Neuralized; This family contains a conserved region approximately 60 residues long within eukaryotic neuralized and neuralized-like proteins. Neuralized belongs to a group of ubiquitin ligases and is required in a subset of Notch pathway-mediated cell fate decisions during development of the Drosophila nervous system. Some family members contain multiple copies of this region.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281361416   27 FHSVHGDNIRISRDGTLARRFESFCRAITFSARPVRINERICVKFAEISNNWNGGIRFGFTSNDPvtleGTLPKYACPDL 106
Cdd:pfam07177   1 FHPVHGKNVRLSNDGRTARRTNSFNNGLVFSSRPLRPGELFEVRIDKLVDKWSGSLRFGVTSCDP----ATLRPKALPDL 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 281361416  107 TN--RPGFWAKALHEQYCEKDNILYYYVNGAGDVIYGINNEEKGVILTGIDTRSLLWTVIDIYGNCTGIEFLD 177
Cdd:pfam07177  77 ATdlRPGYWVVALSGSYLQEGDRLGFWVTSDGELHFSVNGEDQGVALSGVPDSQPLWAVFDLYGQTTQVSILG 149

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein NEURL1A, NEURL1B, and similar proteins; This subfamily includes Drosophila neuralized (D-neu) protein, and its two mammalian homologs, NEURL1A and NEURL1B. D-neu is a regulator of the developmentally important Notch signaling pathway. NEURL1A, also known as NEURL1, NEU, neuralized 1, or RING finger protein 67 (RNF67), is a mammalian homolog of D-neu. It functions as an E3 ubiquitin-protein ligase that directly interacts with and monoubiquitinates cytoplasmic polyadenylation element-binding protein 3 (CPEB3), an RNA binding protein and a translational regulator of local protein synthesis, which facilitates hippocampal plasticity and hippocampal-dependent memory storage. It also acts as a potential tumor suppressor that causes apoptosis and downregulates Notch target genes in medulloblastoma. NEURL1B, also known as neuralized-2 (NEUR2) or neuralized-like protein 3, is another mammalian homolog of D-neu protein. It functions as an E3 ubiquitin-protein ligase that interacts with and ubiquitinates Delta. Thus, it plays a role in the endocytic pathways for Notch signaling by working cooperatively with another E3 ligase, Mind bomb-1 (Mib1), in Delta endocytosis to hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-positive vesicles. Members of this subfamily contain two neuralized homology regions (NHRs) responsible for Neural-ligand interactions and a modified C3HC5-type RING-HC finger required for ubiquitin ligase activity. The C3HC5-type RING-HC finger is distinguished from typical C3HC4-type RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 281361416 616 SAECTICYENPIDSVLYMCGHMCMCYDCAIEQWRgvGGGQCPLCRAVIRDVIRTY 670
Cdd:cd16647    1 GSECVICYERPVDTVLYRCGHMCMCYDCALQLKR--RGGSCPICRAPIKDVIKIY 53

Neuralized; This family contains a conserved region approximately 60 residues long within eukaryotic neuralized and neuralized-like proteins. Neuralized belongs to a group of ubiquitin ligases and is required in a subset of Notch pathway-mediated cell fate decisions during development of the Drosophila nervous system. Some family members contain multiple copies of this region.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281361416   27 FHSVHGDNIRISRDGTLARRFESFCRAITFSARPVRINERICVKFAEISNNWNGGIRFGFTSNDPvtleGTLPKYACPDL 106
Cdd:pfam07177   1 FHPVHGKNVRLSNDGRTARRTNSFNNGLVFSSRPLRPGELFEVRIDKLVDKWSGSLRFGVTSCDP----ATLRPKALPDL 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 281361416  107 TN--RPGFWAKALHEQYCEKDNILYYYVNGAGDVIYGINNEEKGVILTGIDTRSLLWTVIDIYGNCTGIEFLD 177
Cdd:pfam07177  77 ATdlRPGYWVVALSGSYLQEGDRLGFWVTSDGELHFSVNGEDQGVALSGVPDSQPLWAVFDLYGQTTQVSILG 149

domain in neuralized proteins;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281361416    24 PLQFHSVHGDNIRISRDGTLARRFES-FCRAITFSARPVRINERICVKFAEISNNWNGGIRFGFTSNDPVTLE-GTLPKY 101
Cdd:smart00588   2 PLRFHHRHGSNIRLSDSGRVARRSASdFCNALVFSARPLRINELFEVKIEKVVRKWSGALRFGVTTCDPATLRpASLPTN 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 281361416   102 ACPDLTNRPGFWAKALHEQYCEKDNILYYYVNGAGDVIYGIN 143
Cdd:smart00588  82 ACPDLVDMSGFWAKALGEGLAEQGGILGLDVLAEGEVVGVIN 123

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein NEURL1A, NEURL1B, and similar proteins; This subfamily includes Drosophila neuralized (D-neu) protein, and its two mammalian homologs, NEURL1A and NEURL1B. D-neu is a regulator of the developmentally important Notch signaling pathway. NEURL1A, also known as NEURL1, NEU, neuralized 1, or RING finger protein 67 (RNF67), is a mammalian homolog of D-neu. It functions as an E3 ubiquitin-protein ligase that directly interacts with and monoubiquitinates cytoplasmic polyadenylation element-binding protein 3 (CPEB3), an RNA binding protein and a translational regulator of local protein synthesis, which facilitates hippocampal plasticity and hippocampal-dependent memory storage. It also acts as a potential tumor suppressor that causes apoptosis and downregulates Notch target genes in medulloblastoma. NEURL1B, also known as neuralized-2 (NEUR2) or neuralized-like protein 3, is another mammalian homolog of D-neu protein. It functions as an E3 ubiquitin-protein ligase that interacts with and ubiquitinates Delta. Thus, it plays a role in the endocytic pathways for Notch signaling by working cooperatively with another E3 ligase, Mind bomb-1 (Mib1), in Delta endocytosis to hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-positive vesicles. Members of this subfamily contain two neuralized homology regions (NHRs) responsible for Neural-ligand interactions and a modified C3HC5-type RING-HC finger required for ubiquitin ligase activity. The C3HC5-type RING-HC finger is distinguished from typical C3HC4-type RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 281361416 616 SAECTICYENPIDSVLYMCGHMCMCYDCAIEQWRgvGGGQCPLCRAVIRDVIRTY 670
Cdd:cd16647    1 GSECVICYERPVDTVLYRCGHMCMCYDCALQLKR--RGGSCPICRAPIKDVIKIY 53

SPRY domain in neuralized homology repeat; This family contains the neuralized homology repeat 1 (NHR1) domain similar to the SPRY domain (known to mediate specific protein-protein interactions) at the C-terminus of a conserved region within eukaryotic neuralized and neuralized-like proteins. In Drosophila, the neuralized protein (Neur) belongs to a group of ubiquitin ligases and is required in a subset of Notch pathway-mediated cell fate decisions during development of the nervous system. Neur binds to the Notch receptor ligand Delta through its first NHR1 domain and mediates its ubiquitination for endocytosis. Multiple copies of this region are found in some members of the family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281361416 289 FHNTKGRNVRLSQDRFVASRTESDFCQGYVFTARPIRIGEKLIVQVLKTEQMYVGALALGLTSCNPAMLQ-PN---DLPN 364
Cdd:cd12887    2 FHENHGKNIRLSNDGRTATRVKASFNNGVVFSSRPLRPGELFEVRIDKLVDRWSGSLEIGVTTLNPETLDlPPsatDLKS 81

                         90
                 ....*....|....*..
gi 281361416 365 DSdflldrpeyWVVSKD 381
Cdd:cd12887   82 GT---------WILSGS 89

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 281361416   619 CTICYENPIDS-VLYMCGHMcMCYDCaIEQWRGVGGGQCPLC 659
Cdd:smart00184   1 CPICLEEYLKDpVILPCGHT-FCRSC-IRKWLESGNNTCPIC 40

N1R/p28-like protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 281361416 618 ECTIC----YENPIDS----VLYMCGHMcMCYDCaIEQWRGvGGGQCPLCRAVIRDVIRT 669
Cdd:PHA02929 176 ECAICmekvYDKEIKNmyfgILSNCNHV-FCIEC-IDIWKK-EKNTCPVCRTPFISVIKS 232

Neuralized; This family contains a conserved region approximately 60 residues long within eukaryotic neuralized and neuralized-like proteins. Neuralized belongs to a group of ubiquitin ligases and is required in a subset of Notch pathway-mediated cell fate decisions during development of the Drosophila nervous system. Some family members contain multiple copies of this region.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281361416   27 FHSVHGDNIRISRDGTLARRFESFCRAITFSARPVRINERICVKFAEISNNWNGGIRFGFTSNDPvtleGTLPKYACPDL 106
Cdd:pfam07177   1 FHPVHGKNVRLSNDGRTARRTNSFNNGLVFSSRPLRPGELFEVRIDKLVDKWSGSLRFGVTSCDP----ATLRPKALPDL 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 281361416  107 TN--RPGFWAKALHEQYCEKDNILYYYVNGAGDVIYGINNEEKGVILTGIDTRSLLWTVIDIYGNCTGIEFLD 177
Cdd:pfam07177  77 ATdlRPGYWVVALSGSYLQEGDRLGFWVTSDGELHFSVNGEDQGVALSGVPDSQPLWAVFDLYGQTTQVSILG 149

domain in neuralized proteins;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281361416    24 PLQFHSVHGDNIRISRDGTLARRFES-FCRAITFSARPVRINERICVKFAEISNNWNGGIRFGFTSNDPVTLE-GTLPKY 101
Cdd:smart00588   2 PLRFHHRHGSNIRLSDSGRVARRSASdFCNALVFSARPLRINELFEVKIEKVVRKWSGALRFGVTTCDPATLRpASLPTN 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 281361416   102 ACPDLTNRPGFWAKALHEQYCEKDNILYYYVNGAGDVIYGIN 143
Cdd:smart00588  82 ACPDLVDMSGFWAKALGEGLAEQGGILGLDVLAEGEVVGVIN 123

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein NEURL1A, NEURL1B, and similar proteins; This subfamily includes Drosophila neuralized (D-neu) protein, and its two mammalian homologs, NEURL1A and NEURL1B. D-neu is a regulator of the developmentally important Notch signaling pathway. NEURL1A, also known as NEURL1, NEU, neuralized 1, or RING finger protein 67 (RNF67), is a mammalian homolog of D-neu. It functions as an E3 ubiquitin-protein ligase that directly interacts with and monoubiquitinates cytoplasmic polyadenylation element-binding protein 3 (CPEB3), an RNA binding protein and a translational regulator of local protein synthesis, which facilitates hippocampal plasticity and hippocampal-dependent memory storage. It also acts as a potential tumor suppressor that causes apoptosis and downregulates Notch target genes in medulloblastoma. NEURL1B, also known as neuralized-2 (NEUR2) or neuralized-like protein 3, is another mammalian homolog of D-neu protein. It functions as an E3 ubiquitin-protein ligase that interacts with and ubiquitinates Delta. Thus, it plays a role in the endocytic pathways for Notch signaling by working cooperatively with another E3 ligase, Mind bomb-1 (Mib1), in Delta endocytosis to hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-positive vesicles. Members of this subfamily contain two neuralized homology regions (NHRs) responsible for Neural-ligand interactions and a modified C3HC5-type RING-HC finger required for ubiquitin ligase activity. The C3HC5-type RING-HC finger is distinguished from typical C3HC4-type RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 281361416 616 SAECTICYENPIDSVLYMCGHMCMCYDCAIEQWRgvGGGQCPLCRAVIRDVIRTY 670
Cdd:cd16647    1 GSECVICYERPVDTVLYRCGHMCMCYDCALQLKR--RGGSCPICRAPIKDVIKIY 53

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein 1A (NEURL1A) and similar proteins; NEURL1A, also known as NEURL1, NEU, neuralized 1, or RING finger protein 67 (RNF67), is a mammalian homolog of the Drosophila neuralized (D-neu) protein. It functions as an E3 ubiquitin-protein ligase that directly interacts with and monoubiquitinates cytoplasmic polyadenylation element-binding protein 3 (CPEB3), an RNA binding protein and a translational regulator of local protein synthesis, which facilitates hippocampal plasticity and hippocampal-dependent memory storage. It also acts as a potential tumor suppressor that causes apoptosis and downregulates Notch target genes in the medulloblastoma. NEURL1A contains two neuralized homology regions (NHRs) responsible for Neural-ligand interactions and a modified C3HC5-type RING-HC finger required for ubiquitin ligase activity. The C3HC5-type RING-HC finger is distinguished from typical C3HC4-type RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 281361416 616 SAECTICYENPIDSVLYMCGHMCMCYDCAIeQWRGVGGGQCPLCRAVIRDVIRTY 670
Cdd:cd16785    4 SDECTICYENAVDTVIYTCGHMCLCYACGL-RLKKMLNACCPICRRAIKDIIKTY 57

SPRY domain in neuralized homology repeat; This family contains the neuralized homology repeat 1 (NHR1) domain similar to the SPRY domain (known to mediate specific protein-protein interactions) at the C-terminus of a conserved region within eukaryotic neuralized and neuralized-like proteins. In Drosophila, the neuralized protein (Neur) belongs to a group of ubiquitin ligases and is required in a subset of Notch pathway-mediated cell fate decisions during development of the nervous system. Neur binds to the Notch receptor ligand Delta through its first NHR1 domain and mediates its ubiquitination for endocytosis. Multiple copies of this region are found in some members of the family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281361416 289 FHNTKGRNVRLSQDRFVASRTESDFCQGYVFTARPIRIGEKLIVQVLKTEQMYVGALALGLTSCNPAMLQ-PN---DLPN 364
Cdd:cd12887    2 FHENHGKNIRLSNDGRTATRVKASFNNGVVFSSRPLRPGELFEVRIDKLVDRWSGSLEIGVTTLNPETLDlPPsatDLKS 81

                         90
                 ....*....|....*..
gi 281361416 365 DSdflldrpeyWVVSKD 381
Cdd:cd12887   82 GT---------WILSGS 89

RING finger, HC subclass, found in Arabidopsis thaliana protein XB3 homolog 5 (XBAT35) and similar proteins; XBAT35, also known as ankyrin repeat domain and RING finger-containing protein XBAT35, or RING-type E3 ubiquitin transferase XBAT35, has no E3 ubiquitin-protein ligase activity observed when associated with the E2 enzyme UBC8 in vitro. It contains a typical C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 281361416 618 ECTICYENPIDSVLYMCGHMCMCYDCAIE----QWRgvgggqCPLCRAVIRDVIRTY 670
Cdd:cd23129    4 ECVVCMDAPRDAVCVPCGHVAGCMSCLKAlmqsSPL------CPICRAPVRQVIKVY 54

Modified RING finger, HC subclass (C3HC5-type), found in RING finger proteins, RNF26, RNF197 (CGRRF1), RNF156 (MGRN1), RNF157 and similar proteins; This subfamily corresponds to a group of RING finger proteins containing a modified C3HC5-type RING-HC finger, which is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain. Cell growth regulator with RING finger domain protein 1 (CGRRF1), also known as cell growth regulatory gene 19 protein (CGR19) or RING finger protein 197 (RNF197), functions as a novel biomarker to monitor endometrial sensitivity and response to insulin-sensitizing drugs, such as metformin, in the context of obesity. RNF26 is an E3 ubiquitin ligase that temporally regulates virus-triggered type I interferon induction by increasing the stability of Mediator of IRF3 activation, MITA, also known as STING, through K11-linked polyubiquitination after viral infection and promoting degradation of IRF3, another important component required for virus-triggered interferon induction. Mahogunin ring finger-1 (MGRN1), also known as RING finger protein 156 (RNF156), is a cytosolic E3 ubiquitin-protein ligase that inhibits signaling through the G protein-coupled melanocortin receptors-1 (MC1R), -2 (MC2R) and -4 (MC4R) via ubiquitylation-dependent and -independent processes. It suppresses chaperone-associated misfolded protein aggregation and toxicity. RNF157 is a cytoplasmic E3 ubiquitin ligase predominantly expressed in the brain. It is a homolog of the E3 ligase MGRN1. In cultured neurons, it promotes neuronal survival in an E3 ligase-dependent manner. In contrast, it supports growth and maintenance of dendrites independent of its E3 ligase activity. RNF157 interacts with and ubiquitinates the adaptor protein APBB1 (amyloid beta precursor protein-binding, family B, member 1 or Fe65), which regulates neuronal survival, but not dendritic growth downstream of RNF157. The nuclear localization of APBB1 together with its interaction partner RNA-binding protein SART3 (squamous cell carcinoma antigen recognized by T cells 3 or Tip110) is crucial to trigger apoptosis.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 281361416 618 ECTICYENPIDSVLYMCGHMCMCYDCAieqwRGVGGGQCPLCR 660
Cdd:cd16649    2 LCVVCLENPASVLLLPCRHLCLCEVCA----KGLRGKTCPICR 40

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
                 ....*....|....*....|....*....|....*....|..
gi 281361416 618 ECTICYENPIDSVLYMCGHMCmCYDCaIEQWRGVGGGQCPLC 659
Cdd:cd16449    2 ECPICLERLKDPVLLPCGHVF-CREC-IRRLLESGSIKCPIC 41

RING finger, HC subclass, found in apoptosis protein c-IAP1, c-IAP2, livin, and similar proteins; The cellular inhibitor of apoptosis protein c-IAPs function as ubiquitin E3 ligases that mediate the ubiquitination of substrates involved in apoptosis, nuclear factor-kappaB (NF-kappaB) signaling, and oncogenesis. Unlike other IAPs, such as XIAP, c-IAPs exhibit minimal binding to caspases and may not play an important role in the inhibition of these proteases. c-IAP1, also known as baculoviral IAP repeat-containing protein BIRC2, IAP-2, RING finger protein 48, or TNFR2-TRAF-signaling complex protein 2, is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-kappaB signaling pathways in the cytoplasm. It can also regulate E2F1 transcription factor-mediated control of cyclin transcription in the nucleus. c-IAP2, also known as BIRC3, IAP-1, apoptosis inhibitor 2 (API2), or IAP homolog C, also influences ubiquitin-dependent pathways that modulate innate immune signalling by activation of NF-kappaB. c-IAPs contain three N-terminal baculoviral IAP repeat (BIR) domains that enable interactions with proteins, a ubiquitin-association (UBA) domain that is responsible for the binding of polyubiquitin (polyUb), a caspase activation and recruitment domain (CARD) that serves as a protein interaction surface, and a C3HC4-type RING-HC finger at the carboxyl terminus that is required for ubiquitin ligase activity. Livin, also known as baculoviral IAP repeat-containing protein 7 (BIRC7), kidney inhibitor of apoptosis protein (KIAP), melanoma inhibitor of apoptosis protein (ML-IAP), or RING finger protein 50, was identified as the melanoma IAP. It plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Its anti-apoptotic activity is regulated by the inhibition of caspase-3, -7, and -9. Its E3 ubiquitin-ligase-like activity promotes degradation of Smac/DIABLO, a critical endogenous regulator of all IAPs. Unlike other family members, mammalian livin contains a single BIR domain and a C3HC4-type RING-HC finger. The UBA domain can be detected in non-mammalian homologs of livin.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 281361416 619 CTICYENPIDSVLYMCGHMCMCYDCAIEQWRgvgggqCPLCRAVIRDVIRTY 670
Cdd:cd16713   10 CKVCMDKEVSIVFIPCGHLVVCTECAPSLRK------CPICRATIKGTVRTF 55

Modified RING finger, HC subclass (C3HC5-type), found in RING finger protein 26 (RNF26) and similar proteins; RNF26 is an E3 ubiquitin ligase that temporally regulates virus-triggered type I interferon induction by increasing the stability of Mediator of IRF3 activation, MITA, also known as STING, through K11-linked polyubiquitination of MITA after viral infection, and promoting the degradation of IRF3, another important component required for virus-triggered interferon induction. Although RNF26 substrates of ubiquitination remain unclear at present, RNF26 upregulation in gastric cancer might be implicated in carcinogenesis through dysregulation of growth regulators. RNF26 contains an N-terminal leucine zipper domain and a C-terminal modified C3HC5-type RING-HC finger, which is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 281361416 619 CTICYENPIDSVLYMCGHMCMCYDCA---IEQWrgVGGGQCPLCRAVIRDVIRTY 670
Cdd:cd16788    8 CVICQDQSKTVLILPCRHMCLCRQCAnilLQQP--VYRRNCPLCRTMILQTLDVY 60

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 281361416   619 CTICYENPIDS-VLYMCGHMcMCYDCaIEQWRGVGGGQCPLC 659
Cdd:smart00184   1 CPICLEEYLKDpVILPCGHT-FCRSC-IRKWLESGNNTCPIC 40

RING finger, HC subclass, found in RNA-binding proteins of the evolutionarily-conserved MEX-3 family; MEX-3 phosphoproteins are found in vertebrates. They are mediators of post-transcriptional regulation in different organisms, and have been implicated in many core biological processes, including embryonic development, epithelial homeostasis, immune responses, metabolism, and cancer. They contain two K homology (KH) domains that provide RNA-binding capacity, and a C-terminal C3HC4-type RING-HC finger. They shuttle between the nucleus and the cytoplasm via the CRM1-dependent export pathway. The RNA-binding protein MEX-3 from nematode Caenorhabditis elegans is the founding member of the MEX-3 family. Due to the lack of a RING-HC finger, it is not included here.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 281361416 618 ECTICYENPIDSVLYMCGHMCMCYDCAiEQWRGVGGGQCPLCRAVIRDVIRTY 670
Cdd:cd16518    2 DCVVCFESEVVAALVPCGHNLFCMECA-NRICEKSDPECPVCHTPVTQAIRIF 53

RING finger, HC subclass, found in RNA-binding protein MEX3B; MEX3B, also known as RING finger and KH domain-containing protein 3 (RKHD3), or RING finger protein 195 (RNF195), is an RNA-binding phosphoprotein that localizes in P-bodies and stress granules, which are two structures involved in the storage and turnover of mRNAs. It regulates the spatial organization of the Rap1 pathway that orchestrates Sertoli cell functions. It has a 3' long conserved untranslated region (3'LCU)-mediated fine-tuning system for mRNA regulation in early vertebrate development such as anteroposterior (AP) patterning and signal transduction. MEX3B contains two K homology (KH) domains that provide RNA-binding capacity, and a C-terminal C3HC4-type RING-HC finger. Like other MEX-3 family proteins, MEX3B shuttles between the nucleus and the cytoplasm via the CRM1-dependent export pathway.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 281361416 616 SAECTICYENPIDSVLYMCGHMCMCYDCA---IEQwrgvGGGQCPLCRAVIRDVIRTYT 671
Cdd:cd16721    4 SRDCSICFESEVIAALVPCGHNLFCMECAnriCEK----NEPQCPVCHAAVTQAIRIFS 58

RING finger, HC subclass, found in leucine-rich repeat and sterile alpha motif-containing protein 1 (LRSAM1) and similar proteins; LRSAM1, also known as Tsg101-associated ligase (TAL), or RIFLE, is an E3 ubiquitin-protein ligase that physically associates with, and selectively ubiquitylates, Tsg101, an E2-like molecule that regulates vesicular trafficking processes in yeast and mammals. It regulates a Tsg101-associated complex responsible for the sorting of cargo into cytoplasm-containing vesicles that bud at the multivesicular body and at the plasma membrane. LRSAM1 is a multidomain protein containing an N-terminal leucine-rich repeat (LRR), followed by several recognizable motifs, including an ezrin-radixin-moezin (ERM) domain, a coiled-coil (CC) region, a SAM domain, and a C-terminal C3HC4-type RING-HC finger domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 281361416 616 SAECTICYENPIDSVLYMCGHMCMCYDCaieqwrGVGGGQCPLCRAVIRDVIR 668
Cdd:cd16515    1 ESECVVCMDAESQVIFLPCGHVCCCQTC------SSSLSTCPLCRADITQRVR 47

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 281361416 616 SAECTICYENPIDSVLYMCGHMcMCYDCaIEQWRgVGGGQCPLCRAVIRDVI 667
Cdd:cd16561    2 EQECSICLEDLNDPVKLPCDHV-FCEEC-IRQWL-PGQMSCPLCRTELPDDF 50

Modified RING finger, HC subclass (C3HC5-type), found in cell growth regulator with RING finger domain protein 1 (CGRRF1) and similar proteins; CGRRF1, also known as cell growth regulatory gene 19 protein (CGR19) or RING finger protein 197 (RNF197), functions as a novel biomarker to monitor endometrial sensitivity and response to insulin-sensitizing drugs, such as metformin, in the context of obesity. CGRRF1 contains a C-terminal modified C3HC5-type RING-HC finger, which is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 281361416 618 ECTICYENPIDSVLYMCGHMCMCYDCaIEQWRgvgggQCPLCR 660
Cdd:cd16787    2 DCVVCQNAPVNRVLLPCRHACVCDEC-FKRLQ-----RCPMCR 38

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 281361416 617 AECTICYENPIDS-----VLYMCGHmCMCYDCaIEQWRGVGGGQ------CPLCR 660
Cdd:cd16521    1 IECGICMEVVLEKerrfgILSNCNH-VFCLEC-IREWRSSKDFEnsivrsCPICR 53

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 281361416  618 ECTIC---YENPIDSVLYMCGHmCMCYDCaIEQWRGVGGgQCPLCR 660
Cdd:pfam13639   2 ECPICleeFEEGDKVVVLPCGH-HFHREC-LDKWLRSSN-TCPLCR 44

RING finger, HC subclass, found in RNA-binding protein MEX3C; MEX3C, also known as RING finger and KH domain-containing protein 2 (RKHD2), or RING finger protein 194 (RNF194), is an RNA-binding phosphoprotein that acts as a suppressor of chromosomal instability. It functions as an ubiquitin E3 ligase responsible for the post-transcriptional, HLA-A allotype-specific regulation of MHC class I molecules (MHC-I). It also modifies retinoic acid inducible gene-1 (RIG-I) in stress granules and plays a critical role in eliciting antiviral immune responses. Moreover, MEX3C plays an essential role in normal postnatal growth via enhancing the local expression of insulin-like growth factor 1 (IGF1) in bone. It may also be involved in metabolic regulation of energy balance. MEX3C contains two K homology (KH) domains that provide RNA-binding capacity, and a C-terminal C3HC4-type RING-HC finger. Like other MEX-3 family proteins, MEX3C shuttles between the nucleus and the cytoplasm via the CRM1-dependent export pathway.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 281361416 618 ECTICYENPIDSVLYMCGHMCMCYDCAiEQWRGVGGGQCPLCRAVIRDVIRTYT 671
Cdd:cd16722    3 DCVICFENEVIAALVPCGHNLFCMECA-NKICEKETPSCPVCQTAVTQAIQIHS 55

RING finger, HC subclass, found in RING finger protein 185 (RNF185) and similar proteins; RNF185 is an E3 ubiquitin-protein ligase of endoplasmic reticulum-associated degradation (ERAD) that targets cystic fibrosis transmembrane conductance regulator (CFTR). It controls the degradation of CFTR and CFTR F508del allele in a RING- and proteasome-dependent manner, but does not control that of other classical ERAD model substrates. It also negatively regulates osteogenic differentiation by targeting dishevelled2 (Dvl2), a key mediator of the Wnt signaling pathway, for degradation. Moreover, RNF185 regulates selective mitochondrial autophagy through interaction with the Bcl-2 family protein BNIP1. It also plays an important role in cell adhesion and migration through the modulation of cell migration by ubiquitinating paxillin. RNF185 contains a C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 281361416 618 ECTICYENPIDSVLYMCGHMcMCYDCaIEQWRGVGGGQ--CPLCRAVI 663
Cdd:cd16744    2 ECNICLDTAKDAVVSLCGHL-FCWPC-LHQWLETRPNRqvCPVCKAGI 47

Modified RING finger, HC subclass (C3HC5-type), found in RING finger protein 157 (RNF157) and similar proteins; RNF157 is a cytoplasmic E3 ubiquitin ligase predominantly expressed in brain. It is a homolog of the E3 ligase mahogunin ring finger-1 (MGRN1). In cultured neurons, it promotes neuronal survival in an E3 ligase-dependent manner. In contrast, it supports growth and maintenance of dendrites independent of its E3 ligase activity. RNF157 interacts with and ubiquitinates the adaptor protein APBB1 (amyloid beta precursor protein-binding, family B, member 1 or Fe65), which regulates neuronal survival, but not dendritic growth downstream of RNF157. The nuclear localization of APBB1 together with its interaction partner RNA-binding protein SART3 (squamous cell carcinoma antigen recognized by T cells 3 or Tip110) is crucial to trigger apoptosis. RNF157 contains a modified C3HC5-type RING-HC finger, and a functionally uncharacterized region, known as domain associated with RING2 (DAR2), N-terminal to the RING finger. The C3HC5-type RING-HC finger is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 281361416 613 TDSSAECTICYENPIDSVLYMCGHMCMCYDCAiEQWRgVGGGQCPLCRAVIRDVIR 668
Cdd:cd16817    1 SDNSAECVVCLSDVRDTLILPCRHLCLCNACA-DTLR-YQANNCPICRLPFRALLQ 54

RING finger, HC subclass, found in caspases-8 and -10-associated RING finger protein 1 (CARP1) and similar proteins; CARP1, also known as caspase regulator CARP1, FYVE-RING finger protein Momo, RING finger homologous to inhibitor of apoptosis protein (RFI), RING finger protein 34 (RNF34), or RING finger protein RIFF, is a nuclear protein that functions as a specific E3 ubiquitin ligase for the transcriptional coactivator PGC-1alpha, a master regulator of energy metabolism and adaptive thermogenesis in the brown fat cell which negatively regulates brown fat cell metabolism. It is preferentially expressed in esophageal, gastric, and colorectal cancers, suggesting a possible association with the development of digestive tract cancers. It regulates the p53 signaling pathway by degrading 14-3-3 sigma and stabilizing MDM2. CARP1 does not localize to membranes in the cell and is involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8 and caspase 10. CARP1 contains an N-terminal FYVE-like domain and a C-terminal C3HC4-type RING-HC finger domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 281361416 619 CTICYENPIDSVLYMCGHMCMCYDCaieqwrGVGGGQCPLCRA-VIRDV 666
Cdd:cd16706    7 CRICMDAVIDCVLLECGHMVTCTKC------GKRMSECPICRQyVVRAV 49

RING finger, HC subclass, found in Arabidopsis thaliana RING membrane-anchor proteins (AtRMAs) and similar proteins; AtRMAs, including AtRma1, AtRma2, and AtRma3, are endoplasmic reticulum (ER)-localized Arabidopsis homologs of human outer membrane of the ER-anchor E3 ubiquitin-protein ligase, RING finger protein 5 (RNF5). AtRMAs possess E3 ubiquitin ligase activity, and may play a role in the growth and development of Arabidopsis. The AtRMA1 and AtRMA3 genes are predominantly expressed in major tissues, such as cotyledons, leaves, shoot-root junction, roots, and anthers, while AtRMA2 expression is restricted to the root tips and leaf hydathodes. AtRma1 probably functions with the Ubc4/5 subfamily of E2. AtRma2 is likely involved in the cellular regulation of ABP1 expression levels through interacting with auxin binding protein 1 (ABP1). AtRMA proteins contain an N-terminal C3HC4-type RING-HC finger and a trans-membrane-anchoring domain in their extreme C-terminal region.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 281361416 618 ECTICYENPIDSVLYMCGHMcMCYDCaIEQW--RGVGGGQCPLCRA 661
Cdd:cd16745    2 ECNICLDLAQDPVVTLCGHL-FCWPC-LHKWlrRQSSQPECPVCKA 45

RING finger, HC subclass, found in RING finger protein 5 (RNF5) and similar proteins; RNF5, also known as protein G16 or Ram1, is an E3 ubiquitin-protein ligase anchored to the outer membrane of the endoplasmic reticulum (ER). It acts at early stages of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) biosynthesis and functions as a target for therapeutic modalities to antagonize mutant CFTR proteins in CF patients carrying the F508del allele. It also regulates the turnover of specific G protein-coupled receptors by ubiquitinating JNK-associated membrane protein (JAMP) and preventing proteasome recruitment. RNF5 limits basal levels of autophagy and influences susceptibility to bacterial infection through the regulation of ATG4B stability. It is also involved in the degradation of Pendrin, a transmembrane chloride/anion exchanger highly expressed in thyroid, kidney, and inner ear. RNF5 plays an important role in cell adhesion and migration. It can modulate cell migration by ubiquitinating paxillin. Furthermore, RNF5 interacts with virus-induced signaling adaptor (VISA) at mitochondria in a viral infection-dependent manner, and further targets VISA at K362 and K461 for K48-linked ubiquitination and degradation after viral infection. It also negatively regulates virus-triggered signaling by targeting MITA, also known as STING, for ubiquitination and degradation at the mitochondria. In addition, RNF5 determines breast cancer response to ER stress-inducing chemotherapies through the regulation of the L-glutamine carrier proteins SLC1A5 and SLC38A2 (SLC1A5/38A2). It also has been implicated in muscle organization and in recognition and processing of misfolded proteins. RNF5 contains a C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 281361416 618 ECTICYENPIDSVLYMCGHMcMCYDCaIEQWRGV--GGGQCPLCRAVI 663
Cdd:cd16743    2 ECNICLETARDAVVSLCGHL-FCWPC-LHQWLETrpERQECPVCKAGI 47

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl-b and similar proteins; Cbl-b, also known as Casitas B-lineage lymphoma proto-oncogene b, RING finger protein 56 (RNF56), SH3-binding protein Cbl-b, or signal transduction protein Cbl-b, has been identified as a regulator of antigen-specific, T cell-intrinsic, peripheral immune tolerance, a state also known as clonal anergy. It may inhibit activation of the p85 subunit of phosphoinositide 3-kinase (PI3K), protein kinase C-theta (PKC-theta), and phospholipase C-gamma1 (PLC-gamma1) and negatively regulates T-cell receptor-induced transcription factor nuclear factor kappaB (NF-kappaB) activation. In addition, Cbl-b may target multiple signaling molecules involved in transforming growth factor (TGF)-beta-mediated transactivation pathways. Cbl-b contains a tyrosine-kinase-binding domain (TKB, also known as the phosphotyrosine binding PTB domain, is composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain), a proline rich domain, a nuclear localization signal, a C3HC4-type RING-HC finger and an ubiquitin-associated (UBA) domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 281361416 619 CTICYENPIDSVLYMCGHMcMCYDCaIEQWRGVGGGQCPLCRAVIR 664
Cdd:cd16709   23 CKICAENDKDVKIEPCGHL-MCTSC-LTAWQESDGQGCPFCRCEIK 66

RING finger, HC subclass, found in radiation sensitivity protein 5 (RAD5) and similar proteins; RAD5, also known as revertibility protein 2 (REV2), or DNA repair protein RAD5, is a probable helicase, and a member of the UBC2/RAD6 epistasis group. It functions with the DNA repair protein RAD18 in error-free postreplication DNA repair. It is involved in the maintenance of wild-type rates of instability of simple repetitive sequences such as poly(GT) repeats. It may also be involved in maintaining a balance which acts in favor of error-prone non-homologous joining during DNA double-strand breaks repairs. It recruits the UBC13-MMS2 dimer to chromatin for DNA repair. RAD5 contains a typical C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 281361416 616 SAECTICYENPIDS---VLYMCGHmCMCYDCAIE----QWRGVGGGQCPLCRAVI 663
Cdd:cd23131    3 EVECSICTQEPIEVgevVFTECGH-SFCEDCLLEyiefQNKKKLDLKCPNCREPI 56

RING finger, HC subclass, found in RING finger protein 169 (RNF169) and similar proteins; RNF169 is an uncharacterized E3 ubiquitin-protein ligase paralogous to RNF168. It functions as a negative regulator of the DNA damage signaling cascade. RNF169 recognizes polyubiquitin structures but does not itself contribute to double-strand break (DSB)-induced chromatin ubiquitylation. It contributes to regulation of the DSB repair pathway utilization via functionally competing with recruiting repair factors, 53BP1 and RAP80-BRCA1, for association with RNF168-modified chromatin independent of its catalytic activity, limiting the magnitude of the RNF8/RNF168-dependent signaling response to DSBs. RNF169 contains an N-terminal C3HC4-type RING-HC finger and a C-terminal MIU (motif interacting with ubiquitin) domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 281361416 619 CTICYENPIDSVLYMCGHmCMCYDCAIEQWRGVGGG-QCPLCRA 661
Cdd:cd16551    4 CAGCLEVPVEPATLPCGH-TLCRGCANRALDAAEAGpTCPRCRA 46

RING finger, HC subclass, found in Arabidopsis thaliana protein CHROMATIN REMODELING 27 (CHR27) and similar proteins; CHR27, also called protein SNF2-RING-HELICASE-LIKE 1, is a probable helicase-like transcription factor involved in transcriptional gene silencing. It associates with SUVR2 and contributes to transcriptional gene silencing at RNA-directed DNA methylation (RdDM) target loci but also at RdDM-independent target loci. It may be involved in nucleosome positioning to form ordered nucleosome arrays on chromatin. It associates with SUVR2 and functions redundantly with FRG2. It is required for the efficient methylation of a broad range of RdDM target loci. CHR27 contains a typical C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 281361416 617 AECTICYENPIDSVLYMCGHMcMCYDCAIEQWRGVGGGQ----CPLCRA 661
Cdd:cd23142    1 AICPICNDPPEDAVVTLCGHV-FCCECVFQYLSSDRTCRqfnhCPLCRQ 48

RING finger, HC subclass, found in peroxin-10 (PEX10) and similar proteins; PEX10, also known as peroxisome biogenesis factor 10, peroxisomal biogenesis factor 10, peroxisome assembly protein 10, or RING finger protein 69 (RNF69), is an integral peroxisomal membrane protein with two transmembrane regions and a C3HC4-type RING-HC finger within its cytoplasmically exposed C-terminus. It plays an essential role in peroxisome assembly, import of target substrates, and recycling or degradation of protein complexes and amino acids. It is an essential component of the spinal locomotor circuit, and thus its mutations may be involved in peroxisomal biogenesis disorders (PBD). Mutations in human PEX10 also result in autosomal recessive ataxia. Moreover, PEX10 functions as an E3-ubiquitin ligase with an E2, UBCH5C. It mono- or poly-ubiquitinates PEX5, a key player in peroxisomal matrix protein import, in a UBC4-dependent manner, to control PEX5 receptor recycling or degradation. It also links the E2 ubiquitin conjugating enzyme PEX4 to the protein import machinery of the peroxisome.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 281361416 619 CTICYENPIDSVLYMCGHMcMCYDCaIEQWrGVGGGQCPLCRA 661
Cdd:cd16527    3 CSLCLEERRHPTATPCGHL-FCWSC-ITEW-CNEKPECPLCRE 42

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl-c and similar proteins; Cbl-c, also known as RING finger protein 57 (RNF57), SH3-binding protein Cbl-3, SH3-binding protein Cbl-c, or signal transduction protein Cbl-c, is an E3 ubiquitin-protein ligase expressed exclusively in epithelial cells. It contains a tyrosine-kinase-binding domain (TKB, also known as the phosphotyrosine binding PTB domain, composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain), a C3HC4-type RING-HC finger, and a short proline-rich region, but lacks the ubiquitin-associated (UBA) leucine zipper motif that are present in Cbl and Cbl-b. Cbl-c acts as a regulator of epidermal growth factor receptor (EGFR)-mediated signal transduction. It also suppresses v-Src-induced transformation through ubiquitin-dependent protein degradation. Moreover, Cbl-c ubiquitinates and downregulates RETMEN2A and implicates Enigma (PDLIM7) as a positive regulator of RETMEN2A by blocking Cbl-mediated ubiquitination and degradation. The ubiquitin ligase activity of Cbl-c is increased via the interaction of its RING-HC finger domain with a LIM domain of the paxillin homolog, hydrogen peroxide induced construct 5 (Hic-5).

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 281361416 611 QSTDSSAE-CTICYENPIDSVLYMCGHMcMCyDCAIEQWRGVGGGQCPLCRAVIR 664
Cdd:cd16710    7 QAMNSTFElCKICAERDKDVRIEPCGHL-LC-SCCLAAWQHSDSQTCPFCRCEIK 59