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 767947303 214 DMVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECRITS 274
Cdd:cd16730    1 DKVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECRITS 61

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 767947303   26 CKYFQRGYCIYGDRCRYEH 44
Cdd:pfam18345   1 CKFFLKGRCRYGDKCRFAH 19

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 767947303 214 DMVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECRITS 274
Cdd:cd16730    1 DKVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECRITS 61

N1R/p28-like protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767947303 211 RSKDMVCGICMEVVYEKaNPSERRFGILSNCNHTYCLKCIRKWRSAKqfeskiiKSCPECRITSNFVIPSEYWVEE 286
Cdd:PHA02929 171 RSKDKECAICMEKVYDK-EIKNMYFGILSNCNHVFCIECIDIWKKEK-------NTCPVCRTPFISVIKSRFFTKG 238

zinc finger;

                           10        20
                   ....*....|....*....|...
gi 767947303    24 VVCKYFQRGYCIYGDRCRYEHSK 46
Cdd:smart00356   5 ELCKFFKRGYCPRGDRCKFAHPL 27

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767947303 141 TAVETKKQLC-PYAAVGECRYGENCVYLHGDSCDMCGLQVLHPMDAAQRSQHIKScieahEKDMELSFavqrskdmVCGI 219
Cdd:COG5152  135 EVIDTQPDVCkDYKETGYCGYGDSCKFLHDRSDFKTGWKLNQEWNAEYEEAPVIS-----GPGEKIPF--------LCGI 201

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767947303 220 CMEVVYEKanpserrfgILSNCNHTYCLKC-IRKWR 254
Cdd:COG5152  202 CKKDYESP---------VVTECGHSFCSLCaIRKYQ 228

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 767947303 214 DMVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECRITS 274
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 767947303 214 DMVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQFESKIIKSCPECRITS 274
Cdd:cd16732    1 DVACGICMDKVYEKAHAKERVFGILPNCNHAFCVGCIKKWRKSKDFQNEVIKACPQCRVKS 61

p28-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767947303 157 ECRYGENCVYLHGDSCDMCGLQVLHPMDAAQRSQHIKSCIEahEKDMELSFAvqrskdmVCGICMEVVYEKaNPSERRFG 236
Cdd:PHA03096 130 NCYKGKYCEYLHGDICDICEKYLLHPTDIKQRYNEQKTCLS--YQLRLLLSK-------ICGICLENIKAK-YIIKKYYG 199

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767947303 237 ILSNCNHTYCLKCIRKWRSAKQfESKIIKSCPECRITSNFV----------IPSEYWVEEKEEKQKLILKYKEAMSNKAC 306
Cdd:PHA03096 200 ILSEIKHEFNIFCIKIWMTESL-YKETEPENRRLNTVIVFIekinedlknnIPSRYWIDDKYDKNLLSFRYKKMHIRKVC 278

zinc finger-like protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767947303 212 SKDMVCGICMEVVYEKANPSERRFGILSNCNHTYCLKCIRKWRSAKQfESKIIKSCPECRITSNFVIPSEYW 283
Cdd:PHA02926 168 SKEKECGICYEVVYSKRLENDRYFGLLDSCNHIFCITCINIWHRTRR-ETGASDNCPICRTRFRNITMSKFY 238

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 767947303 214 DMVCGICMEVVyekanpsERRFGILSNCNHTYCLKCIRKWrsakqfeSKIIKSCPECR 271
Cdd:cd16574    1 DSSCPICLDRF-------ENEKAFLDGCFHAFCFTCILEW-------SKVKNECPLCK 44

zinc finger;

                           10        20
                   ....*....|....*....|...
gi 767947303    24 VVCKYFQRGYCIYGDRCRYEHSK 46
Cdd:smart00356   5 ELCKFFKRGYCPRGDRCKFAHPL 27

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 767947303 216 VCGICMEvvyekanpseRRFGILSNCNHTYCLKCIRKWRSAKqfeskiiKSCPECR 271
Cdd:cd16545    2 ECCICMD----------RKADLILPCAHSYCQKCIDKWSDRH-------RTCPICR 40

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767947303 214 DMVCGICMEVVYE--KANPserrfgilsnCNHTYCLKCIRKWRSAKQFEskiiksCPECRIT 273
Cdd:cd16503    2 NLTCSICQDLLHDcvSLQP----------CMHNFCAACYSDWMERSNTE------CPTCRAT 47

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767947303 214 DMVCGICMevvyekanpSERRFGILSNCNHTYCLKCIRK-WRSAKQFESkiiKSCPECRITSNFVIP 279
Cdd:cd16553    1 DMECPICL---------QDARFPVETNCGHLFCGPCIITyWRHGSWLGA---VSCPVCRQTVTLLLP 55

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 767947303 217 CGICMEvvyekanpsERRFGILSNCNHTYCLKCIRKWRSAKQfeskiiKSCPEC 270
Cdd:cd16449    3 CPICLE---------RLKDPVLLPCGHVFCRECIRRLLESGS------IKCPIC 41

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767947303 214 DMVCGICMEVVYEkanpserrfGILSNCNHTYCLKCIRKWRSAKqfeskiiKSCPECR--ITS 274
Cdd:cd16535    1 ELQCSICSELFIE---------AVTLNCSHSFCSYCITEWMKRK-------KECPICRkpITS 47

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767947303 214 DMVCGICMevvyekaNPSERrfGILSNCNHTYCLKCIRKWRSAKQfeskiiKSCPECRIT 273
Cdd:cd23138    2 ELNCSFCM-------QLPER--PVTTPCGHNFCLKCFQKWMGQGK------KTCGTCRSP 46

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 767947303 217 CGICMEvvyekanpsERRFGILSNCNHTYCLKCIRKWRSAKQfeskiikSCPECR 271
Cdd:cd16561    5 CSICLE---------DLNDPVKLPCDHVFCEECIRQWLPGQM-------SCPLCR 43

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 767947303  217 CGICMEVVYEKANPSErrfgilsnCNHTYCLKCIRKWRSAKQFeskiikSCPEC 270
Cdd:pfam00097   1 CPICLEEPKDPVTLLP--------CGHLFCSKCIRSWLESGNV------TCPLC 40