FANCL C-terminal domain; This domain is found at the C-terminus of the Fancl protein in humans which is the putative E3 ubiquitin ligase subunit of the FA complex (Fanconi anaemia). Eight subunits of the Fanconi anaemia gene products form a multisubunit nuclear complex which is required for mono-ubiquitination of a downstream FA protein, FANCD2.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 300794353  303 FSMDCGICYARHLNGAIPDQVCNNPQCGQLFHQMCLYEWLRGLSSSRQSFNVFFGECPYCSKPITLKMS 371
Cdd:pfam11793   1 FEMECGICYAYRLGGEIPDQVCDNPKCGQPFHRACLYEWLRGLPSSRQSFNVIFGECPYCSKPITVKMS 69

FANCL UBC-like domain 2; This entry represents the second of three UBC-like domain found in the FANCL protein, which is the catalytic E3 ubiquitin ligase subunit of the FA complex (Fanconi anaemia). Eight subunits of the Fanconi anaemia gene products form a multisubunit nuclear complex which is required for mono-ubiquitination of a downstream FA protein, FANCD2.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300794353  112 KDLLTEIGAIGWDKLACVDTSFTTIKLKADDASGRKHLITVKLKAKYPVEPPDCLVDFPIPFSVSWTP-QSSLVNVYSQF 190
Cdd:pfam18890   5 SRLLEELETLGWDKLLQIDPDFTTIRLKAEDSSGRQHYLTLKLPSKYPAELPECSHDLPEPFVLEWTPsQSSLEEVLQQF 84

                  ....*..
gi 300794353  191 SAALETL 197
Cdd:pfam18890  85 LKVLESL 91

C-terminal double-RWD domain of Fanconi anemia group L protein (FANCL) and related proteins; FANCL, also called E3 ubiquitin-protein ligase FANCL, Fanconi anemia-associated polypeptide of 43 kDa (FAAP43), or RING-type E3 ubiquitin transferase FANCL, is an E3 ubiquitin-protein ligase component of the Fanconi anemia (FA) core complex which functions in the repair of interstrand crosslinks (ICLs), a toxic form of DNA damage. FANCL, works in conjunction with the E2 conjugating enzyme UBE2T (FANCT) to add a single ubiquitin to specific lysine residues on FANCD2 and FANCI. The mono-ubiquitinated FANCI-FANCD2 complex is thought to recruit downstream DNA-repair proteins for ICL processing. FANCL is composed of an N-terminal E2-like fold (ELF) domain, a novel double-RWD (DRWD) domain, and a C-terminal RING domain predicted to facilitate E2 binding. The DRWD domain is responsible for substrate binding. The model corresponds to the C-terminal DRWD domain (DRWD-C).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300794353 200 FWDVMDEIDEKTWVLEPEKPPRSATARRIALGHDVSINIEVDPRHPTMLPEFCFLGADHVTKPLGMRLSGNIHLWDPENS 279
Cdd:cd23832    1 FWDVLDEIDSNCWVLEPEKPTRSDTYRRIALGNHCSLQITIDPLHPRALPECRFLGPESAVAPLRDKLNRNLSLWDPERS 80

                 ....*....
gi 300794353 280 LLQNLKDVL 288
Cdd:cd23832   81 LLENLERLL 89

RING-CH finger, H2 subclass (C4HC3-type), found in Fanconi anemia group L protein (FANCL) and similar proteins; FANCL, also known as fanconi anemia-associated polypeptide of 43 kDa (FAAP43) or PHF9, is a monomeric RING E3 ubiquitin-protein ligase that monoubiquitinates FANCD2 and FANCI. The monoubiquitinated FANCD2-FANCI heterodimer complex in turn recruits key proteins involved in homologous recombination and DNA repair. FANCL is also one of seven components in Fanconi anemia (FA) nuclear core complex, which provides the essential E3 ligase function for spatially defined FANCD2 ubiquitination and FA pathway activation. In the FA core complex, FANCL associates with FANCB and FAAP100 to constitute a catalytic subcomplex that functions as the monoubiquitination module. FANCL specifically interacts with the E2 ubiquitin-conjugating (UBC) enzyme Ube2T to make an E3-E2 pair, which is the catalytic center of the Fanconi Anemia (FA) pathway required for DNA interstrand crosslink repair. Moreover, FANCL has a noncanonical function to regulate the Wnt/beta-catenin signaling, a pathway involved in hematopoietic stem cell self-renewal. It functionally enhances beta-catenin activity by ubiquitinating beta-catenin, with atypical ubiquitin chains (K11 linked). FANCL contains an N-terminal E2-like fold (ELF) domain, a novel double-RWD (DRWD) domain with a clear hydrophobic core, and a C-terminal C4HC3-type RING-CH finger. The DRWD domain is required for substrate binding. The RING-CH finger, also known as vRING or RINGv, is predicted to facilitate E2 binding. It has an unusual arrangement of zinc-coordinating residues. Its cysteines and histidines are arranged in the sequence as C4HC3-type, rather than the C3H2C3-type in canonical RING-H2 finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 300794353 306 DCGICYARHLNGAIPDQVCNNPQCGQLFHQMCLYEWLRGLSSSRQSFNVFFGECPYCS 363
Cdd:cd16490    1 ECGICYAYRLDGEVPDQVCDNARCGQPFHQSCLYEWLRSLPSTRQSFNTIFGECPYCS 58

N-terminal E2-like Fold (ELF) domain of Fanconi anemia group L protein (FANCL) and related proteins; FANCL, also called E3 ubiquitin-protein ligase FANCL, Fanconi anemia-associated polypeptide of 43 kDa (FAAP43), or RING-type E3 ubiquitin transferase FANCL, is an E3 ubiquitin-protein ligase component of the Fanconi anemia (FA) core complex which functions in the repair of interstrand crosslinks (ICLs), a toxic form of DNA damage. FANCL, works in conjunction with the E2 conjugating enzyme UBE2T (FANCT) to add a single ubiquitin to specific lysine residues on FANCD2 and FANCI. The mono-ubiquitinated FANCI-FANCD2 complex is thought to recruit downstream DNA-repair proteins for ICL processing. FANCL is composed of an N-terminal E2-like fold (ELF) domain, a novel double-RWD (DRWD) domain, and a C-terminal RING domain predicted to facilitate E2 binding. The model corresponds to the ELF domain which cannot bind the substrates.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300794353   7 NLLRHFPLLLPQNREKTVYEGFISAQGRDFHLRIVLPKDQQLKKARLLCSWQLKNILNEYHQVVQQRMKHSPDLMSFMME 86
Cdd:cd23786    1 SLLLKFPLLLPQNDSGTSYEGFITVKGEEFRIRISLPNDPSLKGASLECDWELKQLLSGYEDILKQRLQQCKSLESFLLE 80

                 ....*.
gi 300794353  87 LKIILE 92
Cdd:cd23786   81 LKDLLE 86

N-terminal double-RWD domain of Fanconi anemia group L protein (FANCL) and related proteins; FANCL, also called E3 ubiquitin-protein ligase FANCL, Fanconi anemia-associated polypeptide of 43 kDa (FAAP43), or RING-type E3 ubiquitin transferase FANCL, is an E3 ubiquitin-protein ligase component of the Fanconi anemia (FA) core complex which functions in the repair of interstrand crosslinks (ICLs), a toxic form of DNA damage. FANCL, works in conjunction with the E2 conjugating enzyme UBE2T (FANCT) to add a single ubiquitin to specific lysine residues on FANCD2 and FANCI. The mono-ubiquitinated FANCI-FANCD2 complex is thought to recruit downstream DNA-repair proteins for ICL processing. FANCL is composed of an N-terminal E2-like fold (ELF) domain, a novel double-RWD (DRWD) domain, and a C-terminal RING domain predicted to facilitate E2 binding. The DRWD domain is responsible for substrate binding. The model corresponds to the N-terminal DRWD domain (DRWD-N).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 300794353 116 TEIGAIGWDKLACVDTSFTTIKLKADDASGRKHLITVKLKAKYPVEPPDCLVDFPIPFSVSWTPQSSLVNVYSQF 190
Cdd:cd23831    1 EELEAIGWDRVSSIDDDLSSITLKIVDSAGREHLLTVKLPSDYPAEPPTCSADLPEPFEFSWSSSSSLSDIYEQF 75

C-terminal double-RWD domain of Fanconi anemia group L protein (FANCL) and related proteins; FANCL, also called E3 ubiquitin-protein ligase FANCL, Fanconi anemia-associated polypeptide of 43 kDa (FAAP43), or RING-type E3 ubiquitin transferase FANCL, is an E3 ubiquitin-protein ligase component of the Fanconi anemia (FA) core complex which functions in the repair of interstrand crosslinks (ICLs), a toxic form of DNA damage. FANCL, works in conjunction with the E2 conjugating enzyme UBE2T (FANCT) to add a single ubiquitin to specific lysine residues on FANCD2 and FANCI. The mono-ubiquitinated FANCI-FANCD2 complex is thought to recruit downstream DNA-repair proteins for ICL processing. FANCL is composed of an N-terminal E2-like fold (ELF) domain, a novel double-RWD (DRWD) domain, and a C-terminal RING domain predicted to facilitate E2 binding. The DRWD domain is responsible for substrate binding. The model corresponds to the C-terminal DRWD domain (DRWD-C).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300794353 200 FWDVMDEIDEKTWVLEPEKPPRSATARRIALGHDVSINIEVDPRHPTMLPEFCFLGADHVTKPLGMRLSGNIHLWDPENS 279
Cdd:cd23832    1 FWDVLDEIDSNCWVLEPEKPTRSDTYRRIALGNHCSLQITIDPLHPRALPECRFLGPESAVAPLRDKLNRNLSLWDPERS 80

                 ....*....
gi 300794353 280 LLQNLKDVL 288
Cdd:cd23832   81 LLENLERLL 89

RING-CH finger, H2 subclass (C4HC3-type), found in Fanconi anemia group L protein (FANCL) and similar proteins; FANCL, also known as fanconi anemia-associated polypeptide of 43 kDa (FAAP43) or PHF9, is a monomeric RING E3 ubiquitin-protein ligase that monoubiquitinates FANCD2 and FANCI. The monoubiquitinated FANCD2-FANCI heterodimer complex in turn recruits key proteins involved in homologous recombination and DNA repair. FANCL is also one of seven components in Fanconi anemia (FA) nuclear core complex, which provides the essential E3 ligase function for spatially defined FANCD2 ubiquitination and FA pathway activation. In the FA core complex, FANCL associates with FANCB and FAAP100 to constitute a catalytic subcomplex that functions as the monoubiquitination module. FANCL specifically interacts with the E2 ubiquitin-conjugating (UBC) enzyme Ube2T to make an E3-E2 pair, which is the catalytic center of the Fanconi Anemia (FA) pathway required for DNA interstrand crosslink repair. Moreover, FANCL has a noncanonical function to regulate the Wnt/beta-catenin signaling, a pathway involved in hematopoietic stem cell self-renewal. It functionally enhances beta-catenin activity by ubiquitinating beta-catenin, with atypical ubiquitin chains (K11 linked). FANCL contains an N-terminal E2-like fold (ELF) domain, a novel double-RWD (DRWD) domain with a clear hydrophobic core, and a C-terminal C4HC3-type RING-CH finger. The DRWD domain is required for substrate binding. The RING-CH finger, also known as vRING or RINGv, is predicted to facilitate E2 binding. It has an unusual arrangement of zinc-coordinating residues. Its cysteines and histidines are arranged in the sequence as C4HC3-type, rather than the C3H2C3-type in canonical RING-H2 finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 300794353 306 DCGICYARHLNGAIPDQVCNNPQCGQLFHQMCLYEWLRGLSSSRQSFNVFFGECPYCS 363
Cdd:cd16490    1 ECGICYAYRLDGEVPDQVCDNARCGQPFHQSCLYEWLRSLPSTRQSFNTIFGECPYCS 58

N-terminal E2-like Fold (ELF) domain of Fanconi anemia group L protein (FANCL) and related proteins; FANCL, also called E3 ubiquitin-protein ligase FANCL, Fanconi anemia-associated polypeptide of 43 kDa (FAAP43), or RING-type E3 ubiquitin transferase FANCL, is an E3 ubiquitin-protein ligase component of the Fanconi anemia (FA) core complex which functions in the repair of interstrand crosslinks (ICLs), a toxic form of DNA damage. FANCL, works in conjunction with the E2 conjugating enzyme UBE2T (FANCT) to add a single ubiquitin to specific lysine residues on FANCD2 and FANCI. The mono-ubiquitinated FANCI-FANCD2 complex is thought to recruit downstream DNA-repair proteins for ICL processing. FANCL is composed of an N-terminal E2-like fold (ELF) domain, a novel double-RWD (DRWD) domain, and a C-terminal RING domain predicted to facilitate E2 binding. The model corresponds to the ELF domain which cannot bind the substrates.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300794353   7 NLLRHFPLLLPQNREKTVYEGFISAQGRDFHLRIVLPKDQQLKKARLLCSWQLKNILNEYHQVVQQRMKHSPDLMSFMME 86
Cdd:cd23786    1 SLLLKFPLLLPQNDSGTSYEGFITVKGEEFRIRISLPNDPSLKGASLECDWELKQLLSGYEDILKQRLQQCKSLESFLLE 80

                 ....*.
gi 300794353  87 LKIILE 92
Cdd:cd23786   81 LKDLLE 86

N-terminal double-RWD domain of Fanconi anemia group L protein (FANCL) and related proteins; FANCL, also called E3 ubiquitin-protein ligase FANCL, Fanconi anemia-associated polypeptide of 43 kDa (FAAP43), or RING-type E3 ubiquitin transferase FANCL, is an E3 ubiquitin-protein ligase component of the Fanconi anemia (FA) core complex which functions in the repair of interstrand crosslinks (ICLs), a toxic form of DNA damage. FANCL, works in conjunction with the E2 conjugating enzyme UBE2T (FANCT) to add a single ubiquitin to specific lysine residues on FANCD2 and FANCI. The mono-ubiquitinated FANCI-FANCD2 complex is thought to recruit downstream DNA-repair proteins for ICL processing. FANCL is composed of an N-terminal E2-like fold (ELF) domain, a novel double-RWD (DRWD) domain, and a C-terminal RING domain predicted to facilitate E2 binding. The DRWD domain is responsible for substrate binding. The model corresponds to the N-terminal DRWD domain (DRWD-N).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 300794353 116 TEIGAIGWDKLACVDTSFTTIKLKADDASGRKHLITVKLKAKYPVEPPDCLVDFPIPFSVSWTPQSSLVNVYSQF 190
Cdd:cd23831    1 EELEAIGWDRVSSIDDDLSSITLKIVDSAGREHLLTVKLPSDYPAEPPTCSADLPEPFEFSWSSSSSLSDIYEQF 75

H2 subclass of RING (RING-H2) fingers and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serves as a scaffold for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 300794353 307 CGICyarhLNGAIPDQVCNNPQCGQLFHQMCLYEWLRGLSSSrqsfnvffgeCPYC 362
Cdd:cd16448    1 CVIC----LEEFEEGDVVRLLPCGHVFHLACILRWLESGNNT----------CPLC 42

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 300794353  307 CGICYARHlNGAIPDqvCNNP---------QCGQLFHQMCLYEWLRGLSSSrqsfnvffGECPYCSKPITLK 369
Cdd:pfam12861  24 CGICRVSF-DGTCPD--CKFPgddcplvwgKCSHNFHMHCILKWLHTETSK--------GLCPMCRQTFKFA 84