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 1757649832 318 FTMDCGICYAYQLDGTIPDQVCDNSQCGQPFHQICLYEWLRGLLTSRQSFNIIFGECPYCSKPITLKMS 386
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 1757649832 108 PQFYSSLIEEIGTLGWDKLVYADTCFSTIKLKAEDASGREHLITLKLKAKYPAESPDYFVDFPVPFCASWTPQVtdqakm 187
Cdd:pfam18890   1 PNYYSRLLEELETLGWDKLLQIDPDFTTIRLKAEDSSGRQHYLTLKLPSKYPAELPECSHDLPEPFVLEWTPSQ------ 74

                          90       100
                  ....*....|....*....|....*
gi 1757649832 188 dvkiavlpSSLISIYSQFLAAIESL 212
Cdd:pfam18890  75 --------SSLEEVLQQFLKVLESL 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 1757649832 215 FWDVMDEIDEKTWVLEPEKPPRSATARRIALGNNVSINIEVDPRHPTMLPECFFLGADHVVKPLGIKLSRNIHLWDPENS 294
Cdd:cd23832     1 FWDVLDEIDSNCWVLEPEKPTRSDTYRRIALGNHCSLQITIDPLHPRALPECRFLGPESAVAPLRDKLNRNLSLWDPERS 80

                  ....*....
gi 1757649832 295 VLQNLKDVL 303
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 1757649832 321 DCGICYAYQLDGTIPDQVCDNSQCGQPFHQICLYEWLRGLLTSRQSFNIIFGECPYCS 378
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 1757649832   7 SLLRQCPLLLPQNRSKTVYEGFISAQGRDFHLRIVLPEDLQLKNARLLCSWQLRTILSGYHRIVQQRMQHSPDLMSFMME 86
Cdd:cd23786     1 SLLLKFPLLLPQNDSGTSYEGFITVKGEEFRIRISLPNDPSLKGASLECDWELKQLLSGYEDILKQRLQQCKSLESFLLE 80

                  ....*.
gi 1757649832  87 LKMLLE 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1757649832 116 EEIGTLGWDKLVYADTCFSTIKLKAEDASGREHLITLKLKAKYPAESPDYFVDFPVPFCASWTPQvtdqakmdvkiavlp 195
Cdd:cd23831     1 EELEAIGWDRVSSIDDDLSSITLKIVDSAGREHLLTVKLPSDYPAEPPTCSADLPEPFEFSWSSS--------------- 65

                          90
                  ....*....|
gi 1757649832 196 SSLISIYSQF 205
Cdd:cd23831    66 SSLSDIYEQF 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 1757649832 215 FWDVMDEIDEKTWVLEPEKPPRSATARRIALGNNVSINIEVDPRHPTMLPECFFLGADHVVKPLGIKLSRNIHLWDPENS 294
Cdd:cd23832     1 FWDVLDEIDSNCWVLEPEKPTRSDTYRRIALGNHCSLQITIDPLHPRALPECRFLGPESAVAPLRDKLNRNLSLWDPERS 80

                  ....*....
gi 1757649832 295 VLQNLKDVL 303
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 1757649832 321 DCGICYAYQLDGTIPDQVCDNSQCGQPFHQICLYEWLRGLLTSRQSFNIIFGECPYCS 378
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 1757649832   7 SLLRQCPLLLPQNRSKTVYEGFISAQGRDFHLRIVLPEDLQLKNARLLCSWQLRTILSGYHRIVQQRMQHSPDLMSFMME 86
Cdd:cd23786     1 SLLLKFPLLLPQNDSGTSYEGFITVKGEEFRIRISLPNDPSLKGASLECDWELKQLLSGYEDILKQRLQQCKSLESFLLE 80

                  ....*.
gi 1757649832  87 LKMLLE 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1757649832 116 EEIGTLGWDKLVYADTCFSTIKLKAEDASGREHLITLKLKAKYPAESPDYFVDFPVPFCASWTPQvtdqakmdvkiavlp 195
Cdd:cd23831     1 EELEAIGWDRVSSIDDDLSSITLKIVDSAGREHLLTVKLPSDYPAEPPTCSADLPEPFEFSWSSS--------------- 65

                          90
                  ....*....|
gi 1757649832 196 SSLISIYSQF 205
Cdd:cd23831    66 SSLSDIYEQF 75

RING-CH finger, H2 subclass (C4HC3-type), found in E3 ubiquitin-protein ligase listerin and similar proteins; Listerin, also known as RING finger protein 160 or zinc finger protein 294, is the mammalian homolog of yeast Ltn1. It is widely expressed in all tissues, but motor and sensory neurons and neuronal processes in the brainstem and spinal cord are primarily affected in the mutant. Listerin is required for embryonic development and plays an important role in neurodegeneration. It also functions as a critical E3 ligase involving quality control of nonstop proteins. It mediates ubiquitylation of aberrant proteins that become stalled on ribosomes during translation. Ltn1 works with several cofactors to form a large ribosomal subunit-associated quality control complex (RQC), which mediates the ubiquitylation and extraction of ribosome-stalled nascent polypeptide chains for proteasomal degradation. It appears to first associate with nascent chain-stalled 60S subunits together with two proteins of unknown function, Tae2 and Rqc1. Listerin contains a long stretch of HEAT (Huntingtin, Elongation factor 3, PR65/A subunit of protein phosphatase 2A, and TOR) or ARM (Armadillo) repeats in the N terminus and middle region, and a catalytic RING-CH finger, also known as vRING or RINGv, with an unusual arrangement of zinc-coordinating residues in the C-terminus . 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 1757649832 321 DCGICYA--YQLDGTIPDQVCdnSQCGQPFHQICLYEWLRgllTSRQSfniifgECPYC 377
Cdd:cd16491     2 ECPICYSviHGSNHSLPKLKC--KTCKNKFHSACLYKWFR---SSNKS------TCPLC 49