MRNIP_HUMAN
ID MRNIP_HUMAN Reviewed; 343 AA.
AC Q6NTE8; B5MD09; E9PAK6; Q7Z3D8; Q9BUC1; Q9UN54;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=MRN complex-interacting protein {ECO:0000312|HGNC:HGNC:30817};
DE AltName: Full=MRN-interacting protein {ECO:0000303|PubMed:27568553};
GN Name=MRNIP {ECO:0000312|HGNC:HGNC:30817}; Synonyms=C5orf45;
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 MRNA] (ISOFORM 2).
RC TISSUE=Endometrium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 3-343 (ISOFORM 3), AND VARIANTS GLY-154 AND ARG-231.
RC TISSUE=Lung, and Uterus;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 113-343 (ISOFORM 1), AND VARIANT
RP ARG-231.
RA Zhang W., Yuan Z., Wan T., Cao X.;
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, PHOSPHORYLATION AT SER-100 AND SER-115, ASSOCIATION WITH THE MRN
RP COMPLEX, INTERACTION WITH MRE11; NBN AND RAD50, SUBCELLULAR LOCATION,
RP REGION, AND MUTAGENESIS OF SER-100; SER-115; ARG-141; SER-143;
RP 148-ARG--LYS-151; ARG-154 AND 213-LYS--ARG-237.
RX PubMed=27568553; DOI=10.1016/j.celrep.2016.07.087;
RA Staples C.J., Barone G., Myers K.N., Ganesh A., Gibbs-Seymour I.,
RA Patil A.A., Beveridge R.D., Daye C., Beniston R., Maslen S., Ahel I.,
RA Skehel J.M., Collis S.J.;
RT "MRNIP/C5orf45 interacts with the MRN complex and contributes to the DNA
RT damage response.";
RL Cell Rep. 16:2565-2575(2016).
CC -!- FUNCTION: Plays a role in the cellular response to DNA damage and the
CC maintenance of genome stability through its association with the MRN
CC damage-sensing complex (PubMed:27568553). Promotes chromatin loading
CC and activity of the MRN complex to facilitate subsequent ATM-mediated
CC DNA damage response signaling and DNA repair (PubMed:27568553).
CC -!- SUBUNIT: Associates with the MRE11-RAD50-NBN (MRN) damage-sensing
CC complex; this association is constitutive (PubMed:27568553). Interacts
CC with MRE11 (PubMed:27568553). Interacts with NBN (PubMed:27568553).
CC Interacts with RAD50 (PubMed:27568553). {ECO:0000269|PubMed:27568553}.
CC -!- INTERACTION:
CC Q6NTE8; Q9BVJ7: DUSP23; NbExp=3; IntAct=EBI-2857471, EBI-724940;
CC Q6NTE8; Q5JVL4: EFHC1; NbExp=3; IntAct=EBI-2857471, EBI-743105;
CC Q6NTE8; P60228: EIF3E; NbExp=3; IntAct=EBI-2857471, EBI-347740;
CC Q6NTE8; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-2857471, EBI-744099;
CC Q6NTE8; P61970: NUTF2; NbExp=3; IntAct=EBI-2857471, EBI-591778;
CC Q6NTE8; Q9UBU9: NXF1; NbExp=3; IntAct=EBI-2857471, EBI-398874;
CC Q6NTE8; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-2857471, EBI-79165;
CC Q6NTE8; P61925: PKIA; NbExp=3; IntAct=EBI-2857471, EBI-2682139;
CC Q6NTE8; P20618: PSMB1; NbExp=3; IntAct=EBI-2857471, EBI-372273;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:27568553}. Nucleus,
CC nucleoplasm {ECO:0000269|PubMed:27568553}. Note=Recruited to sites of
CC DNA damage (PubMed:27568553). Phosphorylation on Ser-115 induces its
CC nuclear localization and promotes genome stability (PubMed:27568553).
CC {ECO:0000269|PubMed:27568553}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6NTE8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6NTE8-2; Sequence=VSP_032560, VSP_032561, VSP_032562;
CC Name=3;
CC IsoId=Q6NTE8-3; Sequence=VSP_047227;
CC -!- PTM: Phosphorylated; phosphorylation is constitutive and occurs in the
CC absence of any DNA-damaging stimulus. Phosphorylation on Ser-115 is
CC necessary for its nuclear retention. {ECO:0000269|PubMed:27568553}.
CC -!- SIMILARITY: Belongs to the MRNIP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD51611.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAD97932.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; BX537968; CAD97932.1; ALT_INIT; mRNA.
DR EMBL; AC008393; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002739; AAH02739.2; -; mRNA.
DR EMBL; BC050714; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC069051; AAH69051.1; -; mRNA.
DR EMBL; AF153685; AAD51611.1; ALT_FRAME; mRNA.
DR CCDS; CCDS34318.1; -. [Q6NTE8-3]
DR CCDS; CCDS34319.1; -. [Q6NTE8-1]
DR RefSeq; NP_001017987.1; NM_001017987.2. [Q6NTE8-3]
DR RefSeq; NP_057259.2; NM_016175.3. [Q6NTE8-1]
DR AlphaFoldDB; Q6NTE8; -.
DR BioGRID; 119333; 34.
DR IntAct; Q6NTE8; 12.
DR STRING; 9606.ENSP00000292586; -.
DR iPTMnet; Q6NTE8; -.
DR PhosphoSitePlus; Q6NTE8; -.
DR BioMuta; MRNIP; -.
DR DMDM; 215273989; -.
DR EPD; Q6NTE8; -.
DR jPOST; Q6NTE8; -.
DR MassIVE; Q6NTE8; -.
DR MaxQB; Q6NTE8; -.
DR PaxDb; Q6NTE8; -.
DR PeptideAtlas; Q6NTE8; -.
DR PRIDE; Q6NTE8; -.
DR ProteomicsDB; 19034; -.
DR ProteomicsDB; 66668; -. [Q6NTE8-1]
DR ProteomicsDB; 66669; -. [Q6NTE8-2]
DR Antibodypedia; 62814; 108 antibodies from 13 providers.
DR DNASU; 51149; -.
DR Ensembl; ENST00000292586.11; ENSP00000292586.6; ENSG00000161010.16. [Q6NTE8-1]
DR Ensembl; ENST00000376931.6; ENSP00000366130.2; ENSG00000161010.16. [Q6NTE8-3]
DR Ensembl; ENST00000639632.2; ENSP00000491991.1; ENSG00000283918.2. [Q6NTE8-1]
DR Ensembl; ENST00000640658.1; ENSP00000491128.1; ENSG00000283918.2. [Q6NTE8-3]
DR GeneID; 51149; -.
DR KEGG; hsa:51149; -.
DR MANE-Select; ENST00000292586.11; ENSP00000292586.6; NM_016175.4; NP_057259.2.
DR UCSC; uc003mla.4; human. [Q6NTE8-1]
DR CTD; 51149; -.
DR DisGeNET; 51149; -.
DR GeneCards; MRNIP; -.
DR HGNC; HGNC:30817; MRNIP.
DR HPA; ENSG00000161010; Low tissue specificity.
DR MalaCards; MRNIP; -.
DR MIM; 617154; gene.
DR neXtProt; NX_Q6NTE8; -.
DR OpenTargets; ENSG00000161010; -.
DR PharmGKB; PA162380286; -.
DR VEuPathDB; HostDB:ENSG00000161010; -.
DR eggNOG; ENOG502S8YD; Eukaryota.
DR GeneTree; ENSGT00390000006124; -.
DR HOGENOM; CLU_068693_0_0_1; -.
DR InParanoid; Q6NTE8; -.
DR OMA; FPRWKLP; -.
DR OrthoDB; 1146272at2759; -.
DR PhylomeDB; Q6NTE8; -.
DR TreeFam; TF333430; -.
DR PathwayCommons; Q6NTE8; -.
DR SignaLink; Q6NTE8; -.
DR BioGRID-ORCS; 51149; 12 hits in 1050 CRISPR screens.
DR ChiTaRS; C5orf45; human.
DR GenomeRNAi; 51149; -.
DR Pharos; Q6NTE8; Tbio.
DR PRO; PR:Q6NTE8; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q6NTE8; protein.
DR Bgee; ENSG00000161010; Expressed in cerebellar hemisphere and 105 other tissues.
DR ExpressionAtlas; Q6NTE8; baseline and differential.
DR Genevisible; Q6NTE8; HS.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IMP:UniProtKB.
DR GO; GO:0071168; P:protein localization to chromatin; IDA:UniProtKB.
DR GO; GO:2001032; P:regulation of double-strand break repair via nonhomologous end joining; IMP:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; IMP:UniProtKB.
DR InterPro; IPR032739; MRNIP.
DR PANTHER; PTHR15863; PTHR15863; 1.
DR Pfam; PF15749; MRNIP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; DNA damage; DNA repair; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..343
FT /note="MRN complex-interacting protein"
FT /id="PRO_0000326119"
FT REGION 75..104
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 128..178
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 193..212
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 213..237
FT /note="Necessary for the association with the MRN complex"
FT /evidence="ECO:0000269|PubMed:27568553"
FT REGION 230..324
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 148..151
FT /note="Nuclear localization signal (NLS)"
FT /evidence="ECO:0000269|PubMed:27568553"
FT COMPBIAS 83..104
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 100
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27568553"
FT MOD_RES 115
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27568553"
FT VAR_SEQ 1..42
FT /note="MASLQRSRVLRCCSCRLFQAHQVKKSVKWTCKACGEKQSFLQ -> MQSARA
FT WLPGDCTSRDGVASAFSGATLLQLPPLPGAPGKKECQVDMQSLWREAVLFAEFPRHGAP
FT ASELPVPSGSEMDGAESGK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_032560"
FT VAR_SEQ 43..97
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_047227"
FT VAR_SEQ 222..229
FT /note="VTATSSKW -> DGYKEILF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_032561"
FT VAR_SEQ 230..343
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_032562"
FT VARIANT 42
FT /note="Q -> R (in dbSNP:rs1650893)"
FT /id="VAR_054030"
FT VARIANT 97
FT /note="Q -> R (in dbSNP:rs1650893)"
FT /id="VAR_039990"
FT VARIANT 154
FT /note="R -> G (in dbSNP:rs248248)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_039991"
FT VARIANT 231
FT /note="Q -> R (in dbSNP:rs10277)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.4"
FT /id="VAR_039992"
FT MUTAGEN 100
FT /note="S->A: Does not affect nuclear localization.
FT Decreases weakly the association with the MRN complex.
FT Reduces phosphorylation; when associated with A-115 and A-
FT 143."
FT /evidence="ECO:0000269|PubMed:27568553"
FT MUTAGEN 115
FT /note="S->A: Reduces nuclear localization and increases DNA
FT damage accumulation. Decreases weakly the association with
FT the MRN complex. Reduces phosphorylation; when associated
FT with A-100 and A-143."
FT /evidence="ECO:0000269|PubMed:27568553"
FT MUTAGEN 115
FT /note="S->D: Does not affect nuclear localization."
FT /evidence="ECO:0000269|PubMed:27568553"
FT MUTAGEN 141
FT /note="R->A: Reduces nuclear localization and increases DNA
FT damage accumulation and does not affect the association
FT with the MRN complex; when associated with 148-A--A-151 and
FT A-154."
FT /evidence="ECO:0000269|PubMed:27568553"
FT MUTAGEN 143
FT /note="S->A: Reduces phosphorylation; when associated with
FT A-100 and A-115."
FT /evidence="ECO:0000269|PubMed:27568553"
FT MUTAGEN 148..151
FT /note="RKRK->AAAA: Decreases nuclear localization. Reduces
FT nuclear localization and increases DNA damage accumulation
FT and does not affect the association with the MRN complex;
FT when associated with A-141 and A-154."
FT /evidence="ECO:0000269|PubMed:27568553"
FT MUTAGEN 154
FT /note="R->A: Reduces nuclear localization and increases DNA
FT damage accumulation and does not affect the association
FT with the MRN complex; when associated with A-141 and 148-
FT A--A-151."
FT /evidence="ECO:0000269|PubMed:27568553"
FT MUTAGEN 213..237
FT /note="Missing: Reduces the association with the MRN
FT complex."
FT /evidence="ECO:0000269|PubMed:27568553"
FT CONFLICT Q6NTE8-3:42
FT /note="Q -> R (in Ref. 3; BC050714)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 343 AA; 37743 MW; 08C3CE3C1BC827EC CRC64;
MASLQRSRVL RCCSCRLFQA HQVKKSVKWT CKACGEKQSF LQAYGEGSGA DCRRHVQKLN
LLQGQVSELP LRSLEETVSA SEEENVGHQQ AGNVKQQEKS QPSESRWLKY LEKDSQELEL
EGTGVCFSKQ PSSKMEEPGP RFSQDLPRKR KWSRSTVQPP CSRGVQDSGG SEVAWGPQKG
QAGLTWKVKQ GSSPCLQENS ADCSAGELRG PGKELWSPIQ QVTATSSKWA QFVLPPRKSS
HVDSEQPRSL QRDPRPAGPA QAKQGTPRAQ ASREGLSRPT AAVQLPRATH PVTSGSERPC
GKTSWDARTP WAEGGPLVLE AQNPRPTRLC DLFITGEDFD DDV
