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 27-MAR-2024, entry version 175.
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};
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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_001288661.1; NM_001301732.2. [O60524-3]
DR RefSeq; NP_004704.2; NM_004713.5. [O60524-1]
DR PDB; 3J92; EM; 3.60 A; u/v=1-501.
DR PDBsum; 3J92; -.
DR AlphaFoldDB; O60524; -.
DR EMDB; EMD-2832; -.
DR SMR; O60524; -.
DR ComplexPortal; CPX-2656; Ribosome quality control complex.
DR IntAct; O60524; 25.
DR MINT; O60524; -.
DR STRING; 9606.ENSP00000298310; -.
DR iPTMnet; O60524; -.
DR PhosphoSitePlus; O60524; -.
DR BioMuta; NEMF; -.
DR EPD; O60524; -.
DR jPOST; O60524; -.
DR MassIVE; O60524; -.
DR MaxQB; 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; 255 antibodies from 29 providers.
DR DNASU; 9147; -.
DR Ensembl; ENST00000298310.10; ENSP00000298310.5; ENSG00000165525.18. [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 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 neXtProt; NX_O60524; -.
DR OpenTargets; ENSG00000165525; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR PharmGKB; PA35593; -.
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; 129892at2759; -.
DR PhylomeDB; O60524; -.
DR TreeFam; TF300515; -.
DR PathwayCommons; O60524; -.
DR SignaLink; O60524; -.
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 Genevisible; O60524; HS.
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 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 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; 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 742..756
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 757..775
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 778..805
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 806..853
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 878..895
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 903..927
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 934..969
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
//
