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Protein

Granzyme M

Gene

GZMM

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei66 – 661Charge relay system1 Publication
Active sitei111 – 1111Charge relay system1 Publication
Active sitei207 – 2071Charge relay system1 Publication

GO - Molecular functioni

  • serine-type endopeptidase activity Source: UniProtKB
  • serine-type peptidase activity Source: ProtInc

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cell death Source: UniProtKB
  • cytolysis Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Apoptosis, Cytolysis, Immunity, Innate immunity

Enzyme and pathway databases

BRENDAi3.4.21.78. 2681.
3.4.21.B2. 2681.
ReactomeiREACT_8001. Alternative complement activation.

Protein family/group databases

MEROPSiS01.139.

Names & Taxonomyi

Protein namesi
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 namesi
Name:GZMM
Synonyms:MET1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:4712. GZMM.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: UniProtKB-SubCell
  • membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA29090.

Polymorphism and mutation databases

BioMutaiGZMM.
DMDMi296434527.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence AnalysisAdd
BLAST
Propeptidei24 – 252Activation peptideSequence AnalysisPRO_0000027421
Chaini26 – 257232Granzyme MPRO_0000027422Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi51 ↔ 67PROSITE-ProRule annotation1 Publication
Disulfide bondi145 ↔ 213PROSITE-ProRule annotation1 Publication
Disulfide bondi176 ↔ 192PROSITE-ProRule annotation1 Publication
Glycosylationi177 – 1771N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi203 ↔ 230PROSITE-ProRule annotation1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiP51124.
PRIDEiP51124.

PTM databases

PhosphoSiteiP51124.

Expressioni

Tissue specificityi

Highly and constitutively expressed in activated natural killer (NK) cells.1 Publication

Gene expression databases

BgeeiP51124.
CleanExiHS_GZMM.
ExpressionAtlasiP51124. baseline and differential.
GenevisibleiP51124. HS.

Organism-specific databases

HPAiHPA015624.

Interactioni

Protein-protein interaction databases

BioGridi109259. 5 interactions.
STRINGi9606.ENSP00000264553.

Structurei

Secondary structure

1
257
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi40 – 456Combined sources
Beta strandi48 – 5710Combined sources
Beta strandi60 – 634Combined sources
Helixi65 – 684Combined sources
Helixi72 – 743Combined sources
Beta strandi75 – 806Combined sources
Beta strandi82 – 865Combined sources
Beta strandi89 – 9810Combined sources
Turni105 – 1073Combined sources
Beta strandi113 – 1197Combined sources
Beta strandi144 – 1496Combined sources
Beta strandi152 – 1543Combined sources
Beta strandi164 – 1707Combined sources
Helixi173 – 1764Combined sources
Turni179 – 1846Combined sources
Beta strandi190 – 1945Combined sources
Beta strandi210 – 2134Combined sources
Turni214 – 2174Combined sources
Beta strandi218 – 2236Combined sources
Beta strandi238 – 2425Combined sources
Helixi243 – 2453Combined sources
Helixi246 – 2538Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LZPmodel-A26-257[»]
2ZGCX-ray1.96A26-257[»]
2ZGHX-ray2.17A26-257[»]
2ZGJX-ray2.30A26-257[»]
2ZKSX-ray2.70A26-257[»]
ProteinModelPortaliP51124.
SMRiP51124. Positions 26-256.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP51124.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini26 – 254229Peptidase S1PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase S1 family. Granzyme subfamily.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiCOG5640.
GeneTreeiENSGT00760000118895.
HOGENOMiHOG000251820.
HOVERGENiHBG013304.
InParanoidiP51124.
KOiK08649.
OMAiKDQAPCK.
OrthoDBiEOG7HQN8W.
PhylomeDBiP51124.
TreeFamiTF335738.

Family and domain databases

InterProiIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P51124-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEACVSSLLV LALGALSVGS SFGTQIIGGR EVIPHSRPYM ASLQRNGSHL
60 70 80 90 100
CGGVLVHPKW VLTAAHCLAQ RMAQLRLVLG LHTLDSPGLT FHIKAAIQHP
110 120 130 140 150
RYKPVPALEN DLALLQLDGK VKPSRTIRPL ALPSKRQVVA AGTRCSMAGW
160 170 180 190 200
GLTHQGGRLS RVLRELDLQV LDTRMCNNSR FWNGSLSPSM VCLAADSKDQ
210 220 230 240 250
APCKGDSGGP LVCGKGRVLA RVLSFSSRVC TDIFKPPVAT AVAPYVSWIR

KVTGRSA
Length:257
Mass (Da):27,545
Last modified:May 18, 2010 - v2
Checksum:iB4E815CE455F7371
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti221 – 2211R → G.3 Publications
Corresponds to variant rs1599882 [ dbSNP | Ensembl ].
VAR_051829

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS12031.1.
PIRiA55634.
RefSeqiNP_001245280.1. NM_001258351.1.
NP_005308.1. NM_005317.3.
UniGeneiHs.465511.

Genome annotation databases

EnsembliENST00000264553; ENSP00000264553; ENSG00000197540.
GeneIDi3004.
KEGGihsa:3004.
UCSCiuc002low.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS12031.1.
PIRiA55634.
RefSeqiNP_001245280.1. NM_001258351.1.
NP_005308.1. NM_005317.3.
UniGeneiHs.465511.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LZPmodel-A26-257[»]
2ZGCX-ray1.96A26-257[»]
2ZGHX-ray2.17A26-257[»]
2ZGJX-ray2.30A26-257[»]
2ZKSX-ray2.70A26-257[»]
ProteinModelPortaliP51124.
SMRiP51124. Positions 26-256.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109259. 5 interactions.
STRINGi9606.ENSP00000264553.

Protein family/group databases

MEROPSiS01.139.

PTM databases

PhosphoSiteiP51124.

Polymorphism and mutation databases

BioMutaiGZMM.
DMDMi296434527.

Proteomic databases

PaxDbiP51124.
PRIDEiP51124.

Protocols and materials databases

DNASUi3004.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264553; ENSP00000264553; ENSG00000197540.
GeneIDi3004.
KEGGihsa:3004.
UCSCiuc002low.2. human.

Organism-specific databases

CTDi3004.
GeneCardsiGC19P000544.
HGNCiHGNC:4712. GZMM.
HPAiHPA015624.
MIMi600311. gene.
neXtProtiNX_P51124.
PharmGKBiPA29090.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5640.
GeneTreeiENSGT00760000118895.
HOGENOMiHOG000251820.
HOVERGENiHBG013304.
InParanoidiP51124.
KOiK08649.
OMAiKDQAPCK.
OrthoDBiEOG7HQN8W.
PhylomeDBiP51124.
TreeFamiTF335738.

Enzyme and pathway databases

BRENDAi3.4.21.78. 2681.
3.4.21.B2. 2681.
ReactomeiREACT_8001. Alternative complement activation.

Miscellaneous databases

EvolutionaryTraceiP51124.
GeneWikiiGZMM.
GenomeRNAii3004.
NextBioi11912.
PROiP51124.
SOURCEiSearch...

Gene expression databases

BgeeiP51124.
CleanExiHS_GZMM.
ExpressionAtlasiP51124. baseline and differential.
GenevisibleiP51124. HS.

Family and domain databases

InterProiIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiGRAM_HUMAN
AccessioniPrimary (citable) accession number: P51124
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 18, 2010
Last modified: June 24, 2015
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.