ID   TCF25_HUMAN             Reviewed;         676 AA.
AC   Q9BQ70; Q2MK75; Q9UPV3;
DT   19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   28-JAN-2026, entry version 181.
DE   RecName: Full=Ribosome quality control complex subunit TCF25 {ECO:0000305};
DE   AltName: Full=Nuclear localized protein 1 {ECO:0000303|PubMed:16574069};
DE   AltName: Full=Transcription factor 25 {ECO:0000305};
DE            Short=TCF-25;
GN   Name=TCF25 {ECO:0000303|PubMed:30244831, ECO:0000312|HGNC:HGNC:29181};
GN   Synonyms=KIAA1049 {ECO:0000303|PubMed:10470851}, NULP1
GN   {ECO:0000303|PubMed:16574069}; ORFNames=FKSG26 {ECO:0000303|Ref.2};
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 [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=16574069; DOI=10.1016/j.bbrc.2006.02.187;
RA   Cai Z., Wang Y., Yu W., Xiao J., Li Y., Liu L., Zhu C., Tan K., Deng Y.,
RA   Yuan W., Liu M., Wu X.;
RT   "hnulp1, a basic helix-loop-helix protein with a novel transcriptional
RT   repressive domain, inhibits transcriptional activity of serum response
RT   factor.";
RL   Biochem. Biophys. Res. Commun. 343:973-981(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Wang Y.-G., Gong L.;
RT   "Characterization of FKSG26, a novel gene located on human chromosome
RT   16q24.3.";
RL   Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain, Lymph, and Muscle;
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 127-676.
RC   TISSUE=Brain;
RX   PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA   Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA   Kotani H., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XIV. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 6:197-205(1999).
RN   [5]
RP   SUBCELLULAR LOCATION.
RX   PubMed=18068114; DOI=10.1016/j.bbrc.2007.11.146;
RA   Steen H., Lindholm D.;
RT   "Nuclear localized protein-1 (Nulp1) increases cell death of human
RT   osteosarcoma cells and binds the X-linked inhibitor of apoptosis protein.";
RL   Biochem. Biophys. Res. Commun. 366:432-437(2008).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-602, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-602, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-602, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [11]
RP   FUNCTION, AND IDENTIFICATION IN THE RQC COMPLEX.
RX   PubMed=30244831; DOI=10.1016/j.molcel.2018.08.022;
RA   Kuroha K., Zinoviev A., Hellen C.U.T., Pestova T.V.;
RT   "Release of ubiquitinated and non-ubiquitinated nascent chains from stalled
RT   mammalian ribosomal complexes by ANKZF1 and Ptrh1.";
RL   Mol. Cell 72:286-302(2018).
RN   [12]
RP   TISSUE SPECIFICITY.
RX   PubMed=32805187; DOI=10.1161/jaha.120.016419;
RA   Zhang X., Lei F., Wang X.M., Deng K.Q., Ji Y.X., Zhang Y., Li H.,
RA   Zhang X.D., Lu Z., Zhang P.;
RT   "NULP1 Alleviates Cardiac Hypertrophy by Suppressing NFAT3 Transcriptional
RT   Activity.";
RL   J. Am. Heart Assoc. 9:e016419-e016419(2020).
CC   -!- FUNCTION: Component of the ribosome quality control complex (RQC), a
CC       ribosome-associated complex that mediates ubiquitination and extraction
CC       of incompletely synthesized nascent chains for proteasomal degradation
CC       (PubMed:30244831). In the RQC complex, required to promote formation of
CC       'Lys-48'-linked polyubiquitin chains during ubiquitination of
CC       incompletely synthesized proteins by LTN1 (PubMed:30244831). May
CC       negatively regulate the calcineurin-NFAT signaling cascade by
CC       suppressing the activity of transcription factor NFATC4 (By
CC       similarity). May play a role in cell death control (By similarity).
CC       {ECO:0000250|UniProtKB:A0A8I6ASZ5, ECO:0000250|UniProtKB:Q8R3L2,
CC       ECO:0000269|PubMed:30244831}.
CC   -!- SUBUNIT: Component of the ribosome quality control complex (RQC),
CC       composed of the E3 ubiquitin ligase LTN1, TCF25 and NEMF associated
CC       with the 60S ribosomal subunit (PubMed:30244831). Interacts (via C-
CC       terminus) with NFATC4; the interaction leads to suppresson of NFATC4
CC       transcription factor activity and is reduced following stimulation with
CC       angiotensin-2 (By similarity). Interacts with XIAP (By similarity).
CC       {ECO:0000250|UniProtKB:A0A8I6ASZ5, ECO:0000250|UniProtKB:Q8R3L2,
CC       ECO:0000269|PubMed:30244831}.
CC   -!- INTERACTION:
CC       Q9BQ70; Q92624: APPBP2; NbExp=3; IntAct=EBI-745182, EBI-743771;
CC       Q9BQ70; Q9BUN8: DERL1; NbExp=3; IntAct=EBI-745182, EBI-398977;
CC       Q9BQ70; Q96D09: GPRASP2; NbExp=11; IntAct=EBI-745182, EBI-473189;
CC       Q9BQ70; Q96SL4: GPX7; NbExp=3; IntAct=EBI-745182, EBI-749411;
CC       Q9BQ70; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-745182, EBI-749265;
CC       Q9BQ70; O60333-2: KIF1B; NbExp=3; IntAct=EBI-745182, EBI-10975473;
CC       Q9BQ70; Q5S007: LRRK2; NbExp=3; IntAct=EBI-745182, EBI-5323863;
CC       Q9BQ70; P43364: MAGEA11; NbExp=5; IntAct=EBI-745182, EBI-739552;
CC       Q9BQ70; P43364-2: MAGEA11; NbExp=3; IntAct=EBI-745182, EBI-10178634;
CC       Q9BQ70; P21673: SAT1; NbExp=11; IntAct=EBI-745182, EBI-711613;
CC       Q9BQ70; O76024: WFS1; NbExp=3; IntAct=EBI-745182, EBI-720609;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16574069,
CC       ECO:0000269|PubMed:18068114}. Cytoplasm, cytosol
CC       {ECO:0000269|PubMed:18068114}. Note=Mainly nuclear.
CC       {ECO:0000269|PubMed:18068114}.
CC   -!- TISSUE SPECIFICITY: In the embryo, widely expressed with highest levels
CC       in brain (PubMed:16574069). In the adult, highest expression is found
CC       in the heart (PubMed:16574069, PubMed:32805187). Repressed in cardiac
CC       tissue of patients with heart failure (at protein level)
CC       (PubMed:32805187). mRNA levels in the heart are unchanged in patients
CC       with heart failure (PubMed:32805187). {ECO:0000269|PubMed:16574069,
CC       ECO:0000269|PubMed:32805187}.
CC   -!- SIMILARITY: Belongs to the TCF25 family. {ECO:0000305}.
CC   -!- CAUTION: Was reported to have DNA-binding activity (PubMed:16574069).
CC       However, this is uncertain as it was shown with the protein fused to
CC       the yeast GAL4 DNA-binding domain. {ECO:0000269|PubMed:16574069,
CC       ECO:0000305}.
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DR   EMBL; DQ321703; ABC55265.1; -; mRNA.
DR   EMBL; AF322111; AAG50276.1; -; mRNA.
DR   EMBL; BC000959; AAH00959.1; -; mRNA.
DR   EMBL; BC009349; AAH09349.1; -; mRNA.
DR   EMBL; BC011884; AAH11884.1; -; mRNA.
DR   EMBL; AB028972; BAA83001.1; -; mRNA.
DR   CCDS; CCDS10987.1; -.
DR   RefSeq; NP_055787.1; NM_014972.3.
DR   AlphaFoldDB; Q9BQ70; -.
DR   SMR; Q9BQ70; -.
DR   BioGRID; 116629; 107.
DR   ComplexPortal; CPX-2656; Ribosome quality control complex.
DR   FunCoup; Q9BQ70; 3408.
DR   IntAct; Q9BQ70; 74.
DR   MINT; Q9BQ70; -.
DR   STRING; 9606.ENSP00000263346; -.
DR   GlyGen; Q9BQ70; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9BQ70; -.
DR   MetOSite; Q9BQ70; -.
DR   PhosphoSitePlus; Q9BQ70; -.
DR   BioMuta; TCF25; -.
DR   DMDM; 23396596; -.
DR   jPOST; Q9BQ70; -.
DR   MassIVE; Q9BQ70; -.
DR   PaxDb; 9606-ENSP00000263346; -.
DR   PeptideAtlas; Q9BQ70; -.
DR   ProteomicsDB; 78638; -.
DR   Pumba; Q9BQ70; -.
DR   Antibodypedia; 30955; 204 antibodies from 27 providers.
DR   DNASU; 22980; -.
DR   Ensembl; ENST00000263346.13; ENSP00000263346.8; ENSG00000141002.21.
DR   Ensembl; ENST00000640279.1; ENSP00000491638.1; ENSG00000141002.21.
DR   GeneID; 22980; -.
DR   KEGG; hsa:22980; -.
DR   MANE-Select; ENST00000263346.13; ENSP00000263346.8; NM_014972.3; NP_055787.1.
DR   UCSC; uc002fpb.3; human.
DR   AGR; HGNC:29181; -.
DR   ClinPGx; PA145007492; -.
DR   CTD; 22980; -.
DR   DisGeNET; 22980; -.
DR   GeneCards; TCF25; -.
DR   HGNC; HGNC:29181; TCF25.
DR   HPA; ENSG00000141002; Low tissue specificity.
DR   MIM; 612326; gene.
DR   OpenTargets; ENSG00000141002; -.
DR   VEuPathDB; HostDB:ENSG00000141002; -.
DR   eggNOG; KOG2422; Eukaryota.
DR   GeneTree; ENSGT00390000005563; -.
DR   HOGENOM; CLU_008321_3_2_1; -.
DR   InParanoid; Q9BQ70; -.
DR   OMA; IWGKMPP; -.
DR   OrthoDB; 205993at2759; -.
DR   PAN-GO; Q9BQ70; 1 GO annotation based on evolutionary models.
DR   PhylomeDB; Q9BQ70; -.
DR   PathwayCommons; Q9BQ70; -.
DR   SignaLink; Q9BQ70; -.
DR   SIGNOR; Q9BQ70; -.
DR   Agora; ENSG00000141002; -.
DR   BioGRID-ORCS; 22980; 16 hits in 1160 CRISPR screens.
DR   ChiTaRS; TCF25; human.
DR   GenomeRNAi; 22980; -.
DR   Pharos; Q9BQ70; Tbio.
DR   PRO; PR:Q9BQ70; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   RNAct; Q9BQ70; protein.
DR   Bgee; ENSG00000141002; Expressed in sural nerve and 202 other cell types or tissues.
DR   ExpressionAtlas; Q9BQ70; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:1990112; C:RQC complex; IDA:UniProtKB.
DR   GO; GO:0061945; P:regulation of protein K48-linked ubiquitination; IDA:UniProtKB.
DR   GO; GO:0072344; P:rescue of stalled ribosome; IDA:UniProtKB.
DR   FunFam; 1.25.40.10:FF:000483; Transcription factor 25; 1.
DR   Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 1.
DR   InterPro; IPR006994; TCF25/Rqc1.
DR   InterPro; IPR011990; TPR-like_helical_dom_sf.
DR   PANTHER; PTHR22684; NULP1-RELATED; 1.
DR   PANTHER; PTHR22684:SF0; RIBOSOME QUALITY CONTROL COMPLEX SUBUNIT TCF25; 1.
DR   Pfam; PF04910; Tcf25; 1.
DR   SUPFAM; SSF48452; TPR-like; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; Nucleus; Phosphoprotein; Proteomics identification;
KW   Reference proteome; Repressor; Transcription; Transcription regulation.
FT   CHAIN           1..676
FT                   /note="Ribosome quality control complex subunit TCF25"
FT                   /id="PRO_0000087265"
FT   REGION          1..59
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          85..147
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        123..136
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         602
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
SQ   SEQUENCE   676 AA;  76667 MW;  6ECF8A1C78141296 CRC64;
     MSRRALRRLR GEQRGQEPLG PGALHFDLRD DDDAEEEGPK RELGVRRPGG AGKEGVRVNN
     RFELINIDDL EDDPVVNGER SGCALTDAVA PGNKGRGQRG NTESKTDGDD TETVPSEQSH
     ASGKLRKKKK KQKNKKSSTG EASENGLEDI DRILERIEDS TGLNRPGPAP LSSRKHVLYV
     EHRHLNPDTE LKRYFGARAI LGEQRPRQRQ RVYPKCTWLT TPKSTWPRYS KPGLSMRLLE
     SKKGLSFFAF EHSEEYQQAQ HKFLVAVESM EPNNIVVLLQ TSPYHVDSLL QLSDACRFQE
     DQEMARDLVE RALYSMECAF HPLFSLTSGA CRLDYRRPEN RSFYLALYKQ MSFLEKRGCP
     RTALEYCKLI LSLEPDEDPL CMLLLIDHLA LRARNYEYLI RLFQEWEAHR NLSQLPNFAF
     SVPLAYFLLS QQTDLPECEQ SSARQKASLL IQQALTMFPG VLLPLLESCS VRPDASVSSH
     RFFGPNAEIS QPPALSQLVN LYLGRSHFLW KEPATMSWLE ENVHEVLQAV DAGDPAVEAC
     ENRRKVLYQR APRNIHRHVI LSEIKEAVAA LPPDVTTQSV MGFDPLPPSD TIYSYVRPER
     LSPISHGNTI ALFFRSLLPN YTMEGERPEE GVAGGLNRNQ GLNRLMLAVR DMMANFHLND
     LEAPHEDDAE GEGEWD
//