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   24-JAN-2024, entry version 128.
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; 24.
DR   STRING; 9606.ENSP00000482285; -.
DR   GlyGen; Q0D2I5; 3 sites, 1 O-linked glycan (3 sites).
DR   iPTMnet; Q0D2I5; -.
DR   PhosphoSitePlus; Q0D2I5; -.
DR   BioMuta; IFFO1; -.
DR   DMDM; 259016254; -.
DR   EPD; Q0D2I5; -.
DR   MassIVE; Q0D2I5; -.
DR   PaxDb; 9606-ENSP00000482285; -.
DR   PeptideAtlas; 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   Pumba; Q0D2I5; -.
DR   Antibodypedia; 22511; 80 antibodies from 18 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   AGR; HGNC:24970; -.
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; 5318369at2759; -.
DR   PhylomeDB; Q0D2I5; -.
DR   TreeFam; TF331217; -.
DR   PathwayCommons; Q0D2I5; -.
DR   SignaLink; Q0D2I5; -.
DR   BioGRID-ORCS; 25900; 16 hits in 1144 CRISPR screens.
DR   ChiTaRS; IFFO1; human.
DR   GenomeRNAi; 25900; -.
DR   Pharos; Q0D2I5; Tbio.
DR   PRO; PR:Q0D2I5; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; Q0D2I5; Protein.
DR   Bgee; ENSG00000010295; Expressed in tendon of biceps brachii and 196 other cell types or tissues.
DR   ExpressionAtlas; Q0D2I5; baseline and differential.
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   Gene3D; 1.20.5.170; -; 1.
DR   Gene3D; 1.20.5.1160; Vasodilator-stimulated phosphoprotein; 1.
DR   InterPro; IPR039008; IF_rod_dom.
DR   PANTHER; PTHR14516; 1-PYRROLINE-5-CARBOXYLATE DEHYDROGENASE FAMILY MEMBER; 1.
DR   PANTHER; PTHR14516:SF2; NON-HOMOLOGOUS END JOINING FACTOR IFFO1; 1.
DR   SMART; SM01391; Filament; 1.
DR   SUPFAM; SSF64593; Intermediate filament protein, coiled coil region; 1.
DR   PROSITE; PS51842; IF_ROD_2; 1.
DR   Genevisible; Q0D2I5; HS.
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
FT                   H-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
//