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SPINK1 (Serine Peptidase Inhibitor, Kazal Type 1)

Written2014-12Hannu Koistinen, Outi Itkonen, Ulf-Hakan Stenman
Department of Clinical Chemistry, University of Helsinki (HK,OI, UHS),, Laboratory Division HUSLAB, Helsinki University Central Hospital (OI), Helsinki, Finland;;

Abstract Review on SPINK1, with data on DNA, on the protein encoded, and where the gene is implicated.

Keywords SPINK1

(Note : for Links provided by Atlas : click)


Alias (NCBI)PSTI (Pancreatic Secretory Trypsin Inhibitor)
TATI (Tumor-Associated Trypsin Inhibitor)
SPIK (serine protease inhibitor Kazal)
HGNC Alias symbSpink3
HGNC Previous nameserine protease inhibitor, Kazal type 1
LocusID (NCBI) 6690
Atlas_Id 42375
Location 5q32  [Link to chromosome band 5q32]
Location_base_pair Starts at 147824580 and ends at 147839231 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping SPINK1.png]
Local_order Several other SPINK genes have been mapped in the same chromosomal region. From centromere to telomere (Ensembl genome browser 73): DPYSL3 (reverse strand) - JAKMIP-2 (reverse) - SPINK1 (reverse) - SCGB3A2 (forward) - C5orf46 (reverse) - SPINK5 (forward) - SPINK14 (forward) - SPINK6 (forward) - SPINK13 (forward) - SPINK7 (forward).
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
AP5M1 (14q22.3)::SPINK1 (5q32)C5orf46 (5q32)::SPINK1 (5q32)PSG1 (19q13.2)::SPINK1 (5q32)
RBM15B (3p21.2)::SPINK1 (5q32)SPINK1 (5q32)::ARL4A (7p21.3)SPINK1 (5q32)::GRM4 (6p21.31)
SPINK1 (5q32)::NCOA3 (20q13.12)SPINK1 (5q32)::SPINK1 (5q32)SPINK1 (5q32)::TAS2R38 (7q34)
SYT14 (1q32.2)::SPINK1 (5q32)


Note Some other SPINK family members are similar in size, are encoded for by 4 exons and contain a single Kazal type serine protease inhibitor domain.
  Chromosomal location and gene structure of SPINK1 gene (extracted from Ensembl database release 73). Some putative regulatory elements are also shown (Ohmachi et al., 1993; Yasuda et al., 1993; Yasuda et al., 1998; Boulling et al., 2011). After the translation-initiating codon (ATG) exons of the major transcript are shown in black. One splicing variant also contains parts outside of these exons. *, CAATCAATAAC, potential pancreas-specific regulatory element; IL6RE, interleukin-6 responsive element; AP-1, activator protein-1 element; HNF1, hepatic nuclear factor; PTF1, pancreas-specific transcription factor 1.
Description Maps to chromosomal region 5q32: 147,204,131-147,211,349 on reverse (minus) strand (7,219 bp). Gene consists of 4 exons (Horii et al., 1987). Region between 3.8 and 4.0 kb upstream from the translation initiation codon contains an interleukin-6 responsive element (IL6RE) and two potential AP-1 binding sites (Ohmachi et al., 1993; Yasuda et al., 1993). CAATCAATAAC sequence (-149 to -139) is a potential pancreas-specific regulatory element (Yasuda et al., 1998). This region in the SPINK1 promoter has been subsequently identified as a binding site for hepatic nuclear factor (HNF1) (Boulling et al., 2011). A putative binding site for pancreas-specific transcription factor 1 (PTF1) has also been identified within the SPINK1 promoter (Boulling et al., 2011).
Transcription SPINK1 mRNA (NCBI Reference Sequence: NM_003122.3) has 454 bp (Yamamoto et al., 1985). Expression, at least in some cell lines, is regulated by IL-6 (Yasuda et al., 1993). Three differentially spliced mRNA forms have been described (Ensembl, release 73). Two of these have been classified as protein encoding.


Note In the literature, SPINK1 is widely referred to as TATI (tumor-associated trypsin inhibitor) and PSTI (pancreatic secretory trypsin inhibitor).
  Ribbon diagram of recombinant SPINK1 variant (RSCB Protein Data Bank code 1HPT (Hecht et al., 1991)). Protein Workshop program (Moreland et al., 2005) with the surfaces feature (Xu and Zhang, 2009) was used for visualization. Cysteines, forming three disulfide bonds, are shown as balls and sticks. The atoms of asparagine-34 (N34) residue, mutation in which is associated with chronic pancreatitis, and reactive site lysine (K41) are shown as balls without side-chains. Alpha-helix is shown in blue and beta-sheets in yellow.
Description SPINK1(NCBI Reference Sequence: NP_003113.2 ; UniProtKB/Swiss-Prot: ISK1_HUMAN, P00995; PDB: 1cgj; 1cgi; 1hpt) is a 6242 Da secreted protein, containing 79 amino acids. Mature SPINK1 contains 56 amino acids and three disulfide bonds. It has a Kazal-type serine protease inhibitor domain and belongs to the SPINK (serine peptidase inhibitor, Kazal-type) family. SPINK1 has been reported to inhibit several proteases, including human trypsin-1 and -2 (cationic and anionic trypsins), acrosin and granzyme A (Pubols et al., 1974; Huhtala et al., 1984; Turpeinen et al., 1988; Tsuzuki et al., 2003).
Expression SPINK1 was first characterized in bovine pancreas (Kazal et al. 1948) and pancreatic juice (Greene 1966), and later from human pancreatic juice (Fritz et al 1967). SPINK1 is mainly expressed in the pancreas, but to a lesser extent also in several other tissues, e.g., in the gastrointestinal tract, including the liver, duodenum, small intestine, gall bladder, colon, appendix, stomach, and in the genitourinary tract, e.g., prostate and urothelium (Paju and Stenman, 2006; Itkonen and Stenman, 2014). Expression has been found also in kidney, lung, breast, brain, spleen and ovary. SPINK1 is often strongly expressed in ETS-rearrangement-negative prostate cancers (Tomlins et al., 2008). A putative bipartite pancreas-specific transcription factor 1 (PTF1)-binding sequence has been identified (Boulling et al., 2011) in the SPINK1 gene. Outside the pancreas, SPINK1 has been considered an inflammatory pleiotropic cytokine, which is regulated by immune and inflammatory responses. In some cell lines, the expression is regulated by IL-6 (Yasuda et al., 1993). In cultured prostate cancer cells, SPINK1 expression has been shown to be regulated by androgens (Paju et al., 2007). In mouse, the synthesis of Spink3 (mouse orthologue of SPINK1) is dependent upon testicular androgens in the sex accessory tissues, but not in the pancreas (Mills et al., 1987). Very high serum and urine concentrations occur in patients with pancreatitis (Ogawa, 1988). Serum levels of SPINK1 may also be elevated in several cancers, including prostate cancer, ovarian cancer and benign cysts, renal-cell carcinoma, bladder carcinoma, and colorectal cancer (Paju and Stenman, 2006; Itkonen and Stenman, 2014). Severe inflammation, tissue destruction and major trauma leads to an acute phase reaction causing increased circulating SPINK1 concentrations.
  Relative mRNA expression levels of SPINK1 in different tissues. The data is from the IST4 database containing gene expression data in ~10 000 samples ( (Kilpinen et al., 2008).
Localisation SPINK1 is highly expressed in the pancreas (Kazal et al., 1948). It has been localized to the zymogen granules of pancreatic acinar cells, where it protects the pancreas from premature activation of trypsinogens. SPINK1 is secreted into the pancreatic fluid along with digestive enzymes. Many cancers secrete SPINK1 causing elevated serum concentrations (Paju and Stenman, 2006; Itkonen and Stenman, 2014).
Function SPINK1 is a protease inhibitor and has been reported to inhibit human trypsin-1 and -2 (cationic and anionic trypsins), but not trypsin-3 (mesotrypsin)(Sahin-Tóth, 2005). SPINK1 also inhibits granzyme A (Tsuzuki et al., 2003), plasmin, urokinase, tissue plasminogen activator (Turpeinen et al., 1988) and acrosin (Huhtala et al., 1984). SPINK1 has been reported to exert growth stimulation of cultured cells (Niinobu et al., 1990) and to activate the EGF-receptor (Ozaki 2009; Ateeq et al., 2011). However, growth stimulation by mechanisms other than via EGF receptor cannot be ruled out. It has been suggested that SPINK1 mediates tumor growth, differentiation, and angiogenesis via stimulation of the EGF-receptor or by suppression of serine-protease- or caspase-dependent apoptosis (Ateeq et al., 2011; Gouyer et al., 2008). There is evidence that SPINK1 plays a role in tissue differentiation (Ohmuraya et al., 2005) and repair (Marchbank et al., 1996), reproduction (Huhtala, 1984) and regulation of apoptosis (Lu et al., 2011). Over-expression of SPINK1 in cancer could block cancer cell apoptosis resulting in suppression of the immune response and escape of cancer cells from immune surveillance (Lamontagne et al., 2010).
Homology SPINK1 contains a Kazal-type serine protease inhibitor domain, found in many other proteins and especially in members of SPINK family. Apart from this domain, SPINKs do not share high sequence similarity. Apart from SPINK5, SPINKs are of similar size and most genes contain the same number of exons. Some of the family members lack functional annotatation. A functional SPINK1 orthologue, Spink3 (NP_033284.1), has been found in mouse. The rat has two orthologues, Spink1 (NP_690919.1) and Spink3 (NP_036806.1) (HomoloGene, Release 67). Orhologues have been found also in common chimpanzee (XP_001160275.1), rhesus macaque (XP_001102888.1), grey wolf (XP_850557.1) and cattle (NP_001020519.1). Sequence similarity between SPINK1 and EGF has been reported (Hunt et al., 1974).


Note NCBI SNP database ( reports 631 SPINK1 SNPs (Homo sapiens, December 29., 2014). At least 15 missense mutations have been described in the mature polypeptide and three in the signal peptide (Chen and Férec, 2009). Association of mutations with familial pancreatitis and other diseases has been described (see below).

Implicated in

Entity Liver cancer
Note Up-regulation of SPINK1 in tissue has been shown to distinguish hepatocellular carcinoma (HCC) from benign liver disease and normal liver (Marshall A 2013). Elevated serum concentrations of SPINK1 are associated with adverse prognosis of hepatocellular cancer (Lyytinen et al., 2013). Serum SPINK1 is also a useful marker for distinguishing between patients with or without liver metastasis of colorectal and breast cancer (Taccone W 1991; Gaber A 2010).
Disease HCC is the fifth most frequently diagnosed cancer and the second most common cause of cancer death worldwide in men (Jemal et al., 2011). In females the rate is about half of that of men. Half of the cases occur in China and liver cancer is less common in Western countries. HCC is the most common type of liver cancer. It may be caused by viral infections, like hepatitis B and C, or cirrhosis. Most tumors in the liver are not primary liver cancers, but metastases of other cancers.
Prognosis Plasma SPINK1 concentration is elevated in HCC patients and it correlates with tumor size (Ohmachi et al., 1993). Overexpression of SPINK1 mRNA is a stage-independent prognostic factor and a predictor of early tumor recurrence in HCC (Lee et al., 2007) and in cholangiocarcinoma (Tonouchi et al., 2006). Serum SPINK1 has been shown to predict adverse prognosis in HCC (Lyytinen I 2013).
Entity Prostate cancer
Note SPINK1 is often overexpressed in ETS-rearrangement-negative prostate cancers (Tomlins et al., 2008).
Disease Prostate cancer is a considerable health care problem with 342 000 new cases and about 71 000 deaths annually in the EU countries, it is the most frequently diagnosed cancer in men and the third most common cause of cancer death (data from GLOBOCAN 2008). Prostate cancer can be diagnosed by screening at an early stage, when most patients can be cured by radical prostatectomy or radiotherapy. However, about one third of the tumors relapse. Most of these cases can be treated by androgen ablation, but within 3 - 5 years the tumor usually becomes castration-resistant.
Prognosis High SPINK1 expression has been associated with adverse prognosis in prostate cancer in some (Tomlins et al., 2008; Paju et al., 2007), but not all studies (Leinonen et al., 2013; Grupp et al., 2013; Lippolis et al., 2013). The differences may be related to the type of treatment, e.g., surgery or androgen ablation (Leinonen et al., 2013).
Entity Breast cancer
Disease Breast cancer is the most common cancer among women worldwide, accounting for 23% of all cases (Jemal et al., 2011). Although the prognosis has improved due to early diagnosis and therapies, breast cancer remains a major cause of death among women (14% of the cancer deaths). Most neoplasms of the breast originate from the ductal epithelium, while a minority originates from the lobular epithelium. A family history of breast cancer is associated with a 2-3-fold higher risk of the disease.
Prognosis SPINK1 expression is associated with poor prognosis in estrogen receptor-positive breast cancer (Soon et al., 2011).
Entity Colorectal cancer
Note Elevated serum SPINK1 has been observed in some patients with colorectal cancer. (Solakidi et al., 2004; Pasanen et al., 1995)
Disease Colorectal cancer is the third most commonly diagnosed cancer in males and the second in females (Jemal et al., 2011). It originates from colon or rectum, but, based on genetic studies, these are the same tumor. When locally confined, colorectal cancer is often curable by surgery.
Prognosis High expression of SPINK1 has been associated with adverse prognosis and liver metastases (Gaber et al., 2010; Gaber at al., 2009)
Entity Bladder cancer
Note Urinary SPINK1 is a useful marker for high-grade bladder cancer (Kelloniemi et al., 2003; Shariat et al., 2005; Gkialas et al., 2008, Patschan et al., 2012).
Disease Bladder cancer is more common in males than in females and there is great geographic variation in incidence (Jemal et al., 2011). The highest incidence rates are found in Europe, North America and Northern Africa. Smoking, occupational exposures and chronic infection with Schistosoma hematobium are major risk factors. Most bladder cancers originate from the epithelial lining of the urinary bladder. Transitional cell carcinoma is the most common type of bladder cancer.
Prognosis Serum SPINK1 has been shown to be an independent prognostic factor for bladder cancer (Kelloniemi et al., 2003) and for prediction of the response to chemotherapy (Pectasides et al., 1996). SPINK1 expression is stronger in noninvasive than in invasive tumors and decreases with advancing tumor stage (Hotakainen et al., 2006; Patschan et al., 2012).
Entity Ovarian cancer
Note The association of SPINK1 (TATI) and cancer was first observed in a patients with ovarian cancer (Stenman et al. 1982)
Disease Ovarian cancer is the leading cause of death from gynecologic cancer. Most cases are diagnosed at advanced stages and, thus have relatively poor prognosis. The vast majority of ovarian cancers are epithelial. Cancer of the fallopian tubes is similar to ovarian cancer.
Prognosis Increased SPINK1 expression is associated with adverse outcome in epithelial ovarian cancer (Huhtala et al., 1983; Paju et al., 2004). Elevated serum SPINK1 is an independent prognostic factor (Venesmaa et al., 1994; Venesmaa et al., 1998; Paju et al., 2004).
Entity Gastric cancer
Note SPINK1 is detected in the normal gastric mucosa.
Disease Gastric cancers account for 8% of all cancer cases and 10% of the deaths (Jamal et al., 2011). Over 70% of new cases and deaths occur in developing countries and rates are higher in males than in females. Helicobacter pylori infection is the main risk factor, but smoking also increases the risk of gastric cancer.
Prognosis The prognosis of gastric cancer is generally poor and metastases develop frequently. High tissue expression of SPINK1 is a sign of favorable outcome and loss of SPINK1 immunoreactivity in tumor tissue is associated with adverse prognosis (Wiksten et al., 2008). Serum SPINK1 is elevated in 50% of patients with gastric cancer (Solakidi et al., 2004).
Entity Renal cell carcinoma
Disease Renal cancer comprises five distinct histological types. Within each type, there is considerable variation in clinical course and survival. Presently, many tumors are detected at an early stage by sonography performed for various reasons.
Prognosis Prognosis of metastatatic and advanced disease is poor, but surgical treatment of localized disease is often curative. There are no specific serum markers for RCC. Elevated serum SPINK1 has been shown to be an independent prognostic factor in renal cell carcinoma (Meria et al., 1995; Paju et al., 2001).
Entity Pancreatitis, hereditary (Online Mendelian Inheritance in Man (OMIM): 167800)
Note SPINK1 polymorphisms are found more frequently in patients with hereditary and idiopatic chronic pancreatitis (23%) than in healthy controls (0.4%) (Witt et al., 2000; Chen and Férec, 2009). Several mutations of SPINK1 cause loss-of-function by splicing, frameshift, deletion or initiation codon mutation. Some missense mutations have been suggested to affect polypeptide folding, leading to intracellular retention and degradation of the mutated polypeptide (Boulling et al., 2012). These mutations are suggested to cause pancreatitis because of SPINK1 deficiency. The most common mutation worldwide is a 101A>G transition within exon 3 resulting in the substitution of Asp by Ser at codon 34 (N34S) (Witt et al., 2000). The frequency of the N34S mutation in pancreatitis patients is 9-29 % as compared to 0.5-2.5 % in the general population. In functional studies no differences in SPINK1 expression, trypsin inhibitory activity or binding to trypsin have been found between wild-type and N34S-SPINK1. The mutations D50E, Y54H and R67C result in marked reduction or complete loss of SPINK1 secretion, and are classified as disease-causing mutations although trypsin inhibitory activity of the mutated proteins was retained (Király et al., 2007). The P55S mutation of SPINK1 is found in healthy controls as well as in pancreatitis patients with an incidence of 0.5-1.3 % and 0.9-7 %, respectively (Witt et al., 2000; Pfutzer et al., 2000). The role of this mutation in pancreatitis remains unclear.
Disease Elevated serum and urine concentrations are caused by pancreatitis, i.e., inflammation of pancreas. Some hereditary mutations of the SPINK1 gene, increase the risk of pancreatitis. These cases are characterized by recurrent episodes of pancreatitis starting at young age. These episodes often lead to tissue damage and loss of pancreatic function, including insulin production. This also increases the risk of pancreatic cancer.
Prognosis The life expectancy of the pancreatitis patients is close to normal. However, patients have an increased risk of developing pancreatic cancer (Weiss, 2014).
Entity Tropical calcific pancreatitis
Note SPINK1 mutations, especially the N34S mutation has been reported to associate with tropical calcific pancreatitis (Bhatia et al., 2002).
Disease Tropical calcific pancreatitis (OMIM: 608189) is a special type of chronic pancreatitis that occurs only in tropical countries.
Prognosis Patients usually present at young age with recurrent abdominal pain and nutritional deficiencies. The disease often leads to beta-cell deficiency and diabetes requiring insulin before the age of 30. Prognosis is dismal and many patients succumb to complications caused by malnutrition.


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PMID 16517420
Expression of trypsinogen-1, trypsinogen-2, and tumor-associated trypsin inhibitor in ovarian cancer: prognostic study on tissue and serum
Paju A, Vartiainen J, Haglund C, Itkonen O, von Boguslawski K, Leminen A, Wahlström T, Stenman UH
Clin Cancer Res 2004 Jul 15;10(14):4761-8
PMID 15269150
Tumour-associated trypsin inhibitor (TATI) in patients with colorectal cancer: a comparison with CEA, CA 50 and CA 242
Pasanen P, Eskelinen M, Kulju A, Penttilä I, Janatuinen E, Alhava E
Scand J Clin Lab Invest 1995 Apr;55(2):119-24
PMID 7667604
Association of tumor-associated trypsin inhibitor (TATI) expression with molecular markers, pathologic features and clinical outcomes of urothelial carcinoma of the urinary bladder
Patschan O, Shariat SF, Chade DC, Karakiewicz PI, Ashfaq R, Lotan Y, Hotakainen K, Stenman UH, Bjartell A
World J Urol 2012 Dec;30(6):785-94
PMID 21739120
SPINK1/PSTI polymorphisms act as disease modifiers in familial and idiopathic chronic pancreatitis
Pfützer RH, Barmada MM, Brunskill AP, Finch R, Hart PS, Neoptolemos J, Furey WF, Whitcomb DC
Gastroenterology 2000 Sep;119(3):615-23
PMID 10982753
Trypsin inhibitor from human pancreas and pancreatic juice
Pubols MH, Bartelt DC, Greene LJ
J Biol Chem 1974 Apr 10;249(7):2235-42
PMID 4818832
Human mesotrypsin defies natural trypsin inhibitors: from passive resistance to active destruction
Sahin-Toth M
Protein Pept Lett 2005 Jul;12(5):457-64
PMID 16029158
Urinary levels of tumor-associated trypsin inhibitor (TATI) in the detection of transitional cell carcinoma of the urinary bladder
Shariat SF, Herman MP, Casella R, Lotan Y, Karam JA, Stenman UH
Eur Urol 2005 Sep;48(3):424-31
PMID 15963628
Tumour-associated trypsin inhibitor, carcinoembryonic antigen and acute-phase reactant proteins CRP and alpha1-antitrypsin in patients with gastrointestinal malignancies
Solakidi S, Dessypris A, Stathopoulos GP, Androulakis G, Sekeris CE
Clin Biochem 2004 Jan;37(1):56-60
PMID 14675563
Combined genomic and phenotype screening reveals secretory factor SPINK1 as an invasion and survival factor associated with patient prognosis in breast cancer
Soon WW, Miller LD, Black MA, Dalmasso C, Chan XB, Pang B, Ong CW, Salto-Tellez M, Desai KV, Liu ET
EMBO Mol Med 2011 Aug;3(8):451-64
PMID 21656687
Characterization of a tumor-associated serine protease
Stenman UH, Koivunen E, Vuento M
Biol Chem Hoppe Seyler 1988 May;369 Suppl:9-14
PMID 3202976
Evaluation of TATI and other markers in solid tumors
Taccone W, Mazzon W, Belli M
Scand J Clin Lab Invest Suppl 1991;207:25-32
PMID 1780686
The role of SPINK1 in ETS rearrangement-negative prostate cancers
Tomlins SA, Rhodes DR, Yu J, Varambally S, Mehra R, Perner S, Demichelis F, Helgeson BE, Laxman B, Morris DS, Cao Q, Cao X, Andrén O, Fall K, Johnson L, Wei JT, Shah RB, Al-Ahmadie H, Eastham JA, Eggener SE, Fine SW, Hotakainen K, Stenman UH, Tsodikov A, Gerald WL, Lilja H, Reuter VE, Kantoff PW, Scardino PT, Rubin MA, Bjartell AS, Chinnaiyan AM
Cancer Cell 2008 Jun;13(6):519-28
PMID 18538735
Relationship between pancreatic secretory trypsin inhibitor and early recurrence of intrahepatic cholangiocarcinoma following surgical resection
Tonouchi A, Ohtsuka M, Ito H, Kimura F, Shimizu H, Kato M, Nimura Y, Iwase K, Hiwasa T, Seki N, Takiguchi M, Miyazaki M
Am J Gastroenterol 2006 Jul;101(7):1601-10
PMID 16863567
Purification and identification of a binding protein for pancreatic secretory trypsin inhibitor: a novel role of the inhibitor as an anti-granzyme A
Tsuzuki S, Kokado Y, Satomi S, Yamasaki Y, Hirayasu H, Iwanaga T, Fushiki T
Biochem J 2003 May 15;372(Pt 1):227-33
PMID 12590650
Reaction of a tumour-associated trypsin inhibitor with serine proteinases associated with coagulation and tumour invasion
Turpeinen U, Koivunen E, Stenman UH
Biochem J 1988 Sep 15;254(3):911-4
PMID 2461702
Pre-operative serum level of tumour-associated trypsin inhibitor and residual tumour size as prognostic indicators in Stage III epithelial ovarian cancer
Venesmaa P, Stenman UH, Forss M, Leminen A, Lehtovirta P, Vartiainen J, Paavonen J
Br J Obstet Gynaecol 1998 May;105(5):508-11
PMID 9637119
Pancreatic cancer risk in hereditary pancreatitis
Weiss FU
Front Physiol 2014 Feb 20;5:70
PMID 24600409
Comparison of the prognostic value of a panel of tissue tumor markers and established clinicopathological factors in patients with gastric cancer
Wiksten JP, Lundin J, Nordling S, Kokkola A, Haglund C
Anticancer Res 2008 Jul-Aug;28(4C):2279-87
PMID 18751407
Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis
Witt H, Luck W, Hennies HC, Classen M, Kage A, Lass U, Landt O, Becker M
Nat Genet 2000 Jun;25(2):213-6
PMID 10835640
Generating triangulated macromolecular surfaces by Euclidean Distance Transform
Xu D, Zhang Y
PLoS One 2009 Dec 2;4(12):e8140
PMID 19956577
Molecular cloning and nucleotide sequence of human pancreatic secretory trypsin inhibitor (PSTI) cDNA
Yamamoto T, Nakamura Y, Nishide J, Emi M, Ogawa M, Mori T, Matsubara K
Biochem Biophys Res Commun 1985 Oct 30;132(2):605-12
PMID 3877508
Identification of the IL-6-responsive element in an acute-phase-responsive human pancreatic secretory trypsin inhibitor-encoding gene
Yasuda T, Ogawa M, Murata A, Ohmachi Y, Yasuda T, Mori T, Matsubara K
Gene 1993 Sep 15;131(2):275-80
PMID 7691687
Identification of novel pancreas-specific regulatory sequences in the promoter region of human pancreatic secretory trypsin inhibitor gene
Yasuda T, Yasuda T, Ohmachi Y, Katsuki M, Yokoyama M, Murata A, Monden M, Matsubara K
J Biol Chem 1998 Dec 18;273(51):34413-21
PMID 9852108


This paper should be referenced as such :
Hannu Koistinen, Outi Itkonen, Ulf-Hakan Stenman
SPINK1 (Serine Peptidase Inhibitor, Kazal Type 1)
Atlas Genet Cytogenet Oncol Haematol. 2016;20(1):36-44.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)SPINK1   11244
Entrez_Gene (NCBI)SPINK1    serine peptidase inhibitor Kazal type 1
AliasesPCTT; PSTI; Spink3; TATI; 
GeneCards (Weizmann)SPINK1
Ensembl hg19 (Hinxton)ENSG00000164266 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000164266 [Gene_View]  ENSG00000164266 [Sequence]  chr5:147824580-147839231 [Contig_View]  SPINK1 [Vega]
ICGC DataPortalENSG00000164266
Genatlas (Paris)SPINK1
SOURCE (Princeton)SPINK1
Genetics Home Reference (NIH)SPINK1
Genomic and cartography
GoldenPath hg38 (UCSC)SPINK1  -     chr5:147824580-147839231 -  5q32   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SPINK1  -     5q32   [Description]    (hg19-Feb_2009)
GoldenPathSPINK1 - 5q32 [CytoView hg19]  SPINK1 - 5q32 [CytoView hg38]
Genome Data Viewer NCBISPINK1 [Mapview hg19]  
OMIM167790   167800   608189   
Gene and transcription
Genbank (Entrez)AI990990 BC025790 BU074107 CB159576 M11949
RefSeq transcript (Entrez)NM_001354966 NM_001379610 NM_003122
Consensus coding sequences : CCDS (NCBI)SPINK1
Gene ExpressionSPINK1 [ NCBI-GEO ]   SPINK1 [ EBI - ARRAY_EXPRESS ]   SPINK1 [ SEEK ]   SPINK1 [ MEM ]
Gene Expression Viewer (FireBrowse)SPINK1 [ Firebrowse - Broad ]
GenevisibleExpression of SPINK1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6690
GTEX Portal (Tissue expression)SPINK1
Human Protein AtlasENSG00000164266-SPINK1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP00995   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP00995  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP00995
Domaine pattern : Prosite (Expaxy)KAZAL_1 (PS00282)    KAZAL_2 (PS51465)   
Domains : Interpro (EBI)Kazal_dom    Kazal_dom_sf    Prot_inh_Kazal-m   
Domain families : Pfam (Sanger)Kazal_1 (PF00050)   
Domain families : Pfam (NCBI)pfam00050   
Domain families : Smart (EMBL)KAZAL (SM00280)  
Conserved Domain (NCBI)SPINK1
PDB (RSDB)1CGI    1CGJ    1HPT   
PDB Europe1CGI    1CGJ    1HPT   
PDB (PDBSum)1CGI    1CGJ    1HPT   
PDB (IMB)1CGI    1CGJ    1HPT   
Structural Biology KnowledgeBase1CGI    1CGJ    1HPT   
SCOP (Structural Classification of Proteins)1CGI    1CGJ    1HPT   
CATH (Classification of proteins structures)1CGI    1CGJ    1HPT   
AlphaFold pdb e-kbP00995   
Human Protein Atlas [tissue]ENSG00000164266-SPINK1 [tissue]
Protein Interaction databases
IntAct (EBI)P00995
Ontologies - Pathways
Ontology : AmiGOendopeptidase inhibitor activity  serine-type endopeptidase inhibitor activity  protein binding  negative regulation of nitric oxide mediated signal transduction  sperm capacitation  negative regulation of peptidyl-tyrosine phosphorylation  regulation of acrosome reaction  extracellular exosome  negative regulation of calcium ion import  negative regulation of serine-type endopeptidase activity  regulation of store-operated calcium entry  
Ontology : EGO-EBIendopeptidase inhibitor activity  serine-type endopeptidase inhibitor activity  protein binding  negative regulation of nitric oxide mediated signal transduction  sperm capacitation  negative regulation of peptidyl-tyrosine phosphorylation  regulation of acrosome reaction  extracellular exosome  negative regulation of calcium ion import  negative regulation of serine-type endopeptidase activity  regulation of store-operated calcium entry  
NDEx NetworkSPINK1
Atlas of Cancer Signalling NetworkSPINK1
Wikipedia pathwaysSPINK1
Orthology - Evolution
GeneTree (enSembl)ENSG00000164266
Phylogenetic Trees/Animal Genes : TreeFamSPINK1
Homologs : HomoloGeneSPINK1
Homology/Alignments : Family Browser (UCSC)SPINK1
Gene fusions - Rearrangements
Fusion Cancer (Beijing)MUDENG [SPINK1]  -  5q32 [FUSC003165]
Fusion Cancer (Beijing)PSG1 [19q13.2]  -  SPINK1 [5q32]  [FUSC003172]
Fusion Cancer (Beijing)RBM15B [3p21.2]  -  SPINK1 [5q32]  [FUSC003174]
Fusion Cancer (Beijing)SPINK1 [5q32]  -  ARL4A [7p21.3]  [FUSC003178]
Fusion Cancer (Beijing)SPINK1 [5q32]  -  GRM4 [6p21.31]  [FUSC003179]
Fusion Cancer (Beijing)SPINK1 [5q32]  -  TAS2R38 [7q34]  [FUSC003180]
Fusion Cancer (Beijing)SYT14 [1q32.2]  -  SPINK1 [5q32]  [FUSC003182]
Fusion : QuiverSPINK1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSPINK1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SPINK1
Exome Variant ServerSPINK1
GNOMAD BrowserENSG00000164266
Varsome BrowserSPINK1
ACMGSPINK1 variants
Genomic Variants (DGV)SPINK1 [DGVbeta]
DECIPHERSPINK1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSPINK1 
ICGC Data PortalSPINK1 
TCGA Data PortalSPINK1 
Broad Tumor PortalSPINK1
OASIS PortalSPINK1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSPINK1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DSPINK1
Mutations and Diseases : HGMDSPINK1
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)SPINK1
DoCM (Curated mutations)SPINK1
CIViC (Clinical Interpretations of Variants in Cancer)SPINK1
NCG (London)SPINK1
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM167790    167800    608189   
Orphanet937    14991   
Genetic Testing Registry SPINK1
NextProtP00995 [Medical]
Target ValidationSPINK1
Huge Navigator SPINK1 [HugePedia]
ClinGenSPINK1 (curated)
Clinical trials, drugs, therapy
Protein Interactions : CTDSPINK1
Pharm GKB GenePA36074
Clinical trialSPINK1
DataMed IndexSPINK1
PubMed236 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:28:36 CEST 2021

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