P22749 (GNLY_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Granulysin

Alternative name(s):
Lymphokine LAG-2
Protein NKG5
T-cell activation protein 519

Gene names

Name:	GNLY
Synonyms:	LAG2, NKG5, TLA519

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	145 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Antimicrobial protein that kills intracellular pathogens. Active against a broad range of microbes, including Gram-positive and Gram-negative bacteria, fungi, and parasites. Kills Mycobacterium tuberculosis.
Subcellular location	Secreted. Note: Located in the cytotoxic granules of T-cells, which are released upon antigen stimulation.
Tissue specificity	Expressed in natural killer and T-cells.
Induction	By T-cell growth factor and IL2/interleukin-2.
Post-translational modification	A 9 kDa form is produced by proteolytic processing of a 15 kDa protein.
Sequence similarities	Contains 1 saposin B-type domain.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Molecular function	Antibiotic Antimicrobial Fungicide
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular defense response Traceable author statement Ref.7. Source: ProtInc defense response to bacterium Inferred from electronic annotation. Source: UniProtKB-KW defense response to fungus Inferred from electronic annotation. Source: UniProtKB-KW killing of cells of other organism Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular space Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P22749-1)

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.

Isoform Short (identifier: P22749-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-17: MATWALLLLAAMLLGNP → ME

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Potential

Chain

23 – 145

123

Granulysin

PRO_0000031659

Regions

Domain

62 – 142

81

Saposin B-type

Amino acid modifications

Disulfide bond

69 ↔ 132

Disulfide bond

96 ↔ 107

Natural variations

Alternative sequence

1 – 17

17

MATWA…LLGNP → ME in isoform Short.

VSP_006016

Natural variant

119

1

T → I. Ref.1 Ref.3
Corresponds to variant rs11127 [ dbSNP | Ensembl ].

VAR_027868

Experimental info

Sequence conflict

31

1

L → P in CAA28715. Ref.1

Sequence conflict

39

1

E → G in CAA28715. Ref.1

Sequence conflict

46 – 47

2

LA → G in CAA28715. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

145

Helix Strand Turn

Details...

Helix

64 – 79

16

Helix

85 – 94

10

Helix

95 – 97

3

Helix

101 – 123

23

Helix

128 – 132

5

Helix

133 – 135

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified October 17, 2006. Version 3. Checksum: CEC5432FFBDBA1F4	FASTA	145	16,374
	10 20 30 40 50 60 MATWALLLLA AMLLGNPGLV FSRLSPEYYD LARAHLRDEE KSCPCLAQEG PQGDLLTKTQ 70 80 90 100 110 120 ELGRDYRTCL TIVQKLKKMV DKPTQRSVSN AATRVCRTGR SRWRDVCRNF MRRYQSRVTQ 130 140 GLVAGETAQQ ICEDLRLCIP STGPL
	Isoform Short [UniParc]. Checksum: 6F5238713B905CF8	FASTA	130	14,853
	10 20 30 40 50 60 MEGLVFSRLS PEYYDLARAH LRDEEKSCPC LAQEGPQGDL LTKTQELGRD YRTCLTIVQK 70 80 90 100 110 120 LKKMVDKPTQ RSVSNAATRV CRTGRSRWRD VCRNFMRRYQ SRVTQGLVAG ETAQQICEDL 130 RLCIPSTGPL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The isolation and sequence of a novel gene from a human functional T cell line." Jongstra J., Schall T.J., Dyer B.J., Clayberger C., Jorgensen J., Davis M.M., Krensky A.M. J. Exp. Med. 165:601-614(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), VARIANT ILE-119.
[2]	"A cDNA clone expressed in natural killer and T cells that likely encodes a secreted protein." Yabe T., McSherry C., Bach F.H., Houchins J.P. J. Exp. Med. 172:1159-1163(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
[3]	"Genomic structure of NKG5, a human NK and T cell-specific activation gene." Houchins J.P., Kricek F., Chujor C.S., Heise C.P., Yabe T., McSherry C., Bach F.H. Immunogenetics 37:102-107(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ILE-119. Tissue: Placenta.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"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]. Tissue: B-cell.
[6]	"Granulysin: a novel antimicrobial peptide of cytolytic T lymphocytes and natural killer cells." Krensky A.M. Biochem. Pharmacol. 59:317-320(2000) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[7]	"An antimicrobial activity of cytolytic T cells mediated by granulysin." Stenger S., Hanson D.A., Teitelbaum R., Dewan P., Niazi K.R., Froelich C.J., Ganz T., Thoma-Uszynski S., Melian A., Bogdan C., Porcelli S.A., Bloom B.R., Krensky A.M., Modlin R.L. Science 282:121-125(1998) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[8]	"Biosynthesis of granulysin, a novel cytolytic molecule." Hanson D.A., Kaspar A.A., Poulain F.R., Krensky A.M. Mol. Immunol. 36:413-422(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING.
[9]	"Granulysin crystal structure and a structure-derived lytic mechanism." Anderson D.H., Sawaya M.R., Cascio D., Ernst W., Modlin R., Krensky A., Eisenberg D. J. Mol. Biol. 325:355-365(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (0.92 ANGSTROMS) OF 63-136.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X05044 mRNA. Translation: CAA28715.1.
X54101 mRNA. Translation: CAA38035.1.
M85276 Genomic DNA. Translation: AAA59935.1.
CR541859 mRNA. Translation: CAG46657.1.
BC023576 mRNA. Translation: AAH23576.1.

IPI

IPI00301472.
IPI00396242.

PIR

A27562.
I54504.

RefSeq

NP_006424.2. NM_006433.3.
NP_036615.2. NM_012483.2.

UniGene

Hs.105806.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1L9L	X-ray	0.92	A	63-136	[»]

ProteinModelPortal

P22749.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000263863.

Protein family/group databases

TCDB

1.C.35.3.2. amoebapore family.

PTM databases

PhosphoSite

P22749.

Polymorphism databases

DMDM

116242500.

Proteomic databases

PaxDb

P22749.

PRIDE

P22749.

Protocols and materials databases

DNASU

10578.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000263863; ENSP00000263863; ENSG00000115523.
ENST00000409696; ENSP00000387116; ENSG00000115523.

GeneID

10578.

KEGG

hsa:10578.

UCSC

uc002sql.4. human.
uc010fgp.3. human.

Organism-specific databases

CTD

10578.

GeneCards

GC02P085912.

HGNC

HGNC:4414. GNLY.

HPA

CAB025186.

MIM

188855. gene.

neXtProt

NX_P22749.

PharmGKB

PA28793.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG68808.

HOGENOM

HOG000112748.

HOVERGEN

HBG005866.

InParanoid

P22749.

OrthoDB

EOG4VQ9R0.

Gene expression databases

ArrayExpress

P22749.

Bgee

P22749.

CleanEx

HS_GNLY.

Genevestigator

P22749.

GermOnline

ENSG00000115523. Homo sapiens.

Family and domain databases

Gene3D

1.10.225.10. 1 hit.

InterPro

IPR008138. SapB_2.
IPR011001. Saposin-like.
IPR008139. SaposinB.
[Graphical view]

Pfam

PF03489. SapB_2. 1 hit.
[Graphical view]

SMART

SM00741. SapB. 1 hit.
[Graphical view]

SUPFAM

SSF47862. Saposin_like. 1 hit.

PROSITE

PS50015. SAP_B. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

GNLY. human.

EvolutionaryTrace

P22749.

GenomeRNAi

10578.

NextBio

40149.

SOURCE

Search...

Entry information

Entry name

GNLY_HUMAN

Accession

Primary (citable) accession number: P22749
Secondary accession number(s): P09325, Q6GU08

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 128 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.