ISK2_MOUSE
ID ISK2_MOUSE Reviewed; 86 AA.
AC Q8BMY7; D3Z3X9; Q5M8S4;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Serine protease inhibitor Kazal-type 2;
DE Flags: Precursor;
GN Name=Spink2;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Testis;
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 [2] {ECO:0000312|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Proteomes:UP000000589};
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 PARTIAL PROTEIN SEQUENCE (ISOFORM 2), TISSUE SPECIFICITY, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=RIII; TISSUE=Sperm;
RA Bhattacharya R., Dhople V.M., Jesudasan R.A.;
RT "Novel miRNA cluster generated by extensive alternate splicing of a
RT multicopy non-coding RNA from mouse Y-heterochromatin.";
RL Submitted (JUN-2009) to UniProtKB.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=21705336; DOI=10.1074/jbc.m111.244905;
RA Lee B., Park I., Jin S., Choi H., Kwon J.T., Kim J., Jeong J., Cho B.N.,
RA Eddy E.M., Cho C.;
RT "Impaired spermatogenesis and fertility in mice carrying a mutation in the
RT Spink2 gene expressed predominantly in testes.";
RL J. Biol. Chem. 286:29108-29117(2011).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=28554943; DOI=10.15252/emmm.201607461;
RA Kherraf Z.E., Christou-Kent M., Karaouzene T., Amiri-Yekta A., Martinez G.,
RA Vargas A.S., Lambert E., Borel C., Dorphin B., Aknin-Seifer I.,
RA Mitchell M.J., Metzler-Guillemain C., Escoffier J., Nef S., Grepillat M.,
RA Thierry-Mieg N., Satre V., Bailly M., Boitrelle F., Pernet-Gallay K.,
RA Hennebicq S., Faure J., Bottari S.P., Coutton C., Ray P.F., Arnoult C.;
RT "SPINK2 deficiency causes infertility by inducing sperm defects in
RT heterozygotes and azoospermia in homozygotes.";
RL EMBO Mol. Med. 9:1132-1149(2017).
CC -!- FUNCTION: As a strong inhibitor of acrosin, it is required for normal
CC spermiogenesis. It probably hinders premature activation of proacrosin
CC and other proteases, thus preventing the cascade of events leading to
CC spermiogenesis defects (PubMed:21705336, PubMed:28554943). May be
CC involved in the regulation of serine protease-dependent germ cell
CC apoptosis (PubMed:21705336). It also inhibits trypsin
CC (PubMed:21705336). {ECO:0000269|PubMed:21705336,
CC ECO:0000269|PubMed:28554943}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P20155}.
CC Cytoplasmic vesicle, secretory vesicle, acrosome
CC {ECO:0000269|PubMed:28554943}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BMY7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BMY7-2; Sequence=VSP_060766;
CC -!- TISSUE SPECIFICITY: Expressed in sperm (at protein level). Expressed in
CC testis but not in ovary, brain, heart, kidney or lung. Within testis,
CC expressed in epididymis and germ cells. {ECO:0000269|PubMed:21705336,
CC ECO:0000269|Ref.4}.
CC -!- DEVELOPMENTAL STAGE: First expressed at 16 days postpartum (dpp). Level
CC increases until 20 dpp and is maintained into adulthood (at protein
CC level). {ECO:0000269|PubMed:21705336}.
CC -!- DISRUPTION PHENOTYPE: Knockout male mice are completely infertile,
CC whereas no reproductive defects are observed in females. Spermatozoa
CC are completely absent from caudal epididymis, which only contains round
CC cells likely corresponding to round spermatids and multinucleated
CC cells. Seminiferous tubules contain germ cells up to the early round-
CC spermatid stage but condensed and elongated spermatids and mature
CC spermatozoa are completely absent. Round spermatids do not contain an
CC acrosomal vesicle. {ECO:0000269|PubMed:28554943}.
CC -!- MISCELLANEOUS: On the 2D-gel the determined pI of this protein is: 5,
CC its MW is: 8 kDa.
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DR EMBL; AK005709; BAC25122.1; -; mRNA.
DR EMBL; AC165975; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC087876; AAH87876.1; -; mRNA.
DR CCDS; CCDS39121.1; -. [Q8BMY7-1]
DR CCDS; CCDS80306.1; -. [Q8BMY7-2]
DR RefSeq; NP_001276696.1; NM_001289767.1. [Q8BMY7-2]
DR RefSeq; NP_001276697.1; NM_001289768.1.
DR RefSeq; NP_899107.1; NM_183284.3. [Q8BMY7-1]
DR AlphaFoldDB; Q8BMY7; -.
DR SMR; Q8BMY7; -.
DR STRING; 10090.ENSMUSP00000067117; -.
DR MEROPS; I01.012; -.
DR PhosphoSitePlus; Q8BMY7; -.
DR PaxDb; Q8BMY7; -.
DR PeptideAtlas; Q8BMY7; -.
DR PRIDE; Q8BMY7; -.
DR ProteomicsDB; 267012; -. [Q8BMY7-1]
DR ProteomicsDB; 370190; -.
DR Antibodypedia; 12523; 47 antibodies from 18 providers.
DR DNASU; 69982; -.
DR Ensembl; ENSMUST00000065216; ENSMUSP00000067117; ENSMUSG00000053030. [Q8BMY7-1]
DR Ensembl; ENSMUST00000121825; ENSMUSP00000113823; ENSMUSG00000053030. [Q8BMY7-2]
DR GeneID; 69982; -.
DR KEGG; mmu:69982; -.
DR UCSC; uc008xvx.2; mouse. [Q8BMY7-1]
DR CTD; 6691; -.
DR MGI; MGI:1917232; Spink2.
DR VEuPathDB; HostDB:ENSMUSG00000053030; -.
DR eggNOG; KOG3649; Eukaryota.
DR GeneTree; ENSGT00530000064285; -.
DR HOGENOM; CLU_169765_2_0_1; -.
DR InParanoid; Q8BMY7; -.
DR OMA; EYSTPNC; -.
DR OrthoDB; 1560666at2759; -.
DR PhylomeDB; Q8BMY7; -.
DR BioGRID-ORCS; 69982; 4 hits in 71 CRISPR screens.
DR ChiTaRS; Spink2; mouse.
DR PRO; PR:Q8BMY7; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8BMY7; protein.
DR Bgee; ENSMUSG00000053030; Expressed in spermatid and 79 other tissues.
DR ExpressionAtlas; Q8BMY7; baseline and differential.
DR Genevisible; Q8BMY7; MM.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0043005; C:neuron projection; IDA:MGI.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0001675; P:acrosome assembly; IMP:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0009566; P:fertilization; IMP:MGI.
DR GO; GO:0002176; P:male germ cell proliferation; IMP:MGI.
DR GO; GO:0008584; P:male gonad development; IMP:MGI.
DR GO; GO:1900004; P:negative regulation of serine-type endopeptidase activity; IDA:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:MGI.
DR GO; GO:0072520; P:seminiferous tubule development; IMP:MGI.
DR GO; GO:0007286; P:spermatid development; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR InterPro; IPR002350; Kazal_dom.
DR InterPro; IPR036058; Kazal_dom_sf.
DR InterPro; IPR042167; SPINK2.
DR PANTHER; PTHR47608; PTHR47608; 1.
DR Pfam; PF00050; Kazal_1; 1.
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 Alternative initiation; Apoptosis; Cytoplasmic vesicle; Differentiation;
KW Direct protein sequencing; Disulfide bond; Protease inhibitor;
KW Reference proteome; Secreted; Serine protease inhibitor; Signal;
KW Spermatogenesis.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..86
FT /note="Serine protease inhibitor Kazal-type 2"
FT /id="PRO_0000016563"
FT DOMAIN 32..86
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT SITE 48..49
FT /note="Reactive bond"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 38..68
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 46..65
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 54..86
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT VAR_SEQ 1..27
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_060766"
SQ SEQUENCE 86 AA; 9722 MW; 09C26C56B9CB745E CRC64;
MLRLVLLLLV TDFAASHETL DSSDSQIMKR SQFRTPDCGH FDFPACPRNL NPVCGTDMNT
YSNECTLCMK IREDGSHINI IKDEPC
