P49863 (GRAK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Granzyme K
EC=3.4.21.-

Alternative name(s):
Fragmentin-3
Granzyme-3
NK-tryptase-2
Short name=NK-Tryp-2

Gene names

Name:	GZMK
Synonyms:	TRYP2

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	264 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)

Subcellular location	Secreted. Cytoplasmic granule.
Tissue specificity	Expressed in lung, spleen, thymus and peripheral blood leukocytes.
Sequence similarities	Belongs to the peptidase S1 family. Granzyme subfamily. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro serine-type peptidase activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Potential

Propeptide

25 – 26

2

Activation peptide

PRO_0000027415

Chain

27 – 264

238

Granzyme K

PRO_0000027416

Regions

Domain

27 – 259

233

Peptidase S1

Sites

Active site

67

1

Charge relay system

Active site

116

1

Charge relay system

Active site

214

1

Charge relay system

Amino acid modifications

Disulfide bond

52 ↔ 68

Disulfide bond

149 ↔ 220

Disulfide bond

181 ↔ 199

Disulfide bond

210 ↔ 234

Experimental info

Sequence conflict

34

1

S → Q AA sequence Ref.7

Sequence conflict

43

1

S → A AA sequence Ref.7

Secondary structure

1

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264

Helix Strand Turn

Details...

Beta strand

41 – 46

6

Beta strand

49 – 58

10

Beta strand

61 – 64

4

Helix

66 – 68

3

Beta strand

78 – 83

6

Beta strand

85 – 89

5

Beta strand

95 – 104

10

Beta strand

111 – 115

5

Beta strand

118 – 124

7

Beta strand

130 – 132

3

Beta strand

148 – 153

6

Beta strand

169 – 175

7

Helix

178 – 181

4

Turn

184 – 191

8

Beta strand

197 – 201

5

Beta strand

217 – 220

4

Beta strand

223 – 228

6

Beta strand

241 – 245

5

Helix

248 – 257

10

Sequences

	Sequence		Length	Mass (Da)
	P49863 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 2A93FDBAF9286CC5	FASTA	264	28,882
	10 20 30 40 50 60 MTKFSSFSLF FLIVGAYMTH VCFNMEIIGG KEVSPHSRPF MASIQYGGHH VCGGVLIDPQ 70 80 90 100 110 120 WVLTAAHCQY RFTKGQSPTV VLGAHSLSKN EASKQTLEIK KFIPFSRVTS DPQSNDIMLV 130 140 150 160 170 180 KLQTAAKLNK HVKMLHIRSK TSLRSGTKCK VTGWGATDPD SLRPSDTLRE VTVTVLSRKL 190 200 210 220 230 240 CNSQSYYNGD PFITKDMVCA GDAKGQKDSC KGDSGGPLIC KGVFHAIVSG GHECGVATKP 250 260 GIYTLLTKKY QTWIKSNLVP PHTN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of cDNA for human granzyme 3." Przetak M.M., Yoast S., Schmidt B.F. FEBS Lett. 364:268-271(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Ascites.
[2]	"Cloning and expression of a second human natural killer cell granule tryptase, HNK-Tryp-2/granzyme 3." Sayers T.J., Lloyd A.R., McVicar D.W., O'Connor M.D., Kelly J.M., Carter C.R.D., Wiltrout T.A., Wiltrout R.H., Smyth M.J. J. Leukoc. Biol. 59:763-768(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lymphocyte.
[3]	"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: Thymus.
[4]	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].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[6]	"Characterization of three serine esterases isolated from human IL-2 activated killer cells." Hameed A., Lowrey D.M., Lichtenheld M., Podack E.R. J. Immunol. 141:3142-3147(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-42, CHARACTERIZATION.
[7]	"Purification of three cytotoxic lymphocyte granule serine proteases that induce apoptosis through distinct substrate and target cell interactions." Shi L., Kam C.-M., Powers J.C., Aebersold R., Greenberg A.H. J. Exp. Med. 176:1521-1529(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-48.
[8]	"The 2.2-A crystal structure of human pro-granzyme K reveals a rigid zymogen with unusual features." Hink-Schauer C., Estebanez-Perpina E., Wilharm E., Fuentes-Prior P., Klinkert W., Bode W., Jenne D.E. J. Biol. Chem. 277:50923-50933(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 25-264.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U35237 mRNA. Translation: AAA79063.1.
U26174 mRNA. Translation: AAA74578.1.
AK312074 mRNA. Translation: BAG35010.1.
CH471123 Genomic DNA. Translation: EAW54899.1.
BC035802 mRNA. Translation: AAH35802.1.

IPI

IPI00028602.

PIR

S65663.

RefSeq

NP_002095.1. NM_002104.2.

UniGene

Hs.277937.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MZA	X-ray	2.23	A	25-264	[»]
1MZD	X-ray	2.90	A	25-264	[»]

ProteinModelPortal

P49863.

ModBase

Search...

Protein-protein interaction databases

IntAct

P49863. 2 interactions.

STRING

9606.ENSP00000231009.

Protein family/group databases

MEROPS

S01.146.

PTM databases

PhosphoSite

P49863.

Polymorphism databases

DMDM

1708035.

Proteomic databases

PaxDb

P49863.

PRIDE

P49863.

Protocols and materials databases

DNASU

3003.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000231009; ENSP00000231009; ENSG00000113088.

GeneID

3003.

KEGG

hsa:3003.

UCSC

uc003jpl.1. human.

Organism-specific databases

CTD

3003.

GeneCards

GC05P054320.

HGNC

HGNC:4711. GZMK.

MIM

600784. gene.

neXtProt

NX_P49863.

PharmGKB

PA29089.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5640.

HOGENOM

HOG000251820.

HOVERGEN

HBG013304.

InParanoid

P49863.

KO

K08663.

OMA

FLIVGAY.

OrthoDB

EOG4V9TR7.

PhylomeDB

P49863.

Gene expression databases

Bgee

P49863.

CleanEx

HS_GZMK.

Genevestigator

P49863.

GermOnline

ENSG00000113088. Homo sapiens.

Family and domain databases

InterPro

IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]

Pfam

PF00089. Trypsin. 1 hit.
[Graphical view]

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00020. Tryp_SPc. 1 hit.
[Graphical view]

SUPFAM

SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P49863.

ChEMBL

CHEMBL4930.

EvolutionaryTrace

P49863.

GenomeRNAi

3003.

NextBio

11908.

SOURCE

Search...

Entry information

Entry name

GRAK_HUMAN

Accession

Primary (citable) accession number: P49863
Secondary accession number(s): B2R563

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 114 of the entry and version 1 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.