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P51124 (GRAM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length257 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processApoptosis
Cytolysis
Immunity
Innate immunity
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionHydrolase
Protease
Serine protease
   PTMDisulfide bond
Glycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic 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

   Cellular_componentextracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionserine-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Propeptide24 – 252Activation peptide Potential
PRO_0000027421
Chain26 – 257232Granzyme M
PRO_0000027422

Regions

Domain26 – 254229Peptidase S1

Sites

Active site661Charge relay system Ref.7
Active site1111Charge relay system Ref.7
Active site2071Charge relay system Ref.7

Amino acid modifications

Glycosylation1771N-linked (GlcNAc...) Potential
Disulfide bond51 ↔ 67 Ref.7
Disulfide bond145 ↔ 213 Ref.7
Disulfide bond176 ↔ 192 Ref.7
Disulfide bond203 ↔ 230 Ref.7

Natural variations

Natural variant2211R → G. Ref.1 Ref.2 Ref.4
Corresponds to variant rs1599882 [ dbSNP | Ensembl ].
VAR_051829

Secondary structure

........................................ 257
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P51124 [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: B4E815CE455F7371

FASTA25727,545
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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.
CCDSCCDS12031.1.
PIRA55634.
RefSeqNP_001245280.1. NM_001258351.1.
NP_005308.1. NM_005317.3.
UniGeneHs.465511.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LZPmodel-A26-257[»]
2ZGCX-ray1.96A26-257[»]
2ZGHX-ray2.17A26-257[»]
2ZGJX-ray2.30A26-257[»]
2ZKSX-ray2.70A26-257[»]
ProteinModelPortalP51124.
SMRP51124. Positions 26-256.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109259. 5 interactions.
STRING9606.ENSP00000264553.

Protein family/group databases

MEROPSS01.139.

PTM databases

PhosphoSiteP51124.

Polymorphism databases

DMDM296434527.

Proteomic databases

PaxDbP51124.
PRIDEP51124.

Protocols and materials databases

DNASU3004.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264553; ENSP00000264553; ENSG00000197540.
GeneID3004.
KEGGhsa:3004.
UCSCuc002low.2. human.

Organism-specific databases

CTD3004.
GeneCardsGC19P000544.
HGNCHGNC:4712. GZMM.
HPAHPA015624.
MIM600311. gene.
neXtProtNX_P51124.
PharmGKBPA29090.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOGENOMHOG000251820.
HOVERGENHBG013304.
InParanoidP51124.
KOK08649.
OMAKDQAPCK.
OrthoDBEOG7HQN8W.
PhylomeDBP51124.
TreeFamTF335738.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

BgeeP51124.
CleanExHS_GZMM.
GenevestigatorP51124.

Family and domain databases

InterProIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
PROSITEPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP51124.
GeneWikiGZMM.
GenomeRNAi3004.
NextBio11912.
PROP51124.
SOURCESearch...

Entry information

Entry nameGRAM_HUMAN
AccessionPrimary (citable) accession number: P51124
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 18, 2010
Last modified: July 9, 2014
This is version 120 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM