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 1907131870 280 FHALRaGAHVRILDEQTVARLeHGRDERALVFTSRPVRVAETIFIKVTRSGGGRAGALSFGVTTCDPGTLRPADLPFSPE 359
Cdd:pfam07177   1 FHPVH-GKNVRLSNDGRTARR-TNSFNNGLVFSSRPLRPGELFEVRIDKLVDKWSGSLRFGVTSCDPATLRPKALPDLAT 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907131870 360 ALvdRKEFWAVCRVPGPLHSGDILGLVVNADGELHLSHNGAAAG-MQLCVDASQPLWMLFSLHGAITQVRILG 431
Cdd:pfam07177  79 DL--RPGYWVVALSGSYLQEGDRLGFWVTSDGELHFSVNGEDQGvALSGVPDSQPLWAVFDLYGQTTQVSILG 149

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 1907131870 499 GQWSDECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKALHACCPICRRPIKDIIKTYRS 557
Cdd:cd16785     1 GSWSDECTICYENAVDTVIYTCGHMCLCYACGLRLKKMLNACCPICRRAIKDIIKTYRS 59

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 1907131870 280 FHALRaGAHVRILDEQTVARLeHGRDERALVFTSRPVRVAETIFIKVTRSGGGRAGALSFGVTTCDPGTLRPADLPFSPE 359
Cdd:pfam07177   1 FHPVH-GKNVRLSNDGRTARR-TNSFNNGLVFSSRPLRPGELFEVRIDKLVDKWSGSLRFGVTSCDPATLRPKALPDLAT 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907131870 360 ALvdRKEFWAVCRVPGPLHSGDILGLVVNADGELHLSHNGAAAG-MQLCVDASQPLWMLFSLHGAITQVRILG 431
Cdd:pfam07177  79 DL--RPGYWVVALSGSYLQEGDRLGFWVTSDGELHFSVNGEDQGvALSGVPDSQPLWAVFDLYGQTTQVSILG 149

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 1907131870  49 FHpHTKGSQILMDLSHKAVKRQASFCNAITFSNRPVLIYEQVRLKITKKQCCWSGALRLGFTSKDPSRIHPDSLPkyACP 128
Cdd:pfam07177   1 FH-PVHGKNVRLSNDGRTARRTNSFNNGLVFSSRPLRPGELFEVRIDKLVDKWSGSLRFGVTSCDPATLRPKALP--DLA 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907131870 129 DLVsQSGFWAKALPEEFANEGNIIAFWVDKKGRVFYRINESAAMLFFSGVRTVDPLWALVDVYGLTRGVQLLD 201
Cdd:pfam07177  78 TDL-RPGYWVVALSGSYLQEGDRLGFWVTSDGELHFSVNGEDQGVALSGVPDSQPLWAVFDLYGQTTQVSILG 149

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 1907131870 499 GQWSDECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKALHACCPICRRPIKDIIKTYRS 557
Cdd:cd16785     1 GSWSDECTICYENAVDTVIYTCGHMCLCYACGLRLKKMLNACCPICRRAIKDIIKTYRS 59

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1907131870 503 DECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKaLHACCPICRRPIKDI 551
Cdd:pfam13920   3 LLCVICLDRPRNVVLLPCGHLCLCEECAERLLR-KKKKCPICRQPIESV 50

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 1907131870  505 CTICYEH-AVDTVIYTCGHMcLCYSCGLRLKKALHACCPIC 544
Cdd:smart00184   1 CPICLEEyLKDPVILPCGHT-FCRSCIRKWLESGNNTCPIC 40

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 1907131870 280 FHALRaGAHVRILDEQTVARLeHGRDERALVFTSRPVRVAETIFIKVTRSGGGRAGALSFGVTTCDPGTLRPADLPFSPE 359
Cdd:pfam07177   1 FHPVH-GKNVRLSNDGRTARR-TNSFNNGLVFSSRPLRPGELFEVRIDKLVDKWSGSLRFGVTSCDPATLRPKALPDLAT 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907131870 360 ALvdRKEFWAVCRVPGPLHSGDILGLVVNADGELHLSHNGAAAG-MQLCVDASQPLWMLFSLHGAITQVRILG 431
Cdd:pfam07177  79 DL--RPGYWVVALSGSYLQEGDRLGFWVTSDGELHFSVNGEDQGvALSGVPDSQPLWAVFDLYGQTTQVSILG 149

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 1907131870  49 FHpHTKGSQILMDLSHKAVKRQASFCNAITFSNRPVLIYEQVRLKITKKQCCWSGALRLGFTSKDPSRIHPDSLPkyACP 128
Cdd:pfam07177   1 FH-PVHGKNVRLSNDGRTARRTNSFNNGLVFSSRPLRPGELFEVRIDKLVDKWSGSLRFGVTSCDPATLRPKALP--DLA 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907131870 129 DLVsQSGFWAKALPEEFANEGNIIAFWVDKKGRVFYRINESAAMLFFSGVRTVDPLWALVDVYGLTRGVQLLD 201
Cdd:pfam07177  78 TDL-RPGYWVVALSGSYLQEGDRLGFWVTSDGELHFSVNGEDQGVALSGVPDSQPLWAVFDLYGQTTQVSILG 149

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 1907131870 499 GQWSDECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKALHACCPICRRPIKDIIKTYRS 557
Cdd:cd16785     1 GSWSDECTICYENAVDTVIYTCGHMCLCYACGLRLKKMLNACCPICRRAIKDIIKTYRS 59

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 1907131870 502 SDECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKAlHACCPICRRPIKDIIKTY 555
Cdd:cd16647     1 GSECVICYERPVDTVLYRCGHMCMCYDCALQLKRR-GGSCPICRAPIKDVIKIY 53

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1907131870 503 DECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKaLHACCPICRRPIKDI 551
Cdd:pfam13920   3 LLCVICLDRPRNVVLLPCGHLCLCEECAERLLR-KKKKCPICRQPIESV 50

RING finger, HC subclass, found in caspases-8 and -10-associated RING finger protein CARP-1, CARP-2 and similar proteins; The CARP subfamily includes CARP-1 and CARP-2 proteins, both of which are E3 ubiquitin ligases that ubiquitinate apical caspases and target them for proteasome-mediated degradation. As a novel group of caspase regulators with a FYVE-type zinc finger domain, they do not localize to membranes in the cell and are involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8, and caspase 10. Moreover, they stabilize MDM2 by inhibiting MDM2 self-ubiquitination, as well as by targeting 14-3-3sigma for degradation. They work together with MDM2 to enhance p53 degradation, thereby inhibiting p53-mediated cell death. CARPs contain an N-terminal FYVE-like domain that can serve as a membrane-targeting or endosome localizing signal and a C-terminal C3HC4-type RING-HC finger domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907131870 503 DECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKalhacCPICRRPIKDIIKTY 555
Cdd:cd16500     1 DLCKICMDAAIDCVLLECGHMVTCTDCGKKLSE-----CPICRQYVVRVVHFF 48

Modified RING finger, HC subclass (C2H2C4-type), found in E3 ubiquitin-protein ligase MDM2, protein MDM4 and similar proteins; MDM2 (also known as HDM2) and MDM4 (also known as MDMX or HDMX) are the primary p53 tumor suppressor negative regulators. They have non-redundant roles in the regulation of p53. MDM2 mainly functions to control p53 stability, while MDM4 controls p53 transcriptional activity. Both MDM2 and MDM4 contain an N-terminal p53-binding domain, a RanBP2-type zinc finger (zf-RanBP2) domain near the central acidic region, and a C-terminal modified C2H2C4-type RING-HC finger. Mdm2 can form homo-oligomers through its RING domain and displays E3 ubiquitin ligase activity that catalyzes the attachment of ubiquitin to p53 as an essential step in the regulation of its levels in cells. Despite its RING domain and structural similarity with MDM2, MDM4 does not homo-oligomerize and lacks ubiquitin-ligase function, but inhibits the transcriptional activity of p53. In addition, both their RING domains are responsible for the hetero-oligomerization, which is crucial for the suppression of P53 activity during embryonic development and the recruitment of E2 ubiquitin-conjugating enzymes. Moreover, MDM2 and MDM4 can be phosphorylated and destabilized in response to DNA damage stress. In response to ribosomal stress, MDM2-mediated p53 ubiquitination and degradation can be inhibited through the interaction with ribosomal proteins L5, L11, and L23. However, MDM4 is not bound to ribosomal proteins, suggesting its different response to regulation by small basic proteins such as ribosomal proteins and ARF.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907131870 503 DECTICYEHAVDTVIY--TCGHMCLCYSCGLRLKKAlHACCPICRRPIKDIIK 553
Cdd:cd16646     1 DLCVICLSRPRTAAIVhgKTGHQVACYTCAKKLKRR-GKPCPVCRRPIQNVIK 52

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 1907131870 504 ECTICYEHAVDTVIYTCGHMClCYSCGLRLKKALHACCPIC 544
Cdd:cd16449     2 ECPICLERLKDPVLLPCGHVF-CRECIRRLLESGSIKCPIC 41

RING finger, HC subclass, found in RING finger and SPRY domain-containing protein 1 (RSPRY1) and similar proteins; RSPRY1 is a hypothetical RING and SPRY domain-containing protein of unknown physiological function. Mutations in its corresponding gene RSPRY1 may associate with a distinct skeletal dysplasia syndrome. RSPRY1 contains a B30.2/SPRY domain and a C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1907131870 503 DECTICYEHAVDTVIYTCGHMCLCYSCGLRLKkalhaCCPICRRPI 548
Cdd:cd16566     3 DSCTLCFDKVADTELRPCGHSGFCMECALQLE-----TCPLCRQPI 43

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        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907131870 505 CTICYEHAVDTVIYTCGHMCLCYSCGLRLKKalhacCPICRRPIKDIIKTYRS 557
Cdd:cd16706     7 CRICMDAVIDCVLLECGHMVTCTKCGKRMSE-----CPICRQYVVRAVHVFKS 54

RING finger, HC subclass, found in inhibitor of apoptosis proteins (IAPs); IAPs are frequently overexpressed in cancer and associated with tumor cell survival, chemoresistance, disease progression, and poor prognosis. They function primarily as negative regulators of cell death. They regulate caspases and apoptosis through the inhibition of specific members of the caspase family of cysteine proteases. In addition, IAPs has been implicated in a multitude of other cellular processes, including inflammatory signalling and immunity, mitogenic kinase signalling, proliferation and mitosis, as well as cell invasion and metastasis. IAPs in this family includes cellular inhibitor of apoptosis protein c-IAP1 (BIRC2) and c-IAP2 (BIRC3), XIAP (BIRC4), BIRC7, and BIRC8, all of which 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), and a C3HC4-type RING-HC finger at the carboxyl terminus that is required for ubiquitin ligase activity. The UBA domain is only absent in mammalian homologs of BIRC7. Moreover, c-IAPs contains an additional caspase activation and recruitment domain (CARD) between the UBA and C3HC4-type RING-HC domains. The CARD domain may serve as a protein interaction surface.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1907131870 505 CTICYEHAVDTVIYTCGHMCLCYSCGLRLKKalhacCPICR 545
Cdd:cd16510     4 CKICMDREVNIVFLPCGHLVTCAQCAASLRK-----CPICR 39

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 1907131870 505 CTICYEHAVDTVIYTCGHMCLCYSCGLRLKKalhacCPICRRPIKDIIKTYRS 557
Cdd:cd16713    10 CKVCMDKEVSIVFIPCGHLVVCTECAPSLRK-----CPICRATIKGTVRTFLS 57

RING finger, HC subclass, found in mind bomb MIB1, MIB2, RGLG1, RGLG2, and similar proteins; MIBs are large, multi-domain E3 ubiquitin-protein ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. They are also responsible for TBK1 K63-linked ubiquitination and activation, promoting interferon production and controlling antiviral immunity. Moreover, MIBs selectively control responses to cytosolic RNA and regulate type I interferon transcription. Both MIB1 and MIB2 have similar domain architectures, which consist of two Mib-Herc2 domains flanking a ZZ zinc finger, a REP region including two tandem Mib repeats, an ANK region that spans ankyrin repeats, and a RNG region, where MIB1 and MIB2 contain three and two C3HC4-type RING-HC fingers, respectively. This model corresponds to the third RING-HC finger of MIB1, as well as the second RING-HC finger of MIB2. In addition to MIB1 and MIB2, the RING-HC fingers of RING domain ligase RGLG1, RGLG2 and similar proteins from plant are also included in this model. RGLG1 is a ubiquitously expressed E3 ubiquitin-protein ligase that interacts with UBC13 and, together with UBC13, catalyzes the formation of K63-linked polyubiquitin chains, which is involved in DNA damage repair. RGLG1 mediates the formation of canonical, K48-linked polyubiquitin chains that target proteins for degradation. It also regulates apical dominance by acting on the auxin transport proteins abundance. RGLG1 has overlapping functions with its closest sequelog, RGLG2. They both function as RING E3 ligases that interact with ethylene response factor 53 (ERF53) in the nucleus and negatively regulate the plant drought stress response. All RGLG proteins contain a Von Willebrand factor type A (vWA) domain and a C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1907131870 504 ECTICYEHAVDTViYTCGHmCLCYSCGLRLKKalhacCPICRRPI 548
Cdd:cd16520     2 LCPICMERKKNVV-FLCGH-GTCQKCAEKLKK-----CPICRKPI 39

RING finger, HC subclass, found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is a telomere-associated E3 ubiquitin-protein ligase that plays an important role in DNA double-strand break (DSB) repair via histone ubiquitination. It is localized in the nucleus and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless). It recruits UBC13 for lysine 63-based self polyubiquitylation. Its deficiency causes neuronal pathology and cognitive decline, and its loss results in neuron degeneration. RNF8, together with RNF168, catalyzes a series of ubiquitylation events on substrates such as H2A and H2AX, with the H2AK13/15 ubiquitylation being particularly important for recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of DSBs. RNF8 mediates the ubiquitination of gammaH2AX, and recruits 53BP1 and BRCA1 to DNA damage sites which promotes DNA damage response (DDR) and inhibits chromosomal instability. Moreover, RNF8 interacts with retinoid X receptor alpha (RXR alpha) and enhances its transcription-stimulating activity. It also regulates the rate of exit from mitosis and cytokinesis. RNF8 contains an N-terminal forkhead-associated (FHA) domain and a C-terminal C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1907131870 504 ECTICYEHAVDTVIYTCGHM--CLCYSCGLRLKKAlhacCPICRRPIK 549
Cdd:cd16535     3 QCSICSELFIEAVTLNCSHSfcSYCITEWMKRKKE----CPICRKPIT 46

RING finger, HC subclass, found in Arabidopsis thaliana MND1-interacting protein 1 (MIP1) and similar proteins; This subfamily includes Arabidopsis thaliana MIP1, RING finger protein 4 (RF4) and RING finger protein 298 (RF298). MIP1 interacts with MND1, HOP2 and XRI1. RF4 and RF298 are putative E3 ubiquitin-protein ligase that may mediate E2-dependent protein ubiquitination. Members of this subfamily contain a typical C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907131870 504 ECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKALHACCPICRRPIKDIIK 553
Cdd:cd23128     5 ECVMCMEEERSVVFLPCAHQVVCSGCNDLHEKKGMRECPSCRGEIQERIR 54

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 1907131870 502 SDECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKALHAcCPICRRPIKDIIK 553
Cdd:cd16817     4 SAECVVCLSDVRDTLILPCRHLCLCNACADTLRYQANN-CPICRLPFRALLQ 54

RING finger, HC subclass, found in RNA-binding protein MEX3A; MEX3A, also known as RING finger and KH domain-containing protein 4 (RKHD4), 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 has been implicated in the regulation of tumorigenesis. It controls the polarity and stemness of intestinal epithelial cells through the post-transcriptional regulation of the homeobox transcription factor CDX2, which plays a crucial role in intestinal cell fate specification, both during normal development and in tumorigenic processes involving intestinal reprogramming. Moreover, it exhibits a transforming activity when overexpressed in gastric epithelial cells. MEX3A 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, MEX3A shuttles between the nucleus and the cytoplasm via the CRM1-dependent export pathway.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907131870 502 SDECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKALHACCPICRRPIKDIIKTY 555
Cdd:cd16720     2 GRDCMVCFESEVTAALVPCGHNLFCMECAVRICERNEPECPVCHALATQAIRIF 55

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 1907131870 503 DECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKalhACCPICR 545
Cdd:cd16649     1 GLCVVCLENPASVLLLPCRHLCLCEVCAKGLRG---KTCPICR 40

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 1907131870  505 CTICYEH-AVDTVIYTCGHMcLCYSCGLRLKKALHACCPIC 544
Cdd:smart00184   1 CPICLEEyLKDPVILPCGHT-FCRSCIRKWLESGNNTCPIC 40

RING finger, HC subclass, found in zinc finger protein 598 (ZNF598) and similar proteins; ZNF598 associates with eukaryotic initiation factor 4E (eIF4E) homologous protein from mammals (m4EHP) by binding to Grb10-interacting GYF protein 2 (GIGYF2). The m4EHP-GIGYF2 complex functions as a translational repressor and is essential for normal embryonic development of mammalian. ZNF598 harbors a C3HC4-type RING-HC finger at its N-terminus.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1907131870 503 DECTICYEHAVDTVIYTCGHMClCYSCGLRL-----KKAlhacCPICRRPIKDII 552
Cdd:cd16615     1 ETCVICCEEIEYFAVGPCNHPV-CYKCSLRMrvlykDKY----CPICRTELDKVI 50

RING finger, HC subclass, found in RNA-binding protein MEX3D; MEX3D, also known as RING finger and KH domain-containing protein 1 (RKHD1), RING finger protein 193 (RNF193), or TINO, is an RNA-binding phosphoprotein that controls the stability of the transcripts coding for the anti-apoptotic protein BCL-2, and negatively regulates BCL-2 in HeLa cells. MEX3D 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, MEX3D shuttles between the nucleus and the cytoplasm via the CRM1-dependent export pathway.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907131870 504 ECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKALHACCPICRRPIKDIIKTY 555
Cdd:cd16723    12 ECVVCFESEVIAALVPCGHNLFCMECAIRICGKSEPECPACHTPATQAIHIF 63

RING finger, HC subclass, found in Caenorhabditis elegans BRCA1-associated RING domain protein 1 (CeBARD1) and similar proteins; CeBARD1, also called Ce-BRD-1, Cebrd-1, or RING-type E3 ubiquitin transferase BARD1, is a constituent of the CeBCD complex that possesses E3 ubiquitin-protein ligase activity. It plays a role in triggering cellular responses at damage sites in response to DNA damage that may be induced by ionizing radiation. It protects against chromosome non-disjunction and nuclear fragmentation during meiotic double-strand break repair to ensure sister chromatid recombination and aid chromosome stability. CeBARD1 contains a typical C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1907131870 504 ECTICYEHAVDTV-IYTCGHMcLCYSCGLRLKKALHaCCPICRRPI 548
Cdd:cd23143     3 ECVICSEPQIDTFlLSSCGHI-YCWECFTEFIEKRH-MCPSCRFPL 46

RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also known as RING finger protein 53 (RNF53), is a RING finger protein encoded by the tumor suppressor gene BRCA1 that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT (BRCA1 C-terminus domain) repeats at the C-terminus.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1907131870 504 ECTICYEHAVDTVIYTCGHMcLCYSCGLRL--KKALHACCPICRRPI 548
Cdd:cd16498    18 ECPICLELLKEPVSTKCDHQ-FCRFCILKLlqKKKKPAPCPLCKKSV 63

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 1907131870 504 ECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKALHACCPICRRPIKDIIKTY 555
Cdd:cd16722     3 DCVICFENEVIAALVPCGHNLFCMECANKICEKETPSCPVCQTAVTQAIQIH 54

RING finger, HC subclass, found in RING domain ligase RGLG1, RGLG2 and similar proteins from plant; RGLG1 is a ubiquitously expressed E3 ubiquitin-protein ligase that interacts with UBC13 and, together with UBC13, catalyzes the formation of K63-linked polyubiquitin chains, which is involved in DNA damage repair. RGLG1 mediates the formation of canonical, K48-linked polyubiquitin chains that target proteins for degradation. It also regulates apical dominance by acting on the auxin transport proteins abundance. RGLG1 has overlapping functions with its closest sequelog, RGLG2. They both function as RING E3 ligases that interact with ethylene response factor 53 (ERF53) in the nucleus and negatively regulate the plant drought stress response. Members of this subfamily contain a Von Willebrand factor type A (vWA) domain and a C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907131870 502 SDECTICYEHAVDtVIYTCGHMClCYSCGLRLKKalhacCPICRRPIKDIIKTY 555
Cdd:cd16729     2 DQLCPICLSNPKD-MAFGCGHQT-CCECGQSLTH-----CPICRQPITTRIKLY 48

RING finger, HC subclass, found in RING finger protein 222 (RNF222) and similar proteins; RNF222 is an uncharacterized C3HC4-type RING-HC finger-containing protein. It may function as an E3 ubiquitin-protein ligase.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1907131870 504 ECTICYEHAVD-TVIYTCGHMcLCYSCGLRLKKALHACCPICRRPI 548
Cdd:cd16564     2 ECPVCYEDFDDaPRILSCGHS-FCEDCLVKQLVSMTISCPICRRVT 46

RING finger, HC subclass, found in Mus musculus tripartite motif-containing protein 43 (TRIM43) and similar propteins; This subfamily includes TRIM43A, TRIM43B and TRIM43C, which are expressed specifically in mouse preimplantation embryos. They contain a typical C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1907131870 505 CTICYEHAVDTVIYTCGHMcLCYSCGLRLKK--ALHACCPICRRPI 548
Cdd:cd23133     6 CSICQGIFMNPVYLRCGHK-FCEACLLLFQEdiKFPAYCPMCRQPF 50

RING finger, HC subclass, found in RING finger protein RNF5, RNF185 and similar proteins; RNF5 and RNF185 are E3 ubiquitin-protein ligases that are anchored to the outer membrane of the endoplasmic reticulum (ER). RNF5 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. RNF185 controls the degradation of CFTR and CFTR F508del allele in a RING- and proteasome-dependent manner, but does not control that of other classical endoplasmic reticulum-associated degradation (ERAD) model substrates. Moreover, both RNF5 and RNF185 play important roles in cell adhesion and migration through the modulation of cell migration by ubiquitinating paxillin. Arabidopsis thaliana RING membrane-anchor proteins (AtRMAs) are also included in this family. They possess E3 ubiquitin-protein ligase activity and may play a role in the growth and development of Arabidopsis. All members of this family contain a C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1907131870 504 ECTICYEHAVDTVIYTCGHMcLCYSCGLR--LKKALHACCPICR 545
Cdd:cd16534     2 ECNICLDTASDPVVTMCGHL-FCWPCLYQwlETRPDRQTCPVCK 44

RING finger, HC subclass, found in Arabidopsis thaliana SP1-like protein 2 (SPL2) and similar proteins; SPL2, also known as RING-type E3 ubiquitin transferase SPL2, acts as an E3 ubiquitin-protein ligase that mediates E2-dependent protein ubiquitination. SPL2 contains a typical C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1907131870 505 CTICYEHAVDTVIYTCGHMCLCYSCGLRLKKALHACCPICRR 546
Cdd:cd23145     6 CVVCLLRRRRVAFIECGHRVCCELCARRVTREANPRCPVCRQ 47

RING finger, HC subclass, found in RING finger protein 168 (RNF168) and similar proteins; RNF168 is an E3 ubiquitin-protein ligase that promotes noncanonical K27 ubiquitination to signal DNA damage. It, together with RNF8, functions as a DNA damage response (DDR) factor that promotes a series of ubiquitylation events on substrates, such as H2A and H2AX with H2AK13/15 ubiquitylation, facilitates recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of double-strand breaks (DSBs), and inhibits homologous recombination (HR) in cells deficient in the tumor suppressor BRCA1. RNF168 also promotes H2A neddylation, which antagonizes ubiquitylation of H2A and regulates DNA damage repair. Moreover, RNF168 forms a functional complex with RAD6A or RAD6B during the DNA damage response. RNF168 contains an N-terminal C3HC4-type RING-HC finger that catalyzes H2A-K15ub and interacts with H2A, and two MIU (motif interacting with ubiquitin) domains responsible for the interaction with K63 linked poly-ubiquitin.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1907131870 505 CTICYEHAVDTVIYTCGHMcLCYSCGLRLKKALHACCPICRRPI 548
Cdd:cd16550     3 CPICLEILVEPVTLPCNHT-LCMPCFQSTVEKASLCCPLCRLRI 45

first RING finger, HC subclass, found in mind bomb 1 (MIB1) and similar proteins; MIB1, also known as DAPK-interacting protein 1 (DIP-1) or zinc finger ZZ type with ankyrin repeat domain protein 2, is a large, multi-domain E3 ubiquitin-protein ligase that promotes ubiquitination of the cytoplasmic tails of Notch ligands, and thus plays an essential role in controlling metazoan development by Notch signaling. It is also involved in Wnt/beta-catenin signaling and nuclear factor (NF)-kappaB signaling, and has been implicated in innate immunity, neuronal function, genomic stability, and cell death. MIB1 contains an MZM region with two Mib-Herc2 domains flanking a ZZ zinc finger, a REP region including two tandem Mib repeats, an ANK region that spans ankyrin repeats, and a RNG region consisting of three C3HC4-type RING-HC fingers. This model corresponds to the first RING-HC finger.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1907131870 503 DECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKAL 537
Cdd:cd16724     1 EECMVCSDMKRDTLFGPCGHIATCSLCSPRVKKCL 35

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl and similar proteins; Cbl, also known as Casitas B-lineage lymphoma proto-oncogene, proto-oncogene c-Cbl, RING finger protein 55 (RNF55), or signal transduction protein Cbl, is a multi-domain protein that acts as a key negative regulator of various receptor and non-receptor tyrosine kinase signaling. 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 proline-rich domain, a C3HC4-type RING-HC finger, and an ubiquitin-associated (UBA) domain. TKB is responsible for the interactions with many tyrosine kinases, such as the colony-stimulating factor-1 (CSF-1) receptor, Syk/ZAP-70, and Src-family of protein tyrosine kinases. The proline-rich domain can recruit proteins with a SH3 domain. Moreover, Cbl functions as an E3 ubiquitin ligase that can bind ubiquitin-conjugating enzymes (E2s) through the RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1907131870 505 CTICYEHAVDTVIYTCGHMcLCYSCGLRLKKALHACCPICRRPIK 549
Cdd:cd16708    24 CKICAENDKDVKIEPCGHL-MCTSCLTSWQESEGQGCPFCRCEIK 67

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1907131870 503 DECTIC---YEHAVDTVIYTCGHmCLCYSCGLRLKKAlHACCPICR 545
Cdd:pfam13639   1 DECPICleeFEEGDKVVVLPCGH-HFHRECLDKWLRS-SNTCPLCR 44