of RING finger proteins RNF19A, RNF19B and ...
 295-334 7.22e-03

RING finger, HC subclass, found in the family of RING finger proteins RNF19A, RNF19B and similar proteins; The family includes RING finger protein RNF19A and RNF19B, both of which are transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligases. RNF19A, also known as double ring-finger protein (Dorfin) or p38, localizes to the ubiquitylated inclusions in Parkinson's disease (PD), dementia with Lewy bodies, multiple system atrophy, and amyotrophic lateral sclerosis (ALS). It interacts with Psmc3, a protein component of the 19S regulatory cap of the 26S proteasome, and further participates in the ubiquitin-proteasome system in acrosome biogenesis, spermatid head shaping, and development of the head-tail coupling apparatus and tail. It modulates the ubiquitination and degradation of calcium-sensing receptor (CaR), which may contribute to a general mechanism for CaR quality control during biosynthesis. Moreover, RNF19A can also ubiquitylate mutant superoxide dismutase 1 (SOD1), the causative gene of familial ALS. It may associate with endoplasmic reticulum-associated degradation (ERAD) pathway, which is related to the pathogenesis of neurodegenerative disorders, such as PD or Alzheimer's disease. RNF19B, also known as IBR domain-containing protein 3 or natural killer lytic-associated molecule (NKLAM), plays a role in controlling tumor dissemination and metastasis. It is involved in the cytolytic function of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). It interacts with ubiquitin conjugates UbcH7 and UbcH8, and ubiquitinates uridine kinase like-1 (URKL-1) protein, targeting it for degradation. Moreover, RNF19B is a novel component of macrophage phagosomes and plays a role in macrophage anti-bacterial activity. It functions as a novel modulator of macrophage inducible nitric oxide synthase (iNOS) expression. Both RNF19A and RNF19B contain an RBR domain followed by three TMs. The RBR domain was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction. This model corresponds to the RING domain, a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination.


Pssm-ID: 438291 [Multi-domain]  Cd Length: 56  Bit Score: 34.73  E-value: 7.22e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 223468620 295 SERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPEC 334
Cdd:cd16629   11 SPEFFPILLSCEHRSCRDCLRQYLTIEISESRVNISCPEC 50
RING-H2 cd16448
H2 subclass of RING (RING-H2) fingers and its variants; The RING finger is a specialized type ...
 281-335 7.37e-03

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.


Pssm-ID: 438112 [Multi-domain]  Cd Length: 43  Bit Score: 34.30  E-value: 7.37e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 223468620 281 CGICMEVVyekanpSERRFGILSNCNHTYCLKCIRKWRSAKQFeskiikSCPECR 335
Cdd:cd16448    1 CVICLEEF------EEGDVVRLLPCGHVFHLACILRWLESGNN------TCPLCR 43
RING-HC_ORTHRUS_rpt1 cd23138
first RING finger, HC subclass, found in Arabidopsis thaliana ORTHRUS and similar proteins; ...
 278-337 7.88e-03

first RING finger, HC subclass, found in Arabidopsis thaliana ORTHRUS and similar proteins; This subfamily includes Arabidopsis thaliana ORTHRUS 1-5. They are E3 ubiquitin-protein ligases that may participate in CpG methylation-dependent transcriptional regulation and/or epigenetic transcriptional silencing. ORTHRUS 1 mediates ubiquitination with the E2 ubiquitin-conjugating enzymes UBC11, UBC8 and UBC8 homologs (e.g. UBC10, UBC11, UBC28 and UBC29) but not with UBC27, UBC30, UBC32, UBC34 and UBC36. ORTHRUS 2 and 5 mediate ubiquitination with the E2 ubiquitin-conjugating enzyme UBC11. ORTHRUS 1 and 2 promote methylation-mediated gene silencing leading, for example, to early flowering. They can bind to CpG, CpNpG, and CpNpN DNA motifs, with a strong preference for methylated forms, and with highest affinity for CpG substrates. Members of this subfamily contain two typical C3HC4-type RING-HC fingers. This model corresponds to the first one.


Pssm-ID: 438500 [Multi-domain]  Cd Length: 48  Bit Score: 34.34  E-value: 7.88e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 223468620 278 DMVCGICMevvyekaNPSERrfGILSNCNHTYCLKCIRKWRSAKQfeskiiKSCPECRIT 337
Cdd:cd23138    2 ELNCSFCM-------QLPER--PVTTPCGHNFCLKCFQKWMGQGK------KTCGTCRSP 46
RING-HC_RNF213 cd16561
RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; ...
 281-335 9.95e-03

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.


Pssm-ID: 438223 [Multi-domain]  Cd Length: 50  Bit Score: 34.17  E-value: 9.95e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 223468620 281 CGICMEvvyekanpsERRFGILSNCNHTYCLKCIRKWRSAKQfeskiikSCPECR 335
Cdd:cd16561    5 CSICLE---------DLNDPVKLPCDHVFCEECIRQWLPGQM-------SCPLCR 43
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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