ID   ISK2_RAT                Reviewed;          86 AA.
AC   Q6IE49;
DT   27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   03-AUG-2022, entry version 105.
DE   RecName: Full=Serine protease inhibitor Kazal-type 2;
DE   Flags: Precursor;
GN   Name=Spink2;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [2]
RP   IDENTIFICATION.
RX   PubMed=15060002; DOI=10.1101/gr.1946304;
RA   Puente X.S., Lopez-Otin C.;
RT   "A genomic analysis of rat proteases and protease inhibitors.";
RL   Genome Res. 14:609-622(2004).
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. May be involved in the regulation of serine
CC       protease-dependent germ cell apoptosis. It also inhibits trypsin.
CC       {ECO:0000250|UniProtKB:Q8BMY7}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P20155}.
CC       Cytoplasmic vesicle, secretory vesicle, acrosome
CC       {ECO:0000250|UniProtKB:Q8BMY7}.
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DR   EMBL; AC097433; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BN000344; CAE51396.1; -; mRNA.
DR   RefSeq; NP_001008870.1; NM_001008870.2.
DR   RefSeq; XP_003751398.1; XM_003751350.4.
DR   AlphaFoldDB; Q6IE49; -.
DR   SMR; Q6IE49; -.
DR   STRING; 10116.ENSRNOP00000040692; -.
DR   MEROPS; I01.012; -.
DR   PaxDb; Q6IE49; -.
DR   PRIDE; Q6IE49; -.
DR   GeneID; 408234; -.
DR   KEGG; rno:408234; -.
DR   UCSC; RGD:1302956; rat.
DR   CTD; 6691; -.
DR   RGD; 1302956; Spink2.
DR   eggNOG; KOG3649; Eukaryota.
DR   HOGENOM; CLU_169765_2_0_1; -.
DR   InParanoid; Q6IE49; -.
DR   OMA; EYSTPNC; -.
DR   OrthoDB; 1560666at2759; -.
DR   PhylomeDB; Q6IE49; -.
DR   PRO; PR:Q6IE49; -.
DR   Proteomes; UP000002494; Chromosome 14.
DR   Bgee; ENSRNOG00000031710; Expressed in testis and 11 other tissues.
DR   GO; GO:0001669; C:acrosomal vesicle; ISS:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0043005; C:neuron projection; ISO:RGD.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR   GO; GO:0001675; P:acrosome assembly; ISS:UniProtKB.
DR   GO; GO:0009566; P:fertilization; ISO:RGD.
DR   GO; GO:0002176; P:male germ cell proliferation; ISO:RGD.
DR   GO; GO:0008584; P:male gonad development; ISO:RGD.
DR   GO; GO:1900004; P:negative regulation of serine-type endopeptidase activity; ISO:RGD.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR   GO; GO:0072520; P:seminiferous tubule development; ISO:RGD.
DR   GO; GO:0007286; P:spermatid development; ISS:UniProtKB.
DR   GO; GO:0007283; P:spermatogenesis; ISO:RGD.
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   3: Inferred from homology;
KW   Cytoplasmic vesicle; Disulfide bond; Protease inhibitor;
KW   Reference proteome; Secreted; Serine protease inhibitor; Signal.
FT   SIGNAL          1..16
FT                   /evidence="ECO:0000255"
FT   CHAIN           17..86
FT                   /note="Serine protease inhibitor Kazal-type 2"
FT                   /id="PRO_0000016564"
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"
SQ   SEQUENCE   86 AA;  9697 MW;  AF84CB0046559333 CRC64;
     MLRLVLLLLA TDFAASDDSL DSSDSQLIKR SQFRTPDCHR FDYPVCSKHL SPVCGTDMNT
     YGNECTLCMK IREDGSHINI IKDEPC