{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:06:34Z","timestamp":1793689594094,"version":"4.5.1"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2022,8,6]],"date-time":"2022-08-06T00:00:00Z","timestamp":1659744000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,8,6]],"date-time":"2022-08-06T00:00:00Z","timestamp":1659744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"name":"National Institute of Health","award":["1R01DK113409"],"award-info":[{"award-number":["1R01DK113409"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970413"],"award-info":[{"award-number":["31970413"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81960244"],"award-info":[{"award-number":["81960244"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2022,10]]},"DOI":"10.1007\/s12035-022-02979-0","type":"journal-article","created":{"date-parts":[[2022,8,6]],"date-time":"2022-08-06T01:02:38Z","timestamp":1659747758000},"page":"6363-6372","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Deficiency of Murine UFM1-Specific E3 Ligase Causes Microcephaly and Inflammation"],"prefix":"10.1007","volume":"59","author":[{"given":"Jie","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huabin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Quintero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renshi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafei","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3604-0982","authenticated-orcid":false,"given":"Honglin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,6]]},"reference":[{"issue":"9","key":"2979_CR1","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1038\/sj.emboj.7600205","volume":"23","author":"M Komatsu","year":"2004","unstructured":"Komatsu M, Chiba T, Tatsumi K, Iemura S, Tanida I, Okazaki N, Ueno T, Kominami E et al (2004) A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifier. EMBO J 23(9):1977\u20131986","journal-title":"EMBO J"},{"issue":"1","key":"2979_CR2","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.bbrc.2006.02.107","volume":"343","author":"H Sasakawa","year":"2006","unstructured":"Sasakawa H, Sakata E, Yamaguchi Y, Komatsu M, Tatsumi K, Kominami E, Tanaka K, Kato K (2006) Solution structure and dynamics of Ufm1, a ubiquitin-fold modifier 1. Biochem Biophys Res Commun 343(1):21\u201326","journal-title":"Biochem Biophys Res Commun"},{"issue":"8","key":"2979_CR3","doi-asserted-by":"publisher","first-page":"5256","DOI":"10.1074\/jbc.M610590200","volume":"282","author":"SH Kang","year":"2007","unstructured":"Kang SH, Kim GR, Seong M, Baek SH, Seol JH, Bang OS, Ovaa H, Tatsumi K et al (2007) Two novel ubiquitin-fold modifier 1 (Ufm1)-specific proteases, UfSP1 and UfSP2. J Biol Chem 282(8):5256\u20135262","journal-title":"J Biol Chem"},{"issue":"12","key":"2979_CR4","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1016\/j.tcb.2019.09.005","volume":"29","author":"Y Gerakis","year":"2019","unstructured":"Gerakis Y, Quintero M, Li H, Hetz C (2019) The UFMylation system in proteostasis and beyond. Trends Cell Biol 29(12):974\u2013986","journal-title":"Trends Cell Biol"},{"issue":"8","key":"2979_CR5","doi-asserted-by":"publisher","first-page":"5417","DOI":"10.1074\/jbc.M109.036814","volume":"285","author":"K Tatsumi","year":"2010","unstructured":"Tatsumi K, Sou YS, Tada N, Nakamura E, Iemura S, Natsume T, Kang SH, Chung CH et al (2010) A novel type of E3 ligase for the Ufm1 conjugation system. J Biol Chem 285(8):5417\u20135427","journal-title":"J Biol Chem"},{"key":"2979_CR6","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/ncomms1182","volume":"2","author":"K Tatsumi","year":"2011","unstructured":"Tatsumi K, Yamamoto-Mukai H, Shimizu R, Waguri S, Sou YS, Sakamoto A, Taya C, Shitara H et al (2011) The Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in mice. Nat Commun 2:181","journal-title":"Nat Commun"},{"issue":"12","key":"2979_CR7","doi-asserted-by":"publisher","first-page":"1922","DOI":"10.1038\/cdd.2015.51","volume":"22","author":"M Zhang","year":"2015","unstructured":"Zhang M, Zhu X, Zhang Y, Cai Y, Chen J, Sivaprakasam S, Gurav A, Pi W et al (2015) RCAD\/Ufl1, a Ufm1 E3 ligase, is essential for hematopoietic stem cell function and murine hematopoiesis. Cell Death Differ 22(12):1922\u20131934","journal-title":"Cell Death Differ"},{"issue":"11","key":"2979_CR8","doi-asserted-by":"publisher","first-page":"e1005643","DOI":"10.1371\/journal.pgen.1005643","volume":"11","author":"Y Cai","year":"2015","unstructured":"Cai Y, Pi W, Sivaprakasam S, Zhu X, Zhang M, Chen J, Makala L, Lu C et al (2015) UFBP1, a key component of the Ufm1 conjugation system, is essential for Ufmylation-mediated regulation of erythroid development. PLoS Genet 11(11):e1005643","journal-title":"PLoS Genet"},{"issue":"10","key":"2979_CR9","doi-asserted-by":"publisher","first-page":"e004917","DOI":"10.1161\/CIRCHEARTFAILURE.118.004917","volume":"11","author":"J Li","year":"2018","unstructured":"Li J, Yue G, Ma W, Zhang A, Zou J, Cai Y, Tang X, Wang J et al (2018) Ufm1-specific ligase Ufl1 regulates endoplasmic reticulum homeostasis and protects against heart failure. Circ Heart Fail 11(10):e004917","journal-title":"Circ Heart Fail"},{"issue":"3","key":"2979_CR10","doi-asserted-by":"publisher","first-page":"G314","DOI":"10.1152\/ajpgi.00176.2016","volume":"312","author":"C Miller","year":"2017","unstructured":"Miller C, Cai Y, Patton T, Graves SH, Li H, Sabbatini ME (2017) RCAD\/BiP pathway is necessary for the proper synthesis of digestive enzymes and secretory function of the exocrine pancreas. Am J Physiol Gastrointest Liver Physiol 312(3):G314\u2013G326","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"2","key":"2979_CR11","doi-asserted-by":"publisher","first-page":"dev169235","DOI":"10.1242\/dev.169235","volume":"146","author":"R Yang","year":"2019","unstructured":"Yang R, Wang H, Kang B, Chen B, Shi Y, Yang S, Sun L, Liu Y et al (2019) CDK5RAP3, a UFL1 substrate adaptor, is crucial for liver development. Development 146(2):dev169235","journal-title":"Development"},{"key":"2979_CR12","doi-asserted-by":"publisher","first-page":"676789","DOI":"10.3389\/fcell.2021.676789","volume":"9","author":"F Chen","year":"2021","unstructured":"Chen F, Sheng L, Xu C, Li J, Ali I, Li H, Cai Y (2021) Ufbp1, a key player of Ufm1 conjugation system, protects against ketosis-induced liver injury via suppressing Smad3 activation. Front Cell Dev Biol 9:676789","journal-title":"Front Cell Dev Biol"},{"key":"2979_CR13","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/s41421-018-0070-x","volume":"5","author":"Y Cai","year":"2019","unstructured":"Cai Y, Zhu G, Liu S, Pan Z, Quintero M, Poole CJ, Lu C, Zhu H et al (2019) Indispensable role of the Ubiquitin-fold modifier 1-specific E3 ligase in maintaining intestinal homeostasis and controlling gut inflammation. Cell Discov 5:7","journal-title":"Cell Discov"},{"issue":"1","key":"2979_CR14","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/s41419-021-03401-8","volume":"12","author":"M Quintero","year":"2021","unstructured":"Quintero M, Liu S, Xia Y, Huang Y, Zou Y, Li G, Hu L, Singh N et al (2021) Cdk5rap3 is essential for intestinal Paneth cell development and maintenance. Cell Death Dis 12(1):131","journal-title":"Cell Death Dis"},{"issue":"3","key":"2979_CR15","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1016\/j.ajhg.2016.06.020","volume":"99","author":"M Muona","year":"2016","unstructured":"Muona M, Ishimura R, Laari A, Ichimura Y, Linnankivi T, Keski-Filppula R, Herva R, Rantala H et al (2016) Biallelic variants in UBA5 link dysfunctional UFM1 ubiquitin-like modifier pathway to severe infantile-onset encephalopathy. Am J Hum Genet 99(3):683\u2013694","journal-title":"Am J Hum Genet"},{"issue":"4","key":"2979_CR16","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1172\/JCI90193","volume":"127","author":"AT Egunsola","year":"2017","unstructured":"Egunsola AT, Bae Y, Jiang MM, Liu DS, Chen-Evenson Y, Bertin T, Chen S, Lu JT et al (2017) Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepimetaphyseal dysplasia. J Clin Invest 127(4):1475\u20131484","journal-title":"J Clin Invest"},{"issue":"7","key":"2979_CR17","doi-asserted-by":"publisher","first-page":"558","DOI":"10.7196\/SAMJnew.7917","volume":"105","author":"CM Watson","year":"2015","unstructured":"Watson CM, Crinnion LA, Gleghorn L, Newman WG, Ramesar R, Beighton P, Wallis GA (2015) Identification of a mutation in the ubiquitin-fold modifier 1-specific peptidase 2 gene, UFSP2, in an extended South African family with Beukes hip dysplasia. S Afr Med J 105(7):558\u2013563","journal-title":"S Afr Med J"},{"issue":"3","key":"2979_CR18","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.ajhg.2016.06.030","volume":"99","author":"E Colin","year":"2016","unstructured":"Colin E, Daniel J, Ziegler A, Wakim J, Scrivo A, Haack TB, Khiati S, Denomme AS et al (2016) Biallelic variants in UBA5 reveal that disruption of the UFM1 cascade can result in early-onset encephalopathy. Am J Hum Genet 99(3):695\u2013703","journal-title":"Am J Hum Genet"},{"issue":"2","key":"2979_CR19","doi-asserted-by":"publisher","first-page":"e0149039","DOI":"10.1371\/journal.pone.0149039","volume":"11","author":"R Duan","year":"2016","unstructured":"Duan R, Shi Y, Yu L, Zhang G, Li J, Lin Y, Guo J, Wang J et al (2016) UBA5 mutations cause a new form of autosomal recessive cerebellar ataxia. PLoS One 11(2):e0149039","journal-title":"PLoS One"},{"issue":"1","key":"2979_CR20","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s12881-017-0466-8","volume":"18","author":"GA Arnadottir","year":"2017","unstructured":"Arnadottir GA, Jensson BO, Marelsson SE, Sulem G, Oddsson A, Kristjansson RP, Benonisdottir S, Gudjonsson SA et al (2017) Compound heterozygous mutations in UBA5 causing early-onset epileptic encephalopathy in two sisters. BMC Med Genet 18(1):103","journal-title":"BMC Med Genet"},{"issue":"17","key":"2979_CR21","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1212\/WNL.0000000000004578","volume":"89","author":"EMC Hamilton","year":"2017","unstructured":"Hamilton EMC, Bertini E, Kalaydjieva L, Morar B, Dojcakova D, Liu J, Vanderver A, Curiel J et al (2017) UFM1 founder mutation in the Roma population causes recessive variant of H-ABC. Neurology 89(17):1821\u20131828","journal-title":"Neurology"},{"issue":"2","key":"2979_CR22","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.ejmg.2018.06.009","volume":"62","author":"KJ Low","year":"2019","unstructured":"Low KJ, Baptista J, Babiker M, Caswell R, King C, Ellard S, Scurr I (2019) Hemizygous UBA5 missense mutation unmasks recessive disorder in a patient with infantile-onset encephalopathy, acquired microcephaly, small cerebellum, movement disorder and severe neurodevelopmental delay. Eur J Med Genet 62(2):97\u2013102","journal-title":"Eur J Med Genet"},{"issue":"7","key":"2979_CR23","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1002\/humu.23534","volume":"39","author":"C Mignon-Ravix","year":"2018","unstructured":"Mignon-Ravix C, Milh M, Kaiser CS, Daniel J, Riccardi F, Cacciagli P, Nagara M, Busa T et al (2018) Abnormal function of the UBA5 protein in a case of early developmental and epileptic encephalopathy with suppression-burst. Hum Mutat 39(7):934\u2013938","journal-title":"Hum Mutat"},{"issue":"7","key":"2979_CR24","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.1093\/brain\/awy135","volume":"141","author":"MS Nahorski","year":"2018","unstructured":"Nahorski MS, Maddirevula S, Ishimura R, Alsahli S, Brady AF, Begemann A, Mizushima T, Guzman-Vega FJ et al (2018) Biallelic UFM1 and UFC1 mutations expand the essential role of ufmylation in brain development. Brain 141(7):1934\u20131945","journal-title":"Brain"},{"issue":"4","key":"2979_CR25","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1684\/epd.2018.0981","volume":"20","author":"A Daida","year":"2018","unstructured":"Daida A, Hamano SI, Ikemoto S, Matsuura R, Nakashima M, Matsumoto N, Kato M (2018) Biallelic loss-of-function UBA5 mutations in a patient with intractable West syndrome and profound failure to thrive. Epileptic Disord 20(4):313\u2013318","journal-title":"Epileptic Disord"},{"issue":"12","key":"2979_CR26","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1136\/jmedgenet-2019-106496","volume":"57","author":"M Cabrera-Serrano","year":"2020","unstructured":"Cabrera-Serrano M, Coote DJ, Azmanov D, Goullee H, Andersen E, McLean C, Davis M, Ishimura R et al (2020) A homozygous UBA5 pathogenic variant causes a fatal congenital neuropathy. J Med Genet 57(12):835\u2013842","journal-title":"J Med Genet"},{"key":"2979_CR27","doi-asserted-by":"crossref","unstructured":"Briere LC, Walker MA, High FA, Cooper C, Rogers CA, Callahan CJ, Ishimura R, Ichimura Y, et al (2021) A description of novel variants and review of phenotypic spectrum in UBA5-related early epileptic encephalopathy. Cold Spring Harb Mol Case Stud 7(3)","DOI":"10.1101\/mcs.a005827"},{"issue":"14","key":"2979_CR28","doi-asserted-by":"publisher","first-page":"2446","DOI":"10.1038\/emboj.2010.116","volume":"29","author":"H Shiwaku","year":"2010","unstructured":"Shiwaku H, Yoshimura N, Tamura T, Sone M, Ogishima S, Watase K, Tagawa K, Okazawa H (2010) Suppression of the novel ER protein Maxer by mutant ataxin-1 in Bergman glia contributes to non-cell-autonomous toxicity. EMBO J 29(14):2446\u20132460","journal-title":"EMBO J"},{"issue":"7","key":"2979_CR29","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1016\/S0092-8674(00)81826-7","volume":"87","author":"JZ Tsien","year":"1996","unstructured":"Tsien JZ, Chen DF, Gerber D, Tom C, Mercer EH, Anderson DJ, Mayford M, Kandel ER et al (1996) Subregion- and cell type-restricted gene knockout in mouse brain. Cell 87(7):1317\u20131326","journal-title":"Cell"},{"issue":"5","key":"2979_CR30","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1038\/s41436-020-01071-z","volume":"23","author":"M Ni","year":"2021","unstructured":"Ni M, Afroze B, Xing C, Pan C, Shao Y, Cai L, Cantarel BL, Pei J et al (2021) A pathogenic UFSP2 variant in an autosomal recessive form of pediatric neurodevelopmental anomalies and epilepsy. Genet Med 23(5):900\u2013908","journal-title":"Genet Med"},{"issue":"10","key":"2979_CR31","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1038\/ng.3955","volume":"49","author":"D Chang","year":"2017","unstructured":"Chang D, Nalls MA, Hallgrimsdottir IB, Hunkapiller J, van der Brug M, Cai F, International Parkinson\u2019s Disease Genomics C, andMe Research T et al (2017) A meta-analysis of genome-wide association studies identifies 17 new Parkinson\u2019s disease risk loci. Nat Genet 49(10):1511\u20131516","journal-title":"Nat Genet"},{"issue":"10","key":"2979_CR32","doi-asserted-by":"publisher","first-page":"1910","DOI":"10.1038\/npp.2013.84","volume":"38","author":"MD Rubio","year":"2013","unstructured":"Rubio MD, Wood K, Haroutunian V, Meador-Woodruff JH (2013) Dysfunction of the ubiquitin proteasome and ubiquitin-like systems in schizophrenia. Neuropsychopharmacology 38(10):1910\u20131920","journal-title":"Neuropsychopharmacology"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-022-02979-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-022-02979-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-022-02979-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T13:45:10Z","timestamp":1662731110000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-022-02979-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,6]]},"references-count":32,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["2979"],"URL":"https:\/\/doi.org\/10.1007\/s12035-022-02979-0","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,6]]},"assertion":[{"value":"28 April 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors state that all animal research complied with USDA Animal Welfare Act and Regulations, and all experimental procedures were approved by Augusta University and Vanderbilt University IACUCs.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Not applicable","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Publish"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}