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P51124

- GRAM_HUMAN

UniProt

P51124 - GRAM_HUMAN

Protein

Granzyme M

Gene

GZMM

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 2 (18 May 2010)
      Previous versions | rss
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    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

    1. serine-type endopeptidase activity Source: InterPro
    2. serine-type peptidase activity Source: ProtInc

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. cytolysis Source: UniProtKB-KW
    3. innate immune response Source: UniProtKB-KW

    Keywords - Molecular functioni

    Hydrolase, Protease, Serine protease

    Keywords - Biological processi

    Apoptosis, Cytolysis, Immunity, Innate immunity

    Enzyme and pathway databases

    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: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:4712. GZMM.

    Subcellular locationi

    Secreted. Cytoplasmic granule
    Note: Granules of large granular lymphocytes.

    GO - Cellular componenti

    1. extracellular region Source: UniProtKB-SubCell
    2. membrane Source: UniProtKB

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA29090.

    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 ↔ 671 PublicationPROSITE-ProRule annotation
    Disulfide bondi145 ↔ 2131 PublicationPROSITE-ProRule annotation
    Disulfide bondi176 ↔ 1921 PublicationPROSITE-ProRule annotation
    Glycosylationi177 – 1771N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi203 ↔ 2301 PublicationPROSITE-ProRule annotation

    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.
    GenevestigatoriP51124.

    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 – 456
    Beta strandi48 – 5710
    Beta strandi60 – 634
    Helixi65 – 684
    Helixi72 – 743
    Beta strandi75 – 806
    Beta strandi82 – 865
    Beta strandi89 – 9810
    Turni105 – 1073
    Beta strandi113 – 1197
    Beta strandi144 – 1496
    Beta strandi152 – 1543
    Beta strandi164 – 1707
    Helixi173 – 1764
    Turni179 – 1846
    Beta strandi190 – 1945
    Beta strandi210 – 2134
    Turni214 – 2174
    Beta strandi218 – 2236
    Beta strandi238 – 2425
    Helixi243 – 2453
    Helixi246 – 2538

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    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

    MEACVSSLLV LALGALSVGS SFGTQIIGGR EVIPHSRPYM ASLQRNGSHL    50
    CGGVLVHPKW VLTAAHCLAQ RMAQLRLVLG LHTLDSPGLT FHIKAAIQHP 100
    RYKPVPALEN DLALLQLDGK VKPSRTIRPL ALPSKRQVVA AGTRCSMAGW 150
    GLTHQGGRLS RVLRELDLQV LDTRMCNNSR FWNGSLSPSM VCLAADSKDQ 200
    APCKGDSGGP LVCGKGRVLA RVLSFSSRVC TDIFKPPVAT AVAPYVSWIR 250
    KVTGRSA 257
    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:
    EMBL
    GenBank
    DDBJ
    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.

    Polymorphism databases

    DMDMi296434527.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS12031.1.
    PIRi A55634.
    RefSeqi NP_001245280.1. NM_001258351.1.
    NP_005308.1. NM_005317.3.
    UniGenei Hs.465511.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    ProteinModelPortali P51124.
    SMRi P51124. Positions 26-256.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109259. 5 interactions.
    STRINGi 9606.ENSP00000264553.

    Protein family/group databases

    MEROPSi S01.139.

    PTM databases

    PhosphoSitei P51124.

    Polymorphism databases

    DMDMi 296434527.

    Proteomic databases

    PaxDbi P51124.
    PRIDEi P51124.

    Protocols and materials databases

    DNASUi 3004.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000264553 ; ENSP00000264553 ; ENSG00000197540 .
    GeneIDi 3004.
    KEGGi hsa:3004.
    UCSCi uc002low.2. human.

    Organism-specific databases

    CTDi 3004.
    GeneCardsi GC19P000544.
    HGNCi HGNC:4712. GZMM.
    HPAi HPA015624.
    MIMi 600311. gene.
    neXtProti NX_P51124.
    PharmGKBi PA29090.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5640.
    HOGENOMi HOG000251820.
    HOVERGENi HBG013304.
    InParanoidi P51124.
    KOi K08649.
    OMAi KDQAPCK.
    OrthoDBi EOG7HQN8W.
    PhylomeDBi P51124.
    TreeFami TF335738.

    Enzyme and pathway databases

    Reactomei REACT_8001. Alternative complement activation.

    Miscellaneous databases

    EvolutionaryTracei P51124.
    GeneWikii GZMM.
    GenomeRNAii 3004.
    NextBioi 11912.
    PROi P51124.
    SOURCEi Search...

    Gene expression databases

    Bgeei P51124.
    CleanExi HS_GZMM.
    Genevestigatori P51124.

    Family and domain databases

    InterProi IPR001254. Peptidase_S1.
    IPR018114. Peptidase_S1_AS.
    IPR001314. Peptidase_S1A.
    IPR009003. Trypsin-like_Pept_dom.
    [Graphical view ]
    Pfami PF00089. Trypsin. 1 hit.
    [Graphical view ]
    PRINTSi PR00722. CHYMOTRYPSIN.
    SMARTi SM00020. Tryp_SPc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50494. SSF50494. 1 hit.
    PROSITEi PS50240. TRYPSIN_DOM. 1 hit.
    PS00134. TRYPSIN_HIS. 1 hit.
    PS00135. TRYPSIN_SER. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 122 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