GNLY_HUMAN
ID GNLY_HUMAN Reviewed; 145 AA.
AC P22749; P09325; Q6GU08;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Granulysin;
DE AltName: Full=Lymphokine LAG-2;
DE AltName: Full=Protein NKG5;
DE AltName: Full=T-cell activation protein 519;
DE Flags: Precursor;
GN Name=GNLY; Synonyms=LAG2, NKG5, TLA519;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), AND VARIANT ILE-119.
RX PubMed=2434598; DOI=10.1084/jem.165.3.601;
RA Jongstra J., Schall T.J., Dyer B.J., Clayberger C., Jorgensen J.,
RA Davis M.M., Krensky A.M.;
RT "The isolation and sequence of a novel gene from a human functional T cell
RT line.";
RL J. Exp. Med. 165:601-614(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RX PubMed=2212946; DOI=10.1084/jem.172.4.1159;
RA Yabe T., McSherry C., Bach F.H., Houchins J.P.;
RT "A cDNA clone expressed in natural killer and T cells that likely encodes a
RT secreted protein.";
RL J. Exp. Med. 172:1159-1163(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ILE-119.
RC TISSUE=Placenta;
RX PubMed=8423048; DOI=10.1007/bf00216832;
RA Houchins J.P., Kricek F., Chujor C.S., Heise C.P., Yabe T., McSherry C.,
RA Bach F.H.;
RT "Genomic structure of NKG5, a human NK and T cell-specific activation
RT gene.";
RL Immunogenetics 37:102-107(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=B-cell;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP REVIEW.
RX PubMed=10644038; DOI=10.1016/s0006-2952(99)00177-x;
RA Krensky A.M.;
RT "Granulysin: a novel antimicrobial peptide of cytolytic T lymphocytes and
RT natural killer cells.";
RL Biochem. Pharmacol. 59:317-320(2000).
RN [7]
RP CHARACTERIZATION.
RX PubMed=9756476; DOI=10.1126/science.282.5386.121;
RA Stenger S., Hanson D.A., Teitelbaum R., Dewan P., Niazi K.R.,
RA Froelich C.J., Ganz T., Thoma-Uszynski S., Melian A., Bogdan C.,
RA Porcelli S.A., Bloom B.R., Krensky A.M., Modlin R.L.;
RT "An antimicrobial activity of cytolytic T cells mediated by granulysin.";
RL Science 282:121-125(1998).
RN [8]
RP PROTEOLYTIC PROCESSING.
RX PubMed=10449094; DOI=10.1016/s0161-5890(99)00063-2;
RA Hanson D.A., Kaspar A.A., Poulain F.R., Krensky A.M.;
RT "Biosynthesis of granulysin, a novel cytolytic molecule.";
RL Mol. Immunol. 36:413-422(1999).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (0.92 ANGSTROMS) OF 63-136.
RX PubMed=12488100; DOI=10.1016/s0022-2836(02)01234-2;
RA Anderson D.H., Sawaya M.R., Cascio D., Ernst W., Modlin R., Krensky A.,
RA Eisenberg D.;
RT "Granulysin crystal structure and a structure-derived lytic mechanism.";
RL J. Mol. Biol. 325:355-365(2003).
CC -!- FUNCTION: Antimicrobial protein that kills intracellular pathogens.
CC Active against a broad range of microbes, including Gram-positive and
CC Gram-negative bacteria, fungi, and parasites. Kills Mycobacterium
CC tuberculosis.
CC -!- INTERACTION:
CC P22749; Q07817: BCL2L1; NbExp=3; IntAct=EBI-17844792, EBI-78035;
CC P22749; Q96Q80: DERL3; NbExp=3; IntAct=EBI-17844792, EBI-12831318;
CC -!- SUBCELLULAR LOCATION: Secreted. Note=Located in the cytotoxic granules
CC of T-cells, which are released upon antigen stimulation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P22749-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P22749-2; Sequence=VSP_006016;
CC -!- TISSUE SPECIFICITY: Expressed in natural killer and T-cells.
CC -!- INDUCTION: By T-cell growth factor and IL2/interleukin-2.
CC -!- PTM: A 9 kDa form is produced by proteolytic processing of a 15 kDa
CC protein. {ECO:0000269|PubMed:10449094}.
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DR EMBL; X05044; CAA28715.1; -; mRNA.
DR EMBL; X54101; CAA38035.1; -; mRNA.
DR EMBL; M85276; AAA59935.1; -; Genomic_DNA.
DR EMBL; CR541859; CAG46657.1; -; mRNA.
DR EMBL; BC023576; AAH23576.1; -; mRNA.
DR CCDS; CCDS1984.1; -. [P22749-1]
DR CCDS; CCDS46354.1; -. [P22749-2]
DR PIR; A27562; A27562.
DR PIR; I54504; I54504.
DR RefSeq; NP_001289687.1; NM_001302758.1.
DR RefSeq; NP_006424.2; NM_006433.4. [P22749-1]
DR RefSeq; NP_036615.2; NM_012483.3. [P22749-2]
DR PDB; 1L9L; X-ray; 0.92 A; A=63-136.
DR PDBsum; 1L9L; -.
DR AlphaFoldDB; P22749; -.
DR SMR; P22749; -.
DR BioGRID; 115829; 40.
DR IntAct; P22749; 2.
DR STRING; 9606.ENSP00000263863; -.
DR DrugBank; DB03434; 3-(N-morpholino)propanesulfonic acid.
DR TCDB; 1.C.35.3.2; the amoebapore (amoebapore) family.
DR iPTMnet; P22749; -.
DR PhosphoSitePlus; P22749; -.
DR BioMuta; GNLY; -.
DR DMDM; 116242500; -.
DR MassIVE; P22749; -.
DR PaxDb; P22749; -.
DR PeptideAtlas; P22749; -.
DR PRIDE; P22749; -.
DR ProteomicsDB; 54035; -. [P22749-1]
DR ProteomicsDB; 54036; -. [P22749-2]
DR Antibodypedia; 31957; 241 antibodies from 28 providers.
DR DNASU; 10578; -.
DR Ensembl; ENST00000263863.9; ENSP00000263863.5; ENSG00000115523.17. [P22749-1]
DR Ensembl; ENST00000409696.7; ENSP00000387116.3; ENSG00000115523.17. [P22749-2]
DR GeneID; 10578; -.
DR KEGG; hsa:10578; -.
DR MANE-Select; ENST00000263863.9; ENSP00000263863.5; NM_006433.5; NP_006424.2.
DR UCSC; uc002sql.5; human. [P22749-1]
DR CTD; 10578; -.
DR DisGeNET; 10578; -.
DR GeneCards; GNLY; -.
DR HGNC; HGNC:4414; GNLY.
DR HPA; ENSG00000115523; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 188855; gene.
DR neXtProt; NX_P22749; -.
DR OpenTargets; ENSG00000115523; -.
DR PharmGKB; PA28793; -.
DR VEuPathDB; HostDB:ENSG00000115523; -.
DR eggNOG; ENOG502ST3Z; Eukaryota.
DR GeneTree; ENSGT00390000002975; -.
DR InParanoid; P22749; -.
DR OMA; GFDCKIC; -.
DR OrthoDB; 1413739at2759; -.
DR PhylomeDB; P22749; -.
DR TreeFam; TF342210; -.
DR PathwayCommons; P22749; -.
DR Reactome; R-HSA-6803157; Antimicrobial peptides.
DR SignaLink; P22749; -.
DR BioGRID-ORCS; 10578; 13 hits in 1072 CRISPR screens.
DR ChiTaRS; GNLY; human.
DR EvolutionaryTrace; P22749; -.
DR GeneWiki; GNLY; -.
DR GenomeRNAi; 10578; -.
DR Pharos; P22749; Tbio.
DR PRO; PR:P22749; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P22749; protein.
DR Bgee; ENSG00000115523; Expressed in granulocyte and 112 other tissues.
DR ExpressionAtlas; P22749; baseline and differential.
DR Genevisible; P22749; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0097013; C:phagocytic vesicle lumen; TAS:Reactome.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0006968; P:cellular defense response; IDA:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; IDA:UniProtKB.
DR GO; GO:0050832; P:defense response to fungus; IEA:UniProtKB-KW.
DR GO; GO:0031640; P:killing of cells of another organism; IDA:UniProtKB.
DR InterPro; IPR038847; Granulysin-like.
DR InterPro; IPR011001; Saposin-like.
DR InterPro; IPR008139; SaposinB_dom.
DR PANTHER; PTHR15541; PTHR15541; 1.
DR SMART; SM00741; SapB; 1.
DR SUPFAM; SSF47862; SSF47862; 1.
DR PROSITE; PS50015; SAP_B; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Antibiotic; Antimicrobial;
KW Disulfide bond; Fungicide; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..145
FT /note="Granulysin"
FT /id="PRO_0000031659"
FT DOMAIN 62..142
FT /note="Saposin B-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 69..132
FT DISULFID 96..107
FT VAR_SEQ 1..17
FT /note="MATWALLLLAAMLLGNP -> ME (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:2434598"
FT /id="VSP_006016"
FT VARIANT 119
FT /note="T -> I (in dbSNP:rs11127)"
FT /evidence="ECO:0000269|PubMed:2434598,
FT ECO:0000269|PubMed:8423048"
FT /id="VAR_027868"
FT CONFLICT 31
FT /note="L -> P (in Ref. 1; CAA28715)"
FT /evidence="ECO:0000305"
FT CONFLICT 39
FT /note="E -> G (in Ref. 1; CAA28715)"
FT /evidence="ECO:0000305"
FT CONFLICT 46..47
FT /note="LA -> G (in Ref. 1; CAA28715)"
FT /evidence="ECO:0000305"
FT HELIX 64..79
FT /evidence="ECO:0007829|PDB:1L9L"
FT HELIX 85..94
FT /evidence="ECO:0007829|PDB:1L9L"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:1L9L"
FT HELIX 101..123
FT /evidence="ECO:0007829|PDB:1L9L"
FT HELIX 128..132
FT /evidence="ECO:0007829|PDB:1L9L"
FT HELIX 133..135
FT /evidence="ECO:0007829|PDB:1L9L"
SQ SEQUENCE 145 AA; 16374 MW; CEC5432FFBDBA1F4 CRC64;
MATWALLLLA AMLLGNPGLV FSRLSPEYYD LARAHLRDEE KSCPCLAQEG PQGDLLTKTQ
ELGRDYRTCL TIVQKLKKMV DKPTQRSVSN AATRVCRTGR SRWRDVCRNF MRRYQSRVTQ
GLVAGETAQQ ICEDLRLCIP STGPL
