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Protein

E3 ubiquitin-protein ligase FANCL

Gene

FANCL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Ubiquitin ligase protein that mediates monoubiquitination of FANCD2, a key step in the DNA damage pathway. Also mediates monoubiquitination of FANCI. 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.5 Publications

Pathwayi: protein ubiquitination

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.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri307 – 365RING-typeAdd BLAST59

GO - Molecular functioni

  • ligase activity Source: UniProtKB-KW
  • 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: Reactome
  • protein monoubiquitination Source: UniProtKB
  • regulation of cell proliferation Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

DNA damage, DNA repair, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000115392-MONOMER.
ReactomeiR-HSA-6783310. Fanconi Anemia Pathway.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase FANCL (EC:6.3.2.-)
Alternative name(s):
Fanconi anemia group L protein
Fanconi anemia-associated polypeptide of 43 kDa
Short name:
FAAP43
Gene namesi
Name:FANCL
Synonyms:PHF9
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:20748. FANCL.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • Fanconi anaemia nuclear complex Source: UniProtKB
  • nuclear envelope Source: Ensembl
  • nucleoplasm Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Fanconi anemia complementation group L (FANCL)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.
See also OMIM:614083

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi127 – 128VY → AA: Does not affect interaction with FANCI and FANCD2. 1 Publication2
Mutagenesisi149L → A: Does not affect interaction with FANCI and FANCD2; when associated with A-166. 1 Publication1
Mutagenesisi158 – 159YP → AA: Abolishes UBE2T charging. 1 Publication2
Mutagenesisi166F → A: Does not affect interaction with FANCI and FANCD2; when associated with A-149. 1 Publication1
Mutagenesisi212 – 214WVL → AVA: Impairs interaction with FANCI and FANCD2. 1 Publication3
Mutagenesisi248L → A: Impairs interaction with FANCI and FANCD2; when associated with A-252. 1 Publication1
Mutagenesisi252F → A: Impairs interaction with FANCI and FANCD2; when associated with A-248. 1 Publication1
Mutagenesisi254L → A: Impairs interaction with FANCI and FANCD2; when associated with A-265. 1 Publication1
Mutagenesisi265I → A: Impairs interaction with FANCI and FANCD2; when associated with A-254. 1 Publication1
Mutagenesisi307C → A: Abolishes ubiquitin ligase activity. 5 Publications1
Mutagenesisi310C → A: Abolishes ubiquitin ligase activity. 2 Publications1
Mutagenesisi341W → G: Abolishes interaction with UBE2T and ubiquitin ligase activity. 1 Publication1
Mutagenesisi359C → A: Abolishes ubiquitin ligase activity. 1 Publication1

Keywords - Diseasei

Fanconi anemia

Organism-specific databases

DisGeNETi55120.
MalaCardsiFANCL.
MIMi614083. phenotype.
OpenTargetsiENSG00000115392.
Orphaneti84. Fanconi anemia.
PharmGKBiPA134887656.

Polymorphism and mutation databases

BioMutaiFANCL.
DMDMi116241360.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000559082 – 375E3 ubiquitin-protein ligase FANCLAdd BLAST374

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1

Post-translational modificationi

The RING-type zinc finger domain is monoubiquitinated in the presence of UBE2T and UBE2W.

Keywords - PTMi

Acetylation, Ubl conjugation

Proteomic databases

EPDiQ9NW38.
MaxQBiQ9NW38.
PaxDbiQ9NW38.
PeptideAtlasiQ9NW38.
PRIDEiQ9NW38.

PTM databases

iPTMnetiQ9NW38.
PhosphoSitePlusiQ9NW38.

Expressioni

Gene expression databases

BgeeiENSG00000115392.
CleanExiHS_FANCL.
ExpressionAtlasiQ9NW38. baseline and differential.
GenevisibleiQ9NW38. HS.

Organism-specific databases

HPAiCAB033842.
HPA036685.
HPA036686.

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. 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. Interacts with FANCI. Interacts (via the RING-type zinc finger) with UBE2T and UBE2W.By similarity9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CCDC36Q8IYA83EBI-2339898,EBI-8638439
CHCHD3Q9NX633EBI-2339898,EBI-743375
DOCK8Q8NF50-23EBI-2339898,EBI-10174653
EIF4ENIF1Q9NRA83EBI-2339898,EBI-301024
GRNP287993EBI-2339898,EBI-747754
IKZF3Q9UKT93EBI-2339898,EBI-747204
KIFC3Q9BVG83EBI-2339898,EBI-2125614
LZTS2Q9BRK43EBI-2339898,EBI-741037
RBM45Q8IUH33EBI-2339898,EBI-2512147
RIMBP3Q9UFD93EBI-2339898,EBI-10182375
SSX2IPQ9Y2D83EBI-2339898,EBI-2212028
TFCP2Q128003EBI-2339898,EBI-717422

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi120429. 33 interactors.
DIPiDIP-43975N.
IntActiQ9NW38. 20 interactors.
MINTiMINT-2819517.
STRINGi9606.ENSP00000385021.

Structurei

Secondary structure

1375
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi114 – 121Combined sources8
Helixi123 – 125Combined sources3
Beta strandi126 – 129Combined sources4
Beta strandi133 – 141Combined sources9
Beta strandi147 – 153Combined sources7
Turni156 – 160Combined sources5
Beta strandi164 – 166Combined sources3
Helixi183 – 196Combined sources14
Helixi198 – 210Combined sources13
Beta strandi213 – 218Combined sources6
Beta strandi225 – 231Combined sources7
Beta strandi234 – 239Combined sources6
Beta strandi250 – 255Combined sources6
Helixi257 – 270Combined sources14
Helixi271 – 273Combined sources3
Helixi280 – 288Combined sources9
Turni308 – 310Combined sources3
Turni327 – 329Combined sources3
Helixi335 – 342Combined sources8
Beta strandi349 – 351Combined sources3
Beta strandi354 – 358Combined sources5
Turni360 – 362Combined sources3
Beta strandi365 – 369Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3ZQSX-ray2.00A/B109-294[»]
4CCGX-ray2.40X/Y288-375[»]
ProteinModelPortaliQ9NW38.
SMRiQ9NW38.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni104 – 294UBC-RWD region (URD)Add BLAST191

Domaini

The UBC-RWD region (URD) region mediates interaction with FANCI and FANCD2.1 Publication

Sequence similaritiesi

Contains 1 RING-type zinc finger.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri307 – 365RING-typeAdd BLAST59

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3268. Eukaryota.
ENOG410YC2U. LUCA.
GeneTreeiENSGT00390000005537.
HOGENOMiHOG000007643.
HOVERGENiHBG045632.
InParanoidiQ9NW38.
KOiK10606.
OMAiPKMLPEC.
OrthoDBiEOG091G0PRR.
PhylomeDBiQ9NW38.
TreeFamiTF323571.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR026848. Fancl.
IPR026850. FANCL_C.
IPR019162. FancL_WD-rpt_cont_dom.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PANTHERiPTHR13206:SF0. PTHR13206:SF0. 1 hit.
PfamiPF11793. FANCL_C. 1 hit.
PF09765. WD-3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NW38-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:375
Mass (Da):42,905
Last modified:October 17, 2006 - v2
Checksum:iE217DF9D64587E5E
GO
Isoform 2 (identifier: Q9NW38-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     178-178: T → TPQVNS

Show »
Length:380
Mass (Da):43,430
Checksum:iA5FA331CCC1C9C1E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti77S → P in BAA91548 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052082144S → F.Corresponds to variant rs36059257dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041727178T → TPQVNS in isoform 2. 1 Publication1

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.
CCDSiCCDS1860.1. [Q9NW38-1]
CCDS46294.1. [Q9NW38-2]
RefSeqiNP_001108108.1. NM_001114636.1. [Q9NW38-2]
NP_060532.2. NM_018062.3. [Q9NW38-1]
UniGeneiHs.631890.

Genome annotation databases

EnsembliENST00000233741; ENSP00000233741; ENSG00000115392. [Q9NW38-1]
ENST00000402135; ENSP00000385021; ENSG00000115392. [Q9NW38-2]
GeneIDi55120.
KEGGihsa:55120.
UCSCiuc002rzw.5. human. [Q9NW38-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.
CCDSiCCDS1860.1. [Q9NW38-1]
CCDS46294.1. [Q9NW38-2]
RefSeqiNP_001108108.1. NM_001114636.1. [Q9NW38-2]
NP_060532.2. NM_018062.3. [Q9NW38-1]
UniGeneiHs.631890.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3ZQSX-ray2.00A/B109-294[»]
4CCGX-ray2.40X/Y288-375[»]
ProteinModelPortaliQ9NW38.
SMRiQ9NW38.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120429. 33 interactors.
DIPiDIP-43975N.
IntActiQ9NW38. 20 interactors.
MINTiMINT-2819517.
STRINGi9606.ENSP00000385021.

PTM databases

iPTMnetiQ9NW38.
PhosphoSitePlusiQ9NW38.

Polymorphism and mutation databases

BioMutaiFANCL.
DMDMi116241360.

Proteomic databases

EPDiQ9NW38.
MaxQBiQ9NW38.
PaxDbiQ9NW38.
PeptideAtlasiQ9NW38.
PRIDEiQ9NW38.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000233741; ENSP00000233741; ENSG00000115392. [Q9NW38-1]
ENST00000402135; ENSP00000385021; ENSG00000115392. [Q9NW38-2]
GeneIDi55120.
KEGGihsa:55120.
UCSCiuc002rzw.5. human. [Q9NW38-1]

Organism-specific databases

CTDi55120.
DisGeNETi55120.
GeneCardsiFANCL.
GeneReviewsiFANCL.
HGNCiHGNC:20748. FANCL.
HPAiCAB033842.
HPA036685.
HPA036686.
MalaCardsiFANCL.
MIMi608111. gene.
614083. phenotype.
neXtProtiNX_Q9NW38.
OpenTargetsiENSG00000115392.
Orphaneti84. Fanconi anemia.
PharmGKBiPA134887656.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3268. Eukaryota.
ENOG410YC2U. LUCA.
GeneTreeiENSGT00390000005537.
HOGENOMiHOG000007643.
HOVERGENiHBG045632.
InParanoidiQ9NW38.
KOiK10606.
OMAiPKMLPEC.
OrthoDBiEOG091G0PRR.
PhylomeDBiQ9NW38.
TreeFamiTF323571.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000115392-MONOMER.
ReactomeiR-HSA-6783310. Fanconi Anemia Pathway.

Miscellaneous databases

ChiTaRSiFANCL. human.
GeneWikiiFANCL.
GenomeRNAii55120.
PROiQ9NW38.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115392.
CleanExiHS_FANCL.
ExpressionAtlasiQ9NW38. baseline and differential.
GenevisibleiQ9NW38. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR026848. Fancl.
IPR026850. FANCL_C.
IPR019162. FancL_WD-rpt_cont_dom.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PANTHERiPTHR13206:SF0. PTHR13206:SF0. 1 hit.
PfamiPF11793. FANCL_C. 1 hit.
PF09765. WD-3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFANCL_HUMAN
AccessioniPrimary (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: November 30, 2016
This is version 147 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Caution

Although PubMed:12724401 reports that it contains a PHD-type zinc finger, it contains a RING-type zinc finger. Moreover, PHD-type zinc fingers do not have any ubiquitin ligase activity.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.