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P20718

- GRAH_HUMAN

UniProt

P20718 - GRAH_HUMAN

Protein

Granzyme H

Gene

GZMH

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 139 (01 Oct 2014)
      Sequence version 1 (01 Feb 1991)
      Previous versions | rss
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    Functioni

    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.2 Publications

    Enzyme regulationi

    Inhibited by SERPINB1.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei64 – 641Charge relay systemBy similarity
    Active sitei108 – 1081Charge relay systemBy similarity
    Active sitei202 – 2021Charge relay systemBy similarity

    GO - Molecular functioni

    1. serine-type endopeptidase activity Source: UniProtKB

    GO - Biological processi

    1. apoptotic process Source: UniProtKB
    2. cytolysis Source: UniProtKB-KW

    Keywords - Molecular functioni

    Hydrolase, Protease, Serine protease

    Keywords - Biological processi

    Cytolysis

    Enzyme and pathway databases

    ReactomeiREACT_147707. Metabolism of Angiotensinogen to Angiotensins.
    REACT_15428. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).

    Protein family/group databases

    MEROPSiS01.147.

    Names & Taxonomyi

    Protein namesi
    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 namesi
    Name:GZMH
    Synonyms:CGL2, CTSGL2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:4710. GZMH.

    Subcellular locationi

    Cytoplasmic granule
    Note: Cytoplasmic granules of cytolytic T-lymphocytes.

    GO - Cellular componenti

    1. membrane Source: UniProtKB

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA29088.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1818Add
    BLAST
    Propeptidei19 – 202Activation peptidePRO_0000027413
    Chaini21 – 246226Granzyme HPRO_0000027414Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi49 ↔ 65
    Glycosylationi71 – 711N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi104 – 1041N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi142 ↔ 208
    Disulfide bondi172 ↔ 187
    Glycosylationi179 – 1791N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Zymogen

    Proteomic databases

    PaxDbiP20718.
    PRIDEiP20718.

    PTM databases

    PhosphoSiteiP20718.

    Expressioni

    Tissue specificityi

    Constituvely expressed in NK cells.1 Publication

    Gene expression databases

    ArrayExpressiP20718.
    BgeeiP20718.
    CleanExiHS_GZMH.
    GenevestigatoriP20718.

    Organism-specific databases

    HPAiHPA029200.

    Interactioni

    Protein-protein interaction databases

    BioGridi109254. 1 interaction.
    IntActiP20718. 1 interaction.
    MINTiMINT-4790347.
    STRINGi9606.ENSP00000216338.

    Structurei

    Secondary structure

    1
    246
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi35 – 4410
    Beta strandi46 – 5510
    Beta strandi58 – 614
    Helixi63 – 653
    Beta strandi68 – 758
    Beta strandi87 – 9610
    Helixi98 – 1003
    Turni102 – 1054
    Beta strandi110 – 1167
    Beta strandi121 – 1233
    Beta strandi141 – 1477
    Beta strandi149 – 1535
    Beta strandi160 – 1678
    Helixi169 – 1757
    Turni176 – 1783
    Turni182 – 1843
    Beta strandi185 – 1895
    Turni199 – 2035
    Beta strandi205 – 2084
    Beta strandi211 – 2188
    Beta strandi221 – 2233
    Beta strandi227 – 2315
    Turni232 – 2354
    Helixi236 – 2449

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1LXVmodel-A21-246[»]
    3TJUX-ray2.70A21-246[»]
    3TJVX-ray2.40A21-246[»]
    3TK9X-ray2.20A21-246[»]
    4GAWX-ray3.00A/B/C/D/E/F/G/H/I/J/K/L21-246[»]
    ProteinModelPortaliP20718.
    SMRiP20718. Positions 21-246.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini21 – 244224Peptidase S1PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni46 – 483Mediates the preference for acidic residues at the P3' and P4' sites

    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.
    InParanoidiP20718.
    KOiK09616.
    OMAiRKRCGGI.
    OrthoDBiEOG7RRF7Z.
    PhylomeDBiP20718.
    TreeFamiTF333630.

    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]

    Sequences (3)i

    Sequence statusi: Complete.

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

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P20718-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MQPFLLLLAF LLTPGAGTEE IIGGHEAKPH SRPYMAFVQF LQEKSRKRCG    50
    GILVRKDFVL TAAHCQGSSI NVTLGAHNIK EQERTQQFIP VKRPIPHPAY 100
    NPKNFSNDIM LLQLERKAKW TTAVRPLRLP SSKAQVKPGQ LCSVAGWGYV 150
    SMSTLATTLQ EVLLTVQKDC QCERLFHGNY SRATEICVGD PKKTQTGFKG 200
    DSGGPLVCKD VAQGILSYGN KKGTPPGVYI KVSHFLPWIK RTMKRL 246
    Length:246
    Mass (Da):27,315
    Last modified:February 1, 1991 - v1
    Checksum:iCA6A87F3DA5F1E71
    GO
    Isoform 2 (identifier: P20718-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         114-199: Missing.

    Show »
    Length:160
    Mass (Da):17,790
    Checksum:i5EC04B6A4EAE8E19
    GO
    Isoform 3 (identifier: P20718-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         69-199: Missing.

    Show »
    Length:115
    Mass (Da):12,609
    Checksum:i06D2C85F733515FC
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti68 – 681S → R in AAP70248. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti84 – 841R → Q.
    Corresponds to variant rs20545 [ dbSNP | Ensembl ].
    VAR_014556

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei69 – 199131Missing in isoform 3. 1 PublicationVSP_047573Add
    BLAST
    Alternative sequencei114 – 19986Missing in isoform 2. 1 PublicationVSP_047073Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J02907 Genomic DNA. Translation: AAA76859.1.
    M57888 Genomic DNA. Translation: AAA03514.1.
    M36118 mRNA. Translation: AAA03248.1.
    M72150 Genomic DNA. Translation: AAA74885.1.
    AY232657 mRNA. Translation: AAP70247.1.
    AY232658 mRNA. Translation: AAP70248.1.
    AL136018 Genomic DNA. No translation available.
    CH471078 Genomic DNA. Translation: EAW66004.1.
    BC027974 mRNA. Translation: AAH27974.1.
    CCDSiCCDS59243.1. [P20718-2]
    CCDS9632.1. [P20718-1]
    PIRiA32692.
    RefSeqiNP_001257710.1. NM_001270781.1. [P20718-2]
    NP_219491.1. NM_033423.4. [P20718-1]
    UniGeneiHs.348264.

    Genome annotation databases

    EnsembliENST00000216338; ENSP00000216338; ENSG00000100450. [P20718-1]
    ENST00000382548; ENSP00000371988; ENSG00000100450. [P20718-2]
    ENST00000557220; ENSP00000450576; ENSG00000100450.
    GeneIDi2999.
    KEGGihsa:2999.
    UCSCiuc001wpr.2. human. [P20718-1]
    uc010aly.2. human.

    Polymorphism databases

    DMDMi121590.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J02907 Genomic DNA. Translation: AAA76859.1 .
    M57888 Genomic DNA. Translation: AAA03514.1 .
    M36118 mRNA. Translation: AAA03248.1 .
    M72150 Genomic DNA. Translation: AAA74885.1 .
    AY232657 mRNA. Translation: AAP70247.1 .
    AY232658 mRNA. Translation: AAP70248.1 .
    AL136018 Genomic DNA. No translation available.
    CH471078 Genomic DNA. Translation: EAW66004.1 .
    BC027974 mRNA. Translation: AAH27974.1 .
    CCDSi CCDS59243.1. [P20718-2 ]
    CCDS9632.1. [P20718-1 ]
    PIRi A32692.
    RefSeqi NP_001257710.1. NM_001270781.1. [P20718-2 ]
    NP_219491.1. NM_033423.4. [P20718-1 ]
    UniGenei Hs.348264.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    ProteinModelPortali P20718.
    SMRi P20718. Positions 21-246.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109254. 1 interaction.
    IntActi P20718. 1 interaction.
    MINTi MINT-4790347.
    STRINGi 9606.ENSP00000216338.

    Protein family/group databases

    MEROPSi S01.147.

    PTM databases

    PhosphoSitei P20718.

    Polymorphism databases

    DMDMi 121590.

    Proteomic databases

    PaxDbi P20718.
    PRIDEi P20718.

    Protocols and materials databases

    DNASUi 2999.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000216338 ; ENSP00000216338 ; ENSG00000100450 . [P20718-1 ]
    ENST00000382548 ; ENSP00000371988 ; ENSG00000100450 . [P20718-2 ]
    ENST00000557220 ; ENSP00000450576 ; ENSG00000100450 .
    GeneIDi 2999.
    KEGGi hsa:2999.
    UCSCi uc001wpr.2. human. [P20718-1 ]
    uc010aly.2. human.

    Organism-specific databases

    CTDi 2999.
    GeneCardsi GC14M025075.
    HGNCi HGNC:4710. GZMH.
    HPAi HPA029200.
    MIMi 116831. gene.
    neXtProti NX_P20718.
    PharmGKBi PA29088.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5640.
    HOGENOMi HOG000251820.
    HOVERGENi HBG013304.
    InParanoidi P20718.
    KOi K09616.
    OMAi RKRCGGI.
    OrthoDBi EOG7RRF7Z.
    PhylomeDBi P20718.
    TreeFami TF333630.

    Enzyme and pathway databases

    Reactomei REACT_147707. Metabolism of Angiotensinogen to Angiotensins.
    REACT_15428. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).

    Miscellaneous databases

    GeneWikii GZMH.
    GenomeRNAii 2999.
    NextBioi 11892.
    PROi P20718.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P20718.
    Bgeei P20718.
    CleanExi HS_GZMH.
    Genevestigatori P20718.

    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. "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] (ISOFORM 1).
    4. "Identification and characterization of granzyme H splice variants 2 and 3 from large granular lymphocyte leukemia."
      Kothapalli R., Kusmartseva I., Loughran T.P. Jr.
      Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
      Tissue: Leukemic T-cell.
    5. "The DNA sequence and analysis of human chromosome 14."
      Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H.
      , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
      Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "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] (ISOFORM 1).
      Tissue: Pancreas.
    8. "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.
    9. "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.

    Entry informationi

    Entry nameiGRAH_HUMAN
    AccessioniPrimary (citable) accession number: P20718
    Secondary accession number(s): G3V2C5, Q6XGZ0, Q6XGZ1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1991
    Last sequence update: February 1, 1991
    Last modified: October 1, 2014
    This is version 139 of the entry and version 1 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 14
      Human chromosome 14: 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