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Protein

E3 ubiquitin-protein ligase FANCL

Gene

FANCL

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

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 Publications

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

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.4 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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi307Zinc 1Combined sources1
Metal bindingi310Zinc 1Combined sources1
Metal bindingi324Zinc 2Combined sources1
Metal bindingi329Zinc 2Combined sources1
Metal bindingi334Zinc 1; via pros nitrogenCombined sources1
Metal bindingi337Zinc 1Combined sources1
Metal bindingi359Zinc 2Combined sources1
Metal bindingi362Zinc 2Combined sources1

Regions

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

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

Keywordsi

Molecular functionTransferase
Biological processDNA damage, DNA repair, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-6783310 Fanconi Anemia Pathway
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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000115392.11
HGNCiHGNC:20748 FANCL
MIMi608111 gene
neXtProtiNX_Q9NW38

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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: No effect on interaction with FANCI and FANCD2. 1 Publication2
Mutagenesisi149L → A: No effect on 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, A-254 and A-265. 1 Publication1
Mutagenesisi252F → A: Impairs interaction with FANCI and FANCD2; when associated with A-248, A-254 and A-265. 1 Publication1
Mutagenesisi254L → A: Impairs interaction with FANCI and FANCD2; when associated with A-248, A-252 and A-265. 1 Publication1
Mutagenesisi265I → A: Impairs interaction with FANCI and FANCD2; when associated with A-248, A-252 and A-254. 1 Publication1
Mutagenesisi307C → A: Abolishes ubiquitin ligase activity. 5 Publications1
Mutagenesisi309I → A: Loss of interaction with UBE2T. 1 Publication1
Mutagenesisi310C → A: Abolishes ubiquitin ligase activity. 2 Publications1
Mutagenesisi311Y → A: Loss of interaction with UBE2T. 1 Publication1
Mutagenesisi341W → A: Loss of interaction with UBE2T. 1 Publication1
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
GeneReviewsiFANCL
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
ProteomicsDBi82894
82895 [Q9NW38-2]

PTM databases

iPTMnetiQ9NW38
PhosphoSitePlusiQ9NW38

Expressioni

Gene expression databases

BgeeiENSG00000115392 Expressed in 227 organ(s), highest expression level in corpus callosum
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 (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 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi120429, 38 interactors
CORUMiQ9NW38
DIPiDIP-43975N
IntActiQ9NW38, 43 interactors
MINTiQ9NW38
STRINGi9606.ENSP00000385021

Structurei

Secondary structure

1375
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

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
OMAiWTPQSSL
OrthoDBiEOG091G0PRR
PhylomeDBiQ9NW38
TreeFamiTF323571

Family and domain databases

Gene3Di3.10.110.10, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR026848 Fancl
IPR026850 FANCL_C
IPR019162 FancL_WD-rpt_cont_dom
IPR016135 UBQ-conjugating_enzyme/RWD
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR13206 PTHR13206, 1 hit
PfamiView protein in Pfam
PF11793 FANCL_C, 1 hit
PF09765 WD-3, 1 hit

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

This entry has 2 described isoforms and 7 potential isoforms that are computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B5MC31B5MC31_HUMAN
E3 ubiquitin-protein ligase FANCL
FANCL
347Annotation score:
C9JZA9C9JZA9_HUMAN
E3 ubiquitin-protein ligase FANCL
FANCL
301Annotation score:
H7C1M0H7C1M0_HUMAN
E3 ubiquitin-protein ligase FANCL
FANCL
288Annotation score:
B5MCZ6B5MCZ6_HUMAN
E3 ubiquitin-protein ligase FANCL
FANCL
258Annotation score:
C9JPN7C9JPN7_HUMAN
E3 ubiquitin-protein ligase FANCL
FANCL
145Annotation score:
C9J512C9J512_HUMAN
E3 ubiquitin-protein ligase FANCL
FANCL
158Annotation score:
A0A087X0C0A0A087X0C0_HUMAN
E3 ubiquitin-protein ligase FANCL
FANCL
124Annotation score:

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 dbSNP:rs36059257Ensembl.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

Similar 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.
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, 38 interactors
CORUMiQ9NW38
DIPiDIP-43975N
IntActiQ9NW38, 43 interactors
MINTiQ9NW38
STRINGi9606.ENSP00000385021

PTM databases

iPTMnetiQ9NW38
PhosphoSitePlusiQ9NW38

Polymorphism and mutation databases

BioMutaiFANCL
DMDMi116241360

Proteomic databases

EPDiQ9NW38
MaxQBiQ9NW38
PaxDbiQ9NW38
PeptideAtlasiQ9NW38
PRIDEiQ9NW38
ProteomicsDBi82894
82895 [Q9NW38-2]

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
EuPathDBiHostDB:ENSG00000115392.11
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
OMAiWTPQSSL
OrthoDBiEOG091G0PRR
PhylomeDBiQ9NW38
TreeFamiTF323571

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-6783310 Fanconi Anemia Pathway

Miscellaneous databases

ChiTaRSiFANCL human
GeneWikiiFANCL
GenomeRNAii55120
PROiPR:Q9NW38
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115392 Expressed in 227 organ(s), highest expression level in corpus callosum
CleanExiHS_FANCL
ExpressionAtlasiQ9NW38 baseline and differential
GenevisibleiQ9NW38 HS

Family and domain databases

Gene3Di3.10.110.10, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR026848 Fancl
IPR026850 FANCL_C
IPR019162 FancL_WD-rpt_cont_dom
IPR016135 UBQ-conjugating_enzyme/RWD
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR13206 PTHR13206, 1 hit
PfamiView protein in Pfam
PF11793 FANCL_C, 1 hit
PF09765 WD-3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiFANCL_HUMAN
AccessioniPrimary (citable) accession number: Q9NW38
Secondary accession number(s): Q6GU60
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: October 17, 2006
Last modified: September 12, 2018
This is version 161 of the entry and version 2 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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