ID UFSP2_HUMAN Reviewed; 469 AA. AC Q9NUQ7; Q6IA77; Q96FS3; DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot. DT 07-JUL-2009, sequence version 3. DT 28-JAN-2026, entry version 157. DE RecName: Full=Ufm1-specific protease 2 {ECO:0000303|PubMed:26428751}; DE Short=UfSP2 {ECO:0000303|PubMed:26428751}; DE EC=3.4.22.- {ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:30783677, ECO:0000269|PubMed:32160526, ECO:0000269|PubMed:36543799, ECO:0000269|PubMed:36893266, ECO:0000269|PubMed:37795761, ECO:0000269|PubMed:38383785}; GN Name=UFSP2 {ECO:0000303|PubMed:26428751, ECO:0000312|HGNC:HGNC:25640}; GN Synonyms=C4orf20 {ECO:0000312|HGNC:HGNC:25640}; 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]. RC TISSUE=Placenta; 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]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-83. RC TISSUE=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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANT SEMDDR SER-302, RP AND INTERACTION WITH TRIP4. RX PubMed=25219498; DOI=10.1016/j.molcel.2014.08.007; RA Yoo H.M., Kang S.H., Kim J.Y., Lee J.E., Seong M.W., Lee S.W., Ka S.H., RA Sou Y.S., Komatsu M., Tanaka K., Lee S.T., Noh D.Y., Baek S.H., Jeon Y.J., RA Chung C.H.; RT "Modification of ASC1 by UFM1 is crucial for ERalpha transactivation and RT breast cancer development."; RL Mol. Cell 56:261-274(2014). RN [7] RP ACETYLATION AT MET-1. RX PubMed=25732826; DOI=10.1016/j.celrep.2015.01.053; RA Aksnes H., Van Damme P., Goris M., Starheim K.K., Marie M., Stoeve S.I., RA Hoel C., Kalvik T.V., Hole K., Glomnes N., Furnes C., Ljostveit S., RA Ziegler M., Niere M., Gevaert K., Arnesen T.; RT "An organellar nalpha-acetyltransferase, naa60, acetylates cytosolic N RT termini of transmembrane proteins and maintains Golgi integrity."; RL Cell Rep. 10:1362-1374(2015). RN [8] RP INVOLVEMENT IN HDB, VARIANT HDB HIS-290, AND CHARACTERIZATION OF VARIANT RP HDB HIS-290. RX PubMed=26428751; DOI=10.7196/samjnew.7917; RA Watson C.M., Crinnion L.A., Gleghorn L., Newman W.G., Ramesar R., RA Beighton P., Wallis G.A.; RT "Identification of a mutation in the ubiquitin-fold modifier 1-specific RT peptidase 2 gene, UFSP2, in an extended South African family with Beukes RT hip dysplasia."; RL S. Afr. Med. J. 105:558-563(2015). RN [9] RP FUNCTION. RX PubMed=27351204; DOI=10.7554/elife.17290; RA DeJesus R., Moretti F., McAllister G., Wang Z., Bergman P., Liu S., RA Frias E., Alford J., Reece-Hoyes J.S., Lindeman A., Kelliher J., Russ C., RA Knehr J., Carbone W., Beibel M., Roma G., Ng A., Tallarico J.A., RA Porter J.A., Xavier R.J., Mickanin C., Murphy L.O., Hoffman G.R., RA Nyfeler B.; RT "Functional CRISPR screening identifies the ufmylation pathway as a RT regulator of SQSTM1/p62."; RL Elife 5:0-0(2016). RN [10] RP FUNCTION. RX PubMed=27926783; DOI=10.1002/1873-3468.12518; RA Ishimura R., Obata M., Kageyama S., Daniel J., Tanaka K., Komatsu M.; RT "A novel approach to assess the ubiquitin-fold modifier 1-system in RT cells."; RL FEBS Lett. 591:196-204(2017). RN [11] RP FUNCTION, AND CHARACTERIZATION OF VARIANT SEMDDR SER-302. RX PubMed=30783677; DOI=10.1093/nar/gkz110; RA Wang Z., Gong Y., Peng B., Shi R., Fan D., Zhao H., Zhu M., Zhang H., RA Lou Z., Zhou J., Zhu W.G., Cong Y.S., Xu X.; RT "MRE11 UFMylation promotes ATM activation."; RL Nucleic Acids Res. 47:4124-4135(2019). RN [12] RP FUNCTION. RX PubMed=32160526; DOI=10.1016/j.cell.2020.02.017; RA Liang J.R., Lingeman E., Luong T., Ahmed S., Muhar M., Nguyen T., RA Olzmann J.A., Corn J.E.; RT "A genome-wide ER-phagy screen highlights key roles of mitochondrial RT metabolism and ER-Resident UFMylation."; RL Cell 180:1160-1177(2020). RN [13] RP FUNCTION. RX PubMed=31595041; DOI=10.1038/s41422-019-0236-6; RA Wang L., Xu Y., Rogers H., Saidi L., Noguchi C.T., Li H., Yewdell J.W., RA Guydosh N.R., Ye Y.; RT "UFMylation of RPL26 links translocation-associated quality control to RT endoplasmic reticulum protein homeostasis."; RL Cell Res. 30:5-20(2020). RN [14] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=35926457; DOI=10.1016/j.celrep.2022.111168; RA Millrine D., Cummings T., Matthews S.P., Peter J.J., Magnussen H.M., RA Lange S.M., Macartney T., Lamoliatte F., Knebel A., Kulathu Y.; RT "Human UFSP1 is an active protease that regulates UFM1 maturation and RT UFMylation."; RL Cell Rep. 40:111168-111168(2022). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF CYS-302. RX PubMed=36543799; DOI=10.1038/s41467-022-35501-0; RA Ishimura R., El-Gowily A.H., Noshiro D., Komatsu-Hirota S., Ono Y., RA Shindo M., Hatta T., Abe M., Uemura T., Lee-Okada H.C., Mohamed T.M., RA Yokomizo T., Ueno T., Sakimura K., Natsume T., Sorimachi H., Inada T., RA Waguri S., Noda N.N., Komatsu M.; RT "The UFM1 system regulates ER-phagy through the ufmylation of CYB5R3."; RL Nat. Commun. 13:7857-7857(2022). RN [16] RP FUNCTION. RX PubMed=35394863; DOI=10.1073/pnas.2119531119; RA Snider D.L., Park M., Murphy K.A., Beachboard D.C., Horner S.M.; RT "Signaling from the RNA sensor RIG-I is regulated by ufmylation."; RL Proc. Natl. Acad. Sci. U.S.A. 119:e2119531119-e2119531119(2022). RN [17] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=37795761; DOI=10.1096/fj.202300004rrrr; RA Luo H., Jiao Q.B., Shen C.B., Gong W.Y., Yuan J.H., Liu Y.Y., Chen Z., RA Liu J., Xu X.L., Cong Y.S., Zhang X.W.; RT "UFMylation of HRD1 regulates endoplasmic reticulum homeostasis."; RL FASEB J. 37:e23221-e23221(2023). RN [18] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=36893266; DOI=10.1073/pnas.2215732120; RA Zhou J., Ma X., He X., Chen B., Yuan J., Jin Z., Li L., Wang Z., Xiao Q., RA Cai Y., Zou Y., Cong Y.S.; RT "Dysregulation of PD-L1 by UFMylation imparts tumor immune evasion and RT identified as a potential therapeutic target."; RL Proc. Natl. Acad. Sci. U.S.A. 120:e2215732120-e2215732120(2023). RN [19] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=38383785; DOI=10.1038/s41586-024-07073-0; RA DaRosa P.A., Penchev I., Gumbin S.C., Scavone F., Wachalska M., Paulo J.A., RA Ordureau A., Peter J.J., Kulathu Y., Harper J.W., Becker T., Beckmann R., RA Kopito R.R.; RT "UFM1 E3 ligase promotes recycling of 60S ribosomal subunits from the ER."; RL Nature 627:445-452(2024). RN [20] RP INVOLVEMENT IN DEE106, VARIANT DEE106 GLU-115, CHARACTERIZATION OF VARIANT RP DEE106 GLU-115, FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=33473208; DOI=10.1038/s41436-020-01071-z; RA Ni M., Afroze B., Xing C., Pan C., Shao Y., Cai L., Cantarel B.L., Pei J., RA Grishin N.V., Hewson S., Knight D., Mahida S., Michel D., Tarnopolsky M., RA Poduri A., Rotenberg A., Sondheimer N., DeBerardinis R.J.; RT "A pathogenic UFSP2 variant in an autosomal recessive form of pediatric RT neurodevelopmental anomalies and epilepsy."; RL Genet. Med. 23:900-908(2021). RN [21] RP VARIANT SEMDDR ALA-426. RX PubMed=28892125; DOI=10.1111/cge.13134; RA Di Rocco M., Rusmini M., Caroli F., Madeo A., Bertamino M., RA Marre-Brunenghi G., Ceccherini I.; RT "Novel spondyloepimetaphyseal dysplasia due to UFSP2 gene mutation."; RL Clin. Genet. 93:671-674(2018). RN [22] RP VARIANT SEMDDR ARG-428. RX PubMed=32755715; DOI=10.1016/j.ejmg.2020.104021; RA Zhang G., Tang S., Wang H., Pan H., Zhang W., Huang Y., Kong J., Wang Y., RA Gu J., Wang Y.; RT "UFSP2-related spondyloepimetaphyseal dysplasia: A confirmatory report."; RL Eur. J. Med. Genet. 63:104021-104021(2020). RN [23] RP ERRATUM OF PUBMED:32755715. RX PubMed=33514497; DOI=10.1016/j.ejmg.2021.104143; RA Zhang G., Tang S., Wang H., Pan H., Zhang W., Huang Y., Kong J., Wang Y., RA Gu J., Wang Y.; RT "Corrigendum to UFSP2-related spondyloepimetaphyseal dysplasia: A RT confirmatory report [European Journal of Medical Genetics, (2020) Nov; RT 63(11): 104021]."; RL Eur. J. Med. Genet. 64:104143-104143(2021). RN [24] RP VARIANT SEMDDR SER-302. RX PubMed=37214758; DOI=10.1016/j.bonr.2023.101683; RA Mattern L., Begemann M., Delbrueck H., Holschbach P., Schroeder S., RA Schacht S.M., Kurth I., Elbracht M.; RT "Variant of the catalytic cysteine of UFSP2 leads to spondyloepimetaphyseal RT dysplasia type Di Rocco."; RL Bone Rep. 18:101683-101683(2023). CC -!- FUNCTION: Thiol-dependent isopeptidase that specifically cleaves UFM1, CC a ubiquitin-like modifier protein, from conjugated proteins, such as CC CD274/PD-L1, CYB5R3, DDRGK1, MRE11, RPL26/uL24, TRIP4 and RPL26/uL24 CC (PubMed:25219498, PubMed:27351204, PubMed:27926783, PubMed:30783677, CC PubMed:31595041, PubMed:32160526, PubMed:33473208, PubMed:35394863, CC PubMed:35926457, PubMed:36543799, PubMed:36893266, PubMed:37795761, CC PubMed:38383785). While it is also able to mediate the processing of CC UFM1 precursors, a prerequisite for conjugation reactions, UFSP2 mainly CC acts as a protein deUFMylase that mediates deconjugation of UFM1 from CC target proteins (PubMed:27926783). Mediates deUFMylation of RPL26/uL24, CC a critical step to release the UFM1 ribosome E3 ligase (UREL) complex CC during the recycling of 60S ribosome subunits from the endoplasmic CC reticulum (PubMed:38383785). Catalyzes deUFMylation of TRIP4, CC regulating intracellular nuclear receptors transactivation and thereby CC regulate cell proliferation and differentiation (PubMed:25219498). CC {ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:27351204, CC ECO:0000269|PubMed:27926783, ECO:0000269|PubMed:30783677, CC ECO:0000269|PubMed:31595041, ECO:0000269|PubMed:32160526, CC ECO:0000269|PubMed:33473208, ECO:0000269|PubMed:35394863, CC ECO:0000269|PubMed:35926457, ECO:0000269|PubMed:36543799, CC ECO:0000269|PubMed:36893266, ECO:0000269|PubMed:37795761, CC ECO:0000269|PubMed:38383785}. CC -!- INTERACTION: CC Q9NUQ7; P41238: APOBEC1; NbExp=3; IntAct=EBI-11153325, EBI-12819523; CC Q9NUQ7; P25800: LMO1; NbExp=3; IntAct=EBI-11153325, EBI-8639312; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum CC {ECO:0000269|PubMed:35926457}. Cytoplasm CC {ECO:0000250|UniProtKB:Q99K23}. Nucleus {ECO:0000250|UniProtKB:Q99K23}. CC -!- TISSUE SPECIFICITY: Expressed in brain. {ECO:0000269|PubMed:33473208}. CC -!- DISEASE: Beukes hip dysplasia (HDB) [MIM:142669]: A severe progressive CC degenerative osteoarthritis of the hip joint with underlying dysplasia CC confined to that region. Affected individuals are of normal stature and CC have no associated health problems. Inheritance is autosomal dominant. CC {ECO:0000269|PubMed:26428751}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Spondyloepimetaphyseal dysplasia, Di Rocco type (SEMDDR) CC [MIM:617974]: A skeletal disorder characterized by short stature, joint CC pain, genu vara and spondyloepimetaphyseal dysplasia involving the CC hips, knees, ankles, wrists and hands. Patients also exhibit variable CC degrees of metaphysis and spine involvement. SEMDDR transmission CC pattern is consistent with autosomal dominant inheritance. CC {ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:28892125, CC ECO:0000269|PubMed:30783677, ECO:0000269|PubMed:32755715, CC ECO:0000269|PubMed:37214758}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Developmental and epileptic encephalopathy 106 (DEE106) CC [MIM:620028]: A form of epileptic encephalopathy, a heterogeneous group CC of early-onset epilepsies characterized by refractory seizures, CC neurodevelopmental impairment, and poor prognosis. Development is CC normal prior to seizure onset, after which cognitive and motor delays CC become apparent. DEE106 is an autosomal recessive form characterized by CC onset of seizures in the first year of life. Affected individuals have CC profound global developmental delay, limited ability to move, and CC severely impaired intellectual development with absent speech. Non- CC specific brain abnormalities may be observed on MRI. CC {ECO:0000269|PubMed:33473208}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the peptidase C78 family. {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; AK002062; BAA92064.1; -; mRNA. DR EMBL; CR457278; CAG33559.1; -; mRNA. DR EMBL; AC106897; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC010493; AAH10493.1; -; mRNA. DR CCDS; CCDS3842.1; -. DR RefSeq; NP_060829.2; NM_018359.5. DR AlphaFoldDB; Q9NUQ7; -. DR SMR; Q9NUQ7; -. DR BioGRID; 120606; 159. DR FunCoup; Q9NUQ7; 2573. DR IntAct; Q9NUQ7; 111. DR MINT; Q9NUQ7; -. DR STRING; 9606.ENSP00000264689; -. DR MEROPS; C78.002; -. DR GlyGen; Q9NUQ7; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9NUQ7; -. DR PhosphoSitePlus; Q9NUQ7; -. DR SwissPalm; Q9NUQ7; -. DR BioMuta; UFSP2; -. DR DMDM; 251757433; -. DR jPOST; Q9NUQ7; -. DR MassIVE; Q9NUQ7; -. DR PaxDb; 9606-ENSP00000264689; -. DR PeptideAtlas; Q9NUQ7; -. DR ProteomicsDB; 82711; -. DR Pumba; Q9NUQ7; -. DR Antibodypedia; 45789; 99 antibodies from 19 providers. DR DNASU; 55325; -. DR Ensembl; ENST00000264689.11; ENSP00000264689.6; ENSG00000109775.12. DR GeneID; 55325; -. DR KEGG; hsa:55325; -. DR MANE-Select; ENST00000264689.11; ENSP00000264689.6; NM_018359.5; NP_060829.2. DR UCSC; uc003ixo.3; human. DR AGR; HGNC:25640; -. DR ClinPGx; PA162408529; -. DR CTD; 55325; -. DR DisGeNET; 55325; -. DR GeneCards; UFSP2; -. DR HGNC; HGNC:25640; UFSP2. DR HPA; ENSG00000109775; Low tissue specificity. DR MalaCards; UFSP2; -. DR MIM; 142669; phenotype. DR MIM; 611482; gene. DR MIM; 617974; phenotype. DR MIM; 620028; phenotype. DR OpenTargets; ENSG00000109775; -. DR Orphanet; 2114; Hip dysplasia, Beukes type. DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy. DR VEuPathDB; HostDB:ENSG00000109775; -. DR eggNOG; KOG2433; Eukaryota. DR GeneTree; ENSGT00940000157115; -. DR InParanoid; Q9NUQ7; -. DR OMA; MDILFRV; -. DR OrthoDB; 417506at2759; -. DR PAN-GO; Q9NUQ7; 1 GO annotation based on evolutionary models. DR PhylomeDB; Q9NUQ7; -. DR PathwayCommons; Q9NUQ7; -. DR SignaLink; Q9NUQ7; -. DR Agora; ENSG00000109775; -. DR BioGRID-ORCS; 55325; 158 hits in 1175 CRISPR screens. DR ChiTaRS; UFSP2; human. DR GenomeRNAi; 55325; -. DR Pharos; Q9NUQ7; Tbio. DR PRO; PR:Q9NUQ7; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; Q9NUQ7; protein. DR Bgee; ENSG00000109775; Expressed in calcaneal tendon and 204 other cell types or tissues. DR ExpressionAtlas; Q9NUQ7; baseline and differential. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0071567; F:deUFMylase activity; IDA:UniProtKB. DR GO; GO:1903051; P:negative regulation of proteolysis involved in protein catabolic process; IDA:UniProt. DR GO; GO:0006508; P:proteolysis; IMP:UniProtKB. DR GO; GO:0033146; P:regulation of intracellular estrogen receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0032649; P:regulation of type II interferon production; IEA:Ensembl. DR GO; GO:0072344; P:rescue of stalled ribosome; IDA:UniProt. DR GO; GO:0032790; P:ribosome disassembly; IDA:UniProtKB. DR FunFam; 3.90.70.130:FF:000001; Probable Ufm1-specific protease 2; 1. DR Gene3D; 3.90.70.130; -; 1. DR InterPro; IPR012462; UFSP1/2_DUB_cat. DR InterPro; IPR049387; UFSP2-like_2nd. DR PANTHER; PTHR48153; UFM1-SPECIFIC PROTEASE 2; 1. DR PANTHER; PTHR48153:SF2; UFM1-SPECIFIC PROTEASE 2; 1. DR Pfam; PF07910; Peptidase_C78; 1. DR Pfam; PF20908; UfSP2_N; 1. PE 1: Evidence at protein level; KW Acetylation; Cytoplasm; Disease variant; Dwarfism; Endoplasmic reticulum; KW Epilepsy; Hydrolase; Intellectual disability; Nucleus; Protease; KW Proteomics identification; Reference proteome; Thiol protease; KW Ubl conjugation pathway. FT CHAIN 1..469 FT /note="Ufm1-specific protease 2" FT /id="PRO_0000280362" FT ACT_SITE 302 FT /evidence="ECO:0000305|PubMed:25219498, FT ECO:0000305|PubMed:36543799" FT ACT_SITE 426 FT /evidence="ECO:0000250|UniProtKB:Q99K23" FT ACT_SITE 428 FT /evidence="ECO:0000250|UniProtKB:Q99K23" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000269|PubMed:25732826" FT VARIANT 83 FT /note="N -> T (in dbSNP:rs17850669)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_031126" FT VARIANT 115 FT /note="V -> E (in DEE106; decreased function in FT deUFMylation; reduced UFSP2 abundance and increased FT abundance of UFMylated targets in homozygous FT patient-derived fibroblasts; dbSNP:rs142500730)" FT /evidence="ECO:0000269|PubMed:33473208" FT /id="VAR_087725" FT VARIANT 290 FT /note="Y -> H (in HDB; loss of protease activity toward the FT C-terminal of UFM1; dbSNP:rs796052130)" FT /evidence="ECO:0000269|PubMed:26428751" FT /id="VAR_074673" FT VARIANT 302 FT /note="C -> S (in SEMDDR; catalytically inactive; loss of FT protease activity; dbSNP:rs2153279702)" FT /evidence="ECO:0000269|PubMed:25219498, FT ECO:0000269|PubMed:30783677, ECO:0000269|PubMed:37214758" FT /id="VAR_089241" FT VARIANT 426 FT /note="D -> A (in SEMDDR; dbSNP:rs1554022725)" FT /evidence="ECO:0000269|PubMed:28892125" FT /id="VAR_079708" FT VARIANT 428 FT /note="H -> R (in SEMDDR; dbSNP:rs2095515802)" FT /evidence="ECO:0000269|PubMed:32755715" FT /id="VAR_087726" FT MUTAGEN 302 FT /note="C->A: Catalytically inactive; loss of protease FT activity." FT /evidence="ECO:0000269|PubMed:36543799" FT CONFLICT 88 FT /note="I -> V (in Ref. 1; BAA92064)" FT /evidence="ECO:0000305" FT CONFLICT 232 FT /note="D -> G (in Ref. 1; BAA92064)" FT /evidence="ECO:0000305" SQ SEQUENCE 469 AA; 53261 MW; FC9AF622053F8BBA CRC64; MVISESMDIL FRIRGGLDLA FQLATPNEIF LKKALKHVLS DLSTKLSSNA LVFRICHSSV YIWPSSDINT IPGELTDASA CKNILRFIQF EPEEDIKRKF MRKKDKKLSD MHQIVNIDLM LEMSTSLAAV TPIIERESGG HHYVNMTLPV DAVISVAPEE TWGKVRKLLV DAIHNQLTDM EKCILKYMKG TSIVVPEPLH FLLPGKKNLV TISYPSGIPD GQLQAYRKEL HDLFNLPHDR PYFKRSNAYH FPDEPYKDGY IRNPHTYLNP PNMETGMIYV VQGIYGYHHY MQDRIDDNGW GCAYRSLQTI CSWFKHQGYT ERSIPTHREI QQALVDAGDK PATFVGSRQW IGSIEVQLVL NQLIGITSKI LFVSQGSEIA SQGRELANHF QSEGTPVMIG GGVLAHTILG VAWNEITGQI KFLILDPHYT GAEDLQVILE KGWCGWKGPD FWNKDAYYNL CLPQRPNMI //