NRIF1_MOUSE
ID NRIF1_MOUSE Reviewed; 828 AA.
AC Q923B3; Q8BS00; Q9D6I6; Q9QZ07;
DT 05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 3.
DT 25-MAY-2022, entry version 155.
DE RecName: Full=Neurotrophin receptor-interacting factor 1;
DE AltName: Full=Neurotrophin receptor-interacting factor;
DE AltName: Full=Zinc finger protein 110;
GN Name=Nrif1; Synonyms=Nrif, Zfp110;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, INTERACTION
RP WITH NGFR, AND DISRUPTION PHENOTYPE.
RC STRAIN=129/Sv;
RX PubMed=10545116; DOI=10.1093/emboj/18.21.6050;
RA Casademunt E., Carter B.D., Benzel I., Frade J.M., Dechant G., Barde Y.A.;
RT "The zinc finger protein NRIF interacts with the neurotrophin receptor
RT p75(NTR) and participates in programmed cell death.";
RL EMBO J. 18:6050-6061(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Aorta, Hippocampus, and Vein;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary tumor;
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 [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=11750124; DOI=10.1016/s0378-1119(01)00730-2;
RA Benzel I., Barde Y.A., Casademunt E.;
RT "Strain-specific complementation between NRIF1 and NRIF2, two zinc finger
RT proteins sharing structural and biochemical properties.";
RL Gene 281:19-30(2001).
RN [5]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH TRAF6.
RX PubMed=14960584; DOI=10.1074/jbc.m309209200;
RA Gentry J.J., Rutkoski N.J., Burke T.L., Carter B.D.;
RT "A functional interaction between the p75 neurotrophin receptor interacting
RT factors, TRAF6 and NRIF.";
RL J. Biol. Chem. 279:16646-16656(2004).
RN [6]
RP UBIQUITINATION AT LYS-15, SUBCELLULAR LOCATION, INTERACTION WITH SQSTM1 AND
RP TRAF6, AND MUTAGENESIS OF LYS-15.
RX PubMed=16252010; DOI=10.1038/sj.emboj.7600845;
RA Geetha T., Kenchappa R.S., Wooten M.W., Carter B.D.;
RT "TRAF6-mediated ubiquitination regulates nuclear translocation of NRIF, the
RT p75 receptor interactor.";
RL EMBO J. 24:3859-3868(2005).
RN [7]
RP FUNCTION.
RX PubMed=15668238; DOI=10.1074/jbc.m410435200;
RA Linggi M.S., Burke T.L., Williams B.B., Harrington A., Kraemer R.,
RA Hempstead B.L., Yoon S.O., Carter B.D.;
RT "Neurotrophin receptor interacting factor (NRIF) is an essential mediator
RT of apoptotic signaling by the p75 neurotrophin receptor.";
RL J. Biol. Chem. 280:13801-13808(2005).
RN [8]
RP FUNCTION, UBIQUITINATION AT LYS-15, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH NGFR.
RX PubMed=16630834; DOI=10.1016/j.neuron.2006.03.011;
RA Kenchappa R.S., Zampieri N., Chao M.V., Barker P.A., Teng H.K.,
RA Hempstead B.L., Carter B.D.;
RT "Ligand-dependent cleavage of the P75 neurotrophin receptor is necessary
RT for NRIF nuclear translocation and apoptosis in sympathetic neurons.";
RL Neuron 50:219-232(2006).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NGFR.
RX PubMed=18815271; DOI=10.1523/jneurosci.2841-08.2008;
RA Volosin M., Trotter C., Cragnolini A., Kenchappa R.S., Light M.,
RA Hempstead B.L., Carter B.D., Friedman W.J.;
RT "Induction of proneurotrophins and activation of p75NTR-mediated apoptosis
RT via neurotrophin receptor-interacting factor in hippocampal neurons after
RT seizures.";
RL J. Neurosci. 28:9870-9879(2008).
RN [10]
RP FUNCTION.
RX PubMed=18677445; DOI=10.1007/s12031-008-9136-9;
RA Korade Z., Kenchappa R.S., Mirnics K., Carter B.D.;
RT "NRIF is a regulator of neuronal cholesterol biosynthesis genes.";
RL J. Mol. Neurosci. 38:152-158(2009).
CC -!- FUNCTION: Transcription regulator involved in NGFR/p75(NTR)-mediated
CC apoptosis. Essential component of the NGFR/p75(NTR) apoptotic pathway:
CC upon ligand-binding and subsequent cleavage of NGFR/p75(NTR), binds to
CC the intracellular domain (ICD) cleavage product of NGFR/p75(NTR),
CC translocates to the nucleus and induces apoptosis, possibly by
CC regulating expression of key regulators of apoptosis. Induces
CC NGFR/p75(NTR)-mediated apoptosis in retina and sympathetic neurons. May
CC also regulate expression of neuronal cholesterol biosynthesis genes.
CC Probably acts as a transcription repressor: specifically binds to the
CC 3'-end of zinc-finger coding genes and recruiting chromatin-modifying
CC proteins such as SETDB1 and TRIM28/KAP1, leading to transcription
CC repression. {ECO:0000269|PubMed:10545116, ECO:0000269|PubMed:15668238,
CC ECO:0000269|PubMed:16630834, ECO:0000269|PubMed:18677445,
CC ECO:0000269|PubMed:18815271}.
CC -!- SUBUNIT: Interacts with NGFR/p75(NTR). Interacts (via KRAB 1 domain)
CC with TRAF6. Interacts (when ubiquitinated at Lys-15) with SQSTM1/p62.
CC {ECO:0000269|PubMed:10545116, ECO:0000269|PubMed:14960584,
CC ECO:0000269|PubMed:16252010, ECO:0000269|PubMed:16630834,
CC ECO:0000269|PubMed:18815271}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocates into the
CC nucleus following binding to TRAF6 and subsequent ubiquitination at
CC Lys-15.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed at low level. Expressed at
CC higher level in testis.
CC -!- PTM: Ubiquitinated by TRAF6 at Lys-15 through 'Lys-63'-linked
CC polyubiquitination. 'Lys-63'-linked polyubiquitination occurs in
CC response to NGFR/p75(NTR) cleavage by gamma-secretase and promotes
CC binding with the ICD cleavage product of NGFR/p75(NTR), followed by
CC translocation into the nucleus and subsequent apoptosis.
CC {ECO:0000269|PubMed:16252010, ECO:0000269|PubMed:16630834}.
CC -!- DISRUPTION PHENOTYPE: Lethal in a C57BL/6 background, while mice in a
CC 129/Sv background are viable and healthy to adulthood. Mice in a
CC C57BL/6 background do not survive beyond 12 dpc. Mice in a 129/Sv
CC background may survive due to the presence of Nrif2/Zfp369, which is
CC up-regulated in Nrif1 mutant mice in the 129/Sv background.
CC {ECO:0000269|PubMed:10545116, ECO:0000269|PubMed:11750124}.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH06657.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC30771.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ242914; CAB52296.1; -; mRNA.
DR EMBL; AK013583; BAB28915.1; -; mRNA.
DR EMBL; AK040989; BAC30771.1; ALT_INIT; mRNA.
DR EMBL; BC006657; AAH06657.2; ALT_INIT; mRNA.
DR RefSeq; NP_075357.4; NM_022981.4.
DR RefSeq; XP_006540338.1; XM_006540275.3.
DR AlphaFoldDB; Q923B3; -.
DR SMR; Q923B3; -.
DR BioGRID; 211122; 6.
DR IntAct; Q923B3; 2.
DR STRING; 10090.ENSMUSP00000004614; -.
DR iPTMnet; Q923B3; -.
DR PhosphoSitePlus; Q923B3; -.
DR MaxQB; Q923B3; -.
DR PaxDb; Q923B3; -.
DR PRIDE; Q923B3; -.
DR ProteomicsDB; 293895; -.
DR DNASU; 65020; -.
DR GeneID; 65020; -.
DR KEGG; mmu:65020; -.
DR UCSC; uc009fej.2; mouse.
DR CTD; 65020; -.
DR MGI; MGI:1890378; Zfp110.
DR eggNOG; KOG1721; Eukaryota.
DR InParanoid; Q923B3; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q923B3; -.
DR TreeFam; TF338018; -.
DR Reactome; R-MMU-212436; Generic Transcription Pathway.
DR BioGRID-ORCS; 65020; 2 hits in 73 CRISPR screens.
DR PRO; PR:Q923B3; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q923B3; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISO:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005166; F:neurotrophin p75 receptor binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0051402; P:neuron apoptotic process; IMP:UniProtKB.
DR GO; GO:1900112; P:regulation of histone H3-K9 trimethylation; ISO:MGI.
DR GO; GO:0046328; P:regulation of JNK cascade; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:1990009; P:retinal cell apoptotic process; IMP:MGI.
DR CDD; cd07765; KRAB_A-box; 2.
DR CDD; cd07936; SCAN; 1.
DR Gene3D; 1.10.4020.10; -; 1.
DR InterPro; IPR001909; KRAB.
DR InterPro; IPR036051; KRAB_dom_sf.
DR InterPro; IPR003309; SCAN_dom.
DR InterPro; IPR038269; SCAN_sf.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF01352; KRAB; 2.
DR Pfam; PF02023; SCAN; 1.
DR Pfam; PF00096; zf-C2H2; 4.
DR SMART; SM00349; KRAB; 2.
DR SMART; SM00431; SCAN; 1.
DR SMART; SM00355; ZnF_C2H2; 5.
DR SUPFAM; SSF109640; SSF109640; 2.
DR SUPFAM; SSF57667; SSF57667; 3.
DR PROSITE; PS50805; KRAB; 2.
DR PROSITE; PS50804; SCAN_BOX; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 5.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 5.
PE 1: Evidence at protein level;
KW Apoptosis; Cytoplasm; DNA-binding; Isopeptide bond; Metal-binding; Nucleus;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..828
FT /note="Neurotrophin receptor-interacting factor 1"
FT /id="PRO_0000406966"
FT DOMAIN 14..85
FT /note="KRAB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00119"
FT DOMAIN 158..240
FT /note="SCAN box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00187"
FT DOMAIN 280..370
FT /note="KRAB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00119"
FT ZN_FING 684..706
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 712..734
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 740..762
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 768..790
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 796..818
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 328..355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 377..490
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 575..611
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 387..401
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 454..486
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 15
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:16252010,
FT ECO:0000269|PubMed:16630834"
FT MUTAGEN 15
FT /note="K->R: Abolishes ubiquitination by TRAF6, binding to
FT SQSTM1/p62, translocation to the nucleus and NGFR/p75(NTR)-
FT mediated apoptosis."
FT /evidence="ECO:0000269|PubMed:16252010"
FT CONFLICT 348
FT /note="N -> K (in Ref. 1; BAC30771)"
FT /evidence="ECO:0000305"
FT CONFLICT 373
FT /note="S -> T (in Ref. 1; BAC30771)"
FT /evidence="ECO:0000305"
FT CONFLICT 472
FT /note="K -> N (in Ref. 1; BAC30771)"
FT /evidence="ECO:0000305"
FT CONFLICT 505
FT /note="E -> K (in Ref. 1; BAC30771)"
FT /evidence="ECO:0000305"
FT CONFLICT 509
FT /note="F -> L (in Ref. 1; BAC30771)"
FT /evidence="ECO:0000305"
FT CONFLICT 518
FT /note="P -> S (in Ref. 1; BAC30771)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 828 AA; 93650 MW; E08F074002360BBC CRC64;
MASTLPTTWP HESVKFEDVS LTFTEEEWAQ LDFQQKCLYR EIMMENYSNM ISVEHHFSKP
NVISQLEKAE DCWPMQREIP QDTLPECSWP SPDPGMNSFP SKSPLMKIEV VEVLTLNKDV
AGPRNALIQS LYPEDLNPGN LKPAQQPSKR LTDTEASRQK FRHFQYEESA GPQKAMSQLR
KLCHQWLQPN TRSKKQILEL LVLEQFLNAL PEKFRVWVES QHPEDCKAVV ALLENMTSVS
KDDASLACSS EATDQLKEKR KGVATLPVTF AAEVPAEEPV TFQDVAVDFN EEEWRLLGPT
QKTEYHDVML ETLGNLVSVG WEPTLGNREL TPDSPIPVVK PIHDPNTNDL SRNGTQSTVF
ESILEDGVKE MHSIESNQVG NLQEKGHPQK KFSESSKSQD QTSRHKSQGS LNEVLPRKYV
KVKQKGTGKR KGRTNTISMT RGLRIRKQQK DSVEWQGRSG STPVTHGSSI KKQQQGSEQG
KPGTSRDPIT LTVPAKVYQK ATGSEESIFM DSSDAMVPDV PPKIHQKGPE WHKVGESNNS
MLQGSSVQNH QMESGAGRAS DNSLLTHALP VKSHQKGYKE GNVQGNRNSW KHIKPHQKGS
KGERVEELST SEKHVPYVKN HLKTSERGKD REINASIKCD PYIKTYYRGS DVGRLRRANN
CRKAFSLHAQ QISFIKIHKG SQVCRCSECG KLFRNARYFS VHKKIHTGER PYMCMACGKA
FVQSSSLTQH LRIHSGERPF ECSECGRTFN DRSAISQHLR THTGAKPYHC ERCGKAFRQS
SHLTRHERTH TGERPYVCIK CGKAFTQSSH LIGHQKTHGI KFKKQPKL
