GRAK_HUMAN
ID GRAK_HUMAN Reviewed; 264 AA.
AC P49863; B2R563;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Granzyme K;
DE EC=3.4.21.-;
DE AltName: Full=Fragmentin-3;
DE AltName: Full=Granzyme-3;
DE AltName: Full=NK-tryptase-2;
DE Short=NK-Tryp-2;
DE Flags: Precursor;
GN Name=GZMK; Synonyms=TRYP2;
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].
RC TISSUE=Ascites;
RX PubMed=7758581; DOI=10.1016/0014-5793(95)00407-z;
RA Przetak M.M., Yoast S., Schmidt B.F.;
RT "Cloning of cDNA for human granzyme 3.";
RL FEBS Lett. 364:268-271(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lymphocyte;
RX PubMed=8656064; DOI=10.1002/jlb.59.5.763;
RA Sayers T.J., Lloyd A.R., McVicar D.W., O'Connor M.D., Kelly J.M.,
RA Carter C.R.D., Wiltrout T.A., Wiltrout R.H., Smyth M.J.;
RT "Cloning and expression of a second human natural killer cell granule
RT tryptase, HNK-Tryp-2/granzyme 3.";
RL J. Leukoc. Biol. 59:763-768(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 PROTEIN SEQUENCE OF 27-42, AND CHARACTERIZATION.
RX PubMed=3262682;
RA Hameed A., Lowrey D.M., Lichtenheld M., Podack E.R.;
RT "Characterization of three serine esterases isolated from human IL-2
RT activated killer cells.";
RL J. Immunol. 141:3142-3147(1988).
RN [7]
RP PROTEIN SEQUENCE OF 27-48.
RX PubMed=1460416; DOI=10.1084/jem.176.6.1521;
RA Shi L., Kam C.-M., Powers J.C., Aebersold R., Greenberg A.H.;
RT "Purification of three cytotoxic lymphocyte granule serine proteases that
RT induce apoptosis through distinct substrate and target cell interactions.";
RL J. Exp. Med. 176:1521-1529(1992).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 25-264.
RX PubMed=12384499; DOI=10.1074/jbc.m207962200;
RA Hink-Schauer C., Estebanez-Perpina E., Wilharm E., Fuentes-Prior P.,
RA Klinkert W., Bode W., Jenne D.E.;
RT "The 2.2-A crystal structure of human pro-granzyme K reveals a rigid
RT zymogen with unusual features.";
RL J. Biol. Chem. 277:50923-50933(2002).
CC -!- INTERACTION:
CC P49863; P55061: TMBIM6; NbExp=3; IntAct=EBI-3910072, EBI-1045825;
CC -!- SUBCELLULAR LOCATION: Secreted. Cytoplasmic granule.
CC -!- TISSUE SPECIFICITY: Expressed in lung, spleen, thymus and peripheral
CC blood leukocytes.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Granzyme subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
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DR EMBL; U35237; AAA79063.1; -; mRNA.
DR EMBL; U26174; AAA74578.1; -; mRNA.
DR EMBL; AK312074; BAG35010.1; -; mRNA.
DR EMBL; CH471123; EAW54899.1; -; Genomic_DNA.
DR EMBL; BC035802; AAH35802.1; -; mRNA.
DR CCDS; CCDS3964.1; -.
DR PIR; S65663; S65663.
DR RefSeq; NP_002095.1; NM_002104.2.
DR PDB; 1MZA; X-ray; 2.23 A; A=25-264.
DR PDB; 1MZD; X-ray; 2.90 A; A=25-264.
DR PDBsum; 1MZA; -.
DR PDBsum; 1MZD; -.
DR AlphaFoldDB; P49863; -.
DR SMR; P49863; -.
DR BioGRID; 109258; 17.
DR IntAct; P49863; 3.
DR STRING; 9606.ENSP00000231009; -.
DR BindingDB; P49863; -.
DR ChEMBL; CHEMBL4930; -.
DR MEROPS; S01.146; -.
DR iPTMnet; P49863; -.
DR PhosphoSitePlus; P49863; -.
DR BioMuta; GZMK; -.
DR DMDM; 1708035; -.
DR jPOST; P49863; -.
DR MassIVE; P49863; -.
DR PaxDb; P49863; -.
DR PeptideAtlas; P49863; -.
DR PRIDE; P49863; -.
DR ProteomicsDB; 56162; -.
DR TopDownProteomics; P49863; -.
DR Antibodypedia; 11044; 309 antibodies from 32 providers.
DR DNASU; 3003; -.
DR Ensembl; ENST00000231009.3; ENSP00000231009.2; ENSG00000113088.6.
DR GeneID; 3003; -.
DR KEGG; hsa:3003; -.
DR MANE-Select; ENST00000231009.3; ENSP00000231009.2; NM_002104.3; NP_002095.1.
DR UCSC; uc003jpl.2; human.
DR CTD; 3003; -.
DR DisGeNET; 3003; -.
DR GeneCards; GZMK; -.
DR HGNC; HGNC:4711; GZMK.
DR HPA; ENSG00000113088; Tissue enriched (lymphoid).
DR MIM; 600784; gene.
DR neXtProt; NX_P49863; -.
DR OpenTargets; ENSG00000113088; -.
DR PharmGKB; PA29089; -.
DR VEuPathDB; HostDB:ENSG00000113088; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000161886; -.
DR HOGENOM; CLU_006842_1_0_1; -.
DR InParanoid; P49863; -.
DR OMA; KYQAWIK; -.
DR OrthoDB; 1144875at2759; -.
DR PhylomeDB; P49863; -.
DR TreeFam; TF333630; -.
DR BRENDA; 3.4.21.B4; 2681.
DR PathwayCommons; P49863; -.
DR SignaLink; P49863; -.
DR BioGRID-ORCS; 3003; 9 hits in 1064 CRISPR screens.
DR ChiTaRS; GZMK; human.
DR EvolutionaryTrace; P49863; -.
DR GeneWiki; GZMK; -.
DR GenomeRNAi; 3003; -.
DR Pharos; P49863; Tbio.
DR PRO; PR:P49863; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P49863; protein.
DR Bgee; ENSG00000113088; Expressed in lymph node and 139 other tissues.
DR Genevisible; P49863; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008236; F:serine-type peptidase activity; TAS:ProtInc.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 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; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Hydrolase;
KW Protease; Reference proteome; Secreted; Serine protease; Signal; Zymogen.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..26
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:1460416,
FT ECO:0000269|PubMed:3262682"
FT /id="PRO_0000027415"
FT CHAIN 27..264
FT /note="Granzyme K"
FT /id="PRO_0000027416"
FT DOMAIN 27..259
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 67
FT /note="Charge relay system"
FT ACT_SITE 116
FT /note="Charge relay system"
FT ACT_SITE 214
FT /note="Charge relay system"
FT DISULFID 52..68
FT DISULFID 149..220
FT DISULFID 181..199
FT DISULFID 210..234
FT CONFLICT 34
FT /note="S -> Q (in Ref. 7; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 43
FT /note="S -> A (in Ref. 7; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 41..46
FT /evidence="ECO:0007829|PDB:1MZA"
FT STRAND 49..58
FT /evidence="ECO:0007829|PDB:1MZA"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:1MZA"
FT HELIX 66..68
FT /evidence="ECO:0007829|PDB:1MZA"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:1MZA"
FT STRAND 85..89
FT /evidence="ECO:0007829|PDB:1MZA"
FT STRAND 95..104
FT /evidence="ECO:0007829|PDB:1MZA"
FT STRAND 111..115
FT /evidence="ECO:0007829|PDB:1MZA"
FT STRAND 118..124
FT /evidence="ECO:0007829|PDB:1MZA"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:1MZD"
FT STRAND 148..153
FT /evidence="ECO:0007829|PDB:1MZA"
FT STRAND 169..175
FT /evidence="ECO:0007829|PDB:1MZA"
FT HELIX 178..181
FT /evidence="ECO:0007829|PDB:1MZA"
FT TURN 184..191
FT /evidence="ECO:0007829|PDB:1MZA"
FT STRAND 197..201
FT /evidence="ECO:0007829|PDB:1MZA"
FT STRAND 217..220
FT /evidence="ECO:0007829|PDB:1MZA"
FT STRAND 223..228
FT /evidence="ECO:0007829|PDB:1MZA"
FT STRAND 241..245
FT /evidence="ECO:0007829|PDB:1MZA"
FT HELIX 248..257
FT /evidence="ECO:0007829|PDB:1MZA"
SQ SEQUENCE 264 AA; 28882 MW; 2A93FDBAF9286CC5 CRC64;
MTKFSSFSLF FLIVGAYMTH VCFNMEIIGG KEVSPHSRPF MASIQYGGHH VCGGVLIDPQ
WVLTAAHCQY RFTKGQSPTV VLGAHSLSKN EASKQTLEIK KFIPFSRVTS DPQSNDIMLV
KLQTAAKLNK HVKMLHIRSK TSLRSGTKCK VTGWGATDPD SLRPSDTLRE VTVTVLSRKL
CNSQSYYNGD PFITKDMVCA GDAKGQKDSC KGDSGGPLIC KGVFHAIVSG GHECGVATKP
GIYTLLTKKY QTWIKSNLVP PHTN
