ID NEMF_HUMAN Reviewed; 1076 AA. AC O60524; A0JLQ3; B3KSK1; B4DDL3; B4DHA9; B4E3F3; Q32Q66; Q8WW70; Q9NWG1; DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot. DT 24-NOV-2009, sequence version 4. DT 28-JAN-2026, entry version 183. DE RecName: Full=Ribosome quality control complex subunit NEMF {ECO:0000305|PubMed:25578875}; DE AltName: Full=Antigen NY-CO-1; DE AltName: Full=Nuclear export mediator factor {ECO:0000312|HGNC:HGNC:10663}; DE AltName: Full=Serologically defined colon cancer antigen 1 {ECO:0000303|PubMed:9610721}; GN Name=NEMF {ECO:0000303|PubMed:33048237, ECO:0000312|HGNC:HGNC:10663}; GN Synonyms=SDCCAG1 {ECO:0000303|PubMed:9610721}; 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 3), NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 1-1041 (ISOFORM 4), NUCLEOTIDE SEQUENCE [LARGE SCALE RP MRNA] OF 1-1049 (ISOFORM 5), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF RP 1-518 (ISOFORM 1), AND VARIANT CYS-257. RC TISSUE=Astrocyte, Brain, Embryo, Thymus, and Uterus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 418-1076 (ISOFORM 1). RC TISSUE=Small intestine; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-438 AND 620-1076 (ISOFORM 1), RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-432 (ISOFORM 4), AND VARIANT RP CYS-257. RC TISSUE=Brain, Kidney, and Placenta; 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 [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 712-1076. RC TISSUE=Colon carcinoma; RX PubMed=9610721; RX DOI=10.1002/(sici)1097-0215(19980529)76:5<652::aid-ijc7>3.0.co;2-p; RA Scanlan M.J., Chen Y.-T., Williamson B., Gure A.O., Stockert E., RA Gordan J.D., Tuereci O., Sahin U., Pfreundschuh M., Old L.J.; RT "Characterization of human colon cancer antigens recognized by autologous RT antibodies."; RL Int. J. Cancer 76:652-658(1998). RN [6] RP FUNCTION, INTERACTION WITH XPO1, AND TISSUE SPECIFICITY. RX PubMed=16103875; DOI=10.1038/sj.onc.1208962; RA Bi X., Jones T., Abbasi F., Lee H., Stultz B., Hursh D.A., Mortin M.A.; RT "Drosophila caliban, a nuclear export mediator, can function as a tumor RT suppressor in human lung cancer cells."; RL Oncogene 24:8229-8239(2005). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-417; SER-747; SER-748 AND RP SER-763, AND IDENTIFICATION BY 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 [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-417, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-417 AND SER-831, AND RP IDENTIFICATION BY 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 [11] 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 [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-417; SER-747 AND SER-748, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-7; SER-417 AND SER-831, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and 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 [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-417, AND IDENTIFICATION BY RP 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 [15] RP FUNCTION. RX PubMed=32726578; DOI=10.1016/j.molcel.2020.07.007; RA Hickey K.L., Dickson K., Cogan J.Z., Replogle J.M., Schoof M., RA D'Orazio K.N., Sinha N.K., Hussmann J.A., Jost M., Frost A., Green R., RA Weissman J.S., Kostova K.K.; RT "GIGYF2 and 4EHP Inhibit Translation Initiation of Defective Messenger RNAs RT to Assist Ribosome-Associated Quality Control."; RL Mol. Cell 79:950.e6-962.e6(2020). RN [16] {ECO:0007744|PDB:3J92} RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 1-501 AS PART OF THE RP RIBOSOME QUALITY CONTROL COMPLEX, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=25578875; DOI=10.1016/j.molcel.2014.12.015; RA Shao S., Brown A., Santhanam B., Hegde R.S.; RT "Structure and assembly pathway of the ribosome quality control complex."; RL Mol. Cell 57:433-444(2015). RN [17] RP INVOLVEMENT IN IDDSAPN. RX PubMed=27431290; DOI=10.1038/mp.2016.113; RA Anazi S., Maddirevula S., Faqeih E., Alsedairy H., Alzahrani F., RA Shamseldin H.E., Patel N., Hashem M., Ibrahim N., Abdulwahab F., Ewida N., RA Alsaif H.S., Al Sharif H., Alamoudi W., Kentab A., Bashiri F.A., RA Alnaser M., AlWadei A.H., Alfadhel M., Eyaid W., Hashem A., Al Asmari A., RA Saleh M.M., AlSaman A., Alhasan K.A., Alsughayir M., Al Shammari M., RA Mahmoud A., Al-Hassnan Z.N., Al-Husain M., Osama Khalil R., RA Abd El Meguid N., Masri A., Ali R., Ben-Omran T., El Fishway P., RA Hashish A., Ercan Sencicek A., State M., Alazami A.M., Salih M.A., RA Altassan N., Arold S.T., Abouelhoda M., Wakil S.M., Monies D., Shaheen R., RA Alkuraya F.S.; RT "Clinical genomics expands the morbid genome of intellectual disability and RT offers a high diagnostic yield."; RL Mol. Psychiatry 22:615-624(2017). RN [18] RP INVOLVEMENT IN IDDSAPN, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=33048237; DOI=10.1007/s00439-020-02226-3; RA Ahmed A., Wang M., Bergant G., Maroofian R., Zhao R., Alfadhel M., RA Nashabat M., AlRifai M.T., Eyaid W., Alswaid A., Beetz C., Qin Y., Zhu T., RA Tian Q., Xia L., Wu H., Shen L., Dong S., Yang X., Liu C., Ma L., Zhang Q., RA Khan R., Shah A.A., Guo J., Tang B., Leonardis L., Writzl K., Peterlin B., RA Guo H., Malik S., Xia K., Hu Z.; RT "Biallelic loss-of-function variants in NEMF cause central nervous system RT impairment and axonal polyneuropathy."; RL Hum. Genet. 140:579-592(2021). RN [19] RP FUNCTION, IDENTIFICATION IN THE RQC COMPLEX, AND MUTAGENESIS OF RP 96-ASP-ARG-97 AND ASP-96. RX PubMed=33406423; DOI=10.1016/j.celrep.2020.108599; RA Udagawa T., Seki M., Okuyama T., Adachi S., Natsume T., Noguchi T., RA Matsuzawa A., Inada T.; RT "Failure to degrade CAT-tailed proteins disrupts neuronal morphogenesis and RT cell survival."; RL Cell Rep. 34:108599-108599(2021). RN [20] RP FUNCTION, AND IDENTIFICATION IN THE RQC COMPLEX. RX PubMed=33909987; DOI=10.1016/j.molcel.2021.03.004; RA Thrun A., Garzia A., Kigoshi-Tansho Y., Patil P.R., Umbaugh C.S., RA Dallinger T., Liu J., Kreger S., Patrizi A., Cox G.A., Tuschl T., RA Joazeiro C.A.P.; RT "Convergence of mammalian RQC and C-end rule proteolytic pathways via RT alanine tailing."; RL Mol. Cell 81:2112-2122(2021). RN [21] RP VARIANTS IDDSAPN THR-553; 671-ARG--LYS-1076 DEL; 672-LYS--LYS-1076 DEL AND RP 870-ARG--LYS-1076 DEL. RX PubMed=32934225; DOI=10.1038/s41467-020-18327-6; RA Martin P.B., Kigoshi-Tansho Y., Sher R.B., Ravenscroft G., Stauffer J.E., RA Kumar R., Yonashiro R., Mueller T., Griffith C., Allen W., Pehlivan D., RA Harel T., Zenker M., Howting D., Schanze D., Faqeih E.A., RA Almontashiri N.A.M., Maroofian R., Houlden H., Mazaheri N., Galehdari H., RA Douglas G., Posey J.E., Ryan M., Lupski J.R., Laing N.G., Joazeiro C.A.P., RA Cox G.A.; RT "NEMF mutations that impair ribosome-associated quality control are RT associated with neuromuscular disease."; RL Nat. Commun. 11:4625-4625(2020). CC -!- FUNCTION: Key component of the ribosome quality control complex (RQC), CC a ribosome-associated complex that mediates the extraction of CC incompletely synthesized nascent chains from stalled ribosomes as well CC as their ubiquitin-mediated proteasomal degradation (PubMed:25578875, CC PubMed:32726578, PubMed:33406423, PubMed:33909987). Thereby, frees 60S CC subunit ribosomes from the stalled translation complex and prevents the CC accumulation of nascent polypeptide chains that are potentially toxic CC for the cell (PubMed:25578875, PubMed:33406423, PubMed:33909987). CC Within the RQC complex, NEMF specifically binds stalled 60S ribosomal CC subunits by recognizing an exposed, nascent chain-conjugated tRNA CC moiety and promotes the recruitment of LTN1 to stalled 60S subunits CC (PubMed:25578875). Following binding to stalled 60S ribosomal subunits, CC NEMF mediates CAT tailing by recruiting alanine-charged tRNA to the A- CC site and directing the elongation of stalled nascent chains CC independently of mRNA or 40S subunits, leading to non-templated C- CC terminal alanine extensions (CAT tails) (PubMed:33406423, CC PubMed:33909987). Mainly recruits alanine-charged tRNAs, but can also CC other amino acid-charged tRNAs (PubMed:33406423, PubMed:33909987). CAT CC tailing is required to promote ubiquitination of stalled nascent chains CC by different E3 ubiquitin-protein ligases (PubMed:33909987). In the CC canonical RQC pathway (RQC-L), CAT tailing facilitates LTN1-dependent CC ubiquitination by exposing lysine residues that would otherwise remain CC buried in the ribosomal exit tunnel (By similarity). In the alternative CC RQC pathway (RQC-C) CAT tailing creates an C-degron mainly composed of CC alanine that is recognized by the CRL2(KLHDC10) and RCHY1/PIRH2 E3 CC ligases, leading to ubiquitination and degradation of stalled nascent CC chains (PubMed:33909987). NEMF may also indirectly play a role in CC nuclear export (PubMed:16103875). {ECO:0000250|UniProtKB:Q12532, CC ECO:0000269|PubMed:16103875, ECO:0000269|PubMed:25578875, CC ECO:0000269|PubMed:32726578, ECO:0000269|PubMed:33406423, CC ECO:0000269|PubMed:33909987}. 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:25578875, PubMed:33909987). The CC complex probably also contains VCP/p97 and its ubiquitin-binding CC cofactors (By similarity). Interacts (via its N-terminus) with XPO1 CC (PubMed:16103875). {ECO:0000250|UniProtKB:Q12532, CC ECO:0000269|PubMed:16103875, ECO:0000269|PubMed:25578875, CC ECO:0000269|PubMed:33909987}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:25578875}. CC Nucleus {ECO:0000305|PubMed:16103875}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=O60524-1; Sequence=Displayed; CC Name=2; CC IsoId=O60524-2; Sequence=VSP_008396, VSP_010462; CC Name=3; CC IsoId=O60524-3; Sequence=VSP_041066; CC Name=4; CC IsoId=O60524-4; Sequence=VSP_041064; CC Name=5; CC IsoId=O60524-5; Sequence=VSP_041065; CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, liver, lung, spleen, and CC skeletal muscle. Also expressed at lower levels in stomach and testis. CC {ECO:0000269|PubMed:16103875, ECO:0000269|PubMed:33048237}. CC -!- DEVELOPMENTAL STAGE: Expressed in the developing brain. CC {ECO:0000269|PubMed:33048237}. CC -!- DISEASE: Intellectual developmental disorder with speech delay and CC axonal peripheral neuropathy (IDDSAPN) [MIM:619099]: An autosomal CC recessive disorder characterized by mild global developmental delay, CC mild to moderate intellectual disability, motor impairment, unsteady or CC ataxic gait, and severe speech delay apparent in the first years of CC life. Signs of a peripheral axonal neuropathy, including progressive CC distal muscle weakness and atrophy of the lower limbs, foot and hand CC deformities, and dysarthria, are observed in most patients. Some CC patients may have autistic features or attention deficit-hyperactivity CC disorder. {ECO:0000269|PubMed:27431290, ECO:0000269|PubMed:32934225, CC ECO:0000269|PubMed:33048237}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the NEMF family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC18036.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAH06001.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=AAH20794.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH56687.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=AAI07765.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAG52763.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAG58070.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305}; CC Sequence=BAG58070.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAG58070.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK000913; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK093783; BAG52763.1; ALT_INIT; mRNA. DR EMBL; AK293236; BAG56774.1; -; mRNA. DR EMBL; AK295010; BAG58070.1; ALT_SEQ; mRNA. DR EMBL; AK304695; BAG65465.1; -; mRNA. DR EMBL; BX640804; CAE45886.1; -; mRNA. DR EMBL; BX640807; CAE45889.1; -; mRNA. DR EMBL; BX648753; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AL591767; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL627171; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC006001; AAH06001.1; ALT_SEQ; mRNA. DR EMBL; BC020794; AAH20794.2; ALT_INIT; mRNA. DR EMBL; BC056687; AAH56687.1; ALT_SEQ; mRNA. DR EMBL; BC064364; AAH64364.1; -; mRNA. DR EMBL; BC107764; AAI07765.1; ALT_INIT; mRNA. DR EMBL; AF039687; AAC18036.1; ALT_FRAME; mRNA. DR CCDS; CCDS9694.1; -. [O60524-1] DR RefSeq; NP_001288661.2; NM_001301732.3. [O60524-3] DR PDB; 3J92; EM; 3.60 A; u/v=1-501. DR PDB; 9GY4; EM; 3.00 A; Z=1-1076. DR PDBsum; 3J92; -. DR PDBsum; 9GY4; -. DR AlphaFoldDB; O60524; -. DR EMDB; EMD-2832; -. DR EMDB; EMD-51681; -. DR SMR; O60524; -. DR ComplexPortal; CPX-2656; Ribosome quality control complex. DR FunCoup; O60524; 2305. DR IntAct; O60524; 48. DR MINT; O60524; -. DR STRING; 9606.ENSP00000298310; -. DR GlyGen; O60524; 2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site). DR iPTMnet; O60524; -. DR PhosphoSitePlus; O60524; -. DR BioMuta; NEMF; -. DR jPOST; O60524; -. DR MassIVE; O60524; -. DR PaxDb; 9606-ENSP00000298310; -. DR PeptideAtlas; O60524; -. DR ProteomicsDB; 49458; -. [O60524-1] DR ProteomicsDB; 49459; -. [O60524-2] DR ProteomicsDB; 49460; -. [O60524-3] DR ProteomicsDB; 49461; -. [O60524-4] DR ProteomicsDB; 49462; -. [O60524-5] DR Pumba; O60524; -. DR Antibodypedia; 140; 213 antibodies from 30 providers. DR DNASU; 9147; -. DR Ensembl; ENST00000298310.10; ENSP00000298310.5; ENSG00000165525.19. [O60524-1] DR GeneID; 9147; -. DR KEGG; hsa:9147; -. DR MANE-Select; ENST00000298310.10; ENSP00000298310.5; NM_004713.6; NP_004704.3. DR UCSC; uc001wxc.4; human. [O60524-1] DR AGR; HGNC:10663; -. DR ClinPGx; PA35593; -. DR CTD; 9147; -. DR DisGeNET; 9147; -. DR GeneCards; NEMF; -. DR HGNC; HGNC:10663; NEMF. DR HPA; ENSG00000165525; Low tissue specificity. DR MalaCards; NEMF; -. DR MIM; 608378; gene. DR MIM; 619099; phenotype. DR OpenTargets; ENSG00000165525; -. DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability. DR VEuPathDB; HostDB:ENSG00000165525; -. DR eggNOG; KOG2030; Eukaryota. DR GeneTree; ENSGT00390000018516; -. DR HOGENOM; CLU_003612_1_0_1; -. DR InParanoid; O60524; -. DR OMA; MFLEFFA; -. DR OrthoDB; 207084at2759; -. DR PAN-GO; O60524; 5 GO annotations based on evolutionary models. DR PhylomeDB; O60524; -. DR PathwayCommons; O60524; -. DR SignaLink; O60524; -. DR SIGNOR; O60524; -. DR Agora; ENSG00000165525; -. DR BioGRID-ORCS; 9147; 128 hits in 1161 CRISPR screens. DR ChiTaRS; NEMF; human. DR GenomeRNAi; 9147; -. DR Pharos; O60524; Tbio. DR PRO; PR:O60524; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; O60524; protein. DR Bgee; ENSG00000165525; Expressed in calcaneal tendon and 211 other cell types or tissues. DR ExpressionAtlas; O60524; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0022626; C:cytosolic ribosome; IDA:UniProt. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:1990112; C:RQC complex; IDA:UniProtKB. DR GO; GO:1904678; F:alpha-aminoacyl-tRNA binding; IDA:UniProtKB. DR GO; GO:0043023; F:ribosomal large subunit binding; IDA:UniProtKB. DR GO; GO:0000049; F:tRNA binding; IBA:GO_Central. DR GO; GO:0140708; P:CAT tailing; IDA:UniProtKB. DR GO; GO:0051168; P:nuclear export; IMP:UniProtKB. DR GO; GO:0065003; P:protein-containing complex assembly; IMP:UniProtKB. DR GO; GO:0072344; P:rescue of stalled ribosome; IDA:UniProt. DR GO; GO:1990116; P:ribosome-associated ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR FunFam; 2.30.310.10:FF:000001; Nuclear export mediator factor Nemf; 1. DR Gene3D; 2.30.310.10; ibrinogen binding protein from staphylococcus aureus domain; 1. DR InterPro; IPR021846; NFACT-C. DR InterPro; IPR008532; NFACT_RNA-bd. DR InterPro; IPR051608; RQC_Subunit_NEMF. DR PANTHER; PTHR15239; NUCLEAR EXPORT MEDIATOR FACTOR NEMF; 1. DR PANTHER; PTHR15239:SF6; RIBOSOME QUALITY CONTROL COMPLEX SUBUNIT NEMF; 1. DR Pfam; PF11923; NFACT-C; 1. DR Pfam; PF05670; NFACT-R_1; 1. DR Pfam; PF05833; NFACT_N; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm; KW Disease variant; Intellectual disability; Neuropathy; Nucleus; KW Phosphoprotein; Proteomics identification; Reference proteome. FT CHAIN 1..1076 FT /note="Ribosome quality control complex subunit NEMF" FT /id="PRO_0000097642" FT REGION 420..453 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 691..715 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 742..972 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 296..359 FT /evidence="ECO:0000255" FT COILED 483..514 FT /evidence="ECO:0000255" FT COILED 869..894 FT /evidence="ECO:0000255" FT COMPBIAS 429..439 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 440..449 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 691..710 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 742..754 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 755..768 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 777..795 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 839..854 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 870..881 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 937..965 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 7 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 417 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 747 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692" FT MOD_RES 748 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692" FT MOD_RES 763 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 831 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..21 FT /note="MKSRFSTIDLRAVLAELNASL -> MPKTCQCYVGTKTTNPSAWPS (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_008396" FT VAR_SEQ 22..821 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_010462" FT VAR_SEQ 78..119 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_041064" FT VAR_SEQ 221..245 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_041065" FT VAR_SEQ 562..582 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_041066" FT VARIANT 257 FT /note="S -> C (in dbSNP:rs3100906)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334" FT /id="VAR_034488" FT VARIANT 553 FT /note="I -> T (in IDDSAPN; uncertain significance)" FT /evidence="ECO:0000269|PubMed:32934225" FT /id="VAR_085459" FT VARIANT 671..1076 FT /note="Missing (in IDDSAPN)" FT /evidence="ECO:0000269|PubMed:32934225" FT /id="VAR_085460" FT VARIANT 672..1076 FT /note="Missing (in IDDSAPN)" FT /evidence="ECO:0000269|PubMed:32934225" FT /id="VAR_085461" FT VARIANT 870..1076 FT /note="Missing (in IDDSAPN)" FT /evidence="ECO:0000269|PubMed:32934225" FT /id="VAR_085462" FT MUTAGEN 96..97 FT /note="DR->AA: Abolished ability to mediate CAT tailing." FT /evidence="ECO:0000269|PubMed:33406423" FT MUTAGEN 96 FT /note="D->A: Abolished ability to mediate CAT tailing." FT /evidence="ECO:0000269|PubMed:33406423" FT CONFLICT 53 FT /note="E -> K (in Ref. 1; BAG56774)" FT /evidence="ECO:0000305" FT CONFLICT 438 FT /note="P -> S (in Ref. 4; AAH56687)" FT /evidence="ECO:0000305" FT CONFLICT 495 FT /note="E -> G (in Ref. 1; BAG56774)" FT /evidence="ECO:0000305" FT CONFLICT 560 FT /note="P -> PV (in Ref. 1; BAG58070)" FT /evidence="ECO:0000305" FT CONFLICT 593 FT /note="A -> V (in Ref. 2; CAE45889)" FT /evidence="ECO:0000305" FT CONFLICT 696 FT /note="E -> K (in Ref. 1; BAG65465)" FT /evidence="ECO:0000305" FT CONFLICT 766 FT /note="E -> V (in Ref. 2; BX648753)" FT /evidence="ECO:0000305" SQ SEQUENCE 1076 AA; 122954 MW; FCC5F95A0DB22F79 CRC64; MKSRFSTIDL RAVLAELNAS LLGMRVNNVY DVDNKTYLIR LQKPDFKATL LLESGIRIHT TEFEWPKNMM PSSFAMKCRK HLKSRRLVSA KQLGVDRIVD FQFGSDEAAY HLIIELYDRG NIVLTDYEYV ILNILRFRTD EADDVKFAVR ERYPLDHARA AEPLLTLERL TEIVASAPKG ELLKRVLNPL LPYGPALIEH CLLENGFSGN VKVDEKLETK DIEKVLVSLQ KAEDYMKTTS NFSGKGYIIQ KREIKPSLEA DKPVEDILTY EEFHPFLFSQ HSQCPYIEFE SFDKAVDEFY SKIEGQKIDL KALQQEKQAL KKLDNVRKDH ENRLEALQQA QEIDKLKGEL IEMNLQIVDR AIQVVRSALA NQIDWTEIGL IVKEAQAQGD PVASAIKELK LQTNHVTMLL RNPYLLSEEE DDDVDGDVNV EKNETEPPKG KKKKQKNKQL QKPQKNKPLL VDVDLSLSAY ANAKKYYDHK RYAAKKTQKT VEAAEKAFKS AEKKTKQTLK EVQTVTSIQK ARKVYWFEKF LWFISSENYL IIGGRDQQQN EIIVKRYLTP GDIYVHADLH GATSCVIKNP TGEPIPPRTL TEAGTMALCY SAAWDARVIT SAWWVYHHQV SKTAPTGEYL TTGSFMIRGK KNFLPPSYLM MGFSFLFKVD ESCVWRHQGE RKVRVQDEDM ETLASCTSEL ISEEMEQLDG GDTSSDEDKE EHETPVEVEL MTQVDQEDIT LQSGRDELNE ELIQEESSED EGEYEEVRKD QDSVGEMKDE GEETLNYPDT TIDLSHLQPQ RSIQKLASKE ESSNSSDSKS QSRRHLSAKE RREMKKKKLP SDSGDLEALE GKDKEKESTV HIETHQNTSK NVAAVQPMKR GQKSKMKKMK EKYKDQDEED RELIMKLLGS AGSNKEEKGK KGKKGKTKDE PVKKQPQKPR GGQRVSDNIK KETPFLEVIT HELQDFAVDD PHDDKEEQDL DQQGNEENLF DSLTGQPHPE DVLLFAIPIC APYTTMTNYK YKVKLTPGVQ KKGKAAKTAL NSFMHSKEAT AREKDLFRSV KDTDLSRNIP GKVKVSAPNL LNVKRK //