GGRNA | NM_001270780.1

LOCUS       NM_001270780             795 bp    mRNA    linear   PRI 14-MAY-2013
DEFINITION  Homo sapiens granzyme H (cathepsin G-like 2, protein h-CCPX)
            (GZMH), transcript variant 2, mRNA.
ACCESSION   NM_001270780
VERSION     NM_001270780.1  GI:399124764
KEYWORDS    RefSeq.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 795)
  AUTHORS   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. and Fan,Z.
  TITLE     Identification of SERPINB1 as a physiological inhibitor of human
            granzyme H
  JOURNAL   J. Immunol. 190 (3), 1319-1330 (2013)
   PUBMED   23269243
  REMARK    GeneRIF: Upon reactive center loop cleavage at Phe-343,SERPINB1
            covalently complexes with GzmH. SERPINB1 overexpression suppresses
            GzmH- or LAK cell-mediated cytotoxicity. Crystal structures show
            possible conformational changes in GzmH for the suicide inhibition.
REFERENCE   2  (bases 1 to 795)
  AUTHORS   Wang,L., Zhang,K., Wu,L., Liu,S., Zhang,H., Zhou,Q., Tong,L.,
            Sun,F. and Fan,Z.
  TITLE     Structural insights into the substrate specificity of human
            granzyme H: the functional roles of a novel RKR motif
  JOURNAL   J. Immunol. 188 (2), 765-773 (2012)
   PUBMED   22156497
  REMARK    GeneRIF: An unusual RKR motif (Arg39-Lys40-Arg41), conserved only
            in GzmH, helps define the S3' and S4' binding regions, indicating
            the preference for acidic residues at the P3' and P4' sites.
REFERENCE   3  (bases 1 to 795)
  AUTHORS   Tang,H., Li,C., Wang,L., Zhang,H. and Fan,Z.
  TITLE     Granzyme H of cytotoxic lymphocytes is required for clearance of
            the hepatitis B virus through cleavage of the hepatitis B virus X
            protein
  JOURNAL   J. Immunol. 188 (2), 824-831 (2012)
   PUBMED   22156339
  REMARK    GeneRIF: GzmH suppresses viral replication through association with
            the hepatitis B virus x protein.
REFERENCE   4  (bases 1 to 795)
  AUTHORS   Romero,V., Fellows,E., Jenne,D.E. and Andrade,F.
  TITLE     Cleavage of La protein by granzyme H induces cytoplasmic
            translocation and interferes with La-mediated HCV-IRES
            translational activity
  JOURNAL   Cell Death Differ. 16 (2), 340-348 (2009)
   PUBMED   19039329
  REMARK    GeneRIF: Cleavage of La protein by granzyme H generates a
            COOH-terminal truncated form of La protein that loses nuclear
            localization and decreases hepatitis C virus-internal ribosome
            entry site-mediated translational activity.
REFERENCE   5  (bases 1 to 795)
  AUTHORS   Razvi,N.Z., Khurshid,R. and Nagra,S.A.
  TITLE     To study the significance of apoptotic enzyme granzyme H in breast
            cancer patients
  JOURNAL   J Ayub Med Coll Abbottabad 20 (1), 84-86 (2008)
   PUBMED   19024195
REFERENCE   6  (bases 1 to 795)
  AUTHORS   Heusel,J.W., Hanson,R.D., Silverman,G.A. and Ley,T.J.
  TITLE     Structure and expression of a cluster of human hematopoietic serine
            protease genes found on chromosome 14q11.2
  JOURNAL   J. Biol. Chem. 266 (10), 6152-6158 (1991)
   PUBMED   2007574
REFERENCE   7  (bases 1 to 795)
  AUTHORS   Haddad,P., Jenne,D., Tschopp,J., Clement,M.V., Mathieu-Mahul,D. and
            Sasportes,M.
  TITLE     Structure and evolutionary origin of the human granzyme H gene
  JOURNAL   Int. Immunol. 3 (1), 57-66 (1991)
   PUBMED   2049336
REFERENCE   8  (bases 1 to 795)
  AUTHORS   Meier,M., Kwong,P.C., Fregeau,C.J., Atkinson,E.A., Burrington,M.,
            Ehrman,N., Sorensen,O., Lin,C.C., Wilkins,J. and Bleackley,R.C.
  TITLE     Cloning of a gene that encodes a new member of the human cytotoxic
            cell protease family
  JOURNAL   Biochemistry 29 (17), 4042-4049 (1990)
   PUBMED   2193684
REFERENCE   9  (bases 1 to 795)
  AUTHORS   Klein,J.L., Selvakumar,A., Trapani,J.A. and Dupont,B.
  TITLE     Characterization of a novel, human cytotoxic lymphocyte-specific
            serine protease cDNA clone (CSP-C)
  JOURNAL   Tissue Antigens 35 (5), 220-228 (1990)
   PUBMED   2402757
REFERENCE   10 (bases 1 to 795)
  AUTHORS   Hanson,R.D., Hohn,P.A., Popescu,N.C. and Ley,T.J.
  TITLE     A cluster of hematopoietic serine protease genes is found on the
            same chromosomal band as the human alpha/delta T-cell receptor
            locus
  JOURNAL   Proc. Natl. Acad. Sci. U.S.A. 87 (3), 960-963 (1990)
   PUBMED   2300587
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BQ054303.1, AL136018.4,
            CD000418.1 and AW204493.1.
            
            Summary: The protein encoded by this gene is a member of the
            granzyme family. Members of this family are highly conserved serine
            proteases that eliminate transformed cells and virus-infected
            cells. This protein, which has chymotrypsin-like activity, has a
            preference for bulky aromatic amino acids at the P1 position and
            for acidic residues at the P3' and P4' positions. This protein is
            reported to be constitutively expressed in NK cells and may play a
            role in the cytotoxic arm of the innate immune response by inducing
            target cell death and by directly cleaving substrates in
            pathogen-infected cells. Alternative splicing results in multiple
            transcript variants that encode different protein isoforms.
            [provided by RefSeq, Jul 2012].
            
            Transcript Variant: This variant (2) uses an alternate in-frame
            splice site in the coding region compared to variant 1. It encodes
            isoform 2 which is shorter than isoform 1.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: CD000418.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           ERS025084, ERS025088 [ECO:0000348]
            ##Evidence-Data-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-12                BQ054303.1         1-12
            13-13               AL136018.4         53062-53062         c
            14-147              BQ054303.1         14-147
            148-552             CD000418.1         117-521
            553-795             AW204493.1         1-243               c
FEATURES             Location/Qualifiers
     source          1..795
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="14"
                     /map="14q11.2"
     gene            1..795
                     /gene="GZMH"
                     /gene_synonym="CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2"
                     /note="granzyme H (cathepsin G-like 2, protein h-CCPX)"
                     /db_xref="GeneID:2999"
                     /db_xref="HGNC:4710"
                     /db_xref="MIM:116831"
     exon            1..162
                     /gene="GZMH"
                     /gene_synonym="CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2"
                     /inference="alignment:Splign:1.39.8"
     misc_feature    9..11
                     /gene="GZMH"
                     /gene_synonym="CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2"
                     /note="upstream in-frame stop codon"
     CDS             108..656
                     /gene="GZMH"
                     /gene_synonym="CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2"
                     /note="isoform 2 precursor is encoded by transcript
                     variant 2; cytotoxic T-lymphocyte-associated serine
                     esterase 1; cytotoxin serine protease-C; cytotoxic
                     T-lymphocyte proteinase"
                     /codon_start=1
                     /product="granzyme H isoform 2 precursor"
                     /protein_id="NP_001257709.1"
                     /db_xref="GI:399124765"
                     /db_xref="GeneID:2999"
                     /db_xref="HGNC:4710"
                     /db_xref="MIM:116831"
                     /translation="

MQPFLLLLAFLLTPGAGTEEIIGGHEAKPHSRPYMAFVQFLQEKSRKRCGGILVRKDFVLTAAHCQGSSINVTLGAHNIKEQERTQQFIPVKRPIPHPAYNPKNFSNDIMLLQLERKAKWTTAVRPLRLPSSKAQGDSGGPLVCKDVAQGILSYGNKKGTPPGVYIKVSHFLPWIKRTMKRL

"
     sig_peptide     108..161
                     /gene="GZMH"
                     /gene_synonym="CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2"
                     /inference="COORDINATES: ab initio prediction:SignalP:4.0"
     misc_feature    168..>512
                     /gene="GZMH"
                     /gene_synonym="CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2"
                     /note="Trypsin-like serine protease; Many of these are
                     synthesized as inactive precursor zymogens that are
                     cleaved during limited proteolysis to generate their
                     active forms. Alignment contains also inactive enzymes
                     that have substitutions of the catalytic triad...; Region:
                     Tryp_SPc; cd00190"
                     /db_xref="CDD:29152"
     misc_feature    168..170
                     /gene="GZMH"
                     /gene_synonym="CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2"
                     /note="cleavage site"
                     /db_xref="CDD:29152"
     misc_feature    order(297..299,429..431)
                     /gene="GZMH"
                     /gene_synonym="CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2"
                     /note="active site"
                     /db_xref="CDD:29152"
     misc_feature    <510..632
                     /gene="GZMH"
                     /gene_synonym="CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2"
                     /note="Trypsin-like serine protease; Many of these are
                     synthesized as inactive precursor zymogens that are
                     cleaved during limited proteolysis to generate their
                     active forms. Alignment contains also inactive enzymes
                     that have substitutions of the catalytic triad...; Region:
                     Tryp_SPc; cl00149"
                     /db_xref="CDD:206862"
     misc_feature    order(564..566,570..572)
                     /gene="GZMH"
                     /gene_synonym="CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2"
                     /note="substrate binding sites [chemical binding]; other
                     site"
                     /db_xref="CDD:29152"
     exon            163..310
                     /gene="GZMH"
                     /gene_synonym="CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2"
                     /inference="alignment:Splign:1.39.8"
     exon            311..446
                     /gene="GZMH"
                     /gene_synonym="CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2"
                     /inference="alignment:Splign:1.39.8"
     variation       358
                     /gene="GZMH"
                     /gene_synonym="CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2"
                     /replace="a"
                     /replace="c"
                     /replace="g"
                     /db_xref="dbSNP:20545"
     exon            447..512
                     /gene="GZMH"
                     /gene_synonym="CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2"
                     /inference="alignment:Splign:1.39.8"
     exon            513..779
                     /gene="GZMH"
                     /gene_synonym="CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2"
                     /inference="alignment:Splign:1.39.8"
     polyA_signal    752..757
                     /gene="GZMH"
                     /gene_synonym="CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2"
     polyA_site      779
                     /gene="GZMH"
                     /gene_synonym="CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2"
ORIGIN

gaggtctctgagtttactgtacccatccctccttcatctccctccagcatttgtttctggaaggagtcaacaccaacagctctgacctgggcagccttcctgagaaaatgcagccattcctcctcctgttggcctttcttctgacccctggggctgggacagaggagatcatcgggggccatgaggccaagccccactcccgcccctacatggcctttgttcagtttctgcaagagaagagtcggaagaggtgtggcggcatcctagtgagaaaggactttgtgctgacagctgctcactgccagggaagctccataaatgtcaccttgggggcccacaatatcaaggaacaggagcggacccagcagtttatccctgtgaaaagacccatcccccatccagcctataatcctaagaacttctccaacgacatcatgctactgcagctggagagaaaggccaagtggaccacagctgtgcggcctctcaggctacctagcagcaaggcccagggggactccggggggcccctcgtgtgtaaggacgtagcccaaggtattctctcctatggaaacaaaaaagggacacctccaggagtctacatcaaggtctcacacttcctgccctggataaagagaacaatgaagcgcctctaacagcaggcatgagactaaccttcctctgggcctgaccatctctgggacagaggcaagaatccccaaggggtgggcagtcggggttgcaggactgtaataaatggatctctggtgtaaatatgaaaaaaaaaaaaaaaaa

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