IFFO1_HUMAN
ID IFFO1_HUMAN Reviewed; 559 AA.
AC Q0D2I5; Q24JT6; Q7L5J9; Q7Z5X4; Q9BQ46;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Non-homologous end joining factor IFFO1 {ECO:0000303|PubMed:31548606};
DE Short=NHEJ factor IFFO1 {ECO:0000303|PubMed:31548606};
DE AltName: Full=Intermediate filament family orphan 1 {ECO:0000303|PubMed:31548606};
DE AltName: Full=Tumor antigen HOM-TES-103 {ECO:0000303|PubMed:12032826};
GN Name=IFFO1 {ECO:0000312|HGNC:HGNC:24970}; Synonyms=IFFO;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 5; 6 AND 7).
RC TISSUE=Brain, Placenta, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 102-559 (ISOFORM 4), AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=12032826; DOI=10.1038/sj.onc.1205481;
RA Tuereci O., Sahin U., Koslowski M., Buss B., Bell C., Ballweber P.,
RA Zwick C., Eberle T., Zuber M., Villena-Heinsen C., Seitz G.,
RA Pfreundschuh M.;
RT "A novel tumour associated leucine zipper protein targeting to sites of
RT gene transcription and splicing.";
RL Oncogene 21:3879-3888(2002).
RN [4] {ECO:0007744|PDB:6ABO}
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 450-525 IN COMPLEX WITH XRCC4,
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH XRCC4 AND LMNA, AND
RP MUTAGENESIS OF ALA-65; ASN-73; ARG-85; ALA-89; 450-GLU--ARG-525; ILE-480;
RP ALA-487; ASP-490; ASP-509; MET-512; CYS-515 AND ARG-516.
RX PubMed=31548606; DOI=10.1038/s41556-019-0388-0;
RA Li W., Bai X., Li J., Zhao Y., Liu J., Zhao H., Liu L., Ding M., Wang Q.,
RA Shi F.Y., Hou M., Ji J., Gao G., Guo R., Sun Y., Liu Y., Xu D.;
RT "The nucleoskeleton protein IFFO1 immobilizes broken DNA and suppresses
RT chromosome translocation during tumorigenesis.";
RL Nat. Cell Biol. 21:1273-1285(2019).
CC -!- FUNCTION: Nuclear matrix protein involved in the immobilization of
CC broken DNA ends and the suppression of chromosome translocation during
CC DNA double-strand breaks (DSBs) (PubMed:31548606). Interacts with the
CC nuclear lamina component LMNA, resulting in the formation of a
CC nucleoskeleton that relocalizes to the DSB sites in a XRCC4-dependent
CC manner and promotes the immobilization of the broken ends, thereby
CC preventing chromosome translocation (PubMed:31548606). Acts as a
CC scaffold that allows the DNA repair protein XRCC4 and LMNA to assemble
CC into a complex at the DSB sites (PubMed:31548606).
CC {ECO:0000269|PubMed:31548606}.
CC -!- SUBUNIT: Forms a heterotetramer with XRCC4 (PubMed:31548606). The
CC interaction with XRCC4 is direct, involves LIG4-free XRCC4 and leads to
CC relocalization of IFFO1 at the double-strand break (DSB) sites
CC (PubMed:31548606). Interacts with LMNA; the interaction forms an
CC interior nucleoskeleton and the recruitment to DNA double-strand breaks
CC (PubMed:31548606). {ECO:0000269|PubMed:31548606}.
CC -!- INTERACTION:
CC Q0D2I5; P02545-2: LMNA; NbExp=2; IntAct=EBI-742894, EBI-351953;
CC Q0D2I5; Q13426: XRCC4; NbExp=5; IntAct=EBI-742894, EBI-717592;
CC Q0D2I5-5; P02545: LMNA; NbExp=4; IntAct=EBI-21251044, EBI-351935;
CC Q0D2I5-5; Q13426: XRCC4; NbExp=4; IntAct=EBI-21251044, EBI-717592;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:31548606}. Nucleus,
CC nucleoplasm {ECO:0000269|PubMed:31548606}. Nucleus inner membrane
CC {ECO:0000269|PubMed:31548606}. Nucleus matrix
CC {ECO:0000269|PubMed:31548606}. Note=Mainly soluble, the remaining is
CC localized in the nuclear matrix (PubMed:31548606). Localized at double-
CC strand break (DSB) sites near the lamina and nuclear matrix structures
CC (PubMed:31548606). {ECO:0000269|PubMed:31548606}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1;
CC IsoId=Q0D2I5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q0D2I5-2; Sequence=VSP_030781;
CC Name=3;
CC IsoId=Q0D2I5-3; Sequence=VSP_030782, VSP_030783;
CC Name=4;
CC IsoId=Q0D2I5-4; Sequence=VSP_030784;
CC Name=5;
CC IsoId=Q0D2I5-5; Sequence=VSP_030784, VSP_038240;
CC Name=6;
CC IsoId=Q0D2I5-6; Sequence=VSP_030781, VSP_038240;
CC Name=7;
CC IsoId=Q0D2I5-7; Sequence=VSP_039709, VSP_038240;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:12032826}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC {ECO:0000255|PROSITE-ProRule:PRU01188}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AF124432; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; CH471116; EAW88781.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88783.1; -; Genomic_DNA.
DR EMBL; BC002857; AAH02857.2; -; mRNA.
DR EMBL; BC004384; AAH04384.2; -; mRNA.
DR EMBL; BC010431; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC071170; AAH71170.1; -; mRNA.
DR EMBL; BC103817; AAI03818.1; -; mRNA.
DR EMBL; BC103818; AAI03819.1; -; mRNA.
DR EMBL; BC110387; AAI10388.1; -; mRNA.
DR EMBL; BC113848; AAI13849.1; -; mRNA.
DR EMBL; BC114454; AAI14455.1; -; mRNA.
DR EMBL; AF124432; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS41741.1; -. [Q0D2I5-5]
DR CCDS; CCDS81655.1; -. [Q0D2I5-1]
DR CCDS; CCDS8550.2; -. [Q0D2I5-4]
DR RefSeq; NP_001034759.1; NM_001039670.2. [Q0D2I5-5]
DR RefSeq; NP_001317253.1; NM_001330324.1. [Q0D2I5-1]
DR RefSeq; NP_542768.2; NM_080730.4. [Q0D2I5-4]
DR RefSeq; XP_006719038.1; XM_006718975.3. [Q0D2I5-7]
DR PDB; 6ABO; X-ray; 2.65 A; B=450-525.
DR PDBsum; 6ABO; -.
DR AlphaFoldDB; Q0D2I5; -.
DR SMR; Q0D2I5; -.
DR BioGRID; 117407; 52.
DR IntAct; Q0D2I5; 25.
DR STRING; 9606.ENSP00000482285; -.
DR iPTMnet; Q0D2I5; -.
DR PhosphoSitePlus; Q0D2I5; -.
DR BioMuta; IFFO1; -.
DR DMDM; 259016254; -.
DR EPD; Q0D2I5; -.
DR MassIVE; Q0D2I5; -.
DR PaxDb; Q0D2I5; -.
DR PeptideAtlas; Q0D2I5; -.
DR PRIDE; Q0D2I5; -.
DR ProteomicsDB; 58734; -. [Q0D2I5-1]
DR ProteomicsDB; 58735; -. [Q0D2I5-2]
DR ProteomicsDB; 58736; -. [Q0D2I5-3]
DR ProteomicsDB; 58737; -. [Q0D2I5-4]
DR ProteomicsDB; 58738; -. [Q0D2I5-5]
DR ProteomicsDB; 58739; -. [Q0D2I5-6]
DR ProteomicsDB; 58740; -. [Q0D2I5-7]
DR Antibodypedia; 22511; 65 antibodies from 17 providers.
DR DNASU; 25900; -.
DR Ensembl; ENST00000336604.8; ENSP00000337593.4; ENSG00000010295.20. [Q0D2I5-4]
DR Ensembl; ENST00000356896.8; ENSP00000349364.4; ENSG00000010295.20. [Q0D2I5-5]
DR Ensembl; ENST00000396840.6; ENSP00000380052.2; ENSG00000010295.20. [Q0D2I5-1]
DR Ensembl; ENST00000487279.6; ENSP00000432493.2; ENSG00000010295.20. [Q0D2I5-3]
DR GeneID; 25900; -.
DR KEGG; hsa:25900; -.
DR UCSC; uc001qpc.3; human. [Q0D2I5-1]
DR CTD; 25900; -.
DR DisGeNET; 25900; -.
DR GeneCards; IFFO1; -.
DR HGNC; HGNC:24970; IFFO1.
DR HPA; ENSG00000010295; Low tissue specificity.
DR MIM; 610495; gene.
DR neXtProt; NX_Q0D2I5; -.
DR OpenTargets; ENSG00000010295; -.
DR PharmGKB; PA164720809; -.
DR VEuPathDB; HostDB:ENSG00000010295; -.
DR eggNOG; ENOG502QRD7; Eukaryota.
DR GeneTree; ENSGT00510000046803; -.
DR HOGENOM; CLU_085236_0_0_1; -.
DR InParanoid; Q0D2I5; -.
DR OrthoDB; 792412at2759; -.
DR PhylomeDB; Q0D2I5; -.
DR TreeFam; TF331217; -.
DR PathwayCommons; Q0D2I5; -.
DR SignaLink; Q0D2I5; -.
DR BioGRID-ORCS; 25900; 13 hits in 1066 CRISPR screens.
DR ChiTaRS; IFFO1; human.
DR GenomeRNAi; 25900; -.
DR Pharos; Q0D2I5; Tdark.
DR PRO; PR:Q0D2I5; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q0D2I5; protein.
DR Bgee; ENSG00000010295; Expressed in tendon of biceps brachii and 194 other tissues.
DR ExpressionAtlas; Q0D2I5; baseline and differential.
DR Genevisible; Q0D2I5; HS.
DR GO; GO:0005882; C:intermediate filament; IEA:UniProtKB-KW.
DR GO; GO:0005637; C:nuclear inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:1990683; P:DNA double-strand break attachment to nuclear envelope; IDA:UniProtKB.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:UniProtKB.
DR GO; GO:1990166; P:protein localization to site of double-strand break; IMP:UniProtKB.
DR InterPro; IPR039008; IF_rod_dom.
DR SMART; SM01391; Filament; 1.
DR PROSITE; PS51842; IF_ROD_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Intermediate filament;
KW Membrane; Nucleus; Reference proteome.
FT CHAIN 1..559
FT /note="Non-homologous end joining factor IFFO1"
FT /id="PRO_0000316794"
FT DOMAIN 73..526
FT /note="IF rod"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188"
FT REGION 21..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 65..116
FT /note="LMNA binding"
FT /evidence="ECO:0000269|PubMed:31548606"
FT REGION 158..187
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 360..394
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 450..525
FT /note="XCCR4 binding. Required for localization to the
FT double-strand breaks (DSBs)"
FT /evidence="ECO:0000269|PubMed:31548606"
FT REGION 520..559
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 85..117
FT /evidence="ECO:0000255"
FT COILED 237..301
FT /evidence="ECO:0000255"
FT COILED 455..501
FT /evidence="ECO:0000255"
FT COMPBIAS 41..57
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 169..187
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 362..392
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 543..559
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..360
FT /note="Missing (in isoform 2 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030781"
FT VAR_SEQ 259..264
FT /note="WEEEYT -> CFYRVK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030782"
FT VAR_SEQ 265..559
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030783"
FT VAR_SEQ 357
FT /note="Q -> QKKL (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:12032826,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_030784"
FT VAR_SEQ 357
FT /note="Q -> QKL (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039709"
FT VAR_SEQ 451
FT /note="Q -> QQ (in isoform 5, isoform 6 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_038240"
FT MUTAGEN 65
FT /note="A->P,V: Does not affect the interaction with LMNA."
FT /evidence="ECO:0000269|PubMed:31548606"
FT MUTAGEN 73
FT /note="N->D: Decreased interaction with LMNA. Loss of
FT ability to immobilize broken ends; when associated with H-
FT 85."
FT /evidence="ECO:0000269|PubMed:31548606"
FT MUTAGEN 73
FT /note="N->K: Does not affect the interaction with LMNA."
FT /evidence="ECO:0000269|PubMed:31548606"
FT MUTAGEN 85
FT /note="R->H: Decreased interaction with LMNA."
FT /evidence="ECO:0000269|PubMed:31548606"
FT MUTAGEN 89
FT /note="A->T,V: Does not affect the interaction with LMNA."
FT /evidence="ECO:0000269|PubMed:31548606"
FT MUTAGEN 480
FT /note="I->R: Loss of interaction with XRCC4; when
FT associated with R-487."
FT /evidence="ECO:0000269|PubMed:31548606"
FT MUTAGEN 487
FT /note="A->R: Loss of interaction with XRCC4; when
FT associated with R-480."
FT /evidence="ECO:0000269|PubMed:31548606"
FT MUTAGEN 490
FT /note="D->A: Decreased interaction with XRCC4; when
FT associated with A-516. Loss of interaction with XRCC4; when
FT associated with A-509 and A-516."
FT /evidence="ECO:0000269|PubMed:31548606"
FT MUTAGEN 509
FT /note="D->A: Loss of interaction with XRCC4; when
FT associated with A-490 and A-516."
FT /evidence="ECO:0000269|PubMed:31548606"
FT MUTAGEN 512
FT /note="M->R: Loss of interaction with XRCC4."
FT /evidence="ECO:0000269|PubMed:31548606"
FT MUTAGEN 515
FT /note="C->R: Loss of interaction with XRCC4, loss of
FT localization at the sites of DNA damages and loss of
FT ability to immobilize broken ends."
FT /evidence="ECO:0000269|PubMed:31548606"
FT MUTAGEN 516
FT /note="R->A: Decreased interaction with XRCC4; when
FT associated with A-490. Loss of interaction with XRCC4; when
FT associated with A-490 and A-509."
FT /evidence="ECO:0000269|PubMed:31548606"
FT CONFLICT 152..153
FT /note="SA -> LE (in Ref. 3; AF124432)"
FT /evidence="ECO:0000305"
FT CONFLICT 285
FT /note="A -> V (in Ref. 3; AF124432)"
FT /evidence="ECO:0000305"
FT CONFLICT 358
FT /note="V -> F (in Ref. 2; AAI10388)"
FT /evidence="ECO:0000305"
FT CONFLICT 387
FT /note="P -> A (in Ref. 3; AF124432)"
FT /evidence="ECO:0000305"
FT CONFLICT 471
FT /note="K -> M (in Ref. 3; AF124432)"
FT /evidence="ECO:0000305"
FT CONFLICT 474
FT /note="Q -> H (in Ref. 3; AF124432)"
FT /evidence="ECO:0000305"
FT HELIX 450..504
FT /evidence="ECO:0007829|PDB:6ABO"
FT HELIX 506..519
FT /evidence="ECO:0007829|PDB:6ABO"
SQ SEQUENCE 559 AA; 61979 MW; 050FCFFB4953CBD8 CRC64;
MNPLFGPNLF LLQQEQQGLA GPLGDSLGGD HFAGGGDLPP APLSPAGPAA YSPPGPGPAP
PAAMALRNDL GSNINVLKTL NLRFRCFLAK VHELERRNRL LEKQLQQALE EGKQGRRGLG
RRDQAVQTGF VSPIRPLGLQ LGARPAAVCS PSARVLGSPA RSPAGPLAPS AASLSSSSTS
TSTTYSSSAR FMPGTIWSFS HARRLGPGLE PTLVQGPGLS WVHPDGVGVQ IDTITPEIRA
LYNVLAKVKR ERDEYKRRWE EEYTVRIQLQ DRVNELQEEA QEADACQEEL ALKVEQLKAE
LVVFKGLMSN NLSELDTKIQ EKAMKVDMDI CRRIDITAKL CDVAQQRNCE DMIQMFQVPS
MGGRKRERKA AVEEDTSLSE SEGPRQPDGD EEESTALSIN EEMQRMLNQL REYDFEDDCD
SLTWEETEET LLLWEDFSGY AMAAAEAQGE QEDSLEKVIK DTESLFKTRE KEYQETIDQI
ELELATAKND MNRHLHEYME MCSMKRGLDV QMETCRRLIT QSGDRKSPAF TAVPLSDPPP
PPSEAEDSDR DVSSDSSMR
