Q9NW38 (FANCL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	FANCL
Synonyms:	PHF9

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	375 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ubiquitin ligase protein that mediates ubiquitination of FANCD2, a key step in the DNA damage pathway. May stimulate the ubiquitin release from UBE2W By similarity. 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
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 UBE2W via the RING-type zinc finger By similarity. Ref.5 Ref.8
Subcellular location	Cytoplasm. Nucleus Ref.5 Ref.8.
Post-translational modification	The RING-type zinc finger domain is monoubiquitinated in vitro in the presence of UBE2W.
Involvement in disease	Defects in FANCL are the cause of Fanconi anemia complementation group L (FANCL) [MIM:614083]. FANCL is 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. 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.

Ontologies

Keywords
Biological process	DNA damage DNA repair Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Fanconi anemia
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA repair Traceable author statement. Source: Reactome
Cellular component	Fanconi anaemia nuclear complex Inferred from direct assay. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ubiquitin-protein ligase activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 375

375

E3 ubiquitin-protein ligase FANCL

PRO_0000055908

Regions

Zinc finger

307 – 365

59

RING-type

Natural variations

Alternative sequence

178

1

T → TPQVNS in isoform 2.

VSP_041727

Natural variant

144

1

S → F.
Corresponds to variant rs36059257 [ dbSNP | Ensembl ].

VAR_052082

Experimental info

Mutagenesis

307

1

C → A: Abolishes ubiquitin ligase activity. Ref.5

Mutagenesis

310

1

C → A: Abolishes ubiquitin ligase activity. Ref.5

Sequence conflict

77

1

S → P in BAA91548. Ref.1

Secondary structure

1

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375

Helix Strand Turn

Details...

Helix

114 – 121

8

Helix

123 – 125

3

Beta strand

126 – 129

4

Beta strand

133 – 141

9

Beta strand

147 – 153

7

Turn

156 – 160

5

Beta strand

164 – 166

3

Helix

183 – 196

14

Helix

198 – 210

13

Beta strand

213 – 218

6

Beta strand

225 – 231

7

Beta strand

234 – 239

6

Beta strand

250 – 255

6

Helix

257 – 270

14

Helix

271 – 273

3

Helix

280 – 288

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: E217DF9D64587E5E	FASTA	375	42,905
	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
	Isoform 2 [UniParc]. Checksum: A5FA331CCC1C9C1E	FASTA	380	43,430
	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 VNSPQSSLIS IYSQFLAAIE SLKAFWDVMD EIDEKTWVLE PEKPPRSATA RRIALGNNVS 250 260 270 280 290 300 INIEVDPRHP TMLPECFFLG ADHVVKPLGI KLSRNIHLWD PENSVLQNLK DVLEIDFPAR 310 320 330 340 350 360 AILEKSDFTM DCGICYAYQL DGTIPDQVCD NSQCGQPFHQ ICLYEWLRGL LTSRQSFNII 370 380 FGECPYCSKP ITLKMSGRKH

References

	« Hide 'large scale' referencesShow '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. , 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: 14702039] [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. , 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: 15815621] [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: 15489334] [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: 12724401] [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: 12973351] [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: 15502827] [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: 16116422] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH FANCA; FANCB; FANCC; FANCE; FANCF; FANCG AND FANCM.
[8]	"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: 18550849] [Abstract] Cited for: INTERACTION WITH HES1, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Web resources

Fanconi Anemia Mutation Database

GeneReviews

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.

IPI

IPI00018099.
IPI00885015.

RefSeq

NP_001108108.1. NM_001114636.1.
NP_060532.2. NM_018062.3.

UniGene

Hs.631890.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3ZQS	X-ray	2.00	A/B	109-294	[»]

ProteinModelPortal

Q9NW38.

SMR

Q9NW38. Positions 109-294, 302-369.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NW38. 1 interaction.

MINT

MINT-2819517.

STRING

Q9NW38.

Polymorphism databases

DMDM

116241360.

Proteomic databases

PRIDE

Q9NW38.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000233741; ENSP00000233741; ENSG00000115392.

GeneID

55120.

KEGG

hsa:55120.

UCSC

uc002rzw.2. human.

Organism-specific databases

CTD

55120.

GeneCards

GC02M058298.

H-InvDB

HIX0002071.

HGNC

HGNC:20748. FANCL.

HPA

CAB033842.
HPA036685.
HPA036686.

MIM

608111. gene.
614083. phenotype.

neXtProt

NX_Q9NW38.

Orphanet

84. Fanconi anemia.

PharmGKB

PA134887656.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04061.

GeneTree

ENSGT00390000005537.

HOVERGEN

HBG045632.

PhylomeDB

Q9NW38.

Enzyme and pathway databases

Pathway_Interaction_DB

bard1pathway. BARD1 signaling events.

Reactome

REACT_216. DNA Repair.

Gene expression databases

ArrayExpress

Q9NW38.

Bgee

Q9NW38.

CleanEx

HS_FANCL.

Genevestigator

Q9NW38.

GermOnline

ENSG00000115392. Homo sapiens.

Family and domain databases

InterPro

IPR019162. FancL_WD-rpt_cont_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]

Gene3D

G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.

KO

K10606.

Pfam

PF09765. WD-3. 1 hit.
[Graphical view]

SMART

SM00184. RING. 1 hit.
[Graphical view]

PROSITE

PS00518. ZF_RING_1. False negative.
PS50089. ZF_RING_2. False negative.
[Graphical view]

ProtoNet

Search...

Other

NextBio

58768.

SOURCE

Search...

Entry information

Entry name

FANCL_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.