ID UFSP1_HUMAN Reviewed; 218 AA. AC Q6NVU6; A0A5F9ZGY7; A4D2E4; A8K8V2; B6ZDG6; Q9BXP6; DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot. DT 24-JUL-2024, sequence version 3. DT 24-JUL-2024, entry version 127. DE RecName: Full=Ufm1-specific protease 1 {ECO:0000305}; DE Short=UfSP1 {ECO:0000303|PubMed:35926457}; DE EC=3.4.22.- {ECO:0000269|PubMed:35525273, ECO:0000269|PubMed:35926457}; GN Name=UFSP1 {ECO:0000303|PubMed:35926457, ECO:0000312|HGNC:HGNC:33821}; 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 [GENOMIC DNA]. RX PubMed=11239002; DOI=10.1093/nar/29.6.1352; RA Wilson M.D., Riemer C., Martindale D.W., Schnupf P., Boright A.P., RA Cheung T.L., Hardy D.M., Schwartz S., Scherer S.W., Tsui L.-C., Miller W., RA Koop B.F.; RT "Comparative analysis of the gene-dense ACHE/TFR2 region on human RT chromosome 7q22 with the orthologous region on mouse chromosome 5."; RL Nucleic Acids Res. 29:1352-1365(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-123. RC TISSUE=Testis; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-123. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [6] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND IDENTIFICATION BY RP MASS SPECTROMETRY. 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 [7] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, IDENTIFICATION BY MASS RP SPECTROMETRY, AND MUTAGENESIS OF CYS-45. RX PubMed=35525273; DOI=10.1016/j.jbc.2022.102016; RA Liang Q., Jin Y., Xu S., Zhou J., Mao J., Ma X., Wang M., Cong Y.S.; RT "Human UFSP1 translated from an upstream near-cognate initiation codon RT functions as an active UFM1-specific protease."; RL J. Biol. Chem. 298:102016-102016(2022). CC -!- FUNCTION: Thiol-dependent isopeptidase that specifically mediate the CC processing of UFM1 precursors as well as the deconjugation of UFM1 from CC target proteins (PubMed:35525273, PubMed:35926457). Mainly responsible CC for the maturation of the UFM1 precursor, a prerequisite for CC conjugation reactions (PubMed:35525273, PubMed:35926457). CC {ECO:0000269|PubMed:35525273, ECO:0000269|PubMed:35926457}. CC -!- INTERACTION: CC Q6NVU6; Q5SWW7: C10orf55; NbExp=3; IntAct=EBI-12068150, EBI-12809220; CC Q6NVU6; Q9UHD4: CIDEB; NbExp=3; IntAct=EBI-12068150, EBI-7062247; CC Q6NVU6; Q96AQ7: CIDEC; NbExp=3; IntAct=EBI-12068150, EBI-14151404; CC Q6NVU6; Q9Y2V7: COG6; NbExp=3; IntAct=EBI-12068150, EBI-3866319; CC Q6NVU6; Q02930-3: CREB5; NbExp=3; IntAct=EBI-12068150, EBI-10192698; CC Q6NVU6; P33240: CSTF2; NbExp=3; IntAct=EBI-12068150, EBI-711360; CC Q6NVU6; Q8WU58: FAM222B; NbExp=3; IntAct=EBI-12068150, EBI-2807642; CC Q6NVU6; Q9NW38: FANCL; NbExp=3; IntAct=EBI-12068150, EBI-2339898; CC Q6NVU6; O75593: FOXH1; NbExp=3; IntAct=EBI-12068150, EBI-1759806; CC Q6NVU6; Q12951-2: FOXI1; NbExp=3; IntAct=EBI-12068150, EBI-12018822; CC Q6NVU6; Q8IVS8: GLYCTK; NbExp=3; IntAct=EBI-12068150, EBI-748515; CC Q6NVU6; Q9Y4H4: GPSM3; NbExp=3; IntAct=EBI-12068150, EBI-347538; CC Q6NVU6; P35680: HNF1B; NbExp=3; IntAct=EBI-12068150, EBI-2798841; CC Q6NVU6; P31274: HOXC9; NbExp=3; IntAct=EBI-12068150, EBI-1779423; CC Q6NVU6; Q9ULV5-2: HSF4; NbExp=3; IntAct=EBI-12068150, EBI-12056251; CC Q6NVU6; Q0VD86: INCA1; NbExp=3; IntAct=EBI-12068150, EBI-6509505; CC Q6NVU6; Q3LI76: KRTAP15-1; NbExp=3; IntAct=EBI-12068150, EBI-11992140; CC Q6NVU6; Q14847-2: LASP1; NbExp=3; IntAct=EBI-12068150, EBI-9088686; CC Q6NVU6; Q8IXL7-2: MSRB3; NbExp=3; IntAct=EBI-12068150, EBI-10699187; CC Q6NVU6; Q8TDC0: MYOZ3; NbExp=3; IntAct=EBI-12068150, EBI-5662487; CC Q6NVU6; P78337: PITX1; NbExp=3; IntAct=EBI-12068150, EBI-748265; CC Q6NVU6; Q99697-2: PITX2; NbExp=3; IntAct=EBI-12068150, EBI-12138495; CC Q6NVU6; Q7Z3K3: POGZ; NbExp=3; IntAct=EBI-12068150, EBI-1389308; CC Q6NVU6; P78424: POU6F2; NbExp=3; IntAct=EBI-12068150, EBI-12029004; CC Q6NVU6; O75360: PROP1; NbExp=3; IntAct=EBI-12068150, EBI-9027467; CC Q6NVU6; Q6ZRY4: RBPMS2; NbExp=3; IntAct=EBI-12068150, EBI-11987469; CC Q6NVU6; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-12068150, EBI-6257312; CC Q6NVU6; Q92922: SMARCC1; NbExp=3; IntAct=EBI-12068150, EBI-355653; CC Q6NVU6; P09234: SNRPC; NbExp=3; IntAct=EBI-12068150, EBI-766589; CC Q6NVU6; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-12068150, EBI-742688; CC Q6NVU6; O15119: TBX3; NbExp=3; IntAct=EBI-12068150, EBI-3452216; CC Q6NVU6; Q9NQB0-10: TCF7L2; NbExp=3; IntAct=EBI-12068150, EBI-11746252; CC Q6NVU6; O43711: TLX3; NbExp=3; IntAct=EBI-12068150, EBI-3939165; CC Q6NVU6; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-12068150, EBI-947187; CC Q6NVU6; Q08AM6: VAC14; NbExp=3; IntAct=EBI-12068150, EBI-2107455; CC Q6NVU6; Q9UIW0: VAX2; NbExp=3; IntAct=EBI-12068150, EBI-12090999; CC Q6NVU6; A8MV65-2: VGLL3; NbExp=3; IntAct=EBI-12068150, EBI-11957216; CC Q6NVU6; A5D8V6: VPS37C; NbExp=3; IntAct=EBI-12068150, EBI-2559305; CC Q6NVU6; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-12068150, EBI-12040603; CC Q6NVU6; Q15915: ZIC1; NbExp=3; IntAct=EBI-12068150, EBI-11963196; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:35926457}. CC -!- SIMILARITY: Belongs to the peptidase C78 family. {ECO:0000305}. CC -!- CAUTION: UFSP1 initiates at a non-canonical GUG codon (PubMed:35525273, CC PubMed:35926457). Was initially thought to initiate from Met-77 and CC constitute a inactive isopeptidase that lacks a functional protease CC domain (PubMed:35525273, PubMed:35926457). CC {ECO:0000269|PubMed:35525273, ECO:0000269|PubMed:35926457}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH67904.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305}; CC Sequence=AAK21004.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305}; CC Sequence=BAF85156.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305}; CC Sequence=EAL23814.1; Type=Erroneous gene model prediction; 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; AF312032; AAK21004.1; ALT_SEQ; Genomic_DNA. DR EMBL; AK292467; BAF85156.1; ALT_SEQ; mRNA. DR EMBL; CH236956; EAL23814.1; ALT_SEQ; Genomic_DNA. DR EMBL; AC011895; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC067904; AAH67904.1; ALT_SEQ; mRNA. DR CCDS; CCDS34710.1; -. DR RefSeq; NP_001015072.2; NM_001015072.3. DR AlphaFoldDB; Q6NVU6; -. DR SMR; Q6NVU6; -. DR BioGRID; 135544; 53. DR IntAct; Q6NVU6; 40. DR STRING; 9606.ENSP00000373413; -. DR MEROPS; C78.001; -. DR iPTMnet; Q6NVU6; -. DR PhosphoSitePlus; Q6NVU6; -. DR BioMuta; UFSP1; -. DR DMDM; 296452856; -. DR MassIVE; Q6NVU6; -. DR PaxDb; 9606-ENSP00000373413; -. DR PeptideAtlas; Q6NVU6; -. DR ProteomicsDB; 66720; -. DR Pumba; Q6NVU6; -. DR Antibodypedia; 16700; 26 antibodies from 14 providers. DR DNASU; 402682; -. DR Ensembl; ENST00000388761.4; ENSP00000373413.2; ENSG00000176125.7. DR GeneID; 402682; -. DR KEGG; hsa:402682; -. DR MANE-Select; ENST00000388761.4; ENSP00000373413.2; NM_001015072.4; NP_001015072.2. DR UCSC; uc003uxc.4; human. DR AGR; HGNC:33821; -. DR CTD; 402682; -. DR DisGeNET; 402682; -. DR GeneCards; UFSP1; -. DR HGNC; HGNC:33821; UFSP1. DR HPA; ENSG00000176125; Low tissue specificity. DR MIM; 611481; gene. DR neXtProt; NX_Q6NVU6; -. DR OpenTargets; ENSG00000176125; -. DR PharmGKB; PA162408522; -. DR VEuPathDB; HostDB:ENSG00000176125; -. DR eggNOG; KOG2433; Eukaryota. DR GeneTree; ENSGT00940000162936; -. DR HOGENOM; CLU_1815130_0_0_1; -. DR InParanoid; Q6NVU6; -. DR OMA; PCKVVHV; -. DR OrthoDB; 11265at2759; -. DR PhylomeDB; Q6NVU6; -. DR PathwayCommons; Q6NVU6; -. DR SignaLink; Q6NVU6; -. DR BioGRID-ORCS; 402682; 20 hits in 1148 CRISPR screens. DR GenomeRNAi; 402682; -. DR Pharos; Q6NVU6; Tdark. DR PRO; PR:Q6NVU6; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q6NVU6; Protein. DR Bgee; ENSG00000176125; Expressed in primordial germ cell in gonad and 93 other cell types or tissues. DR ExpressionAtlas; Q6NVU6; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0008234; F:cysteine-type peptidase activity; IDA:UniProtKB. DR GO; GO:0071567; F:deUFMylase activity; IDA:UniProtKB. DR GO; GO:0051604; P:protein maturation; IDA:UniProtKB. DR Gene3D; 3.90.70.130; -; 1. DR InterPro; IPR051250; UFM1_isopeptidase. DR InterPro; IPR012462; UfSP1/2_DUB_cat. DR PANTHER; PTHR48153:SF3; INACTIVE UFM1-SPECIFIC PROTEASE 1; 1. DR PANTHER; PTHR48153; UFM1-SPECIFIC PROTEASE 2; 1. DR Pfam; PF07910; Peptidase_C78; 1. PE 1: Evidence at protein level; KW Cytoplasm; Hydrolase; Protease; Reference proteome; Thiol protease; KW Ubl conjugation pathway. FT CHAIN 1..218 FT /note="Ufm1-specific protease 1" FT /id="PRO_0000280360" FT ACT_SITE 45 FT /evidence="ECO:0000305|PubMed:35525273" FT ACT_SITE 167 FT /evidence="ECO:0000250|UniProtKB:Q9CZP0" FT ACT_SITE 169 FT /evidence="ECO:0000250|UniProtKB:Q9CZP0" FT VARIANT 123 FT /note="L -> V (in dbSNP:rs12666989)" FT /evidence="ECO:0000269|PubMed:12690205, FT ECO:0000269|PubMed:14702039" FT /id="VAR_031125" FT MUTAGEN 45 FT /note="C->A: Abolished isopeptidase activity." FT /evidence="ECO:0000269|PubMed:35525273" SQ SEQUENCE 218 AA; 23253 MW; C9CB6404D95B1BEF CRC64; MEPLRDVHVG LSPPSRGPVR LALLSGHYLY YHYGCDGLDD RGWGCGYRTL QTLCSWPEGQ PAGVPGLAAV QAALEDMGDK PPGFRGSRDW IGCVEASLCL AHFGGPQGRL CHVPRGVGLH GELERLYSHF AGGGGPVMVG GDADARSKAL LGVCVGSGTE AYVLVLDPHY WGTPKSPSEL QAAGWVGWQE VSAAFDPNSF YNLCLTSLSS QQQQRTLD //