UFSP2_HUMAN
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 03-AUG-2022, entry version 140.
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:32160526};
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, MUTAGENESIS OF CYS-302, AND INTERACTION WITH
RP 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 BFHD, VARIANT BFHD HIS-290, AND CHARACTERIZATION OF VARIANT
RP BFHD 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=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 [10]
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).
CC -!- FUNCTION: Thiol-dependent isopeptidase that recognizes and hydrolyzes
CC the peptide bond at the C-terminal Gly of UFM1, a ubiquitin-like
CC modifier protein bound to a number of target proteins (PubMed:25219498,
CC PubMed:32160526). Does not hydrolyze SUMO1 or ISG15 ubiquitin-like
CC proteins (PubMed:25219498). Through TRIP4 deufmylation may regulate
CC intracellular nuclear receptors transactivation and thereby regulate
CC cell proliferation and differentiation (PubMed:25219498).
CC {ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:32160526}.
CC -!- SUBUNIT: Interacts with DDRGK1 (By similarity). Interacts with TRIP4;
CC deufmylates TRIP4 (PubMed:25219498). {ECO:0000250|UniProtKB:Q99K23,
CC ECO:0000269|PubMed:25219498}.
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: Cytoplasm {ECO:0000250|UniProtKB:Q99K23}.
CC Endoplasmic reticulum {ECO:0000250|UniProtKB:Q99K23}. Nucleus
CC {ECO:0000250|UniProtKB:Q99K23}.
CC -!- DISEASE: Beukes familial hip dysplasia (BFHD) [MIM:142669]: A severe
CC progressive degenerative osteoarthritis of the hip joint with
CC underlying dysplasia confined to that region. Affected individuals are
CC of normal stature and have no associated health problems.
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:28892125}. 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}.
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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_018359.3.
DR AlphaFoldDB; Q9NUQ7; -.
DR SMR; Q9NUQ7; -.
DR BioGRID; 120606; 133.
DR IntAct; Q9NUQ7; 26.
DR STRING; 9606.ENSP00000264689; -.
DR MEROPS; C78.002; -.
DR iPTMnet; Q9NUQ7; -.
DR PhosphoSitePlus; Q9NUQ7; -.
DR BioMuta; UFSP2; -.
DR DMDM; 251757433; -.
DR EPD; Q9NUQ7; -.
DR jPOST; Q9NUQ7; -.
DR MassIVE; Q9NUQ7; -.
DR MaxQB; Q9NUQ7; -.
DR PaxDb; Q9NUQ7; -.
DR PeptideAtlas; Q9NUQ7; -.
DR PRIDE; Q9NUQ7; -.
DR ProteomicsDB; 82711; -.
DR Antibodypedia; 45789; 105 antibodies from 20 providers.
DR DNASU; 55325; -.
DR Ensembl; ENST00000264689.11; ENSP00000264689.6; ENSG00000109775.11.
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 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 neXtProt; NX_Q9NUQ7; -.
DR OpenTargets; ENSG00000109775; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR Orphanet; 2114; Hip dysplasia, Beukes type.
DR PharmGKB; PA162408529; -.
DR VEuPathDB; HostDB:ENSG00000109775; -.
DR eggNOG; KOG2433; Eukaryota.
DR GeneTree; ENSGT00940000157115; -.
DR InParanoid; Q9NUQ7; -.
DR OMA; GHIKYLI; -.
DR OrthoDB; 444004at2759; -.
DR PhylomeDB; Q9NUQ7; -.
DR TreeFam; TF325896; -.
DR PathwayCommons; Q9NUQ7; -.
DR SignaLink; Q9NUQ7; -.
DR BioGRID-ORCS; 55325; 152 hits in 1098 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 203 other tissues.
DR ExpressionAtlas; Q9NUQ7; baseline and differential.
DR Genevisible; Q9NUQ7; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0071567; F:deUFMylase activity; IMP:UniProtKB.
DR GO; GO:0016790; F:thiolester hydrolase activity; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IMP:UniProtKB.
DR GO; GO:0033146; P:regulation of intracellular estrogen receptor signaling pathway; IMP:UniProtKB.
DR InterPro; IPR012462; Peptidase_C78_UfSP1/2.
DR Pfam; PF07910; Peptidase_C78; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Disease variant; Dwarfism; Endoplasmic reticulum;
KW Hydrolase; Nucleus; Protease; 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 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 290
FT /note="Y -> H (in BFHD; loss of protease activity toward
FT the C-terminal of UFM1; dbSNP:rs796052130)"
FT /evidence="ECO:0000269|PubMed:26428751"
FT /id="VAR_074673"
FT VARIANT 426
FT /note="D -> A (in SEMDDR; dbSNP:rs1554022725)"
FT /evidence="ECO:0000269|PubMed:28892125"
FT /id="VAR_079708"
FT MUTAGEN 302
FT /note="C->S: Catalytically inactive."
FT /evidence="ECO:0000269|PubMed:25219498"
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
