ISK1_MOUSE
ID ISK1_MOUSE Reviewed; 80 AA.
AC P09036; Q5M9M3;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Serine protease inhibitor Kazal-type 1 {ECO:0000312|MGI:MGI:106202};
DE AltName: Full=P12 {ECO:0000303|PubMed:3428272};
DE AltName: Full=Prostatic secretory glycoprotein {ECO:0000303|PubMed:3428272};
DE AltName: Full=Serine protease inhibitor Kazal-type 3 {ECO:0000303|PubMed:16083722};
DE Flags: Precursor;
GN Name=Spink1 {ECO:0000312|MGI:MGI:106202};
GN Synonyms=Spink3 {ECO:0000303|PubMed:22228629};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INDUCTION.
RC STRAIN=C57BL/6J;
RX PubMed=3428272; DOI=10.1002/j.1460-2075.1987.tb02705.x;
RA Mills J.S., Needham M., Parker M.G.;
RT "A secretory protease inhibitor requires androgens for its expression in
RT male sex accessory tissues but is expressed constitutively in pancreas.";
RL EMBO J. 6:3711-3717(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Pancreas;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [4]
RP PROTEIN SEQUENCE OF 43-47; 49-61 AND 63-72, AND SUBCELLULAR LOCATION.
RX PubMed=1929395; DOI=10.1016/0003-9861(91)90540-y;
RA Lai M.-L., Chen S.-W., Chen Y.-H.;
RT "Purification and characterization of a trypsin inhibitor from mouse
RT seminal vesicle secretion.";
RL Arch. Biochem. Biophys. 290:265-271(1991).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=9828198; DOI=10.1095/biolreprod59.6.1498;
RA Chen L.-Y., Lin Y.-H., Lai M.-L., Chen Y.-H.;
RT "Developmental profile of a caltrin-like protease inhibitor, P12, in mouse
RT seminal vesicle and characterization of its binding sites on sperm
RT surface.";
RL Biol. Reprod. 59:1498-1505(1998).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF ARG-42; TYR-44; ASP-45; ARG-66; LYS-67 AND
RP ARG-68.
RX PubMed=14645103; DOI=10.1095/biolreprod.103.020552;
RA Luo C.W., Lin H.J., Gopinath S.C., Chen Y.H.;
RT "Distinction of sperm-binding site and reactive site for trypsin inhibition
RT on p12 secreted from the accessory sex glands of male mice.";
RL Biol. Reprod. 70:965-971(2004).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16083722; DOI=10.1053/j.gastro.2005.05.057;
RA Ohmuraya M., Hirota M., Araki M., Mizushima N., Matsui M., Mizumoto T.,
RA Haruna K., Kume S., Takeya M., Ogawa M., Araki K., Yamamura K.;
RT "Autophagic cell death of pancreatic acinar cells in serine protease
RT inhibitor Kazal type 3-deficient mice.";
RL Gastroenterology 129:696-705(2005).
RN [8]
RP FUNCTION.
RX PubMed=22228629; DOI=10.1530/rep-11-0107;
RA Zalazar L., Saez Lancellotti T.E., Clementi M., Lombardo C., Lamattina L.,
RA De Castro R., Fornes M.W., Cesari A.;
RT "SPINK3 modulates mouse sperm physiology through the reduction of nitric
RT oxide level independently of its trypsin inhibitory activity.";
RL Reproduction 143:281-295(2012).
CC -!- FUNCTION: Serine protease inhibitor which exhibits anti-trypsin
CC activity (PubMed:3428272, PubMed:14645103, PubMed:22228629). In the
CC pancreas, protects against trypsin-catalyzed premature activation of
CC zymogens (PubMed:16083722). {ECO:0000269|PubMed:14645103,
CC ECO:0000269|PubMed:16083722, ECO:0000269|PubMed:22228629,
CC ECO:0000269|PubMed:3428272}.
CC -!- FUNCTION: In the male reproductive tract, binds to sperm heads where it
CC modulates sperm capacitance by inhibiting calcium uptake and nitrogen
CC oxide (NO) production (PubMed:9828198, PubMed:14645103,
CC PubMed:16083722, PubMed:22228629). {ECO:0000269|PubMed:14645103,
CC ECO:0000269|PubMed:16083722, ECO:0000269|PubMed:22228629,
CC ECO:0000269|PubMed:9828198}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1929395}.
CC -!- TISSUE SPECIFICITY: In the genital tract, expressed only in male
CC accessory glands including seminal vesicle, coagulating gland and
CC prostate. {ECO:0000269|PubMed:9828198}.
CC -!- DEVELOPMENTAL STAGE: In the seminal vesicle, not expressed during
CC prepubertal stages; expression coincides with maturation.
CC {ECO:0000269|PubMed:9828198}.
CC -!- INDUCTION: By androgens in adult male sex accessory glands. Expressed
CC constitutively in pancreas. {ECO:0000269|PubMed:3428272}.
CC -!- DISRUPTION PHENOTYPE: Lethal with no survival past two weeks of age.
CC Animals are small and show severe, progressive degeneration of
CC pancreatic tissue associated with autophagic cell death.
CC {ECO:0000269|PubMed:16083722}.
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DR EMBL; X06342; CAA29648.1; -; mRNA.
DR EMBL; AK007841; BAB25298.1; -; mRNA.
DR EMBL; AK007985; BAB25389.1; -; mRNA.
DR EMBL; BC086887; AAH86887.1; -; mRNA.
DR CCDS; CCDS37803.1; -.
DR PIR; S01498; S01498.
DR RefSeq; NP_033284.1; NM_009258.5.
DR AlphaFoldDB; P09036; -.
DR SMR; P09036; -.
DR BioGRID; 203452; 1.
DR STRING; 10090.ENSMUSP00000025381; -.
DR MEROPS; I01.011; -.
DR PhosphoSitePlus; P09036; -.
DR PaxDb; P09036; -.
DR PeptideAtlas; P09036; -.
DR PRIDE; P09036; -.
DR ProteomicsDB; 269509; -.
DR Antibodypedia; 27654; 281 antibodies from 32 providers.
DR DNASU; 20730; -.
DR Ensembl; ENSMUST00000025381; ENSMUSP00000025381; ENSMUSG00000024503.
DR GeneID; 20730; -.
DR KEGG; mmu:20730; -.
DR UCSC; uc008eul.2; mouse.
DR CTD; 6690; -.
DR MGI; MGI:106202; Spink1.
DR VEuPathDB; HostDB:ENSMUSG00000024503; -.
DR eggNOG; KOG3649; Eukaryota.
DR GeneTree; ENSGT00530000064228; -.
DR HOGENOM; CLU_169765_2_1_1; -.
DR InParanoid; P09036; -.
DR OMA; EPSCENF; -.
DR OrthoDB; 1591004at2759; -.
DR PhylomeDB; P09036; -.
DR BioGRID-ORCS; 20730; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Spink1; mouse.
DR PRO; PR:P09036; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; P09036; protein.
DR Bgee; ENSMUSG00000024503; Expressed in prostate gland ventral lobe and 79 other tissues.
DR Genevisible; P09036; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0030414; F:peptidase inhibitor activity; IDA:MGI.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:MGI.
DR GO; GO:0090281; P:negative regulation of calcium ion import; IDA:MGI.
DR GO; GO:0010751; P:negative regulation of nitric oxide mediated signal transduction; IDA:MGI.
DR GO; GO:0010466; P:negative regulation of peptidase activity; IDA:MGI.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:1900004; P:negative regulation of serine-type endopeptidase activity; IDA:MGI.
DR GO; GO:0007263; P:nitric oxide mediated signal transduction; IDA:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0060046; P:regulation of acrosome reaction; IDA:MGI.
DR GO; GO:2001256; P:regulation of store-operated calcium entry; IDA:MGI.
DR GO; GO:0048240; P:sperm capacitation; IDA:MGI.
DR InterPro; IPR002350; Kazal_dom.
DR InterPro; IPR036058; Kazal_dom_sf.
DR InterPro; IPR001239; Prot_inh_Kazal-m.
DR Pfam; PF00050; Kazal_1; 1.
DR PRINTS; PR00290; KAZALINHBTR.
DR SMART; SM00280; KAZAL; 1.
DR SUPFAM; SSF100895; SSF100895; 1.
DR PROSITE; PS00282; KAZAL_1; 1.
DR PROSITE; PS51465; KAZAL_2; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Protease inhibitor;
KW Reference proteome; Secreted; Serine protease inhibitor; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..80
FT /note="Serine protease inhibitor Kazal-type 1"
FT /id="PRO_0000016568"
FT DOMAIN 27..80
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT SITE 42..43
FT /note="Reactive bond for trypsin"
FT /evidence="ECO:0000269|PubMed:14645103,
FT ECO:0000269|PubMed:1929395"
FT SITE 44..45
FT /note="Necessary for sperm binding"
FT /evidence="ECO:0000269|PubMed:9828198"
FT DISULFID 33..62
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 40..59
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 48..80
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT MUTAGEN 42
FT /note="R->L: Abolishes trypsin inhibitor activity. No
FT effect on sperm binding."
FT /evidence="ECO:0000269|PubMed:14645103"
FT MUTAGEN 44
FT /note="Y->V: Severely impairs sperm binding. No effect on
FT trypsin inhibitor activity."
FT /evidence="ECO:0000269|PubMed:14645103"
FT MUTAGEN 45
FT /note="D->G: Fails to bind sperm. No effect on trypsin
FT inhibitor activity."
FT /evidence="ECO:0000269|PubMed:14645103"
FT MUTAGEN 66
FT /note="R->G: No effect on trypsin inhibitor activity or
FT sperm binding."
FT /evidence="ECO:0000269|PubMed:14645103"
FT MUTAGEN 67
FT /note="K->S: No effect on trypsin inhibitor activity or
FT sperm binding."
FT /evidence="ECO:0000269|PubMed:14645103"
FT MUTAGEN 68
FT /note="R->T: No effect on trypsin inhibitor activity or
FT sperm binding."
FT /evidence="ECO:0000269|PubMed:14645103"
SQ SEQUENCE 80 AA; 8488 MW; 4DC1F2EC4804CCA6 CRC64;
MKVAVIFLLS ALALLSLAGN TFSAKVTGKE ASCHDAVAGC PRIYDPVCGT DGITYANECV
LCFENRKRIE PVLIRKGGPC
