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Protein

Serine protease inhibitor Kazal-type 1

Gene

Spink1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine protease inhibitor which exhibits anti-trypsin activity (PubMed:3428272, PubMed:14645103, PubMed:22228629). In the pancreas, protects against trypsin-catalyzed premature activation of zymogens (PubMed:16083722).4 Publications
In the male reproductive tract, binds to sperm heads where it modulates sperm capacitance by inhibiting calcium uptake and nitrogen oxide (NO) production (PubMed:9828198, PubMed:14645103, PubMed:16083722, PubMed:22228629).4 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei42 – 432Reactive bond for trypsin2 Publications
Sitei44 – 452Necessary for sperm binding1 Publication

GO - Molecular functioni

  • peptidase inhibitor activity Source: MGI
  • serine-type endopeptidase inhibitor activity Source: MGI

GO - Biological processi

  • negative regulation of calcium ion import Source: MGI
  • negative regulation of nitric oxide mediated signal transduction Source: MGI
  • negative regulation of peptidase activity Source: MGI
  • negative regulation of peptidyl-tyrosine phosphorylation Source: MGI
  • negative regulation of serine-type endopeptidase activity Source: MGI
  • regulation of acrosome reaction Source: MGI
  • regulation of store-operated calcium entry Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Protein family/group databases

MEROPSiI01.011.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine protease inhibitor Kazal-type 1Imported
Alternative name(s):
P121 Publication
Prostatic secretory glycoprotein1 Publication
Serine protease inhibitor Kazal-type 31 Publication
Gene namesi
Name:Spink1Imported
Synonyms:Spink31 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:106202. Spink1.

Subcellular locationi

GO - Cellular componenti

  • acrosomal vesicle Source: GO_Central
  • extracellular exosome Source: MGI
  • extracellular space Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Disruption phenotypei

Lethal with no survival past two weeks of age. Animals are small and show severe, progressive degeneration of pancreatic tissue associated with autophagic cell death.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi42 – 421R → L: Abolishes trypsin inhibitor activity. No effect on sperm binding. 1 Publication
Mutagenesisi44 – 441Y → V: Severely impairs sperm binding. No effect on trypsin inhibitor activity. 1 Publication
Mutagenesisi45 – 451D → G: Fails to bind sperm. No effect on trypsin inhibitor activity. 1 Publication
Mutagenesisi66 – 661R → G: No effect on trypsin inhibitor activity or sperm binding. 1 Publication
Mutagenesisi67 – 671K → S: No effect on trypsin inhibitor activity or sperm binding. 1 Publication
Mutagenesisi68 – 681R → T: No effect on trypsin inhibitor activity or sperm binding. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence analysisAdd
BLAST
Chaini24 – 8057Serine protease inhibitor Kazal-type 1PRO_0000016568Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi33 ↔ 62PROSITE-ProRule annotation
Disulfide bondi40 ↔ 59PROSITE-ProRule annotation
Disulfide bondi48 ↔ 80PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiP09036.
PRIDEiP09036.

Expressioni

Tissue specificityi

In the genital tract, expressed only in male accessory glands including seminal vesicle, coagulating gland and prostate.1 Publication

Developmental stagei

In the seminal vesicle, not expressed during prepubertal stages; expression coincides with maturation.1 Publication

Inductioni

By androgens in adult male sex accessory glands. Expressed constitutively in pancreas.1 Publication

Gene expression databases

BgeeiP09036.
CleanExiMM_SPINK3.
GenevisibleiP09036. MM.

Interactioni

Protein-protein interaction databases

IntActiP09036. 1 interaction.
MINTiMINT-4098780.
STRINGi10090.ENSMUSP00000025381.

Structurei

3D structure databases

ProteinModelPortaliP09036.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini27 – 8054Kazal-likePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 Kazal-like domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3649. Eukaryota.
ENOG410YC3T. LUCA.
GeneTreeiENSGT00530000064228.
HOGENOMiHOG000090244.
HOVERGENiHBG006182.
InParanoidiP09036.
OMAiCTKIYNP.
OrthoDBiEOG7BW0M2.
PhylomeDBiP09036.

Family and domain databases

InterProiIPR002350. Kazal_dom.
IPR001239. Prot_inh_Kazal-m.
[Graphical view]
PfamiPF00050. Kazal_1. 1 hit.
[Graphical view]
PRINTSiPR00290. KAZALINHBTR.
SMARTiSM00280. KAZAL. 1 hit.
[Graphical view]
PROSITEiPS00282. KAZAL_1. 1 hit.
PS51465. KAZAL_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P09036-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKVAVIFLLS ALALLSLAGN TFSAKVTGKE ASCHDAVAGC PRIYDPVCGT
60 70 80
DGITYANECV LCFENRKRIE PVLIRKGGPC
Length:80
Mass (Da):8,488
Last modified:November 1, 1988 - v1
Checksum:i4DC1F2EC4804CCA6
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06342 mRNA. Translation: CAA29648.1.
AK007841 mRNA. Translation: BAB25298.1.
AK007985 mRNA. Translation: BAB25389.1.
BC086887 mRNA. Translation: AAH86887.1.
CCDSiCCDS37803.1.
PIRiS01498.
RefSeqiNP_033284.1. NM_009258.5.
UniGeneiMm.272.

Genome annotation databases

EnsembliENSMUST00000025381; ENSMUSP00000025381; ENSMUSG00000024503.
GeneIDi20730.
KEGGimmu:20730.
UCSCiuc008eul.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06342 mRNA. Translation: CAA29648.1.
AK007841 mRNA. Translation: BAB25298.1.
AK007985 mRNA. Translation: BAB25389.1.
BC086887 mRNA. Translation: AAH86887.1.
CCDSiCCDS37803.1.
PIRiS01498.
RefSeqiNP_033284.1. NM_009258.5.
UniGeneiMm.272.

3D structure databases

ProteinModelPortaliP09036.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP09036. 1 interaction.
MINTiMINT-4098780.
STRINGi10090.ENSMUSP00000025381.

Protein family/group databases

MEROPSiI01.011.

Proteomic databases

PaxDbiP09036.
PRIDEiP09036.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000025381; ENSMUSP00000025381; ENSMUSG00000024503.
GeneIDi20730.
KEGGimmu:20730.
UCSCiuc008eul.2. mouse.

Organism-specific databases

CTDi6690.
MGIiMGI:106202. Spink1.

Phylogenomic databases

eggNOGiKOG3649. Eukaryota.
ENOG410YC3T. LUCA.
GeneTreeiENSGT00530000064228.
HOGENOMiHOG000090244.
HOVERGENiHBG006182.
InParanoidiP09036.
OMAiCTKIYNP.
OrthoDBiEOG7BW0M2.
PhylomeDBiP09036.

Miscellaneous databases

NextBioi299347.
PROiP09036.
SOURCEiSearch...

Gene expression databases

BgeeiP09036.
CleanExiMM_SPINK3.
GenevisibleiP09036. MM.

Family and domain databases

InterProiIPR002350. Kazal_dom.
IPR001239. Prot_inh_Kazal-m.
[Graphical view]
PfamiPF00050. Kazal_1. 1 hit.
[Graphical view]
PRINTSiPR00290. KAZALINHBTR.
SMARTiSM00280. KAZAL. 1 hit.
[Graphical view]
PROSITEiPS00282. KAZAL_1. 1 hit.
PS51465. KAZAL_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A secretory protease inhibitor requires androgens for its expression in male sex accessory tissues but is expressed constitutively in pancreas."
    Mills J.S., Needham M., Parker M.G.
    EMBO J. 6:3711-3717(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION.
    Strain: C57BL/6J.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Pancreas.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Kidney.
  4. "Purification and characterization of a trypsin inhibitor from mouse seminal vesicle secretion."
    Lai M.-L., Chen S.-W., Chen Y.-H.
    Arch. Biochem. Biophys. 290:265-271(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 43-47; 49-61 AND 63-72, SUBCELLULAR LOCATION.
  5. "Developmental profile of a caltrin-like protease inhibitor, P12, in mouse seminal vesicle and characterization of its binding sites on sperm surface."
    Chen L.-Y., Lin Y.-H., Lai M.-L., Chen Y.-H.
    Biol. Reprod. 59:1498-1505(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  6. "Distinction of sperm-binding site and reactive site for trypsin inhibition on p12 secreted from the accessory sex glands of male mice."
    Luo C.W., Lin H.J., Gopinath S.C., Chen Y.H.
    Biol. Reprod. 70:965-971(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF ARG-42; TYR-44; ASP-45; ARG-66; LYS-67 AND ARG-68.
  7. "Autophagic cell death of pancreatic acinar cells in serine protease inhibitor Kazal type 3-deficient mice."
    Ohmuraya M., Hirota M., Araki M., Mizushima N., Matsui M., Mizumoto T., Haruna K., Kume S., Takeya M., Ogawa M., Araki K., Yamamura K.
    Gastroenterology 129:696-705(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  8. "SPINK3 modulates mouse sperm physiology through the reduction of nitric oxide level independently of its trypsin inhibitory activity."
    Zalazar L., Saez Lancellotti T.E., Clementi M., Lombardo C., Lamattina L., De Castro R., Fornes M.W., Cesari A.
    Reproduction 143:281-295(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiISK1_MOUSE
AccessioniPrimary (citable) accession number: P09036
Secondary accession number(s): Q5M9M3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: January 20, 2016
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.