UniProtKB - Q9NW38 (FANCL_HUMAN)
E3 ubiquitin-protein ligase FANCL
FANCL
Functioni
Ubiquitin ligase protein that mediates monoubiquitination of FANCD2 in the presence of UBE2T, a key step in the DNA damage pathway (PubMed:12973351, PubMed:16916645, PubMed:17938197, PubMed:19111657, PubMed:24389026).
Also mediates monoubiquitination of FANCI (PubMed:19589784).
May stimulate the ubiquitin release from UBE2W. May be required for proper primordial germ cell proliferation in the embryonic stage, whereas it is probably not needed for spermatogonial proliferation after birth.
6 PublicationsCaution
Catalytic activityi
- S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.4 Publications EC:2.3.2.27
: protein ubiquitination Pathwayi
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 307 | Zinc 1Combined sources | 1 | |
Metal bindingi | 310 | Zinc 1Combined sources | 1 | |
Metal bindingi | 324 | Zinc 2Combined sources | 1 | |
Metal bindingi | 329 | Zinc 2Combined sources | 1 | |
Metal bindingi | 334 | Zinc 1; via pros nitrogenCombined sources | 1 | |
Metal bindingi | 337 | Zinc 1Combined sources | 1 | |
Metal bindingi | 359 | Zinc 2Combined sources | 1 | |
Metal bindingi | 362 | Zinc 2Combined sources | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 307 – 365 | RING-typeAdd BLAST | 59 |
GO - Molecular functioni
- metal ion binding Source: UniProtKB-KW
- ubiquitin protein ligase activity Source: MGI
- ubiquitin protein ligase binding Source: UniProtKB
- ubiquitin-protein transferase activity Source: UniProtKB
GO - Biological processi
- cellular response to DNA damage stimulus Source: UniProtKB
- DNA repair Source: UniProtKB
- gamete generation Source: Ensembl
- interstrand cross-link repair Source: ComplexPortal
- protein monoubiquitination Source: UniProtKB
- regulation of cell population proliferation Source: Ensembl
Keywordsi
Molecular function | Transferase |
Biological process | DNA damage, DNA repair, Ubl conjugation pathway |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 2.3.2.27, 2681 |
PathwayCommonsi | Q9NW38 |
Reactomei | R-HSA-6783310, Fanconi Anemia Pathway |
SignaLinki | Q9NW38 |
SIGNORi | Q9NW38 |
UniPathwayi | UPA00143 |
Names & Taxonomyi
Protein namesi | Recommended name: E3 ubiquitin-protein ligase FANCL (EC:2.3.2.274 Publications)Alternative name(s): Fanconi anemia group L protein Fanconi anemia-associated polypeptide of 43 kDa Short name: FAAP43 RING-type E3 ubiquitin transferase FANCLCurated |
Gene namesi | Name:FANCL Synonyms:PHF9 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:20748, FANCL |
MIMi | 608111, gene |
neXtProti | NX_Q9NW38 |
VEuPathDBi | HostDB:ENSG00000115392 |
Subcellular locationi
Nucleus
- Fanconi anaemia nuclear complex Source: UniProtKB
- nuclear body Source: HPA
- nuclear envelope Source: Ensembl
- nucleoplasm Source: Reactome
- nucleus Source: GO_Central
Other locations
- chromatin Source: ComplexPortal
- cytoplasm Source: UniProtKB-SubCell
- intracellular membrane-bounded organelle Source: HPA
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Involvement in diseasei
Fanconi anemia complementation group L (FANCL)1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 127 – 128 | VY → AA: No effect on interaction with FANCI and FANCD2. 1 Publication | 2 | |
Mutagenesisi | 149 | L → A: No effect on interaction with FANCI and FANCD2; when associated with A-166. 1 Publication | 1 | |
Mutagenesisi | 158 – 159 | YP → AA: Abolishes UBE2T charging. 1 Publication | 2 | |
Mutagenesisi | 166 | F → A: Does not affect interaction with FANCI and FANCD2; when associated with A-149. 1 Publication | 1 | |
Mutagenesisi | 212 – 214 | WVL → AVA: Impairs interaction with FANCI and FANCD2. 1 Publication | 3 | |
Mutagenesisi | 248 | L → A: Impairs interaction with FANCI and FANCD2; when associated with A-252, A-254 and A-265. 1 Publication | 1 | |
Mutagenesisi | 252 | F → A: Impairs interaction with FANCI and FANCD2; when associated with A-248, A-254 and A-265. 1 Publication | 1 | |
Mutagenesisi | 254 | L → A: Impairs interaction with FANCI and FANCD2; when associated with A-248, A-252 and A-265. 1 Publication | 1 | |
Mutagenesisi | 265 | I → A: Impairs interaction with FANCI and FANCD2; when associated with A-248, A-252 and A-254. 1 Publication | 1 | |
Mutagenesisi | 307 | C → A: Abolishes ubiquitin ligase activity. 5 Publications | 1 | |
Mutagenesisi | 309 | I → A: Loss of interaction with UBE2T. 1 Publication | 1 | |
Mutagenesisi | 310 | C → A: Abolishes ubiquitin ligase activity. 2 Publications | 1 | |
Mutagenesisi | 311 | Y → A: Loss of interaction with UBE2T. 1 Publication | 1 | |
Mutagenesisi | 341 | W → A: Loss of interaction with UBE2T. 1 Publication | 1 | |
Mutagenesisi | 341 | W → G: Abolishes interaction with UBE2T and ubiquitin ligase activity. 1 Publication | 1 | |
Mutagenesisi | 359 | C → A: Abolishes ubiquitin ligase activity. 1 Publication | 1 |
Keywords - Diseasei
Fanconi anemiaOrganism-specific databases
DisGeNETi | 55120 |
GeneReviewsi | FANCL |
MalaCardsi | FANCL |
MIMi | 614083, phenotype |
OpenTargetsi | ENSG00000115392 |
Orphaneti | 84, Fanconi anemia |
PharmGKBi | PA134887656 |
Miscellaneous databases
Pharosi | Q9NW38, Tbio |
Genetic variation databases
BioMutai | FANCL |
DMDMi | 116241360 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000055908 | 2 – 375 | E3 ubiquitin-protein ligase FANCLAdd BLAST | 374 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Ubl conjugationProteomic databases
EPDi | Q9NW38 |
jPOSTi | Q9NW38 |
MassIVEi | Q9NW38 |
MaxQBi | Q9NW38 |
PaxDbi | Q9NW38 |
PeptideAtlasi | Q9NW38 |
PRIDEi | Q9NW38 |
ProteomicsDBi | 82894 [Q9NW38-1] 82895 [Q9NW38-2] |
PTM databases
iPTMneti | Q9NW38 |
PhosphoSitePlusi | Q9NW38 |
Expressioni
Gene expression databases
Bgeei | ENSG00000115392, Expressed in corpus callosum and 240 other tissues |
ExpressionAtlasi | Q9NW38, baseline and differential |
Genevisiblei | Q9NW38, HS |
Organism-specific databases
HPAi | ENSG00000115392, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with GGN (By similarity). Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM (PubMed:12973351, PubMed:15502827, PubMed:16116422, PubMed:22343915). The complex is not found in FA patients. In complex with FANCF, FANCA and FANCG, but not with FANCC, nor FANCE, interacts with HES1; this interaction may be essential for the stability and nuclear localization of FA core complex proteins (PubMed:18550849).
Interacts with FANCI (PubMed:21775430). Directly interacts (via the RING-type zinc finger) with UBE2T and UBE2W (PubMed:16916645, PubMed:17938197, PubMed:19111657, PubMed:21775430, PubMed:24389026).
By similarity10 PublicationsBinary interactionsi
Q9NW38
Isoform 1 [Q9NW38-1]
With | #Exp. | IntAct |
---|---|---|
UBE2T [Q9NPD8] | 3 | EBI-16088720,EBI-2130165 |
GO - Molecular functioni
- ubiquitin protein ligase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 120429, 67 interactors |
ComplexPortali | CPX-6263, Fanconi anemia ubiquitin ligase complex |
CORUMi | Q9NW38 |
DIPi | DIP-43975N |
IntActi | Q9NW38, 54 interactors |
MINTi | Q9NW38 |
STRINGi | 9606.ENSP00000385021 |
Miscellaneous databases
RNActi | Q9NW38, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q9NW38 |
SMRi | Q9NW38 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 104 – 294 | UBC-RWD region (URD)Add BLAST | 191 |
Domaini
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 307 – 365 | RING-typeAdd BLAST | 59 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG3268, Eukaryota |
GeneTreei | ENSGT00390000005537 |
InParanoidi | Q9NW38 |
OMAi | HTVFGEC |
OrthoDBi | 1002812at2759 |
PhylomeDBi | Q9NW38 |
TreeFami | TF323571 |
Family and domain databases
Gene3Di | 3.10.110.10, 1 hit 3.10.110.20, 1 hit 3.30.40.10, 1 hit |
InterProi | View protein in InterPro IPR026848, Fancl IPR026850, FANCL_C IPR043898, FANCL_d2 IPR044037, FANCL_d3 IPR043003, FANCL_d3_sf IPR019162, FancL_WD-rpt_cont_dom IPR016135, UBQ-conjugating_enzyme/RWD IPR013083, Znf_RING/FYVE/PHD |
PANTHERi | PTHR13206, PTHR13206, 1 hit |
Pfami | View protein in Pfam PF11793, FANCL_C, 1 hit PF09765, FANCL_d1, 1 hit PF18890, FANCL_d2, 1 hit PF18891, FANCL_d3, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAVTEASLLR QCPLLLPQNR SKTVYEGFIS AQGRDFHLRI VLPEDLQLKN
60 70 80 90 100
ARLLCSWQLR TILSGYHRIV QQRMQHSPDL MSFMMELKML LEVALKNRQE
110 120 130 140 150
LYALPPPPQF YSSLIEEIGT LGWDKLVYAD TCFSTIKLKA EDASGREHLI
160 170 180 190 200
TLKLKAKYPA ESPDYFVDFP VPFCASWTPQ SSLISIYSQF LAAIESLKAF
210 220 230 240 250
WDVMDEIDEK TWVLEPEKPP RSATARRIAL GNNVSINIEV DPRHPTMLPE
260 270 280 290 300
CFFLGADHVV KPLGIKLSRN IHLWDPENSV LQNLKDVLEI DFPARAILEK
310 320 330 340 350
SDFTMDCGIC YAYQLDGTIP DQVCDNSQCG QPFHQICLYE WLRGLLTSRQ
360 370
SFNIIFGECP YCSKPITLKM SGRKH
Computationally mapped potential isoform sequencesi
There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketC9JZA9 | C9JZA9_HUMAN | E3 ubiquitin-protein ligase FANCL | FANCL | 301 | Annotation score: | ||
B5MC31 | B5MC31_HUMAN | E3 ubiquitin-protein ligase FANCL | FANCL | 347 | Annotation score: | ||
H7C1M0 | H7C1M0_HUMAN | E3 ubiquitin-protein ligase FANCL | FANCL | 288 | Annotation score: | ||
B5MCZ6 | B5MCZ6_HUMAN | E3 ubiquitin-protein ligase FANCL | FANCL | 258 | Annotation score: | ||
C9J512 | C9J512_HUMAN | E3 ubiquitin-protein ligase FANCL | FANCL | 158 | Annotation score: | ||
C9JPN7 | C9JPN7_HUMAN | E3 ubiquitin-protein ligase FANCL | FANCL | 145 | Annotation score: | ||
A0A087X0C0 | A0A087X0C0_HUMAN | E3 ubiquitin-protein ligase FANCL | FANCL | 124 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 77 | S → P in BAA91548 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_052082 | 144 | S → F. Corresponds to variant dbSNP:rs36059257Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_041727 | 178 | T → TPQVNS in isoform 2. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK001197 mRNA Translation: BAA91548.1 AC007250 Genomic DNA Translation: AAY15020.1 BC009042 mRNA Translation: AAH09042.1 BC054517 mRNA Translation: AAH54517.1 BC037570 mRNA No translation available. |
CCDSi | CCDS1860.1 [Q9NW38-1] CCDS46294.1 [Q9NW38-2] |
RefSeqi | NP_001108108.1, NM_001114636.1 [Q9NW38-2] NP_060532.2, NM_018062.3 [Q9NW38-1] |
Genome annotation databases
Ensembli | ENST00000233741.9; ENSP00000233741.5; ENSG00000115392.12 ENST00000402135.7; ENSP00000385021.3; ENSG00000115392.12 [Q9NW38-2] |
GeneIDi | 55120 |
KEGGi | hsa:55120 |
MANE-Selecti | ENST00000233741.9; ENSP00000233741.5; NM_018062.4; NP_060532.2 |
UCSCi | uc002rzw.5, human [Q9NW38-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Fanconi Anemia Mutation Database |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK001197 mRNA Translation: BAA91548.1 AC007250 Genomic DNA Translation: AAY15020.1 BC009042 mRNA Translation: AAH09042.1 BC054517 mRNA Translation: AAH54517.1 BC037570 mRNA No translation available. |
CCDSi | CCDS1860.1 [Q9NW38-1] CCDS46294.1 [Q9NW38-2] |
RefSeqi | NP_001108108.1, NM_001114636.1 [Q9NW38-2] NP_060532.2, NM_018062.3 [Q9NW38-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3ZQS | X-ray | 2.00 | A/B | 109-294 | [»] | |
4CCG | X-ray | 2.40 | X/Y | 288-375 | [»] | |
7KZP | electron microscopy | 3.10 | L/M | 1-375 | [»] | |
7KZQ | electron microscopy | 4.20 | L/M | 1-375 | [»] | |
7KZR | electron microscopy | 4.20 | L/M | 1-375 | [»] | |
7KZS | electron microscopy | 4.20 | L/M | 1-375 | [»] | |
7KZT | electron microscopy | 4.20 | L/M | 1-375 | [»] | |
7KZV | electron microscopy | 4.20 | L/M | 1-375 | [»] | |
AlphaFoldDBi | Q9NW38 | |||||
SMRi | Q9NW38 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 120429, 67 interactors |
ComplexPortali | CPX-6263, Fanconi anemia ubiquitin ligase complex |
CORUMi | Q9NW38 |
DIPi | DIP-43975N |
IntActi | Q9NW38, 54 interactors |
MINTi | Q9NW38 |
STRINGi | 9606.ENSP00000385021 |
PTM databases
iPTMneti | Q9NW38 |
PhosphoSitePlusi | Q9NW38 |
Genetic variation databases
BioMutai | FANCL |
DMDMi | 116241360 |
Proteomic databases
EPDi | Q9NW38 |
jPOSTi | Q9NW38 |
MassIVEi | Q9NW38 |
MaxQBi | Q9NW38 |
PaxDbi | Q9NW38 |
PeptideAtlasi | Q9NW38 |
PRIDEi | Q9NW38 |
ProteomicsDBi | 82894 [Q9NW38-1] 82895 [Q9NW38-2] |
Protocols and materials databases
Antibodypediai | 30496, 229 antibodies from 32 providers |
DNASUi | 55120 |
Genome annotation databases
Ensembli | ENST00000233741.9; ENSP00000233741.5; ENSG00000115392.12 ENST00000402135.7; ENSP00000385021.3; ENSG00000115392.12 [Q9NW38-2] |
GeneIDi | 55120 |
KEGGi | hsa:55120 |
MANE-Selecti | ENST00000233741.9; ENSP00000233741.5; NM_018062.4; NP_060532.2 |
UCSCi | uc002rzw.5, human [Q9NW38-1] |
Organism-specific databases
CTDi | 55120 |
DisGeNETi | 55120 |
GeneCardsi | FANCL |
GeneReviewsi | FANCL |
HGNCi | HGNC:20748, FANCL |
HPAi | ENSG00000115392, Low tissue specificity |
MalaCardsi | FANCL |
MIMi | 608111, gene 614083, phenotype |
neXtProti | NX_Q9NW38 |
OpenTargetsi | ENSG00000115392 |
Orphaneti | 84, Fanconi anemia |
PharmGKBi | PA134887656 |
VEuPathDBi | HostDB:ENSG00000115392 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3268, Eukaryota |
GeneTreei | ENSGT00390000005537 |
InParanoidi | Q9NW38 |
OMAi | HTVFGEC |
OrthoDBi | 1002812at2759 |
PhylomeDBi | Q9NW38 |
TreeFami | TF323571 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
BRENDAi | 2.3.2.27, 2681 |
PathwayCommonsi | Q9NW38 |
Reactomei | R-HSA-6783310, Fanconi Anemia Pathway |
SignaLinki | Q9NW38 |
SIGNORi | Q9NW38 |
Miscellaneous databases
BioGRID-ORCSi | 55120, 102 hits in 1123 CRISPR screens |
ChiTaRSi | FANCL, human |
GeneWikii | FANCL |
GenomeRNAii | 55120 |
Pharosi | Q9NW38, Tbio |
PROi | PR:Q9NW38 |
RNActi | Q9NW38, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000115392, Expressed in corpus callosum and 240 other tissues |
ExpressionAtlasi | Q9NW38, baseline and differential |
Genevisiblei | Q9NW38, HS |
Family and domain databases
Gene3Di | 3.10.110.10, 1 hit 3.10.110.20, 1 hit 3.30.40.10, 1 hit |
InterProi | View protein in InterPro IPR026848, Fancl IPR026850, FANCL_C IPR043898, FANCL_d2 IPR044037, FANCL_d3 IPR043003, FANCL_d3_sf IPR019162, FancL_WD-rpt_cont_dom IPR016135, UBQ-conjugating_enzyme/RWD IPR013083, Znf_RING/FYVE/PHD |
PANTHERi | PTHR13206, PTHR13206, 1 hit |
Pfami | View protein in Pfam PF11793, FANCL_C, 1 hit PF09765, FANCL_d1, 1 hit PF18890, FANCL_d2, 1 hit PF18891, FANCL_d3, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | FANCL_HUMAN | |
Accessioni | Q9NW38Primary (citable) accession number: Q9NW38 Secondary accession number(s): Q6GU60 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 10, 2003 |
Last sequence update: | October 17, 2006 | |
Last modified: | May 25, 2022 | |
This is version 182 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references