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Q9NW38 (FANCL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:FANCL
Synonyms:PHF9
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length375 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.8 Ref.9 Ref.11 Ref.12

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.15

Subcellular location

Cytoplasm. Nucleus Ref.5 Ref.10.

Domain

The UBC-RWD region (URD) region mediates interaction with FANCI and FANCD2 (Ref.15).

Post-translational modification

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

Involvement in disease

Fanconi anemia complementation group L (FANCL) [MIM:614083]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.6

Sequence similarities

Contains 1 RING-type zinc finger.

Caution

Although Ref.4 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.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NW38-1)

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.
Isoform 2 (identifier: Q9NW38-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.14
Chain2 – 375374E3 ubiquitin-protein ligase FANCL
PRO_0000055908

Regions

Zinc finger307 – 36559RING-type
Region104 – 294191UBC-RWD region (URD)

Amino acid modifications

Modified residue21N-acetylalanine Ref.14

Natural variations

Alternative sequence1781T → TPQVNS in isoform 2.
VSP_041727
Natural variant1441S → F.
Corresponds to variant rs36059257 [ dbSNP | Ensembl ].
VAR_052082

Experimental info

Mutagenesis127 – 1282VY → AA: Does not affect interaction with FANCI and FANCD2.
Mutagenesis1491L → A: Does not affect interaction with FANCI and FANCD2; when associatec witt A-166. Ref.15
Mutagenesis158 – 1592YP → AA: Abolishes UBE2T charging.
Mutagenesis1661F → A: Does not affect interaction with FANCI and FANCD2; when associatec witt A-149. Ref.15
Mutagenesis212 – 2143WVL → AVA: Impairs interaction with FANCI and FANCD2. Ref.15
Mutagenesis2481L → A: Impairs interaction with FANCI and FANCD2; when associatec witt A-252. Ref.15
Mutagenesis2521F → A: Impairs interaction with FANCI and FANCD2; when associatec witt A-248. Ref.15
Mutagenesis2541L → A: Impairs interaction with FANCI and FANCD2; when associatec witt A-265. Ref.15
Mutagenesis2651I → A: Impairs interaction with FANCI and FANCD2; when associatec witt A-254. Ref.15
Mutagenesis3071C → A: Abolishes ubiquitin ligase activity. Ref.5 Ref.8 Ref.9 Ref.11 Ref.12
Mutagenesis3101C → A: Abolishes ubiquitin ligase activity. Ref.5 Ref.9
Mutagenesis3411W → G: Abolishes interaction with UBE2T and ubiquitin ligase activity. Ref.8
Mutagenesis3591C → A: Abolishes ubiquitin ligase activity. Ref.11
Sequence conflict771S → P in BAA91548. Ref.1

Secondary structure

............................................. 375
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 17, 2006. Version 2.
Checksum: E217DF9D64587E5E

FASTA37542,905
        10         20         30         40         50         60 
MAVTEASLLR QCPLLLPQNR SKTVYEGFIS AQGRDFHLRI VLPEDLQLKN ARLLCSWQLR 

        70         80         90        100        110        120 
TILSGYHRIV QQRMQHSPDL MSFMMELKML LEVALKNRQE LYALPPPPQF YSSLIEEIGT 

       130        140        150        160        170        180 
LGWDKLVYAD TCFSTIKLKA EDASGREHLI TLKLKAKYPA ESPDYFVDFP VPFCASWTPQ 

       190        200        210        220        230        240 
SSLISIYSQF LAAIESLKAF WDVMDEIDEK TWVLEPEKPP RSATARRIAL GNNVSINIEV 

       250        260        270        280        290        300 
DPRHPTMLPE CFFLGADHVV KPLGIKLSRN IHLWDPENSV LQNLKDVLEI DFPARAILEK 

       310        320        330        340        350        360 
SDFTMDCGIC YAYQLDGTIP DQVCDNSQCG QPFHQICLYE WLRGLLTSRQ SFNIIFGECP 

       370 
YCSKPITLKM SGRKH 

« Hide

Isoform 2 [UniParc].

Checksum: A5FA331CCC1C9C1E
Show »

FASTA38043,430

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Teratocarcinoma.
[2]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Brain and Eye.
[4]"A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome."
Meetei A.R., Sechi S., Wallisch M., Yang D., Young M.K., Joenje H., Hoatlin M.E., Wang W.
Mol. Cell. Biol. 23:3417-3426(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY IN A BRAFT COMPLEX WITH FANCA; FANCC; FANCE; FANCF AND FANCG.
[5]"A novel ubiquitin ligase is deficient in Fanconi anemia."
Meetei A.R., de Winter J.P., Medhurst A.L., Wallisch M., Waisfisz Q., van de Vrugt H.J., Oostra A.B., Yan Z., Ling C., Bishop C.E., Hoatlin M.E., Joenje H., Wang W.
Nat. Genet. 35:165-170(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN FANCL, INTERACTION WITH FANCA; FANCC; FANCF AND FANCG, MUTAGENESIS OF CYS-307 AND CYS-310.
[6]"X-linked inheritance of Fanconi anemia complementation group B."
Meetei A.R., Levitus M., Xue Y., Medhurst A.L., Zwaan M., Ling C., Rooimans M.A., Bier P., Hoatlin M., Pals G., de Winter J.P., Wang W., Joenje H.
Nat. Genet. 36:1219-1224(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH FANCA; FANCB; FANCC; FANCE; FANCF AND FANCLG.
[7]"A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M."
Meetei A.R., Medhurst A.L., Ling C., Xue Y., Singh T.R., Bier P., Steltenpool J., Stone S., Dokal I., Mathew C.G., Hoatlin M., Joenje H., de Winter J.P., Wang W.
Nat. Genet. 37:958-963(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH FANCA; FANCB; FANCC; FANCE; FANCF; FANCG AND FANCM.
[8]"UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation."
Machida Y.J., Machida Y., Chen Y., Gurtan A.M., Kupfer G.M., D'Andrea A.D., Dutta A.
Mol. Cell 23:589-596(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH UBE2T, UBIQUITINATION, MUTAGENESIS OF CYS-307 AND TRP-341.
[9]"UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited independently to chromatin: a basis for the regulation of FANCD2 monoubiquitination."
Alpi A., Langevin F., Mosedale G., Machida Y.J., Dutta A., Patel K.J.
Mol. Cell. Biol. 27:8421-8430(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH UBE2T, MUTAGENESIS OF CYS-307 AND CYS-310.
[10]"HES1 is a novel interactor of the Fanconi anemia core complex."
Tremblay C.S., Huang F.F., Habi O., Huard C.C., Godin C., Levesque G., Carreau M.
Blood 112:2062-2070(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HES1, SUBCELLULAR LOCATION.
[11]"Mechanistic insight into site-restricted monoubiquitination of FANCD2 by Ube2t, FANCL, and FANCI."
Alpi A.F., Pace P.E., Babu M.M., Patel K.J.
Mol. Cell 32:767-777(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH UBE2T AND UBE2W, MUTAGENESIS OF 158-TYR-PRO-159; CYS-307 AND CYS-359.
[12]"FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL."
Longerich S., San Filippo J., Liu D., Sung P.
J. Biol. Chem. 284:23182-23186(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF CYS-307.
[13]"FAAP20: a novel ubiquitin-binding FA nuclear core-complex protein required for functional integrity of the FA-BRCA DNA repair pathway."
Ali A.M., Pradhan A., Singh T.R., Du C., Li J., Wahengbam K., Grassman E., Auerbach A.D., Pang Q., Meetei A.R.
Blood 119:3285-3294(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE FA COMPLEX.
[14]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[15]"Structural analysis of human FANCL, the E3 ligase in the Fanconi anemia pathway."
Hodson C., Cole A.R., Lewis L.P., Miles J.A., Purkiss A., Walden H.
J. Biol. Chem. 286:32628-32637(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 109-294, INTERACTION WITH FANCI AND UBE2T, MUTAGENESIS OF 127-VAL-TYR-128; LEU-149; PHE-166; 212-TRP--LEU-214; LEU-248; PHE-252; LEU-254 AND ILE-265.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001108108.1. NM_001114636.1.
NP_060532.2. NM_018062.3.
UniGeneHs.631890.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3ZQSX-ray2.00A/B109-294[»]
4CCGX-ray2.40X/Y288-375[»]
ProteinModelPortalQ9NW38.
SMRQ9NW38. Positions 109-367.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120429. 24 interactions.
IntActQ9NW38. 4 interactions.
MINTMINT-2819517.
STRING9606.ENSP00000385021.

PTM databases

PhosphoSiteQ9NW38.

Polymorphism databases

DMDM116241360.

Proteomic databases

PaxDbQ9NW38.
PRIDEQ9NW38.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000233741; ENSP00000233741; ENSG00000115392. [Q9NW38-1]
ENST00000402135; ENSP00000385021; ENSG00000115392. [Q9NW38-2]
GeneID55120.
KEGGhsa:55120.
UCSCuc002rzw.4. human. [Q9NW38-1]
uc002rzx.4. human. [Q9NW38-2]

Organism-specific databases

CTD55120.
GeneCardsGC02M058298.
HGNCHGNC:20748. FANCL.
HPACAB033842.
HPA036685.
HPA036686.
MIM608111. gene.
614083. phenotype.
neXtProtNX_Q9NW38.
Orphanet84. Fanconi anemia.
PharmGKBPA134887656.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG311231.
HOGENOMHOG000007643.
HOVERGENHBG045632.
KOK10606.
OMAWTPQSSL.
PhylomeDBQ9NW38.
TreeFamTF323571.

Enzyme and pathway databases

ReactomeREACT_216. DNA Repair.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ9NW38.
BgeeQ9NW38.
CleanExHS_FANCL.
GenevestigatorQ9NW38.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR026848. Fancl.
IPR019162. FancL_WD-rpt_cont_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PANTHERPTHR13206:SF0. PTHR13206:SF0. 1 hit.
PfamPF09765. WD-3. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFancl. human.
GeneWikiFANCL.
GenomeRNAi55120.
NextBio58768.
PROQ9NW38.
SOURCESearch...

Entry information

Entry nameFANCL_HUMAN
AccessionPrimary (citable) accession number: Q9NW38
Secondary accession number(s): Q6GU60
Entry history
Integrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: October 17, 2006
Last modified: April 16, 2014
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM