P20718 (GRAH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Granzyme H
EC=3.4.21.-

Alternative name(s):
CCP-X
Cathepsin G-like 2
Short name=CTSGL2
Cytotoxic T-lymphocyte proteinase
Cytotoxic serine protease C
Short name=CSP-C

Gene names

Name:	GZMH
Synonyms:	CGL2, CTSGL2

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	246 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	Cytotoxic chymotrypsin-like serine protease with preference for bulky and aromatic residues at the P1 position and acidic residues at the P3' and P4' sites. Probably necessary for target cell lysis in cell-mediated immune responses. Participates in the antiviral response via direct cleavage of several proteins essential for viral replication. Ref.5 Ref.6
Enzyme regulation	Inhibited by SERPINB1. Ref.6
Subcellular location	Cytoplasmic granule. Note: Cytoplasmic granules of cytolytic T-lymphocytes.
Tissue specificity	Constituvely expressed in NK cells. Ref.6
Sequence similarities	Belongs to the peptidase S1 family. Granzyme subfamily. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Biological process	Cytolysis
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Non-traceable author statement Ref.1Ref.3. Source: UniProtKB cytolysis Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Non-traceable author statement. Source: UniProtKB
Cellular_component	cytoplasm Non-traceable author statement. Source: UniProtKB
Molecular_function	serine-type endopeptidase activity Non-traceable author statement Ref.1Ref.3. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Propeptide

19 – 20

2

Activation peptide

PRO_0000027413

Chain

21 – 246

226

Granzyme H

PRO_0000027414

Regions

Domain

21 – 244

224

Peptidase S1

Region

46 – 48

3

Mediates the preference for acidic residues at the P3' and P4' sites

Sites

Active site

64

1

Charge relay system By similarity

Active site

108

1

Charge relay system By similarity

Active site

202

1

Charge relay system By similarity

Amino acid modifications

Glycosylation

71

1

N-linked (GlcNAc...) Potential

Glycosylation

104

1

N-linked (GlcNAc...) Potential

Glycosylation

179

1

N-linked (GlcNAc...) Potential

Disulfide bond

49 ↔ 65

Ref.5 Ref.6

Disulfide bond

142 ↔ 208

Ref.5 Ref.6

Disulfide bond

172 ↔ 187

Ref.5 Ref.6

Natural variations

Natural variant

84

1

R → Q.
Corresponds to variant rs20545 [ dbSNP | Ensembl ].

VAR_014556

Secondary structure

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246

Helix Strand Turn

Details...

Beta strand

35 – 44

10

Beta strand

46 – 55

10

Beta strand

58 – 61

4

Helix

63 – 65

3

Beta strand

68 – 75

8

Beta strand

87 – 96

10

Helix

98 – 100

3

Turn

102 – 105

4

Beta strand

110 – 116

7

Beta strand

121 – 123

3

Beta strand

141 – 147

7

Beta strand

149 – 153

5

Beta strand

160 – 167

8

Helix

169 – 175

7

Turn

176 – 178

3

Turn

182 – 184

3

Beta strand

185 – 189

5

Turn

199 – 203

5

Beta strand

205 – 208

4

Beta strand

211 – 218

8

Beta strand

221 – 223

3

Beta strand

227 – 231

5

Turn

232 – 235

4

Helix

236 – 244

9

Sequences

	Sequence		Length	Mass (Da)
	P20718 [UniParc]. Last modified February 1, 1991. Version 1. Checksum: CA6A87F3DA5F1E71	FASTA	246	27,315
	10 20 30 40 50 60 MQPFLLLLAF LLTPGAGTEE IIGGHEAKPH SRPYMAFVQF LQEKSRKRCG GILVRKDFVL 70 80 90 100 110 120 TAAHCQGSSI NVTLGAHNIK EQERTQQFIP VKRPIPHPAY NPKNFSNDIM LLQLERKAKW 130 140 150 160 170 180 TTAVRPLRLP SSKAQVKPGQ LCSVAGWGYV SMSTLATTLQ EVLLTVQKDC QCERLFHGNY 190 200 210 220 230 240 SRATEICVGD PKKTQTGFKG DSGGPLVCKD VAQGILSYGN KKGTPPGVYI KVSHFLPWIK RTMKRL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a gene that encodes a new member of the human cytotoxic cell protease family." Meier M., Kwong P.C., Fregeau C.J., Atkinson E.A., Burrington M., Ehrman N., Sorensen O., Lin C.C., Wilkins J., Bleackley R.C. Biochemistry 29:4042-4049(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Structure and evolutionary origin of the human granzyme H gene." Haddad P., Jenne D.E., Tschopp J., Clement M.-V., Mathieu-Mahul D., Sasportes M. Int. Immunol. 3:57-66(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Characterization of a novel, human cytotoxic lymphocyte-specific serine protease cDNA clone (CSP-C)." Klein J.L., Selvakumar A., Trapani J.A., Dupont B. Tissue Antigens 35:220-228(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"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.
[5]	"Structural insights into the substrate specificity of human granzyme H: the functional roles of a novel RKR motif." Wang L., Zhang K., Wu L., Liu S., Zhang H., Zhou Q., Tong L., Sun F., Fan Z. J. Immunol. 188:765-773(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 21-246 OF MUTANT ASN-102 ALONE AND IN COMPLEX WITH SUBSTRATE PEPTIDE AND INHIBITOR, FUNCTION, SUBSTRATE SPECIFICITY, DISULFIDE BONDS.
[6]	"Identification of SERPINB1 as a physiological inhibitor of human granzyme H." Wang L., Li Q., Wu L., Liu S., Zhang Y., Yang X., Zhu P., Zhang H., Zhang K., Lou J., Liu P., Tong L., Sun F., Fan Z. J. Immunol. 190:1319-1330(2013) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 21-246 IN COMPLEX WITH SERPINB1, FUNCTION, DISULFIDE BONDS, TISSUE SPECIFICITY, ENZYME REGULATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J02907 Genomic DNA. Translation: AAA76859.1.
M57888 Genomic DNA. Translation: AAA03514.1.
M36118 mRNA. Translation: AAA03248.1.
M72150 Genomic DNA. Translation: AAA74885.1.
BC027974 mRNA. Translation: AAH27974.1.

IPI

IPI00025400.

PIR

A32692.

RefSeq

NP_219491.1. NM_033423.4.

UniGene

Hs.348264.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LXV	model	-	A	21-246	[»]
3TJU	X-ray	2.70	A	21-246	[»]
3TJV	X-ray	2.40	A	21-246	[»]
3TK9	X-ray	2.20	A	21-246	[»]
4GAW	X-ray	3.00	A/B/C/D/E/F/G/H/I/J/K/L	21-246	[»]

ProteinModelPortal

P20718.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-4790347.

STRING

9606.ENSP00000216338.

Protein family/group databases

MEROPS

S01.147.

PTM databases

PhosphoSite

P20718.

Polymorphism databases

DMDM

121590.

Proteomic databases

PaxDb

P20718.

PRIDE

P20718.

Protocols and materials databases

DNASU

2999.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000216338; ENSP00000216338; ENSG00000100450.

GeneID

2999.

KEGG

hsa:2999.

UCSC

uc001wpr.1. human.

Organism-specific databases

CTD

2999.

GeneCards

GC14M025075.

HGNC

HGNC:4710. GZMH.

HPA

HPA029200.

MIM

116831. gene.

neXtProt

NX_P20718.

PharmGKB

PA29088.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5640.

HOGENOM

HOG000251820.

HOVERGEN

HBG013304.

InParanoid

P20718.

KO

K09616.

OMA

LVCKDVA.

OrthoDB

EOG4KWJTW.

Gene expression databases

ArrayExpress

P20718.

Bgee

P20718.

CleanEx

HS_GZMH.

Genevestigator

P20718.

GermOnline

ENSG00000100450. 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

GenomeRNAi

2999.

NextBio

11892.

SOURCE

Search...

Entry information

Entry name

GRAH_HUMAN

Accession

Primary (citable) accession number: P20718

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	February 1, 1991
Last modified:	May 1, 2013
This is version 126 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.