P20155 (ISK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine protease inhibitor Kazal-type 2

Alternative name(s):
Acrosin-trypsin inhibitor
Epididymis tissue protein Li 172
HUSI-II

Gene names

Name:

SPINK2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	84 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	Strong inhibitor of acrosin in male and/or female genital tract. Also inhibits trypsin. Ref.9
Subcellular location	Secreted.
Tissue specificity	Expressed in epididymis (at protein level). Ref.3
Sequence similarities	Contains 1 Kazal-like domain.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Disulfide bond Pyrrolidone carboxylic acid
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	endopeptidase inhibitor activity Traceable author statement Ref.2. Source: ProtInc 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.8

Chain

24 – 84

61

Serine protease inhibitor Kazal-type 2

PRO_0000016561

Regions

Domain

30 – 84

55

Kazal-like

Sites

Site

46 – 47

2

Reactive bond

Amino acid modifications

Modified residue

24

1

Pyrrolidone carboxylic acid Ref.8

Disulfide bond

36 ↔ 66

Ref.9

Disulfide bond

44 ↔ 63

Ref.9

Disulfide bond

52 ↔ 84

Ref.9

Experimental info

Mutagenesis

45

1

P → A: No effect on inhibitory activity towards trypsin. Ref.9

Mutagenesis

46

1

R → A: Loss of inhibitory activity towards trypsin. Ref.9

Mutagenesis

47

1

H → A: Reduces inhibitory activity towards trypsin. Ref.9

Mutagenesis

48

1

F → A: Reduces inhibitory activity towards trypsin. Ref.9

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

84

Helix Strand Turn

Details...

Beta strand

27 – 32

6

Beta strand

51 – 53

3

Turn

62 – 64

3

Helix

65 – 70

6

Beta strand

73 – 75

3

Beta strand

78 – 82

5

Sequences

	Sequence		Length	Mass (Da)
	P20155 [UniParc]. Last modified December 1, 1992. Version 2. Checksum: E1DE1792BFB1BB85	FASTA	84	9,291
	10 20 30 40 50 60 MALSVLRLAL LLLAVTFAAS LIPQFGLFSK YRTPNCSQYR LPGCPRHFNP VCGSDMSTYA 70 80 NECTLCMKIR EGGHNIKIIR NGPC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and sequence analysis of the cDNA encoding the human acrosin-trypsin inhibitor (HUSI-II)." Moeritz A., Lilja H., Fink E. FEBS Lett. 278:127-130(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Organization and sequence of the gene encoding the human acrosin-trypsin inhibitor (HUSI-II)." Moeritz A., Grzeschik K.H., Wingender E., Fink E. Gene 123:277-281(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Systematic mapping and functional analysis of a family of human epididymal secretory sperm-located proteins." Li J., Liu F., Wang H., Liu X., Liu J., Li N., Wan F., Wang W., Zhang C., Jin S., Liu J., Zhu P., Liu Y. Mol. Cell. Proteomics 9:2517-2528(2010) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Epididymis.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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: Brain.
[8]	"Amino acid sequence elucidation of human acrosin-trypsin inhibitor (HUSI-II) reveals that Kazal-type proteinase inhibitors are structurally related to beta-subunits of glycoprotein hormones." Fink E., Hehlein-Fink C., Eulitz M. FEBS Lett. 270:222-224(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-84. Tissue: Semen.
[9]	"Identification of trypsin-inhibitory site and structure determination of human SPINK2 serine proteinase inhibitor." Chen T., Lee T.-R., Liang W.-G., Chang W.-S., Lyu P.-C. Proteins 77:209-219(2009) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 23-84, FUNCTION, MUTAGENESIS OF PRO-45; ARG-46; HIS-47 AND PHE-48, MASS SPECTROMETRY, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M91438 Genomic DNA. Translation: AAB59431.1.
X57655 mRNA. Translation: CAB37834.1.
M84967 Genomic DNA. No translation available.
GU727622 mRNA. Translation: ADU87624.1.
AK312222 mRNA. Translation: BAG35155.1.
CR542135 mRNA. Translation: CAG46932.1.
CH471057 Genomic DNA. Translation: EAX05513.1.
BC022514 mRNA. Translation: AAH22514.1.

IPI

IPI00022231.

PIR

JU0152.

RefSeq

NP_001258650.1. NM_001271721.1.
NP_001258651.1. NM_001271722.1.
NP_066937.1. NM_021114.3.

UniGene

Hs.98243.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JXD	NMR	-	A	23-84	[»]

ProteinModelPortal

P20155.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000248701.

Protein family/group databases

MEROPS

I01.012.

PTM databases

PhosphoSite

P20155.

Polymorphism databases

DMDM

123985.

Proteomic databases

PaxDb

P20155.

PRIDE

P20155.

Protocols and materials databases

DNASU

6691.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000248701; ENSP00000248701; ENSG00000128040.

GeneID

6691.

KEGG

hsa:6691.

UCSC

uc003hcg.1. human.

Organism-specific databases

CTD

6691.

GeneCards

GC04M057676.

HGNC

HGNC:11245. SPINK2.

HPA

CAB020824.
HPA026813.

MIM

605753. gene.

neXtProt

NX_P20155.

PharmGKB

PA36075.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG255629.

HOGENOM

HOG000090244.

InParanoid

P20155.

OrthoDB

EOG4P5KBW.

Gene expression databases

ArrayExpress

P20155.

Bgee

P20155.

CleanEx

HS_SPINK2.

Genevestigator

P20155.

GermOnline

ENSG00000128040. Homo sapiens.

Family and domain databases

InterPro

IPR002350. Kazal_dom.
[Graphical view]

Pfam

PF00050. Kazal_1. 1 hit.
[Graphical view]

SMART

SM00280. KAZAL. 1 hit.
[Graphical view]

PROSITE

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

ProtoNet

Search...

Other

EvolutionaryTrace

P20155.

GenomeRNAi

6691.

NextBio

26077.

SOURCE

Search...

Entry information

Entry name

ISK2_HUMAN

Accession

Primary (citable) accession number: P20155
Secondary accession number(s): Q6FGH2

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	December 1, 1992
Last modified:	May 1, 2013
This is version 116 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.