P51124 (GRAM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Granzyme M
EC=3.4.21.-

Alternative name(s):
Met-1 serine protease
Short name=Hu-Met-1
Met-ase
Natural killer cell granular protease

Gene names

Name:	GZMM
Synonyms:	MET1

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	257 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	Cleaves peptide substrates after methionine, leucine, and norleucine. Physiological substrates include EZR, alpha-tubulins and the apoptosis inhibitor BIRC5/Survivin. Promotes caspase activation and subsequent apoptosis of target cells. Ref.5 Ref.6
Subcellular location	Secreted. Cytoplasmic granule. Note: Granules of large granular lymphocytes.
Tissue specificity	Highly and constitutively expressed in activated natural killer (NK) cells. Ref.5
Sequence similarities	Belongs to the peptidase S1 family. Granzyme subfamily. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Biological process	Apoptosis Cytolysis Immunity Innate immunity
Cellular component	Secreted
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 Inferred from electronic annotation. Source: UniProtKB-KW cytolysis Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: UniProtKB-KW 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 – 23

23

Potential

Propeptide

24 – 25

2

Activation peptide Potential

PRO_0000027421

Chain

26 – 257

232

Granzyme M

PRO_0000027422

Regions

Domain

26 – 254

229

Peptidase S1

Sites

Active site

66

1

Charge relay system Ref.7

Active site

111

1

Charge relay system Ref.7

Active site

207

1

Charge relay system Ref.7

Amino acid modifications

Glycosylation

177

1

N-linked (GlcNAc...) Potential

Disulfide bond

51 ↔ 67

Ref.7

Disulfide bond

145 ↔ 213

Ref.7

Disulfide bond

176 ↔ 192

Ref.7

Disulfide bond

203 ↔ 230

Ref.7

Natural variations

Natural variant

221

1

R → G. Ref.1 Ref.2 Ref.4
Corresponds to variant rs1599882 [ dbSNP | Ensembl ].

VAR_051829

Secondary structure

1

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257

Helix Strand Turn

Details...

Beta strand

40 – 45

6

Beta strand

48 – 57

10

Beta strand

60 – 63

4

Helix

65 – 68

4

Helix

72 – 74

3

Beta strand

75 – 80

6

Beta strand

82 – 86

5

Beta strand

89 – 98

10

Turn

105 – 107

3

Beta strand

113 – 119

7

Beta strand

144 – 149

6

Beta strand

152 – 154

3

Beta strand

164 – 170

7

Helix

173 – 176

4

Turn

179 – 184

6

Beta strand

190 – 194

5

Beta strand

210 – 213

4

Turn

214 – 217

4

Beta strand

218 – 223

6

Beta strand

238 – 242

5

Helix

243 – 245

3

Helix

246 – 253

8

Sequences

	Sequence		Length	Mass (Da)
	P51124 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: B4E815CE455F7371	FASTA	257	27,545
	10 20 30 40 50 60 MEACVSSLLV LALGALSVGS SFGTQIIGGR EVIPHSRPYM ASLQRNGSHL CGGVLVHPKW 70 80 90 100 110 120 VLTAAHCLAQ RMAQLRLVLG LHTLDSPGLT FHIKAAIQHP RYKPVPALEN DLALLQLDGK 130 140 150 160 170 180 VKPSRTIRPL ALPSKRQVVA AGTRCSMAGW GLTHQGGRLS RVLRELDLQV LDTRMCNNSR 190 200 210 220 230 240 FWNGSLSPSM VCLAADSKDQ APCKGDSGGP LVCGKGRVLA RVLSFSSRVC TDIFKPPVAT 250 AVAPYVSWIR KVTGRSA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Met-ase: cloning and distinct chromosomal location of a serine protease preferentially expressed in human natural killer cells." Smyth M.J., Sayers T.J., Wiltrout T., Powers J.C., Trapani J.A. J. Immunol. 151:6195-6205(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLY-221.
[2]	"The human Met-ase gene (GZMM): structure, sequence, and close physical linkage to the serine protease gene cluster on 19p13.3." Pilat D., Fink T.M., Obermaier-Skrobanek B., Zimmer M., Wekerle H., Lichter P., Jenne D.E. Genomics 24:445-450(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLY-221.
[3]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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], VARIANT GLY-221. Tissue: Pancreas and Spleen.
[5]	"NK cell protease granzyme M targets alpha-tubulin and disorganizes the microtubule network." Bovenschen N., de Koning P.J., Quadir R., Broekhuizen R., Damen J.M., Froelich C.J., Slijper M., Kummer J.A. J. Immunol. 180:8184-8191(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, SUBSTRATES.
[6]	"Cleavage of survivin by Granzyme M triggers degradation of the survivin-X-linked inhibitor of apoptosis protein (XIAP) complex to free caspase activity leading to cytolysis of target tumor cells." Hu D., Liu S., Shi L., Li C., Wu L., Fan Z. J. Biol. Chem. 285:18326-18335(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Structural basis for proteolytic specificity of the human apoptosis-inducing granzyme M." Wu L., Wang L., Hua G., Liu K., Yang X., Zhai Y., Bartlam M., Sun F., Fan Z. J. Immunol. 183:421-429(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 26-257, ACTIVE SITE, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L23134 mRNA. Translation: AAA59582.1.
L36922 Genomic DNA. Translation: AAA57262.1.
L36936 Genomic DNA. Translation: AAA57257.1.
AC011556 Genomic DNA. No translation available.
BC025701 mRNA. Translation: AAH25701.1.

IPI

IPI00016282.

PIR

A55634.

RefSeq

NP_001245280.1. NM_001258351.1.
NP_005308.1. NM_005317.3.

UniGene

Hs.465511.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LZP	model	-	A	26-257	[»]
2ZGC	X-ray	1.96	A	26-257	[»]
2ZGH	X-ray	2.17	A	26-257	[»]
2ZGJ	X-ray	2.30	A	26-257	[»]
2ZKS	X-ray	2.70	A	26-257	[»]

ProteinModelPortal

P51124.

SMR

P51124. Positions 26-256.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000264553.

Protein family/group databases

MEROPS

S01.139.

PTM databases

PhosphoSite

P51124.

Polymorphism databases

DMDM

296434527.

Proteomic databases

PaxDb

P51124.

PRIDE

P51124.

Protocols and materials databases

DNASU

3004.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264553; ENSP00000264553; ENSG00000197540.

GeneID

3004.

KEGG

hsa:3004.

UCSC

uc002low.1. human.

Organism-specific databases

CTD

3004.

GeneCards

GC19P000544.

HGNC

HGNC:4712. GZMM.

HPA

HPA015624.

MIM

600311. gene.

neXtProt

NX_P51124.

PharmGKB

PA29090.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5640.

HOGENOM

HOG000251820.

HOVERGEN

HBG013304.

InParanoid

P51124.

KO

K08649.

OMA

KDQAPCK.

OrthoDB

EOG4TMR2V.

PhylomeDB

P51124.

Gene expression databases

Bgee

P51124.

CleanEx

HS_GZMM.

Genevestigator

P51124.

GermOnline

ENSG00000197540. 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

EvolutionaryTrace

P51124.

GenomeRNAi

3004.

NextBio

11912.

SOURCE

Search...

Entry information

Entry name

GRAM_HUMAN

Accession

Primary (citable) accession number: P51124

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	May 18, 2010
Last modified:	April 3, 2013
This is version 112 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.