Modified RING finger found in peroxin-12 (PEX12) and similar proteins; PEX12, also known as peroxisome assembly protein 12 or peroxisome assembly factor 3 (PAF-3), is a RING finger domain-containing integral membrane peroxin required for protein import into peroxisomes. Mutations in human PEX12 result in the peroxisome deficiency Zellweger syndrome of complementation group III (CG-III), a lethal neurological disorder. PEX12 also functions as an E3-ubiquitin ligase that facilitates the PEX4-dependent monoubiquitination of PEX5, a key player in peroxisomal matrix protein import, to control PEX5 receptor recycling or degradation. PEX12 contains a modified RING finger that lacks the third, fourth, and eighth zinc-binding residues of the consensus RING finger motif, suggesting PEX12 may only bind one zinc ion.

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                  ....*....|....*....|....*....|....*....|....*....|....
gi 1123949140 302 TVCPLCRKTRVNDTVLATSGYVFCYRCVFNYVRSHQACPVTGYPTEVQHLIKLY 355
Cdd:cd16451     1 GICPLCRKKRTNPTALATSGYVFCYPCIYRYVKEHGRCPVTGYPASLDHLIKLY 54

Modified RING finger found in peroxin-12 (PEX12) and similar proteins; PEX12, also known as peroxisome assembly protein 12 or peroxisome assembly factor 3 (PAF-3), is a RING finger domain-containing integral membrane peroxin required for protein import into peroxisomes. Mutations in human PEX12 result in the peroxisome deficiency Zellweger syndrome of complementation group III (CG-III), a lethal neurological disorder. PEX12 also functions as an E3-ubiquitin ligase that facilitates the PEX4-dependent monoubiquitination of PEX5, a key player in peroxisomal matrix protein import, to control PEX5 receptor recycling or degradation. PEX12 contains a modified RING finger that lacks the third, fourth, and eighth zinc-binding residues of the consensus RING finger motif, suggesting PEX12 may only bind one zinc ion.

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                  ....*....|....*....|....*....|....*....|....*....|....
gi 1123949140 302 TVCPLCRKTRVNDTVLATSGYVFCYRCVFNYVRSHQACPVTGYPTEVQHLIKLY 355
Cdd:cd16451     1 GICPLCRKKRTNPTALATSGYVFCYPCIYRYVKEHGRCPVTGYPASLDHLIKLY 54

Zinc finger, C3HC4 type (RING finger);

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                  ....*....|....*....|....*....|....*....
gi 1123949140 303 VCPLCRKTRVNDTVLATSGYVFCYRCVFNYVRSHQACPV 341
Cdd:pfam13923   1 MCPICMDMLKDPSTTTPCGHVFCQDCILRALRAGNECPL 39

Modified RING finger found in peroxin-12 (PEX12) and similar proteins; PEX12, also known as peroxisome assembly protein 12 or peroxisome assembly factor 3 (PAF-3), is a RING finger domain-containing integral membrane peroxin required for protein import into peroxisomes. Mutations in human PEX12 result in the peroxisome deficiency Zellweger syndrome of complementation group III (CG-III), a lethal neurological disorder. PEX12 also functions as an E3-ubiquitin ligase that facilitates the PEX4-dependent monoubiquitination of PEX5, a key player in peroxisomal matrix protein import, to control PEX5 receptor recycling or degradation. PEX12 contains a modified RING finger that lacks the third, fourth, and eighth zinc-binding residues of the consensus RING finger motif, suggesting PEX12 may only bind one zinc ion.

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                  ....*....|....*....|....*....|....*....|....*....|....
gi 1123949140 302 TVCPLCRKTRVNDTVLATSGYVFCYRCVFNYVRSHQACPVTGYPTEVQHLIKLY 355
Cdd:cd16451     1 GICPLCRKKRTNPTALATSGYVFCYPCIYRYVKEHGRCPVTGYPASLDHLIKLY 54

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.

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 1123949140 304 CPLCRKTRVNDTvlATS-GYVFCYRCVFNYVRSHQACPVTGYPTEVQHLIKL 354
Cdd:cd16527     3 CSLCLEERRHPT--ATPcGHLFCWSCITEWCNEKPECPLCREPFQPQRLVPL 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.

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                  ....*....|....*....|....*....|....*....
gi 1123949140 304 CPLCRKtRVNDTVLATSGYVFCYRCVFNYVRS-HQACPV 341
Cdd:cd16449     3 CPICLE-RLKDPVLLPCGHVFCRECIRRLLESgSIKCPI 40

Modified RING finger, HC subclass (C3HC3D-type), found in ligand of Numb protein LNX1, LNX2, and similar proteins; The ligand of Numb protein X (LNX) family, also known as PDZ and RING (PDZRN) family, includes LNX1-5, which can interact with Numb, a key regulator of neurogenesis and neuronal differentiation. LNX5 (also known as PDZK4 or PDZRN4L) shows high sequence homology to LNX3 and LNX4, but it lacks the RING domain. LNX1-4 proteins function as E3 ubiquitin ligases and have a unique domain architecture consisting of an N-terminal RING-HC finger for E3 ubiquitin ligase activity and either two or four PDZ domains necessary for substrate-binding. LNX1/LNX2-like proteins contain a modified C3HC3D-type RING-HC finger and four PDZ domains. This model corresponds to the RING finger.

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                  ....*....|....*....|....*....|....*....
gi 1123949140 303 VCPLCRKTrVNDTVLATSGYVFCYRCVFNYVRSHQACPV 341
Cdd:cd16637     3 TCHICLQP-LVEPLDTPCGHTFCYKCLTNYLKIQQCCPL 40

RING finger, HC subclass, found in RING finger protein RNF20, RNF40, and similar proteins; RNF20, also known as BRE1A, and RNF40, also known as BRE1B, are E3 ubiquitin-protein ligases that work together to form a heterodimeric complex that facilitate the K120 monoubiquitination of histone H2B (H2Bub1), a DNA damage-induced histone modification that is crucial for recruitment of the chromatin remodeler SNF2h to DNA double-strand break (DSB) damage sites. RNF20 regulates the cell cycle and differentiation of neural precursor cells (NPCs) and links histone H2B ubiquitylation with inflammation and inflammation-associated cancer. RNF40, also known as 95 kDa retinoblastoma-associated protein (RBP95), was identified as a novel leucine zipper retinoblastoma protein (pRb)-associated protein that may function as a regulation factor in RNA polymerase II-mediated transcription and/or transcriptional processing. All subfamily members contain a C3HC4-type RING-HC finger at its C-terminus.

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                  ....*....|....*....|....*....|....*....|...
gi 1123949140 299 KMKTVCPLCrKTRVNDTVLATSGYVFCYRCV-FNYVRSHQACP 340
Cdd:cd16704     8 KARLTCPCC-NTRKKDAVLTKCFHVFCFECLkTRYETRQRKCP 49

RING finger, HC subclass, found in RING finger protein 40 (RNF40); RNF40, also known as BRE1B or 95 kDa retinoblastoma-associated protein (RBP95), was identified as a novel leucine zipper retinoblastoma protein (pRb)-associated protein that may function as a regulation factor in RNA polymerase II-mediated transcription and/or transcriptional processing. RNF40 also functions as an E3 ubiquitin-protein ligase that forms a heterodimeric complex with BRE1B, also known as RNF40, to facilitate the K120 monoubiquitination of histone H2B (H2Bub1), a DNA damage-induced histone modification that is crucial for recruitment of the chromatin remodeler SNF2h to DNA double-strand break (DSB) damage sites. It cooperates with SUPT16H to induce dynamic changes in chromatin structure during DSB repair. RNF40 contains a C3HC4-type RING-HC finger at the C-terminus.

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                  ....*....|....*....|....*....|....*....|...
gi 1123949140 299 KMKTVCPLCrKTRVNDTVLATSGYVFCYRCVFNYVRSHQ-ACP 340
Cdd:cd16815    21 KARLTCPCC-NTRKKDAVLTKCFHVFCFECVKTRYESRQrKCP 62

Modified RING finger, HC subclass (C2H2C4-type), found in protein MDM4 and similar proteins; MDM4, also known as double minute 4 protein (Hdm4), MDM2-like p53-binding protein, protein MDMX, HDMX, or p53-binding protein MDM4, exerts its oncogenic activity predominantly by binding p53 tumor suppressor and blocking its transcriptional activity. MDM4 is phosphorylated and destabilized in response to DNA damage stress. It can also be specifically dephosphorylated by directly interacting with protein phosphatase 1 (PP1), which may increase its stability and thus inhibit p53 activity. Meanwhile, MDM4 has a p53-independent role in tumorigenesis and cell growth regulation. MDM4 contains an N-terminal p53-binding domain and a C-terminal modified C2H2C4-type RING-HC finger responsible for its hetero-oligomerization, which is crucial for the suppression of P53 activity during embryonic development and the recruitment of E2 ubiquitin-conjugating enzymes. MDM4 also harbors a RanBP2-type zinc finger (zf-RanBP2) domain near the central acidic region.

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                  ....*....|....*....|....*....|....*....|....*....|....
gi 1123949140 304 CPLCRKTRVNDTVL--ATSGYVFCYRCVFNYVRSHQACPVTGYPteVQHLIKLY 355
Cdd:cd16784     6 CSLCQKRPRNGNIVhgRTAHLVTCFHCARRLKKAGAPCPVCKKE--IQMVIKIF 57