P00995 (ISK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pancreatic secretory trypsin inhibitor

Alternative name(s):
Serine protease inhibitor Kazal-type 1
Tumor-associated trypsin inhibitor
Short name=TATI

Gene names

Name:	SPINK1
Synonyms:	PSTI

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	79 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	This is a trypsin inhibitor, its physiological function is to prevent the trypsin-catalyzed premature activation of zymogens within the pancreas.
Subcellular location	Secreted.
Involvement in disease	Defects in SPINK1 are a cause of pancreatitis (PCTT) [MIM:167800]. A disease characterized by the presence of calculi in pancreatic ducts. It causes severe abdominal pain attacks. Ref.4 Ref.10 Ref.13 Defects in SPINK1 are the cause of susceptibility to tropical calcific pancreatitis (TCP) [MIM:608189]. TCP is an idiopathic, juvenile, nonalcoholic form of chronic pancreatitis widely prevalent in several tropical countries. It can be associated with fibrocalculous pancreatic diabetes (FCPD) depending on both environmental and genetic factors. TCP differs from alcoholic pancreatitis by a much younger age of onset, pancreatic calcification, a high incidence of insulin dependent but ketosis resistant diabetes mellitus, and an exceptionally high incidence of pancreatic cancer. Ref.11 Ref.12
Sequence similarities	Contains 1 Kazal-like domain.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB serine-type endopeptidase inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Ref.6 Ref.7

Chain

24 – 79

56

Pancreatic secretory trypsin inhibitor

PRO_0000016557

Regions

Domain

26 – 79

54

Kazal-like

Sites

Site

41 – 42

2

Reactive bond

Amino acid modifications

Disulfide bond

32 ↔ 61

Disulfide bond

39 ↔ 58

Disulfide bond

47 ↔ 79

Natural variations

Natural variant

12

1

L → F in PCTT. Ref.13
Corresponds to variant rs35877720 [ dbSNP | Ensembl ].

VAR_032011

Natural variant

14

1

L → P in PCTT. Ref.4

VAR_011688

Natural variant

34

1

N → S in PCTT and TCP; may confer susceptibility to fibrocalculous pancreatic diabetes. Ref.4 Ref.10 Ref.11 Ref.12
Corresponds to variant rs17107315 [ dbSNP | Ensembl ].

VAR_011689

Natural variant

55

1

P → S. Ref.4 Ref.10 Ref.12

VAR_011690

Natural variant

67

1

R → H.
Corresponds to variant rs35523678 [ dbSNP | Ensembl ].

VAR_032012

Experimental info

Sequence conflict

44

1

D → N AA sequence Ref.6

Sequence conflict

44

1

D → N AA sequence Ref.7

Sequence conflict

52

1

N → D AA sequence Ref.6

Sequence conflict

64

1

N → G in CAA68697. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

79

Helix Strand Turn

Details...

Beta strand

26 – 28

3

Beta strand

46 – 48

3

Beta strand

53 – 56

4

Helix

57 – 67

11

Beta strand

73 – 77

5

Sequences

	Sequence		Length	Mass (Da)
	P00995 [UniParc]. Last modified July 1, 1989. Version 2. Checksum: 3583C8196952EB3A	FASTA	79	8,507
	10 20 30 40 50 60 MKVTGIFLLS ALALLSLSGN TGADSLGREA KCYNELNGCT KIYDPVCGTD GNTYPNECVL 70 CFENRKRQTS ILIQKSGPC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of human pancreatic secretory trypsin inhibitor (PSTI) gene." Horii A., Kobayashi T., Tomita N., Yamamoto T., Fukushige S., Murotsu T., Ogawa M., Mori T., Matsubara K. Biochem. Biophys. Res. Commun. 149:635-641(1987) [PubMed: 3501289] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Molecular cloning and nucleotide sequence of human pancreatic secretory trypsin inhibitor (PSTI) cDNA." Yamamoto T., Nakamura Y., Nishide T., Emi M., Ogawa M., Mori T., Matsubara K. Biochem. Biophys. Res. Commun. 132:605-612(1985) [PubMed: 3877508] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Expression of pancreatic secretory trypsin inhibitor gene in neoplastic tissues." Tomita N., Horii A., Yamamoto T., Ogawa M., Mori T., Matsubara K. FEBS Lett. 225:113-119(1987) [PubMed: 2961612] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis." Witt H., Luck W., Hennies H.C., Classen M., Kage A., Lass U., Landt O., Becker M. Nat. Genet. 25:213-216(2000) [PubMed: 10835640] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PCTT PRO-14 AND SER-34, VARIANT SER-55.
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas and Spleen.
[6]	"The primary structure of the human pancreatic secretory trypsin inhibitor. Amino acid sequence of the reduced S-aminoethylated protein." Bartelt D.C., Shapanka R., Greene L.J. Arch. Biochem. Biophys. 179:189-199(1977) [PubMed: 843082] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-79.
[7]	"Purification and characterization of a tumor-associated trypsin inhibitor from the urine of a patient with ovarian cancer." Huhtala M.-L., Pesonen K., Kalkkinen N., Stenman U.-H. J. Biol. Chem. 257:13713-13716(1982) [PubMed: 7142173] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-46.
[8]	"Three-dimensional structure of a recombinant variant of human pancreatic secretory trypsin inhibitor (Kazal type)." Hecht H.-J., Szardenings M., Collins J., Schomburg D. J. Mol. Biol. 225:1095-1103(1992) [PubMed: 1613792] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[9]	"Solution structure of a variant of human pancreatic secretory trypsin inhibitor determined by nuclear magnetic resonance spectroscopy." Klaus W., Schomburg D. J. Mol. Biol. 229:695-706(1993) [PubMed: 8433367] [Abstract] Cited for: STRUCTURE BY NMR OF MUTANT LEU-41/ARG-44.
[10]	"Mutational analysis of the human pancreatic secretory trypsin inhibitor (PSTI) gene in hereditary and sporadic chronic pancreatitis." Chen J.-M., Mercier B., Audrezet M.-P., Ferec C. J. Med. Genet. 37:67-69(2000) [PubMed: 10691414] [Abstract] Cited for: VARIANT PCTT SER-34, VARIANT SER-55.
[11]	"SPINK1 is a susceptibility gene for fibrocalculous pancreatic diabetes in subjects from the Indian subcontinent." Hassan Z., Mohan V., Ali L., Allotey R., Barakat K., Faruque M.O., Deepa R., McDermott M.F., Jackson A.E., Cassell P., Curtis D., Gelding S.V., Vijayaravaghan S., Gyr N., Whitcomb D.C., Azad Khan A.K., Hitman G.A. Am. J. Hum. Genet. 71:964-968(2002) [PubMed: 12187509] [Abstract] Cited for: VARIANT TCP SER-34, INVOLVEMENT IN FIBROCALCULOUS PANCREATIC DIABETES.
[12]	"Mutations in the pancreatic secretory trypsin inhibitor gene (PSTI/SPINK1) rather than the cationic trypsinogen gene (PRSS1) are significantly associated with tropical calcific pancreatitis." Chandak G.R., Idris M.M., Reddy D.N., Bhaskar S., Sriram P.V.J., Singh L. J. Med. Genet. 39:347-351(2002) [PubMed: 12011155] [Abstract] Cited for: VARIANT TCP SER-34, VARIANT SER-55.
[13]	"Gene symbol: Spink1-Omim 167790. Disease: hereditary pancreatitis." Deybach J.-C.D., Phung L., Lamoril J., Bouizegarene P., Levy P., Deybach J.-C., Ruszniewski P. Hum. Genet. 113:369-369(2003) [PubMed: 12974284] [Abstract] Cited for: VARIANT PCTT PHE-12.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M20530 , M22971, M20528, M20529 Genomic DNA. Translation: AAA36522.1.
Y00705 mRNA. Translation: CAA68697.1.
M11949 mRNA. Translation: AAA36521.1.
AF286028 Genomic DNA. Translation: AAG00531.1.
BC025790 mRNA. Translation: AAH25790.1.

IPI

IPI00020687.

PIR

TIHUA. A27484.

RefSeq

NP_003113.2. NM_003122.3.

UniGene

Hs.407856.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CGI	X-ray	2.30	I	24-79	[»]
1CGJ	X-ray	2.30	I	24-79	[»]
1HPT	X-ray	2.30	A	24-79	[»]

ProteinModelPortal

P00995.

SMR

P00995. Positions 24-79.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-1504272.

STRING

P00995.

Protein family/group databases

MEROPS

I01.011.

Polymorphism databases

DMDM

124856.

Proteomic databases

PeptideAtlas

P00995.

PRIDE

P00995.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000296695; ENSP00000296695; ENSG00000164266.

GeneID

6690.

KEGG

hsa:6690.

UCSC

uc003los.1. human.

Organism-specific databases

CTD

6690.

GeneCards

GC05M147184.

H-InvDB

HIX0005285.

HGNC

HGNC:11244. SPINK1.

HPA

CAB026366.
HPA027498.

MIM

167790. gene.
167800. phenotype.
608189. phenotype.

neXtProt

NX_P00995.

Orphanet

676. Hereditary chronic pancreatitis.

PharmGKB

PA36074.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG20976.

GeneTree

ENSGT00530000064228.

HOGENOM

HBG278042.

HOVERGEN

HBG006182.

InParanoid

P00995.

OMA

IYNPVCG.

OrthoDB

EOG4K0QQ4.

Gene expression databases

ArrayExpress

P00995.

Bgee

P00995.

CleanEx

HS_SPINK1.

Genevestigator

P00995.

GermOnline

ENSG00000164266. Homo sapiens.

Family and domain databases

InterPro

IPR002350. Prot_inh_Kazal.
IPR001239. Prot_inh_Kazal-m.
[Graphical view]

Pfam

PF00050. Kazal_1. 1 hit.
[Graphical view]

PRINTS

PR00290. KAZALINHBTR.

SMART

SM00280. KAZAL. 1 hit.
[Graphical view]

PROSITE

PS00282. KAZAL_1. 1 hit.
PS51465. KAZAL_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

26073.

PMAP-CutDB

P00995.

SOURCE

Search...

Entry information

Entry name

ISK1_HUMAN

Accession

Primary (citable) accession number: P00995

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 1, 1989
Last modified:	January 25, 2012
This is version 134 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.