TMPS9_HUMAN
ID TMPS9_HUMAN Reviewed; 1059 AA.
AC Q7Z410; Q6ZND6; Q7Z411;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Transmembrane protease serine 9;
DE EC=3.4.21.-;
DE AltName: Full=Polyserase-I;
DE AltName: Full=Polyserine protease 1;
DE Short=Polyserase-1;
DE Contains:
DE RecName: Full=Serase-1;
DE Contains:
DE RecName: Full=Serase-2;
DE Contains:
DE RecName: Full=Serase-3;
GN Name=TMPRSS9;
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], ENZYME ACTIVITY, ACTIVITY REGULATION, CLEAVAGE,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=12886014; DOI=10.1073/pnas.1633392100;
RA Cal S., Quesada V., Garabaya C., Lopez-Otin C.;
RT "Polyserase-I, a human polyprotease with the ability to generate
RT independent serine protease domains from a single translation product.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:9185-9190(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 472-1059, AND VARIANTS ASN-793
RP AND LYS-938.
RC TISSUE=Thalamus;
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).
CC -!- FUNCTION: Serase-1 and serase-2 are serine proteases that hydrolyze the
CC peptides N-t-Boc-Gln-Ala-Arg-AMC and N-t-Boc-Gln-Gly-Arg-AMC. In
CC contrast, N-t-Boc-Ala-Phe-Lys-AMC and N-t-Boc-Ala-Pro-Ala-AMC are not
CC significantly hydrolyzed.
CC -!- ACTIVITY REGULATION: Inhibited by serine protease inhibitors PMSF and
CC 4-(2-aminoethyl)benzenesulfonyl fluoride, but not by EDTA.
CC {ECO:0000269|PubMed:12886014}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12886014};
CC Single-pass type II membrane protein {ECO:0000269|PubMed:12886014}.
CC -!- TISSUE SPECIFICITY: Expressed in fetal human tissues, such as kidney,
CC liver, lung and brain, and in a variety of tumor cell lines. Weakly
CC expressed in adult tissues including skeletal muscle, liver, placenta
CC and heart. {ECO:0000269|PubMed:12886014}.
CC -!- DOMAIN: The serine protease 1 and 2 domains are catalytically active,
CC whereas the serine protease 3 domain lacks the essential Ser residue of
CC the catalytic triad at position 1009 and is predicted to be inactive.
CC -!- PTM: Proteolytically cleaved to generate 3 independent serine protease
CC chains. The cleaved chains may remain attached to the membrane thanks
CC to disulfide bonds. It is unclear whether cleavage always takes place.
CC {ECO:0000269|PubMed:12886014}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD18439.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAD35759.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
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DR EMBL; AJ488946; CAD35758.1; -; mRNA.
DR EMBL; AJ488947; CAD35759.1; ALT_SEQ; mRNA.
DR EMBL; AC011522; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011542; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK131261; BAD18439.1; ALT_FRAME; mRNA.
DR CCDS; CCDS12088.1; -.
DR RefSeq; NP_892018.1; NM_182973.2.
DR AlphaFoldDB; Q7Z410; -.
DR SMR; Q7Z410; -.
DR BioGRID; 131860; 9.
DR STRING; 9606.ENSP00000330264; -.
DR MEROPS; S01.969; -.
DR GlyGen; Q7Z410; 4 sites.
DR iPTMnet; Q7Z410; -.
DR PhosphoSitePlus; Q7Z410; -.
DR BioMuta; TMPRSS9; -.
DR DMDM; 61217609; -.
DR MassIVE; Q7Z410; -.
DR PaxDb; Q7Z410; -.
DR PeptideAtlas; Q7Z410; -.
DR PRIDE; Q7Z410; -.
DR ProteomicsDB; 69126; -.
DR TopDownProteomics; Q7Z410; -.
DR Antibodypedia; 57199; 76 antibodies from 13 providers.
DR DNASU; 360200; -.
DR Ensembl; ENST00000649857.1; ENSP00000497651.1; ENSG00000178297.14.
DR GeneID; 360200; -.
DR KEGG; hsa:360200; -.
DR UCSC; uc010xgx.3; human.
DR CTD; 360200; -.
DR DisGeNET; 360200; -.
DR GeneCards; TMPRSS9; -.
DR HGNC; HGNC:30079; TMPRSS9.
DR HPA; ENSG00000178297; Tissue enhanced (liver, lymphoid tissue, testis).
DR MIM; 610477; gene.
DR neXtProt; NX_Q7Z410; -.
DR OpenTargets; ENSG00000178297; -.
DR PharmGKB; PA134967594; -.
DR VEuPathDB; HostDB:ENSG00000178297; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000159993; -.
DR HOGENOM; CLU_004497_2_0_1; -.
DR InParanoid; Q7Z410; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; Q7Z410; -.
DR TreeFam; TF330647; -.
DR PathwayCommons; Q7Z410; -.
DR BioGRID-ORCS; 360200; 15 hits in 1065 CRISPR screens.
DR ChiTaRS; TMPRSS9; human.
DR GenomeRNAi; 360200; -.
DR Pharos; Q7Z410; Tbio.
DR PRO; PR:Q7Z410; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q7Z410; protein.
DR Bgee; ENSG00000178297; Expressed in right lobe of liver and 99 other tissues.
DR ExpressionAtlas; Q7Z410; baseline and differential.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00112; LDLa; 1.
DR CDD; cd00190; Tryp_SPc; 3.
DR Gene3D; 2.40.10.10; -; 4.
DR Gene3D; 4.10.400.10; -; 1.
DR InterPro; IPR036055; LDL_receptor-like_sf.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR017324; Tmprss9.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF00057; Ldl_recept_a; 1.
DR Pfam; PF00089; Trypsin; 3.
DR PIRSF; PIRSF037931; TMPRSS9_polyserase-1; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00192; LDLa; 1.
DR SMART; SM00020; Tryp_SPc; 3.
DR SUPFAM; SSF50494; SSF50494; 3.
DR SUPFAM; SSF57424; SSF57424; 1.
DR PROSITE; PS01209; LDLRA_1; 1.
DR PROSITE; PS50068; LDLRA_2; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 3.
DR PROSITE; PS00134; TRYPSIN_HIS; 3.
DR PROSITE; PS00135; TRYPSIN_SER; 2.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Glycoprotein; Hydrolase; Membrane; Protease;
KW Reference proteome; Repeat; Serine protease; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1059
FT /note="Transmembrane protease serine 9"
FT /evidence="ECO:0000255"
FT /id="PRO_0000027867"
FT CHAIN 203..503
FT /note="Serase-1"
FT /evidence="ECO:0000255"
FT /id="PRO_0000027868"
FT CHAIN 504..826
FT /note="Serase-2"
FT /evidence="ECO:0000255"
FT /id="PRO_0000027869"
FT CHAIN 827..1059
FT /note="Serase-3"
FT /evidence="ECO:0000255"
FT /id="PRO_0000027870"
FT TOPO_DOM 1..29
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 30..50
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 51..1059
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 153..190
FT /note="LDL-receptor class A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 203..436
FT /note="Peptidase S1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DOMAIN 504..736
FT /note="Peptidase S1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DOMAIN 827..1058
FT /note="Peptidase S1 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 443..469
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 758..814
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 774..800
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 243
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 292
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 387
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 544
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 592
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 687
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT SITE 202..203
FT /note="Cleavage"
FT /evidence="ECO:0000255"
FT SITE 503..504
FT /note="Cleavage"
FT /evidence="ECO:0000255"
FT SITE 826..827
FT /note="Cleavage"
FT /evidence="ECO:0000255"
FT CARBOHYD 547
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 638
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 663
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 786
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 154..166
FT /evidence="ECO:0000250"
FT DISULFID 161..180
FT /evidence="ECO:0000250"
FT DISULFID 174..189
FT /evidence="ECO:0000250"
FT DISULFID 228..244
FT /evidence="ECO:0000250"
FT DISULFID 326..393
FT /evidence="ECO:0000250"
FT DISULFID 358..372
FT /evidence="ECO:0000250"
FT DISULFID 383..412
FT /evidence="ECO:0000250"
FT DISULFID 529..545
FT /evidence="ECO:0000250"
FT DISULFID 626..693
FT /evidence="ECO:0000250"
FT DISULFID 658..672
FT /evidence="ECO:0000250"
FT DISULFID 683..712
FT /evidence="ECO:0000250"
FT DISULFID 853..869
FT /evidence="ECO:0000250"
FT DISULFID 949..1015
FT /evidence="ECO:0000250"
FT DISULFID 980..994
FT /evidence="ECO:0000250"
FT DISULFID 1005..1034
FT /evidence="ECO:0000250"
FT VARIANT 4
FT /note="T -> A (in dbSNP:rs8100709)"
FT /id="VAR_051845"
FT VARIANT 30
FT /note="S -> T (in dbSNP:rs891174)"
FT /id="VAR_021508"
FT VARIANT 73
FT /note="R -> W (in dbSNP:rs17685098)"
FT /id="VAR_033650"
FT VARIANT 456
FT /note="A -> T (in dbSNP:rs10153474)"
FT /id="VAR_051846"
FT VARIANT 659
FT /note="S -> T (in dbSNP:rs60568869)"
FT /id="VAR_061774"
FT VARIANT 793
FT /note="S -> N (in dbSNP:rs735911)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_021509"
FT VARIANT 938
FT /note="E -> K (in dbSNP:rs7247162)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_021510"
FT CONFLICT 657
FT /note="T -> P (in Ref. 3; BAD18439)"
FT /evidence="ECO:0000305"
FT CONFLICT 899
FT /note="A -> V (in Ref. 3; BAD18439)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1059 AA; 114021 MW; 17D27A2D99F2A264 CRC64;
MEPTVADVHL VPRTTKEVPA LDAACCRAAS IGVVATSLVV LTLGVLLAFL STQGFHVDHT
AELRGIRWTS SLRRETSDYH RTLTPTLEAL LHFLLRPLQT LSLGLEEELL QRGIRARLRE
HGISLAAYGT IVSAELTGRH KGPLAERDFK SGRCPGNSFS CGNSQCVTKV NPECDDQEDC
SDGSDEAHCE CGLQPAWRMA GRIVGGMEAS PGEFPWQASL RENKEHFCGA AIINARWLVS
AAHCFNEFQD PTKWVAYVGA TYLSGSEAST VRAQVVQIVK HPLYNADTAD FDVAVLELTS
PLPFGRHIQP VCLPAATHIF PPSKKCLISG WGYLKEDFLV KPEVLQKATV ELLDQALCAS
LYGHSLTDRM VCAGYLDGKV DSCQGDSGGP LVCEEPSGRF FLAGIVSWGI GCAEARRPGV
YARVTRLRDW ILEATTKASM PLAPTMAPAP AAPSTAWPTS PESPVVSTPT KSMQALSTVP
LDWVTVPKLQ ECGARPAMEK PTRVVGGFGA ASGEVPWQVS LKEGSRHFCG ATVVGDRWLL
SAAHCFNHTK VEQVRAHLGT ASLLGLGGSP VKIGLRRVVL HPLYNPGILD FDLAVLELAS
PLAFNKYIQP VCLPLAIQKF PVGRKCMISG WGNTQEGNAT KPELLQKASV GIIDQKTCSV
LYNFSLTDRM ICAGFLEGKV DSCQGDSGGP LACEEAPGVF YLAGIVSWGI GCAQVKKPGV
YTRITRLKGW ILEIMSSQPL PMSPPSTTRM LATTSPRTTA GLTVPGATPS RPTPGAASRV
TGQPANSTLS AVSTTARGQT PFPDAPEATT HTQLPDCGLA PAALTRIVGG SAAGRGEWPW
QVSLWLRRRE HRCGAVLVAE RWLLSAAHCF DVYGDPKQWA AFLGTPFLSG AEGQLERVAR
IYKHPFYNLY TLDYDVALLE LAGPVRRSRL VRPICLPEPA PRPPDGTRCV ITGWGSVREG
GSMARQLQKA AVRLLSEQTC RRFYPVQISS RMLCAGFPQG GVDSCSGDAG GPLACREPSG
RWVLTGVTSW GYGCGRPHFP GVYTRVAAVR GWIGQHIQE
