POLS2_HUMAN
ID POLS2_HUMAN Reviewed; 855 AA.
AC Q5K4E3; A8K2P5; B4DW80; B7ZMK8; E7EX56; Q8NBY4;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Polyserase-2;
DE EC=3.4.21.-;
DE AltName: Full=Polyserine protease 2;
DE AltName: Full=Serine protease 36;
DE Flags: Precursor;
GN Name=PRSS36;
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 [MRNA] (ISOFORM 1), ENZYME ACTIVITY, ACTIVITY
RP REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND GLYCOSYLATION.
RC TISSUE=Liver;
RX PubMed=15536082; DOI=10.1074/jbc.m409139200;
RA Cal S., Quesada V., Llamazares M., Diaz-Perales A., Garabaya C.,
RA Lopez-Otin C.;
RT "Human polyserase-2, a novel enzyme with three tandem serine protease
RT domains in a single polypeptide chain.";
RL J. Biol. Chem. 280:1953-1961(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Placenta, Synovium, and Tongue;
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].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
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).
CC -!- FUNCTION: Serine protease. Hydrolyzes the peptides N-t-Boc-Gln-Ala-Arg-
CC AMC and N-t-Boc-Gln-Gly-Arg-AMC and, to a lesser extent, N-t-Boc-Ala-
CC Phe-Lys-AMC and N-t-Boc-Val-Leu-Lys-AMC. Has a preference for
CC substrates with an Arg instead of a Lys residue in position P1.
CC -!- ACTIVITY REGULATION: Inhibited by serine proteinase inhibitor 4-(2-
CC aminoethyl)-benzenesulfonyl fluoride, but not with EDTA or E-64.
CC {ECO:0000269|PubMed:15536082}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:15536082}. Note=Not attached to membranes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q5K4E3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5K4E3-2; Sequence=VSP_044718;
CC Name=3;
CC IsoId=Q5K4E3-3; Sequence=VSP_046639;
CC -!- TISSUE SPECIFICITY: Expressed in fetal kidney, skeletal muscle, liver,
CC placenta and heart. Also expressed in tumor cell lines derived from
CC lung and colon adenocarcinomas. {ECO:0000269|PubMed:15536082}.
CC -!- DOMAIN: The first serine protease domain is catalytically active,
CC whereas the second domain lacks the essential His residue of the
CC catalytic triad at position 363, and the third domain lacks the
CC essential Asp residue of the catalytic triad at position 679. The
CC second and third domains are therefore predicted to be inactive (By
CC similarity). {ECO:0000250}.
CC -!- PTM: The 3 protease domains are not proteolytically cleaved.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15536082}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; AJ627034; CAF25303.1; -; mRNA.
DR EMBL; AK075142; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK290310; BAF82999.1; -; mRNA.
DR EMBL; AK301409; BAG62942.1; -; mRNA.
DR EMBL; AC009088; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC137396; AAI37397.1; -; mRNA.
DR EMBL; BC144615; AAI44616.1; -; mRNA.
DR CCDS; CCDS32436.1; -. [Q5K4E3-1]
DR CCDS; CCDS58452.1; -. [Q5K4E3-2]
DR CCDS; CCDS58453.1; -. [Q5K4E3-3]
DR RefSeq; NP_001245219.1; NM_001258290.1. [Q5K4E3-3]
DR RefSeq; NP_001245220.1; NM_001258291.1. [Q5K4E3-2]
DR RefSeq; NP_775773.2; NM_173502.4. [Q5K4E3-1]
DR AlphaFoldDB; Q5K4E3; -.
DR SMR; Q5K4E3; -.
DR STRING; 9606.ENSP00000268281; -.
DR MEROPS; S01.414; -.
DR MEROPS; S01.940; -.
DR MEROPS; S01.941; -.
DR GlyGen; Q5K4E3; 9 sites.
DR BioMuta; PRSS36; -.
DR DMDM; 209572670; -.
DR MassIVE; Q5K4E3; -.
DR PaxDb; Q5K4E3; -.
DR PeptideAtlas; Q5K4E3; -.
DR PRIDE; Q5K4E3; -.
DR ProteomicsDB; 18987; -.
DR ProteomicsDB; 63543; -. [Q5K4E3-1]
DR ProteomicsDB; 7266; -.
DR Antibodypedia; 27673; 62 antibodies from 17 providers.
DR DNASU; 146547; -.
DR Ensembl; ENST00000268281.9; ENSP00000268281.4; ENSG00000178226.11. [Q5K4E3-1]
DR Ensembl; ENST00000418068.6; ENSP00000407160.2; ENSG00000178226.11. [Q5K4E3-2]
DR Ensembl; ENST00000569305.1; ENSP00000454768.1; ENSG00000178226.11. [Q5K4E3-3]
DR GeneID; 146547; -.
DR KEGG; hsa:146547; -.
DR MANE-Select; ENST00000268281.9; ENSP00000268281.4; NM_173502.5; NP_775773.2.
DR UCSC; uc002ebd.5; human. [Q5K4E3-1]
DR CTD; 146547; -.
DR DisGeNET; 146547; -.
DR GeneCards; PRSS36; -.
DR HGNC; HGNC:26906; PRSS36.
DR HPA; ENSG00000178226; Tissue enhanced (pituitary).
DR MIM; 610560; gene.
DR neXtProt; NX_Q5K4E3; -.
DR OpenTargets; ENSG00000178226; -.
DR PharmGKB; PA142671123; -.
DR VEuPathDB; HostDB:ENSG00000178226; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000161761; -.
DR HOGENOM; CLU_004497_2_2_1; -.
DR InParanoid; Q5K4E3; -.
DR OMA; QESGTWF; -.
DR PhylomeDB; Q5K4E3; -.
DR TreeFam; TF351678; -.
DR PathwayCommons; Q5K4E3; -.
DR BioGRID-ORCS; 146547; 9 hits in 1063 CRISPR screens.
DR GenomeRNAi; 146547; -.
DR Pharos; Q5K4E3; Tbio.
DR PRO; PR:Q5K4E3; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q5K4E3; protein.
DR Bgee; ENSG00000178226; Expressed in right adrenal gland cortex and 93 other tissues.
DR ExpressionAtlas; Q5K4E3; baseline and differential.
DR Genevisible; Q5K4E3; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:MGI.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 3.
DR InterPro; IPR017326; Pept_S1A_polyserase-2.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF00089; Trypsin; 3.
DR PIRSF; PIRSF037933; Polyserase-2; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 3.
DR SUPFAM; SSF50494; SSF50494; 3.
DR PROSITE; PS50240; TRYPSIN_DOM; 3.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Extracellular matrix; Glycoprotein;
KW Hydrolase; Protease; Reference proteome; Repeat; Secreted; Serine protease;
KW Signal; Zymogen.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..46
FT /evidence="ECO:0000255"
FT /id="PRO_0000027879"
FT CHAIN 47..855
FT /note="Polyserase-2"
FT /id="PRO_0000027880"
FT DOMAIN 47..291
FT /note="Peptidase S1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DOMAIN 323..555
FT /note="Peptidase S1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DOMAIN 590..808
FT /note="Peptidase S1 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 292..316
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 87
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 139
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 243
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 217
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 317
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 369
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 402
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 407
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 421
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 508
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 72..88
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 173..249
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 206..228
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 239..267
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 348..364
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 444..516
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 506..534
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 615..631
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 711..772
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 739..751
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT VAR_SEQ 503..507
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046639"
FT VAR_SEQ 661..763
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044718"
FT CONFLICT 135
FT /note="E -> K (in Ref. 2; BAG62942)"
FT /evidence="ECO:0000305"
FT CONFLICT 812
FT /note="F -> L (in Ref. 1; CAF25303)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 855 AA; 91955 MW; D1AF7888311FB871 CRC64;
MARHLLLPLV MLVISPIPGA FQDSALSPTQ EEPEDLDCGR PEPSARIVGG SNAQPGTWPW
QVSLHHGGGH ICGGSLIAPS WVLSAAHCFM TNGTLEPAAE WSVLLGVHSQ DGPLDGAHTR
AVAAIVVPAN YSQVELGADL ALLRLASPAS LGPAVWPVCL PRASHRFVHG TACWATGWGD
VQEADPLPLP WVLQEVELRL LGEATCQCLY SQPGPFNLTL QILPGMLCAG YPEGRRDTCQ
GDSGGPLVCE EGGRWFQAGI TSFGFGCGRR NRPGVFTAVA TYEAWIREQV MGSEPGPAFP
TQPQKTQSDP QEPREENCTI ALPECGKAPR PGAWPWEAQV MVPGSRPCHG ALVSESWVLA
PASCFLDPNS SDSPPRDLDA WRVLLPSRPR AERVARLVQH ENASWDNASD LALLQLRTPV
NLSAASRPVC LPHPEHYFLP GSRCRLARWG RGEPALGPGA LLEAELLGGW WCHCLYGRQG
AAVPLPGDPP HALCPAYQEK EEVGSCWNDS RWSLLCQEEG TWFLAGIRDF PSGCLRPRAF
FPLQTHGPWI SHVTRGAYLE DQLAWDWGPD GEETETQTCP PHTEHGACGL RLEAAPVGVL
WPWLAEVHVA GDRVCTGILL APGWVLAATH CVLRPGSTTV PYIEVYLGRA GASSLPQGHQ
VSRLVISIRL PQHLGLRPPL ALLELSSRVE PSPSALPICL HPAGIPPGAS CWVLGWKEPQ
DRVPVAAAVS ILTQRICDCL YQGILPPGTL CVLYAEGQEN RCEMTSAPPL LCQMTEGSWI
LVGMAVQGSR ELFAAIGPEE AWISQTVGEA NFLPPSGSPH WPTGGSNLCP PELAKASGSP
HAVYFLLLLT LLIQS
