first RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, proteins with double RING-H2 fingers may act as scaffolds for binding several proteins that function in the same pathway. This model corresponds to the first RING-H2 finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 109069031 126 PCPICKEEFELRPQVLLSCSHVFHRACLQAFEKFTNKKTCPLCRKNQYQ 174
Cdd:cd16677    1 PCPICLEDFGLQQQVLLSCSHVFHRACLESFERFSGKKTCPMCRKEQYQ 49

IQ (isoleucine-glutamine) motif containing D (IQCD); IQCD, also called dynein regulatory complex protein 10 (DRC10), belongs to the IQ motif-containing protein family which contains a C-terminal conserved IQ motif domain and two coiled-coil domains. The IQ motif ([ILV]QxxxRxxxx[RK]), where x stands for any amino-acid residue, interacts with calmodulin (CaM) in a calcium-independent manner and is present in proteins with a wide diversity of biological functions. The IQCD protein was found to primarily accumulate in the acrosome area of round and elongating spermatids of the testis during late stage of spermiogenesis and was then localized to the acrosome and tail regions of mature spermatozoa. The expression of IQCD follows the trajectory of acrosome development during spermatogenesis. IQCD is associated with neuroblastoma and neurodegenerative diseases, and is reported to interact with the nuclear retinoid X receptor in the presence of 9-cis-retinoic acid, thereby activating the transcriptional activity of the receptor.

                         10
                 ....*....|....*....
gi 109069031 186 RIKCVTRIQAYWRGYVVRK 204
Cdd:cd23767    8 MNRAATLIQALWRGYKVRK 26

first RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, proteins with double RING-H2 fingers may act as scaffolds for binding several proteins that function in the same pathway. This model corresponds to the first RING-H2 finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 109069031 126 PCPICKEEFELRPQVLLSCSHVFHRACLQAFEKFTNKKTCPLCRKNQYQ 174
Cdd:cd16677    1 PCPICLEDFGLQQQVLLSCSHVFHRACLESFERFSGKKTCPMCRKEQYQ 49

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 109069031  127 CPICKEEFELRPQVL-LSCSHVFHRACLQAFekFTNKKTCPLCR 169
Cdd:pfam13639   3 CPICLEEFEEGDKVVvLPCGHHFHRECLDKW--LRSSNTCPLCR 44

IQ (isoleucine-glutamine) motif containing D (IQCD); IQCD, also called dynein regulatory complex protein 10 (DRC10), belongs to the IQ motif-containing protein family which contains a C-terminal conserved IQ motif domain and two coiled-coil domains. The IQ motif ([ILV]QxxxRxxxx[RK]), where x stands for any amino-acid residue, interacts with calmodulin (CaM) in a calcium-independent manner and is present in proteins with a wide diversity of biological functions. The IQCD protein was found to primarily accumulate in the acrosome area of round and elongating spermatids of the testis during late stage of spermiogenesis and was then localized to the acrosome and tail regions of mature spermatozoa. The expression of IQCD follows the trajectory of acrosome development during spermatogenesis. IQCD is associated with neuroblastoma and neurodegenerative diseases, and is reported to interact with the nuclear retinoid X receptor in the presence of 9-cis-retinoic acid, thereby activating the transcriptional activity of the receptor.

                         10
                 ....*....|....*....
gi 109069031 186 RIKCVTRIQAYWRGYVVRK 204
Cdd:cd23767    8 MNRAATLIQALWRGYKVRK 26

IQ calmodulin-binding motif; Calmodulin-binding motif.

                          10        20
                  ....*....|....*....|
gi 109069031  188 KCVTRIQAYWRGYVVRKWYR 207
Cdd:pfam00612   2 KAAIKIQAAWRGYLARKRYK 21

Calmodulin-binding motif; Short calmodulin-binding motif containing conserved Ile and Gln residues.

                           10        20
                   ....*....|....*....|..
gi 109069031   186 RIKCVTRIQAYWRGYVVRKWYR 207
Cdd:smart00015   2 LTRAAIIIQAAWRGYLARKRYK 23

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109069031 257 INRSVLQQFEEKYGHEMTEEEWEKIQVQALRRETH--ECSICLAPLSPagGQRVGAgqrsretalLSCSHVFHHACllaL 334
Cdd:COG5540  288 NFDVGFYSSSEAIPTTTTKGSLKPLSIERAVEADKgvECAICMSNFIK--NDRLRV---------LPCDHRFHVGC---V 353

                         90
                 ....*....|....*....
gi 109069031 335 EEFSVGDRppfHACPLCRS 353
Cdd:COG5540  354 DKWLLGYS---NKCPVCRT 369

first RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, proteins with double RING-H2 fingers may act as scaffolds for binding several proteins that function in the same pathway. This model corresponds to the first RING-H2 finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 109069031 126 PCPICKEEFELRPQVLLSCSHVFHRACLQAFEKFTNKKTCPLCRKNQYQ 174
Cdd:cd16677    1 PCPICLEDFGLQQQVLLSCSHVFHRACLESFERFSGKKTCPMCRKEQYQ 49

RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, proteins with double RING-H2 fingers may act as scaffolds for binding several proteins that function in the same pathway.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 109069031 126 PCPICKEEFELRPQVLLSCSHVFHRACLQAFEKFTNKK--TCPLCR 169
Cdd:cd16471    1 ECPICLCAFKGRKCTLLSCSHVFHEACLSAFEKFIESKnqKCPLCR 46

second RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, proteins with double RING-H2 fingers may act as scaffolds for binding several proteins that function in the same pathway. This model corresponds to the second RING-H2 finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 109069031 127 CPIC------------KEEFELRPQVLLSCSHVFHRACLQAFEKFT--NKKTCPLCR 169
Cdd:cd16678    2 CPICltplqssgdssdAKRVSSRPTVLLSCSHVFHATCLEAFEEFSvgEELVCPVCR 58

RING finger, H2 subclass, found in the PA-TM-RING ubiquitin ligase family; The PA-TM-RING family represents a group of transmembrane-type E3 ubiquitin ligases, which has been characterized by an N-terminal transient signal peptide, a PA (protease-associated) domain, a TM (transmembrane) domain, as well as a C-terminal C3H2C3-type RING-H2 finger domain. It includes RNF13, RNF167, ZNRF4 (zinc and RING finger 4), GRAIL (gene related to anergy in lymphocytes)/RNF128, RNF130, RNF133, RNF148, RNF149 and RNF150 (which are more closely related), as well as RNF43 and ZNRF3, which have substantially longer C-terminal tail extensions compared with the others. PA-TM-RING proteins are expressed at low levels in all mammalian tissues and species, but they are not present in yeast. They play a common regulatory role in intracellular trafficking/sorting, suggesting that abrogation of their function may result in dysregulation of cellular signaling events in cancer.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 109069031 126 PCPICKEEFELRPQV-LLSCSHVFHRACLQAFekFTNKKTCPLCR 169
Cdd:cd16454    1 TCAICLEEFKEGEKVrVLPCNHLFHKDCIDPW--LEQHNTCPLCR 43

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 109069031  127 CPICKEEFELRPQVL-LSCSHVFHRACLQAFekFTNKKTCPLCR 169
Cdd:pfam13639   3 CPICLEEFEEGDKVVvLPCGHHFHRECLDKW--LRSSNTCPLCR 44

RING finger, H2 subclass, found in RING finger protein 115 (RNF115) and similar proteins; RNF115, also known as Rab7-interacting ring finger protein (Rabring 7), or zinc finger protein 364 (ZNF364), or breast cancer-associated gene 2 (BCA2), is an E3 ubiquitin-protein ligase that is an endogenous inhibitor of adenosine monophosphate-activated protein kinase (AMPK) activation and its inhibition increases the efficacy of metformin in breast cancer cells. It also functions as a co-factor in the restriction imposed by tetherin on HIV-1, and targets HIV-1 Gag for lysosomal degradation, impairing virus assembly and release, in a tetherin-independent manner. Moreover, RNF115 is a Rab7-binding protein that stimulates c-Myc degradation through mono-ubiquitination of MM-1. It also plays crucial roles as a Rab7 target protein in vesicle traffic to late endosome/lysosome and lysosome biogenesis. Furthermore, RNF115 and the related protein, RNF126 associate with the epidermal growth factor receptor (EGFR) and promote ubiquitylation of EGFR, suggesting they play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors. RNF115 contains an N-terminal BCA2 Zinc-finger domain (BZF), the AKT-phosphorylation sites, and the C-terminal C3H2C3-type RING-H2 finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 109069031 127 CPICKEEFELRPQV-LLSCSHVFHRACLQAFEKFTNkkTCPLCRKN 171
Cdd:cd16800    3 CPVCKEDYTVGEQVrQLPCNHFFHSDCIVPWLELHD--TCPVCRKS 46

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
                   ....*....|....*....|....*....|....*....|..
gi 109069031   127 CPICKEEFELRPqVLLSCSHVFHRACLQAFEKfTNKKTCPLC 168
Cdd:smart00184   1 CPICLEEYLKDP-VILPCGHTFCRSCIRKWLE-SGNNTCPIC 40

RING finger, H2 subclass, found in RING finger proteins RNF126, RNF115, and similar proteins; This subfamily includes RING finger proteins RNF126, RNF115, and similar proteins. RNF126 is a Bag6-dependent E3 ubiquitin ligase that is involved in the mislocalized protein (MLP) pathway of quality control. It regulates the retrograde sorting of the cation-independent mannose 6-phosphate receptor (CI-MPR). RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation, and could be a novel therapeutic target in breast and prostate cancers. It is also able to ubiquitylate cytidine deaminase (AID), a poorly soluble protein that is essential for antibody diversification. RNF115, also known as Rab7-interacting ring finger protein (Rabring 7), or zinc finger protein 364 (ZNF364), or breast cancer-associated gene 2 (BCA2), is an E3 ubiquitin-protein ligase that is an endogenous inhibitor of adenosine monophosphate-activated protein kinase (AMPK) activation; this inhibition increases the efficacy of metformin in breast cancer cells. It also functions as a cofactor in the restriction imposed by tetherin on HIV-1, and targets HIV-1 Gag for lysosomal degradation, impairing virus assembly and release, in a tetherin-independent manner. Moreover, RNF115 is a Rab7-binding protein that stimulates c-Myc degradation through mono-ubiquitination of MM-1. It also plays crucial roles as a Rab7 target protein in vesicle traffic to late endosome/lysosome and lysosome biogenesis. RNF115 and RNF126 associate with the epidermal growth factor receptor (EGFR) and promote ubiquitylation of EGFR, suggesting they play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors. Both of them contain an N-terminal BCA2 Zinc-finger domain (BZF), AKT-phosphorylation sites, and a C-terminal C3H2C3-type RING-H2 finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 109069031 126 PCPICKEEFELRPQVL-LSCSHVFHRACLQAFEKFTNkkTCPLCR 169
Cdd:cd16667    1 ECAVCKEDFEVGEEVRqLPCKHLFHPDCIVPWLELHN--SCPVCR 43

RING finger, H2 subclass, found in DAZ (deleted in azoospermia)-interacting protein 3 (DZIP3) and similar proteins; DZIP3, also known as RNA-binding ubiquitin ligase of 138 kDa (RUL138) or 2A-HUB protein, is an RNA-binding E3 ubiquitin-protein ligase that interacts with coactivator-associated arginine methyltransferase 1 (CARM1) and acts as a transcriptional coactivator of estrogen receptor (ER) alpha. It is also a histone H2A ubiquitin ligase that catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatorial component of the repression machinery required for repressing a specific chemokine gene expression program, critically modulating migratory responses to Toll-like receptors (TLR) activation. DZIP3 contains a C3H2C3-type RING-H2 finger at the C-terminus.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 109069031 125 QPCPICKEEFELRPQVL-LSCSHVFHRACLQAFekFTNKKTCPLCR 169
Cdd:cd16460    1 TPCVICHEAFSDGDRLLvLPCAHKFHTQCIGPW--LDGQQTCPTCR 44

RING finger, HC subclass, found in tripartite motif-containing protein 69 (TRIM69) and similar proteins; TRIM69, also known as RFP-like domain-containing protein trimless or RING finger protein 36 (RNF36), is a testis E3 ubiquitin-protein ligase that plays a specific role in apoptosis and may also play an important role in germ cell homeostasis during spermatogenesis. TRIM69 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 109069031 127 CPICKEEFelRPQVLLSCSHVFHRACLQAF-EKFTNKKTCPLCRK 170
Cdd:cd16611    7 CPLCLDFF--RDPVMLSCGHNFCQSCITGFwELQAEDTTCPECRE 49

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 109069031 293 CSICLAPLSPaggqrvgagqrSRETALLSCSHVFHHACLLALEEFSvgdrppFHACPLCR 352
Cdd:cd16448    1 CVICLEEFEE-----------GDVVRLLPCGHVFHLACILRWLESG------NNTCPLCR 43

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 2(RNFT2); RNFT2, also known as transmembrane protein 118 (TMEM118), is a multi-pass membrane protein containing a C3HC4-type RING-HC finger. Its biological role remains unclear.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 109069031 127 CPICKEEFelRPQVLLSCSHVFHRACLQAFekFTNKKTCPLCRKNQYQT-RVIHDG 181
Cdd:cd16742   16 CAICQAEF--REPLILICQHVFCEECLCLW--FDRERTCPLCRSVVVETlRCWKDG 67

RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 109069031  127 CPICKEEFElRPqvLLSCSHVFHRACLQAFEKFTNKK-TCP 166
Cdd:pfam13445   1 CPICLELFT-DP--VLPCGHTFCRECLEEMSQKKGGKfKCP 38

RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins; TTC3, also known as protein DCRR1, TPR repeat protein D, TPR repeat protein 3, or RING finger protein 105 (RNF105), is an E3 ubiquitin-protein ligase encoded by a gene within the Down syndrome (DS) critical region on chromosome 21. It affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways. It inhibits the neuronal-like differentiation of pheocromocytoma cells by activating RhoA and by binding to Citron proteins. TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. It contains four N-terminal TPR motifs, a potential coiled-coil region and a Citron binding region in the central part, and a C-terminal C3H2C2-type RING-H2 finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 109069031 126 PCPICKEEFELRPQVLLSCSHVFHRACLQAFEKftNKKTCPLCRK 170
Cdd:cd16481    1 PCIICHDDLKPDQLAKLECGHIFHKECIKQWLK--EQSTCPTCRV 43

RING finger, H2 subclass, found in RING finger protein 103 (RNF103) and similar proteins; RNF103, also known as KF-1 or zinc finger protein 103 homolog (Zfp-103), is an endoplasmic reticulum (ER)-resident E3 ubiquitin-protein ligase that is widely expressed in many different organs, including brain, heart, kidney, spleen, and lung. It is involved in the ER-associated degradation (ERAD) pathway by interacting with components of the ERAD pathway, including Derlin-1 and VCP. RNF103 contains several hydrophobic regions at its N-terminal and middle regions, as well as a C-terminal C3H2C3-type RING-H2 finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 109069031 127 CPICKEEFELRPQV-LLSCSHVFHRACLQAFEKFTNkKTCPLCRKNQYQ 174
Cdd:cd16473    7 CAICLENYQNGDLLrGLPCGHVFHQNCIDVWLERDN-HCCPVCRWPVYK 54

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
                 ....*....|....*....|....*....|....*....|....*
gi 109069031 125 QPCPICKEEFElRPqVLLSCSHVFHRACLQAFekFTNKKTCPLCR 169
Cdd:cd16561    3 QECSICLEDLN-DP-VKLPCDHVFCEECIRQW--LPGQMSCPLCR 43

RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; RNF138, also known as Nemo-like kinase-associated RING finger protein (NARF) or NLK-associated RING finger protein, is an E3 ubiquitin-protein ligase that plays an important role in glioma cell proliferation, apoptosis, and cell cycle. It specifically cooperates with the E2 conjugating enzyme E2-25K (Hip-2/UbcH1), regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF), and further suppresses Wnt-beta-catenin signaling. RNF138, together with three closely related proteins: RNF114, RNF125 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 109069031 127 CPICKEEFElRPQVLLSCSHVFHRACLQAFEKFTNKKtCPLCRKN 171
Cdd:cd16544    5 CPVCQEVLK-DPVELPPCRHIFCKACILLALRSSGAR-CPLCRGP 47

RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 109069031 109 EWEKVKQRSLLQGDSVQPCPICKEEFELRpqVLLSCSHVFHRACLQAFekFTNKKTCPLCRKNQYQTR 176
Cdd:COG5432   10 DWNQTKIPSLKGLDSMLRCRICDCRISIP--CETTCGHTFCSLCIRRH--LGTQPFCPVCREDPCESR 73

RING finger, H2 subclass, found in Arabidopsis thaliana protein SUGAR INSENSITIVE 3 (SIS3) and similar proteins; SIS3 is an E3 ubiquitin-protein ligase that acts as a positive regulator of sugar signaling during early seedling development. SIS3 contains a C3H2C3-type RING-H2 finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 109069031 127 CPICKEEFELRPQV-LLSCSHVFHRACLQAFekFTNKKTCPLCR 169
Cdd:cd23118    3 CTICLEDFEDGEKLrVLPCQHQFHSECVDQW--LRRNPKCPVCR 44

RING finger, H2 subclass, found in RING finger protein 11 (RNF11) and similar proteins; RNF11 is an E3 ubiquitin-protein ligase that acts both as an adaptor and a modulator of itch-mediated control of ubiquitination events underlying membrane traffic. It acts downstream of an enzymatic cascade for the ubiquitination of specific substrates. It is also a molecular adaptor of homologous to E6-associated protein C-terminus (HECT)-type ligases. RNF11 has been implicated in the regulation of several signaling pathways. It enhances transforming growth factor receptor (TGFR) signaling by both abrogating Smurf2-mediated receptor ubiquitination and by promoting the Smurf2-mediated degradation of AMSH (associated molecule with the SH3 domain of STAM), a de-ubiquitinating enzyme that enhances TGF-beta signaling and epidermal growth factor receptor (EGFR) endosomal recycling. It also acts directly on Smad4 to enhance Smad4 function, and plays a role in prolonged TGF-beta signaling. RNF11 also functions as a critical component of the A20 ubiquitin-editing protein complex that negatively regulates tumor necrosis factor (TNF)-mediated nuclear factor (NF)-kappaB activation. It interacts with Smad anchor for receptor activation (SARA) and the endosomal sorting complex required for transport (ESCRT)-0 complex, thus participating in the regulation of lysosomal degradation of EGFR. RNF11 acts as a novel GGA cargo actively participating in regulating the ubiquitination of the GGA protein family. RNF11 functions together with TAX1BP1 to target TANK-binding kinase 1 (TBK1)/IkappaB kinase IKKi, and further restricts antiviral signaling and type I interferon (IFN)-beta production. RNF11 contains an N-terminal PPPY motif that binds WW domain-containing proteins such as AIP4/itch, Nedd4 and Smurf1/2 (SMAD-specific E3 ubiquitin-protein ligase 1/2), and a C-terminal C3H2C3-type RING-H2 finger that functions as a scaffold for the coordinated transfer of ubiquitin to substrate proteins together with the E2 enzymes UbcH527 and Ubc13.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 109069031 127 CPICKEEFELRPQV-LLSCSHVFHRACLQAFekFTNKKTCPLC 168
Cdd:cd16468    2 CVICMADFVVGDPIrYLPCMHIYHVDCIDDW--LMRSFTCPSC 42

zinc-RING finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 109069031  127 CPICKEEFEL-RPQVLLSCSHVFHRACLQafeKFTNKKTCPLCRK 170
Cdd:pfam14634   2 CNKCFKELSKtRPFYLTSCGHIFCEECLT---RLLQERQCPICKK 43

RING finger, H2 subclass, found in RING finger proteins RNF24, RNF122, and similar proteins; This subfamily includes RNF24, RNF122, and similar proteins. RNF24 is an intrinsic membrane protein localized in the Golgi apparatus. It specifically interacts with the ankyrin-repeats domains (ARDs) of TRPC1, -3, -4, -5, -6, and -7, and affects TRPC intracellular trafficking without affecting their activity. RNF122 is a RING finger protein associated with HEK 293T cell viability. It is localized to the endoplasmic reticulum (ER) and the Golgi apparatus, and overexpressed in anaplastic thyroid cancer cells. RNF122 functions as an E3 ubiquitin ligase that can ubiquitinate itself and undergo degradation through its RING finger in a proteasome-dependent manner. Both RNF24 and RNF122 contain an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 109069031 127 CPICKEEFELRPQV-LLSCSHVFHRACLQAFekFTNKKTCPLCRK 170
Cdd:cd16469    3 CAVCLEEFKLKEELgVCPCGHAFHTKCLKKW--LEVRNSCPICKS 45

RING-H2 zinc finger domain; There are 8 cysteine/ histidine residues which are proposed to be the conserved residues involved in zinc binding. The protein, of which this domain is the conserved region, participates in diverse functions relevant to chromosome metabolism and cell cycle control.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 109069031  125 QPCPICKEEFELR-PQVLLSCSHVFHRACLQAFEKFtnKKTCPLCR 169
Cdd:pfam12678  12 EPCPECQAPGDDEcPVVWGECGHAFHLHCISRWLKT--NNTCPLCR 55

RING finger, HC subclass, found in tripartite motif-containing proteins, TRIM7, TRIM11 and TRIM27, and similar proteins; TRIM7, TRIM11 and TRIM27, closely related tripartite motif-containing proteins, belong to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM7, also known as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90), is an E3 ubiquitin-protein ligase that mediates c-Jun/AP-1 activation by Ras signalling. Its phosphorylation and activation by MSK1 in response to direct activation by the Ras-Raf-MEK-ERK pathway can stimulate TRIM7 E3 ubiquitin ligase activity in mediating Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilization. Moreover, TRIM7 binds and activates glycogenin, the self-glucosylating initiator of glycogen biosynthesis. TRIM11, also known as protein BIA1, or RING finger protein 92 (RNF92), is an E3 ubiquitin-protein ligase involved in the development of the central nervous system. It is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 acts as a potential therapeutic target for congenital central hypoventilation syndrome (CCHS) by mediating the degradation of CCHS-associated polyalanine-expanded Phox2b. TRIM11 modulates the function of neurogenic transcription factor Pax6 through the ubiquitin-proteosome system, and thus plays an essential role for Pax6-dependent neurogenesis. It also binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105), humanin, a neuroprotective peptide against Alzheimer's disease-relevant insults, and further regulates ARC105 function in transforming growth factor beta (TGFbeta) signaling. Moreover, TRIM11 negatively regulates retinoic acid-inducible gene-I (RIG-I)-mediated interferon-beta (IFNbeta) production and antiviral activity by targeting TANK-binding kinase-1 (TBK1). It may contribute to the endogenous restriction of retroviruses in cells. It enhances N-tropic murine leukemia virus (N-MLV) entry by interfering with Ref1 restriction. It also suppresses the early steps of human immunodeficiency virus HIV-1 transduction, resulting in decreased reverse transcripts. TRIM27, also known as RING finger protein 76 (RNF76), RET finger protein (RFP), or zinc finger protein RFP, is a nuclear E3 ubiquitin-protein ligase that is highly expressed in testis and in various tumor cell lines. Expression of TRIM27 is associated with prognosis of colon and endometrial cancers. TRIM27 was first identified as a fusion partner of the RET receptor tyrosine kinase. It functions as a transcriptional repressor and associates with several proteins involved in transcriptional activity, such as enhancer of polycomb 1 (Epc1), a member of the Polycomb group proteins, and Mi-2beta, a main component of the nucleosome remodeling and deacetylase (NuRD) complex, and the cell cycle regulator retinoblastoma protein (RB1). It also interacts with HDAC1, leading to downregulation of thioredoxin binding protein 2 (TBP-2), which inhibits the function of thioredoxin. Moreover, TRIM27 mediates Pax7-induced ubiquitination of MyoD in skeletal muscle atrophy. In addition, it inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. TRIM27 promotes a non-canonical polyubiquitination of PTEN, a lipid phosphatase that catalyzes PtdIns(3,4,5)P3 (PIP3) to PtdIns(4,5)P2 (PIP2). It is an IKKepsilon-interacting protein that regulates IkappaB kinase (IKK) function and negatively regulates signaling involved in the antiviral response and inflammation. TRIM27 also forms a protein complex with MBD4 or MBD2 or MBD3, and thus plays an important role in the enhancement of transcriptional repression through MBD proteins in tumorigenesis, spermatogenesis, and embryogenesis. It is a component of an estrogen receptor 1 (ESR1) regulatory complex that is involved in estrogen receptor-mediated transcription in MCF-7 cells.

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                 ....*....|....*....|....*....|....*....|....*.
gi 109069031 127 CPICKEEFelRPQVLLSCSHVFHRACL-QAFEKFTNKKTCPLCRKN 171
Cdd:cd16594    8 CPICLDYF--TDPVTLDCGHSFCRACIaRCWEEPETSASCPQCRET 51

RING finger, H2 subclass, found in RING finger protein 13 (RNF13) and similar proteins; RNF13 is a widely expressed membrane-associated E3 ubiquitin-protein ligase that is functionally significant in the regulation of cancer development, muscle cell growth, and neuronal development. Its expression is developmentally regulated during myogenesis and is upregulated in various tumors. RNF13 negatively regulates cell proliferation through its E3 ligase activity. It functions as an important regulator of inositol-requiring transmembrane kinase/endonuclease IRE1alpha, mediating endoplasmic reticulum (ER) stress-induced apoptosis through the activation of the IRE1alpha-TRAF2-JNK signaling pathway. Moreover, RNF13 is involved in the regulation of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) complex via the ubiquitination of snapin, a SNAP25-interacting protein, which thereby controls synaptic function. In addition, RNF13 participates in regulating the function of satellite cells by modulating cytokine composition. RNF13 is evolutionarily conserved among many metazoans and contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 109069031 120 QGDSVQPCPICKEEFELRPQV-LLSCSHVFHRACLQAFEKFTnKKTCPLCRK 170
Cdd:cd16796    4 KGDEYDVCAICLDEYEEGDKLrILPCSHAYHCKCVDPWLTKT-KKTCPVCKQ 54

RING finger, H2 subclass, found in TRAF-interacting protein (TRAIP) and similar proteins; TRAIP, also known as RING finger protein 206 (RNF206) or TRIP, is a ubiquitously expressed nucleolar E3 ubiquitin ligase important for cellular proliferation and differentiation. It is found near mitotic chromosomes and functions as a regulator of the spindle assembly checkpoint. TRAIP interacts with tumor necrosis factor (TNF)-receptor-associated factor (TRAF) proteins and inhibits TNF-alpha-mediated nuclear factor (NF)-kappaB activation. It also interacts with two tumor suppressors CYLD and spleen tyrosine kinase (Syk), and DNA polymerase eta, which facilitates translesional synthesis after DNA damage. TRAIP contains an N-terminal C3H2C2-type RING-H2 finger and an extended coiled-coil domain.

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                 ....*....|....*....|....*....|....*....|....
gi 109069031 127 CPICKEEFELRPQVL-LSCSHVFHRACLqaFEKFTNKKTCPLCR 169
Cdd:cd16480    2 CTICSDFFDNSRDVAaIHCGHTFHYDCL--LQWFDTSRTCPQCR 43

RING finger, H2 subclass, found in RING finger proteins RNF43, ZNRF3, and similar proteins; RNF43 and ZNRF3 (also known as RNF203) are transmembrane E3 ubiquitin-protein ligases that belong to the PA-TM-RING ubiquitin ligase family, characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger followed by a long C-terminal region. Both RNF43 and RNF203 function as tumor suppressors involved in the regulation of Wnt/beta-catenin signaling. They negatively regulate Wnt signaling by interacting with complexes of frizzled (FZD) receptors and low-density lipoprotein receptor-related protein (LRP) 5/6, which leads to ubiquitination of FZD and endocytosis of the Wnt receptor. Dishevelled (DVL), a positive Wnt regulator, is required for ZNRF3/RNF43-mediated ubiquitination and degradation of FZD. They also associate with R-spondin 1 (RSPO1). This interaction may block FZD ubiquitination and enhances Wnt signaling.

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                 ....*....|....*....|....*....|....*....|....*....
gi 109069031 127 CPICKEEF----ELRpqvLLSCSHVFHRACLQAFekFTNKKTCPLCRKN 171
Cdd:cd16666    2 CAICLEEYeegqELR---VLPCQHEFHRKCVDPW--LLQNHTCPLCLFN 45

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.

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                  ....*....|....*....|....*....|....*....|..
gi 109069031  127 CPICKEEFElRPQVLLSCSHVFHRACLQAFEKfTNKKTCPLC 168
Cdd:pfam00097   1 CPICLEEPK-DPVTLLPCGHLFCSKCIRSWLE-SGNVTCPLC 40

RING finger (Really Interesting New Gene) domain and U-box domain superfamily; 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). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are 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 enable efficient transfer of ubiquitin from E2 to the substrates.

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gi 109069031 127 CPICKEEF-ELRPQVLLSCSHVFHRACLQAFeKFTNKKTCPLC 168
Cdd:cd00162    1 CPICREEMnDRRPVVLLSCGHTFSRSAIARW-LEGSKQKCPFC 42

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Deltex3 (DTX3), Deltex-3-like (DTX3L) and similar proteins; This subfamily contains Deltex3 (DTX3) and Deltex-3-like (DTX3L), both of which are E3 ubiquitin-protein ligases belonging to the Deltex (DTX) family. DTX3, also known as RING finger protein 154 (RNF154), has a biological function that remains unclear. DTX3L, also known as B-lymphoma- and BAL-associated protein (BBAP) or Rhysin-2 (Rhysin2), regulates endosomal sorting of the G protein-coupled receptor CXCR4 from endosomes to lysosomes. It also regulates subcellular localization of its partner protein, B aggressive lymphoma (BAL), by a dynamic nucleocytoplasmic trafficking mechanism. In contrast to other DTXs, both DTX3 and DTX3L contain a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain. DTX3L can associate with DTX1 through its unique N termini and further enhance self-ubiquitination.

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                 ....*....|....*....|....*....|....*....|...
gi 109069031 127 CPICKEEFElRPQVLLSCSHVFHRACLQAfeKFTNKKTCPLCR 169
Cdd:cd16506    3 CPICLDEIQ-NKKTLEKCKHSFCEDCIDR--ALQVKPVCPVCG 42

RING finger, H2 subclass, found in RING finger protein 103 (RNF103) and similar proteins; RNF103, also known as KF-1 or zinc finger protein 103 homolog (Zfp-103), is an endoplasmic reticulum (ER)-resident E3 ubiquitin-protein ligase that is widely expressed in many different organs, including brain, heart, kidney, spleen, and lung. It is involved in the ER-associated degradation (ERAD) pathway by interacting with components of the ERAD pathway, including Derlin-1 and VCP. RNF103 contains several hydrophobic regions at its N-terminal and middle regions, as well as a C-terminal C3H2C3-type RING-H2 finger.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 109069031 292 ECSICLAplSPAGGQRVgagqrsretALLSCSHVFHHACL-LALEEfsvgdrpPFHACPLCR 352
Cdd:cd16473    6 ECAICLE--NYQNGDLL---------RGLPCGHVFHQNCIdVWLER-------DNHCCPVCR 49

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).

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                 ....*....|....*....|....*....|....*....|...
gi 109069031 127 CPICKEEFELRPQVLLSCSHVFHRACLQAFEKFTNkkTCPLCR 169
Cdd:cd16574    4 CPICLDRFENEKAFLDGCFHAFCFTCILEWSKVKN--ECPLCK 44

Anaphase-promoting complex subunit 11 RING-H2 finger; Apc11 is one of the subunits of the anaphase-promoting complex or cyclosome. The APC subunits are cullin family proteins with ubiquitin ligase activity. Polyubiquitination marks proteins for degradation by the 26S proteasome and is carried out by a cascade of enzymes that includes ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). Apc11 acts as an E3 enzyme and is responsible for recruiting E2s to the APC and for mediating the subsequent transfer of ubiquitin to APC substrates in vivo. In Saccharomyces cerevisiae this RING-H2 finger protein defines the minimal ubiquitin ligase activity of the APC, and the integrity of the RING-H2 finger is essential for budding yeast cell viability.

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                  ....*....|....*....|....*....|....*....|....*
gi 109069031  127 CPICKEEFELRPQVLLSCSHVFHRACLQAF-EKFTNKKTCPLCRK 170
Cdd:pfam12861  35 CPDCKFPGDDCPLVWGKCSHNFHMHCILKWlHTETSKGLCPMCRQ 79

RING finger, H2 subclass, found in RING finger protein 149 (RNF149) and similar proteins; RNF149, also known as DNA polymerase-transactivated protein 2, is an E3 ubiquitin-protein ligase that interacts with wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), a RING domain-containing E3 ubiquitin ligase involved in control of gene transcription, translation, cytoskeletal organization, cell adhesion, and epithelial development. RNF149 induces the ubiquitination of wild-type BRAF and promotes its proteasome-dependent degradation. Mutated RNF149 has been found in some human breast, ovarian, and colorectal cancers. RNF149 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

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                 ....*....|....*....|....*....|....*....|....
gi 109069031 127 CPICKEEFELRPQV-LLSCSHVFHRACLQAFekFTNKKTCPLCR 169
Cdd:cd16804    2 CAVCIENYKSKDVVrILPCKHVFHRICIDPW--LLEHRTCPMCK 43

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.

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gi 109069031 127 CPICKEEFelRPQVLLSCSHVFHRACLQAFEKftNKKTCPLCRKN-QYQTRVI 178
Cdd:cd16535    4 CSICSELF--IEAVTLNCSHSFCSYCITEWMK--RKKECPICRKPiTSKTRSL 52

RING finger, HC subclass, found in bifunctional apoptosis regulator (BAR); BAR, also known as RING finger protein 47, was originally identified as an inhibitor of Bax-induced apoptosis. It participates in the block of apoptosis induced by TNF-family death receptors (extrinsic pathway) and mitochondria-dependent apoptosis (intrinsic pathway). BAR is predominantly expressed by neurons in the central nervous system and is involved in the regulation of neuronal survival. It is an endoplasmic reticulum (ER)-associated RING-type E3 ubiquitin ligase that interacts with BI-1 protein and post-translationally regulates its stability, as well as functioning in ER stress. BAR contains an N-terminal C3HC4-type RING-HC finger, a SAM domain, a coiled-coil domain, and a C-terminal transmembrane (TM) domain. This model corresponds to the RING-HC finger responsible for the binding of ubiquitin conjugating enzymes (E2s).

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gi 109069031 127 CPICKEeFELRPQvLLSCSHVFHRACLQAFEKFTNKKTCPLCRK 170
Cdd:cd16497    4 CHCCYD-LLVNPT-TLNCGHSFCRHCLALWWKSSKKTECPECRQ 45

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.

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gi 109069031 127 CPICkeeFELRPQVLLSCSHVFhraCLQAFEKFT-NKKTCPLCR 169
Cdd:cd16545    3 CCIC---MDRKADLILPCAHSY---CQKCIDKWSdRHRTCPICR 40

RING finger, H2 subclass, found in RING finger protein 130 (RNF130) and similar proteins; RNF130, also known as Goliath homolog (H-Goliath), is a paralog of RNF128, also known as gene related to anergy in lymphocytes protein (GRAIL). It is a transmembrane E3 ubiquitin-protein ligase expressed in leukocytes. It has a self-ubiquitination property, and controls the development of T cell clonal anergy by ubiquitination. RNF130 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

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                 ....*....|....*....|....*....|....*....|....*.
gi 109069031 127 CPICKEEFELRPQV-LLSCSHVFHRACLQAFekFTNKKTCPLCRKN 171
Cdd:cd16803    3 CAVCIEGYKQNDVVrILPCKHVFHKSCVDPW--LNEHCTCPMCKLN 46

Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins; RFWD3, also known as RING finger protein 201 (RNF201) or FLJ10520, is an E3 ubiquitin-protein ligase that forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and acts as a positive regulator of p53 stability in response to DNA damage. It is phosphorylated by checkpoint kinase ATM/ATR and the phosphorylation mutant fails to stimulate p53 ubiquitination. RFWD3 also functions as a novel replication protein A (RPA)-associated protein involved in DNA replication checkpoint control. RFWD3 contains an N-terminal SQ-rich region followed by a RING finger domain that exhibits robust E3 ubiquitin ligase activity toward p53, a coiled-coil domain and three WD40 repeats in the C-terminus, the latter two of which may be responsible for protein-protein interaction. The RING finger in this family is a modified C3HGC3-type RING finger, but not a canonical C3H2C3-type RING-H2 finger or C3HC4-type RING-HC finger.

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gi 109069031 127 CPICKEEFELRPQ---VLLSCSHVFHRACLQAFEKfTNKKTCPLCRK 170
Cdd:cd16450    5 CPICFEPWTSSGEhrlVSLKCGHLFGYSCIEKWLK-GKGKKCPQCNK 50

RING finger, HC subclass, found in helicase-like transcription factor (HLTF) and similar proteins; HLTF, also known as DNA-binding protein/plasminogen activator inhibitor 1 regulator, HIP116, RING finger protein 80, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 3, or sucrose nonfermenting protein 2-like 3, is a yeast RAD5 homolog found in mammals. It has both E3 ubiquitin ligase and DNA helicase activities, and plays a pivotal role in the template-switching pathway of DNA damage tolerance. It is involved in Lys-63-linked poly-ubiquitination of proliferating cell nuclear antigen (PCNA) at Lys-164 and in the regulation of DNA damage tolerance. It shows double-stranded DNA translocase activity with 3'-5' polarity, thereby facilitating regression of the replication fork. HLTF contains an N-terminal HIRAN (HIP116 and RAD5 N-terminal) domain, a SWI/SNF helicase domain that is divided into N- and C-terminal parts by an insertion of a C3HC4-type RING-HC finger involved in the poly-ubiquitination of PCNA.

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gi 109069031 127 CPICKEEfeLRPQVLLSCSHVFHRACL-QAFEkfTNKKTCPLCR 169
Cdd:cd16509    6 CAICLDS--LTNPVITPCAHVFCRRCIcEVIQ--REKAKCPMCR 45

Ring finger domain;

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                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 109069031  292 ECSICLAPLSPaggqrvgagqrSRETALLSCSHVFHHACLLALEEFSvgdrppfHACPLCR 352
Cdd:pfam13639   2 ECPICLEEFEE-----------GDKVVVLPCGHHFHRECLDKWLRSS-------NTCPLCR 44

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase deltex1 (DTX1), deltex4 (DTX4), and similar proteins; DTX1 functions as a Notch downstream transcription regulator that mediates a Notch signal to block differentiation of neural progenitor cells. It interacts with the transcription coactivator p300 and inhibits transcription activation mediated by the neural specific transcription factor MASH1. It is also a transcription target of nuclear factor of activated T cells (NFAT) and participates in T cell anergy and Foxp3 protein level maintenance in vivo. Moreover, DTX1 appears to promote B-cell development at the expense of T-cell development. It also promotes protein kinase C theta degradation and sustains Casitas B-lineage lymphoma expression. DTX4, also known as RING finger protein 155, shares the highest degree of sequence similarity with DTX1 and likely interacts with the intracellular domain of Notch as well. Both DTX1 and DTX4 contain two Notch-binding WWE domains at the N-terminus that physically interact with the Notch ankyrin domains, a proline-rich motif that shares homology with SH3-binding domains, and a C3H2C3-type RING-H2 finger at the C-terminus. They also harbor two nuclear localization signals.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 109069031 292 ECSICLAPL-SPAG--GQRVGAGQRSRETALLS-CSHVFHHACLLALeeFSVGDRPPFHACPLCRSCY 355
Cdd:cd16671    3 DCTICMERLvTPSGyeGVLSHKGVKPELVGKLSrCGHMYHLLCLVAM--YNNGNKDGSLQCPTCKAIY 68