KLK2_HUMAN
ID KLK2_HUMAN Reviewed; 261 AA.
AC P20151; B4DU93; B4DUB0; F5H8L3; Q15946; Q9UJZ9;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Kallikrein-2;
DE EC=3.4.21.35;
DE AltName: Full=Glandular kallikrein-1;
DE Short=hGK-1;
DE AltName: Full=Tissue kallikrein-2;
DE Flags: Precursor;
GN Name=KLK2;
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 [GENOMIC DNA] (ISOFORM 1).
RX PubMed=2824146; DOI=10.1089/dna.1987.6.429;
RA Schedlich L.J., Bennetts B.H., Morris B.J.;
RT "Primary structure of a human glandular kallikrein gene.";
RL DNA 6:429-437(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Prostate;
RX PubMed=1726490; DOI=10.1016/0303-7207(91)90272-t;
RA Riegman P.H., Vlietstra R.J., der Korput H.A., Romijn J.C., Trapman J.;
RT "Identification and androgen-regulated expression of two major human
RT glandular kallikrein-1 (hGK-1) mRNA species.";
RL Mol. Cell. Endocrinol. 76:181-190(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING.
RX PubMed=10544017; DOI=10.1006/bbrc.1999.1595;
RA Liu X.F., Essand M., Vasmatzis G., Lee B., Pastan I.;
RT "Identification of three new alternate human kallikrein 2 transcripts:
RT evidence of long transcript and alternative splicing.";
RL Biochem. Biophys. Res. Commun. 264:833-839(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11054574; DOI=10.1016/s0378-1119(00)00382-6;
RA Gan L., Lee I., Smith R., Argonza-Barrett R., Lei H., McCuaig J., Moss P.,
RA Paeper B., Wang K.;
RT "Sequencing and expression analysis of the serine protease gene cluster
RT located in chromosome 19q13 region.";
RL Gene 257:119-130(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
RC TISSUE=Prostate;
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 [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Prostate;
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 [9]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [10]
RP VARIANT LEU-18.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions of
RT human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [11]
RP ERRATUM OF PUBMED:10391209.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
CC -!- FUNCTION: Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in
CC kininogen to release Lys-bradykinin.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferential cleavage of Arg-|-Xaa bonds in small molecule
CC substrates. Highly selective action to release kallidin (lysyl-
CC bradykinin) from kininogen involves hydrolysis of Met-|-Xaa or Leu-|-
CC Xaa.; EC=3.4.21.35;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P20151-1; Sequence=Displayed;
CC Name=2; Synonyms=PGK-10A;
CC IsoId=P20151-2; Sequence=VSP_005399;
CC Name=3;
CC IsoId=P20151-3; Sequence=VSP_005400;
CC Name=4;
CC IsoId=P20151-4; Sequence=VSP_044709;
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Kallikrein subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD13817.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M18156; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M18157; AAA74454.1; -; Genomic_DNA.
DR EMBL; S39329; AAD13816.1; -; mRNA.
DR EMBL; S39329; AAD13817.1; ALT_SEQ; mRNA.
DR EMBL; AF188745; AAF08275.1; -; mRNA.
DR EMBL; AF188746; AAF08276.1; -; mRNA.
DR EMBL; AF188747; AAF08277.1; -; mRNA.
DR EMBL; AF243527; AAG33356.1; -; Genomic_DNA.
DR EMBL; BT006650; AAP35296.1; -; mRNA.
DR EMBL; AK300549; BAG62255.1; -; mRNA.
DR EMBL; AK300566; BAG62272.1; -; mRNA.
DR EMBL; AC037199; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC005196; AAH05196.1; -; mRNA.
DR CCDS; CCDS12808.1; -. [P20151-1]
DR CCDS; CCDS42597.1; -. [P20151-2]
DR CCDS; CCDS58675.1; -. [P20151-4]
DR PIR; A29586; A29586.
DR RefSeq; NP_001002231.1; NM_001002231.2. [P20151-2]
DR RefSeq; NP_001243009.1; NM_001256080.1. [P20151-4]
DR RefSeq; NP_005542.1; NM_005551.4. [P20151-1]
DR PDB; 4NFE; X-ray; 1.90 A; A=25-261.
DR PDB; 4NFF; X-ray; 1.90 A; A=25-261.
DR PDBsum; 4NFE; -.
DR PDBsum; 4NFF; -.
DR AlphaFoldDB; P20151; -.
DR SMR; P20151; -.
DR BioGRID; 110017; 44.
DR IntAct; P20151; 3.
DR STRING; 9606.ENSP00000313581; -.
DR BindingDB; P20151; -.
DR ChEMBL; CHEMBL2442; -.
DR GuidetoPHARMACOLOGY; 2372; -.
DR Allergome; 2836; Hom s PSA.
DR MEROPS; S01.161; -.
DR GlyGen; P20151; 1 site.
DR iPTMnet; P20151; -.
DR PhosphoSitePlus; P20151; -.
DR BioMuta; KLK2; -.
DR DMDM; 125174; -.
DR jPOST; P20151; -.
DR MassIVE; P20151; -.
DR MaxQB; P20151; -.
DR PaxDb; P20151; -.
DR PeptideAtlas; P20151; -.
DR PRIDE; P20151; -.
DR ProteomicsDB; 27819; -.
DR ProteomicsDB; 53728; -. [P20151-1]
DR ProteomicsDB; 53729; -. [P20151-2]
DR ProteomicsDB; 53730; -. [P20151-3]
DR ABCD; P20151; 2 sequenced antibodies.
DR Antibodypedia; 32384; 400 antibodies from 36 providers.
DR DNASU; 3817; -.
DR Ensembl; ENST00000325321.8; ENSP00000313581.2; ENSG00000167751.13. [P20151-1]
DR Ensembl; ENST00000358049.8; ENSP00000350748.3; ENSG00000167751.13. [P20151-2]
DR Ensembl; ENST00000391810.6; ENSP00000375686.2; ENSG00000167751.13. [P20151-4]
DR Ensembl; ENST00000597439.1; ENSP00000471214.1; ENSG00000167751.13. [P20151-3]
DR GeneID; 3817; -.
DR KEGG; hsa:3817; -.
DR MANE-Select; ENST00000325321.8; ENSP00000313581.2; NM_005551.5; NP_005542.1.
DR UCSC; uc002ptu.4; human. [P20151-1]
DR CTD; 3817; -.
DR DisGeNET; 3817; -.
DR GeneCards; KLK2; -.
DR HGNC; HGNC:6363; KLK2.
DR HPA; ENSG00000167751; Tissue enriched (prostate).
DR MIM; 147960; gene.
DR neXtProt; NX_P20151; -.
DR OpenTargets; ENSG00000167751; -.
DR PharmGKB; PA30152; -.
DR VEuPathDB; HostDB:ENSG00000167751; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT01020000230389; -.
DR HOGENOM; CLU_006842_1_1_1; -.
DR InParanoid; P20151; -.
DR OMA; KWIKETI; -.
DR PhylomeDB; P20151; -.
DR TreeFam; TF331065; -.
DR PathwayCommons; P20151; -.
DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-5625886; Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3.
DR SignaLink; P20151; -.
DR SIGNOR; P20151; -.
DR BioGRID-ORCS; 3817; 16 hits in 1069 CRISPR screens.
DR ChiTaRS; KLK2; human.
DR GenomeRNAi; 3817; -.
DR Pharos; P20151; Tchem.
DR PRO; PR:P20151; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P20151; protein.
DR Bgee; ENSG00000167751; Expressed in prostate gland and 129 other tissues.
DR ExpressionAtlas; P20151; baseline and differential.
DR Genevisible; P20151; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0030141; C:secretory granule; IBA:GO_Central.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0003073; P:regulation of systemic arterial blood pressure; IBA:GO_Central.
DR GO; GO:0031638; P:zymogen activation; IBA:GO_Central.
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; Alternative splicing; Disulfide bond; Glycoprotein;
KW Hydrolase; Protease; Reference proteome; Serine protease; Signal; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000305"
FT PROPEP 19..24
FT /note="Activation peptide"
FT /evidence="ECO:0000305"
FT /id="PRO_0000027929"
FT CHAIN 25..261
FT /note="Kallikrein-2"
FT /id="PRO_0000027930"
FT DOMAIN 25..258
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 65
FT /note="Charge relay system"
FT ACT_SITE 120
FT /note="Charge relay system"
FT ACT_SITE 213
FT /note="Charge relay system"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 31..173
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 50..66
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 152..219
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 184..198
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 209..234
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT VAR_SEQ 1..102
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044709"
FT VAR_SEQ 165..261
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_005400"
FT VAR_SEQ 211..261
FT /note="GDSGGPLVCNGVLQGITSWGPEPCALPEKPAVYTKVVHYRKWIKDTIAANP
FT -> VSHPYSQHLEGKG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:1726490"
FT /id="VSP_005399"
FT VARIANT 18
FT /note="V -> L (in dbSNP:rs6072)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_014164"
FT VARIANT 250
FT /note="R -> W (in dbSNP:rs198977)"
FT /id="VAR_020178"
FT VARIANT 255
FT /note="D -> A (in dbSNP:rs60268688)"
FT /id="VAR_061775"
FT CONFLICT 143
FT /note="T -> A (in Ref. 6; BAG62255)"
FT /evidence="ECO:0000305"
FT STRAND 39..44
FT /evidence="ECO:0007829|PDB:4NFE"
FT STRAND 47..56
FT /evidence="ECO:0007829|PDB:4NFE"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:4NFE"
FT HELIX 64..66
FT /evidence="ECO:0007829|PDB:4NFE"
FT STRAND 72..76
FT /evidence="ECO:0007829|PDB:4NFE"
FT STRAND 88..97
FT /evidence="ECO:0007829|PDB:4NFE"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:4NFF"
FT STRAND 122..128
FT /evidence="ECO:0007829|PDB:4NFE"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:4NFF"
FT STRAND 151..158
FT /evidence="ECO:0007829|PDB:4NFE"
FT STRAND 160..164
FT /evidence="ECO:0007829|PDB:4NFE"
FT STRAND 172..179
FT /evidence="ECO:0007829|PDB:4NFE"
FT HELIX 181..187
FT /evidence="ECO:0007829|PDB:4NFE"
FT STRAND 196..200
FT /evidence="ECO:0007829|PDB:4NFE"
FT STRAND 216..219
FT /evidence="ECO:0007829|PDB:4NFE"
FT STRAND 222..229
FT /evidence="ECO:0007829|PDB:4NFE"
FT STRAND 241..245
FT /evidence="ECO:0007829|PDB:4NFE"
FT HELIX 246..249
FT /evidence="ECO:0007829|PDB:4NFE"
FT HELIX 250..259
FT /evidence="ECO:0007829|PDB:4NFE"
FT CONFLICT P20151-2:223
FT /note="G -> GE (in Ref. 6; BAG62272)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 261 AA; 28671 MW; 9CF7F4A1162EF42D CRC64;
MWDLVLSIAL SVGCTGAVPL IQSRIVGGWE CEKHSQPWQV AVYSHGWAHC GGVLVHPQWV
LTAAHCLKKN SQVWLGRHNL FEPEDTGQRV PVSHSFPHPL YNMSLLKHQS LRPDEDSSHD
LMLLRLSEPA KITDVVKVLG LPTQEPALGT TCYASGWGSI EPEEFLRPRS LQCVSLHLLS
NDMCARAYSE KVTEFMLCAG LWTGGKDTCG GDSGGPLVCN GVLQGITSWG PEPCALPEKP
AVYTKVVHYR KWIKDTIAAN P
