KLK12_HUMAN
ID KLK12_HUMAN Reviewed; 248 AA.
AC Q9UKR0; Q9UKR1; Q9UKR2;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Kallikrein-12;
DE EC=3.4.21.-;
DE AltName: Full=Kallikrein-like protein 5;
DE Short=KLK-L5;
DE Flags: Precursor;
GN Name=KLK12; Synonyms=KLKL5; ORFNames=UNQ669/PRO1303;
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=10652563;
RA Yousef G.M., Luo L.-Y., Diamandis E.P.;
RT "Identification of novel human kallikrein-like genes on chromosome 19q13.3-
RT q13.4.";
RL Anticancer Res. 19:2843-2852(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
RA Yousef G.M., Magklara A., Scorilas A., Diamandis E.P.;
RT "Cloning of new alternatively spliced forms of the kallikrein-like gene 5
RT (KLK-L5).";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3).
RX PubMed=10675891; DOI=10.1016/s1043-2760(99)00225-8;
RA Diamandis E.P., Yousef G.M., Luo L.Y., Magklara A., Obiezu C.V.;
RT "The new human kallikrein gene family: implications in carcinogenesis.";
RL Trends Endocrinol. Metab. 11:54-60(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
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).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-24.
RC TISSUE=Milk;
RX PubMed=18780401; DOI=10.1002/pmic.200701057;
RA Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F.;
RT "Identification of N-linked glycoproteins in human milk by hydrophilic
RT interaction liquid chromatography and mass spectrometry.";
RL Proteomics 8:3833-3847(2008).
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9UKR0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UKR0-2; Sequence=VSP_005403;
CC Name=3;
CC IsoId=Q9UKR0-3; Sequence=VSP_045851, VSP_045852;
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Kallikrein subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
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; AF135025; AAD26426.2; -; Genomic_DNA.
DR EMBL; AF135025; AAF06065.1; -; Genomic_DNA.
DR EMBL; AF135025; AAF06066.1; -; Genomic_DNA.
DR EMBL; AF243527; AAG33365.1; -; Genomic_DNA.
DR EMBL; AY358524; AAQ88888.1; -; mRNA.
DR EMBL; AC011473; AAG23258.1; -; Genomic_DNA.
DR EMBL; CH471135; EAW71976.1; -; Genomic_DNA.
DR CCDS; CCDS12820.1; -. [Q9UKR0-2]
DR CCDS; CCDS12821.1; -. [Q9UKR0-1]
DR RefSeq; NP_062544.1; NM_019598.2. [Q9UKR0-2]
DR RefSeq; NP_665901.1; NM_145894.1. [Q9UKR0-1]
DR RefSeq; NP_665902.1; NM_145895.1.
DR RefSeq; XP_005259008.1; XM_005258951.3. [Q9UKR0-3]
DR AlphaFoldDB; Q9UKR0; -.
DR SMR; Q9UKR0; -.
DR BioGRID; 119064; 27.
DR STRING; 9606.ENSP00000250351; -.
DR BindingDB; Q9UKR0; -.
DR ChEMBL; CHEMBL4943; -.
DR MEROPS; S01.020; -.
DR GlyGen; Q9UKR0; 2 sites.
DR iPTMnet; Q9UKR0; -.
DR PhosphoSitePlus; Q9UKR0; -.
DR BioMuta; KLK12; -.
DR DMDM; 9296989; -.
DR MassIVE; Q9UKR0; -.
DR PaxDb; Q9UKR0; -.
DR PeptideAtlas; Q9UKR0; -.
DR PRIDE; Q9UKR0; -.
DR ProteomicsDB; 84837; -. [Q9UKR0-1]
DR ProteomicsDB; 84838; -. [Q9UKR0-2]
DR ProteomicsDB; 84839; -.
DR Antibodypedia; 18973; 138 antibodies from 29 providers.
DR DNASU; 43849; -.
DR Ensembl; ENST00000250351.4; ENSP00000250351.4; ENSG00000186474.16. [Q9UKR0-2]
DR Ensembl; ENST00000319590.8; ENSP00000324181.4; ENSG00000186474.16. [Q9UKR0-1]
DR Ensembl; ENST00000525263.5; ENSP00000436458.1; ENSG00000186474.16. [Q9UKR0-1]
DR Ensembl; ENST00000529888.5; ENSP00000434036.1; ENSG00000186474.16. [Q9UKR0-3]
DR Ensembl; ENST00000684732.1; ENSP00000508282.1; ENSG00000186474.16. [Q9UKR0-1]
DR GeneID; 43849; -.
DR KEGG; hsa:43849; -.
DR MANE-Select; ENST00000684732.1; ENSP00000508282.1; NM_001370125.1; NP_001357054.1.
DR UCSC; uc002pvg.1; human. [Q9UKR0-1]
DR CTD; 43849; -.
DR DisGeNET; 43849; -.
DR GeneCards; KLK12; -.
DR HGNC; HGNC:6360; KLK12.
DR HPA; ENSG00000186474; Tissue enhanced (cervix, esophagus, salivary gland, vagina).
DR MIM; 605539; gene.
DR neXtProt; NX_Q9UKR0; -.
DR OpenTargets; ENSG00000186474; -.
DR PharmGKB; PA30149; -.
DR VEuPathDB; HostDB:ENSG00000186474; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT01020000230389; -.
DR HOGENOM; CLU_006842_1_1_1; -.
DR InParanoid; Q9UKR0; -.
DR OMA; GPCGQEG; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; Q9UKR0; -.
DR TreeFam; TF331065; -.
DR BRENDA; 3.4.21.B43; 2681.
DR PathwayCommons; Q9UKR0; -.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR BioGRID-ORCS; 43849; 14 hits in 1063 CRISPR screens.
DR GeneWiki; KLK12; -.
DR GenomeRNAi; 43849; -.
DR Pharos; Q9UKR0; Tbio.
DR PRO; PR:Q9UKR0; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9UKR0; protein.
DR Bgee; ENSG00000186474; Expressed in lower esophagus mucosa and 102 other tissues.
DR ExpressionAtlas; Q9UKR0; baseline and differential.
DR Genevisible; Q9UKR0; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; NAS:UniProtKB.
DR GO; GO:0030141; C:secretory granule; IBA:GO_Central.
DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; NAS:UniProtKB.
DR GO; GO:0008236; F:serine-type peptidase activity; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
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 Alternative splicing; Disulfide bond; Glycoprotein; Hydrolase; Protease;
KW Reference proteome; Secreted; Serine protease; Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..248
FT /note="Kallikrein-12"
FT /id="PRO_0000027956"
FT DOMAIN 22..246
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 62
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 108
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 200
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT CARBOHYD 24
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:18780401"
FT CARBOHYD 163
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 28..161
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 47..63
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 133..235
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 140..206
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 172..186
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 196..222
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT VAR_SEQ 66..111
FT /note="SRYWVRLGEHSLSQLDWTEQIRHSGFSVTHPGYLGASTSHEHDLRL -> RP
FT IPGSAPVPQPLHRLPCHLPWCVSRENHEQHGVCRRRPGAGCLPG (in isoform
FT 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_045851"
FT VAR_SEQ 112..248
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_045852"
FT VAR_SEQ 236..248
FT /note="KYVDWIRMIMRNN -> NSTLVGLGTSWNFNSCQPF (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_005403"
SQ SEQUENCE 248 AA; 26734 MW; BB473E98F8BAF703 CRC64;
MGLSIFLLLC VLGLSQAATP KIFNGTECGR NSQPWQVGLF EGTSLRCGGV LIDHRWVLTA
AHCSGSRYWV RLGEHSLSQL DWTEQIRHSG FSVTHPGYLG ASTSHEHDLR LLRLRLPVRV
TSSVQPLPLP NDCATAGTEC HVSGWGITNH PRNPFPDLLQ CLNLSIVSHA TCHGVYPGRI
TSNMVCAGGV PGQDACQGDS GGPLVCGGVL QGLVSWGSVG PCGQDGIPGV YTYICKYVDW
IRMIMRNN
