TYSD1_HUMAN
ID TYSD1_HUMAN Reviewed; 566 AA.
AC Q2T9J0; Q5SQT4; Q5SQU1; Q8N6H2; Q96AR5;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 3.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Peroxisomal leader peptide-processing protease;
DE EC=3.4.21.-;
DE AltName: Full=Trypsin domain-containing protein 1;
DE Contains:
DE RecName: Full=Peroxisomal leader peptide-processing protease, 15 kDa form;
DE Contains:
DE RecName: Full=Peroxisomal leader peptide-processing protease, 45 kDa form;
GN Name=TYSND1;
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 GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ALA-65.
RC TISSUE=Brain, and Lung;
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 [3]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-481, AND INTERACTION
RP WITH PEX5 AND LONP2.
RX PubMed=22002062; DOI=10.1074/jbc.m111.285197;
RA Okumoto K., Kametani Y., Fujiki Y.;
RT "Two proteases, trypsin domain-containing 1 (Tysnd1) and peroxisomal lon
RT protease (PsLon), cooperatively regulate fatty acid beta-oxidation in
RT peroxisomal matrix.";
RL J. Biol. Chem. 286:44367-44379(2011).
CC -!- FUNCTION: Peroxisomal protease that mediates both the removal of the
CC leader peptide from proteins containing a PTS2 target sequence and
CC processes several PTS1-containing proteins. Catalyzes the processing of
CC PTS1-proteins involved in the peroxisomal beta-oxidation of fatty
CC acids. {ECO:0000269|PubMed:22002062}.
CC -!- SUBUNIT: Homodimer. Forms a heterodimer with the C-terminal cleavage
CC product (45 kDa form). Forms a heterodimer with the N-terminal cleavage
CC product (15 kDa form). Interacts with PEX5. Interacts with LONP2.
CC {ECO:0000269|PubMed:22002062}.
CC -!- INTERACTION:
CC Q2T9J0-1; Q2T9J0-1: TYSND1; NbExp=5; IntAct=EBI-5239076, EBI-5239076;
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:22002062}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q2T9J0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q2T9J0-2; Sequence=VSP_025000, VSP_025001;
CC -!- PTM: Self-cleavage gives rise to an N-terminal 15-kDa fragment and C-
CC terminal 45-kDa fragment upon import into the peroxisomes. The full-
CC lengh TYSND1 is the active the proteolytic processing of PTS1- and
CC PTS2-proteins and in self-cleavage, and intermolecular self-cleavage of
CC TYSND1 down-regulates its protease activity.
CC -!- SIMILARITY: Belongs to the peptidase S1B family. {ECO:0000305}.
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DR EMBL; AL731540; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016840; AAH16840.1; -; mRNA.
DR EMBL; BC030242; AAH30242.1; -; mRNA.
DR EMBL; BC111501; AAI11502.2; -; mRNA.
DR CCDS; CCDS31213.1; -. [Q2T9J0-1]
DR CCDS; CCDS31214.1; -. [Q2T9J0-2]
DR RefSeq; NP_001035363.1; NM_001040273.2. [Q2T9J0-2]
DR RefSeq; NP_775826.2; NM_173555.3. [Q2T9J0-1]
DR AlphaFoldDB; Q2T9J0; -.
DR SMR; Q2T9J0; -.
DR BioGRID; 128571; 47.
DR IntAct; Q2T9J0; 19.
DR STRING; 9606.ENSP00000287078; -.
DR MEROPS; S01.286; -.
DR iPTMnet; Q2T9J0; -.
DR PhosphoSitePlus; Q2T9J0; -.
DR BioMuta; TYSND1; -.
DR DMDM; 146325807; -.
DR EPD; Q2T9J0; -.
DR jPOST; Q2T9J0; -.
DR MassIVE; Q2T9J0; -.
DR MaxQB; Q2T9J0; -.
DR PaxDb; Q2T9J0; -.
DR PeptideAtlas; Q2T9J0; -.
DR PRIDE; Q2T9J0; -.
DR ProteomicsDB; 61444; -. [Q2T9J0-1]
DR ProteomicsDB; 61445; -. [Q2T9J0-2]
DR Antibodypedia; 48786; 66 antibodies from 17 providers.
DR DNASU; 219743; -.
DR Ensembl; ENST00000287078.7; ENSP00000287078.6; ENSG00000156521.14. [Q2T9J0-1]
DR Ensembl; ENST00000335494.5; ENSP00000335673.5; ENSG00000156521.14. [Q2T9J0-2]
DR GeneID; 219743; -.
DR KEGG; hsa:219743; -.
DR MANE-Select; ENST00000287078.7; ENSP00000287078.6; NM_173555.4; NP_775826.2.
DR UCSC; uc001jqr.5; human. [Q2T9J0-1]
DR CTD; 219743; -.
DR DisGeNET; 219743; -.
DR GeneCards; TYSND1; -.
DR HGNC; HGNC:28531; TYSND1.
DR HPA; ENSG00000156521; Low tissue specificity.
DR MIM; 611017; gene.
DR neXtProt; NX_Q2T9J0; -.
DR OpenTargets; ENSG00000156521; -.
DR PharmGKB; PA134968651; -.
DR VEuPathDB; HostDB:ENSG00000156521; -.
DR eggNOG; KOG1320; Eukaryota.
DR GeneTree; ENSGT00390000014627; -.
DR HOGENOM; CLU_034855_1_0_1; -.
DR InParanoid; Q2T9J0; -.
DR OMA; IACGSPF; -.
DR OrthoDB; 1307240at2759; -.
DR PhylomeDB; Q2T9J0; -.
DR TreeFam; TF331254; -.
DR PathwayCommons; Q2T9J0; -.
DR Reactome; R-HSA-9033241; Peroxisomal protein import.
DR Reactome; R-HSA-9033500; TYSND1 cleaves peroxisomal proteins.
DR SignaLink; Q2T9J0; -.
DR SIGNOR; Q2T9J0; -.
DR BioGRID-ORCS; 219743; 15 hits in 1088 CRISPR screens.
DR ChiTaRS; TYSND1; human.
DR GenomeRNAi; 219743; -.
DR Pharos; Q2T9J0; Tbio.
DR PRO; PR:Q2T9J0; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q2T9J0; protein.
DR Bgee; ENSG00000156521; Expressed in left testis and 125 other tissues.
DR Genevisible; Q2T9J0; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005782; C:peroxisomal matrix; TAS:Reactome.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0002020; F:protease binding; IPI:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0016485; P:protein processing; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IMP:UniProtKB.
DR GO; GO:0031998; P:regulation of fatty acid beta-oxidation; IMP:UniProtKB.
DR InterPro; IPR017345; Pept_S1A_Tysnd1.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR039245; TYSND1/DEG15.
DR PANTHER; PTHR21004; PTHR21004; 1.
DR PIRSF; PIRSF037989; Peptidase_S1B_Tysnd1; 1.
DR SUPFAM; SSF50494; SSF50494; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Hydrolase; Peroxisome; Protease; Reference proteome;
KW Serine protease.
FT CHAIN 1..566
FT /note="Peroxisomal leader peptide-processing protease"
FT /id="PRO_0000286124"
FT CHAIN 1..110
FT /note="Peroxisomal leader peptide-processing protease, 15
FT kDa form"
FT /id="PRO_0000286125"
FT CHAIN 111..566
FT /note="Peroxisomal leader peptide-processing protease, 45
FT kDa form"
FT /id="PRO_0000286126"
FT REGION 319..531
FT /note="Serine protease"
FT ACT_SITE 372
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 408
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 481
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT SITE 110..111
FT /note="Cleavage"
FT /evidence="ECO:0000250"
FT VAR_SEQ 390..398
FT /note="SVAIWGRVV -> HNHQQHPGQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_025000"
FT VAR_SEQ 399..566
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_025001"
FT VARIANT 65
FT /note="T -> A (in dbSNP:rs4746970)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_059758"
FT MUTAGEN 481
FT /note="S->A: Abrogates the self-cleaving activity of
FT TYSND1."
FT /evidence="ECO:0000269|PubMed:22002062"
FT CONFLICT 203
FT /note="P -> L (in Ref. 2; AAH30242)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 566 AA; 59309 MW; 530B895B8698F2E6 CRC64;
MRRQWGSAMR AAEQAGCMVS ASRAGQPEAG PWSCSGVILS RSPGLVLCHG GIFVPFLRAG
SEVLTAAGAV FLPGDSCRDD LRLHVQWAPT AAGPGGGAER GRPGLCTPQC ASLEPGPPAP
SRGRPLQPRL PAELLLLLSC PAFWAHFARL FGDEAAEQWR FSSAARDDEV SEDEEADQLR
ALGWFALLGV RLGQEEVEEE RGPAMAVSPL GAVPKGAPLL VCGSPFGAFC PDIFLNTLSC
GVLSNVAGPL LLTDARCLPG TEGGGVFTAR PAGALVALVV APLCWKAGEW VGFTLLCAAA
PLFRAARDAL HRLPHSTAAL AALLPPEVGV PWGLPLRDSG PLWAAAAVLV ECGTVWGSGV
AVAPRLVVTC RHVSPREAAR VLVRSTTPKS VAIWGRVVFA TQETCPYDIA VVSLEEDLDD
VPIPVPAEHF HEGEAVSVVG FGVFGQSCGP SVTSGILSAV VQVNGTPVML QTTCAVHSGS
SGGPLFSNHS GNLLGIITSN TRDNNTGATY PHLNFSIPIT VLQPALQQYS QTQDLGGLRE
LDRAAEPVRV VWRLQRPLAE APRSKL
