Q9UNG2 (TNF18_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tumor necrosis factor ligand superfamily member 18

Alternative name(s):
Activation-inducible TNF-related ligand
Short name=AITRL
Glucocorticoid-induced TNF-related ligand
Short name=hGITRL

Gene names

Name:	TNFSF18
Synonyms:	AITRL, GITRL, TL6
ORF Names:	UNQ149/PRO175

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	199 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cytokine that binds to TNFRSF18/AITR/GITR. Regulates T-cell responses. Can function as costimulator and lower the threshold for T-cell activation and T-cell proliferation. Important for interactions between activated T-lymphocytes and endothelial cells. Mediates activation of NF-kappa-B.
Subunit structure	Homodimer By similarity. Homotrimer.
Subcellular location	Cell membrane; Single-pass type II membrane protein.
Tissue specificity	Expressed at high levels in the small intestine, ovary, testis, kidney and endothelial cells.
Induction	Up-regulated after stimulation by bacterial lipopolysaccharides (LPS).
Sequence similarities	Belongs to the tumor necrosis factor family.
Caution	It is uncertain whether Met-1 or Met-23 is the initiator.
Sequence caution	The sequence AAH93986.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAI12033.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAQ89227.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAG36082.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence EAW90937.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity
Cellular component	Cell membrane Membrane
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Cytokine
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	anti-apoptosis Traceable author statement. Source: ProtInc cell-cell signaling Traceable author statement. Source: ProtInc immune response Inferred from electronic annotation. Source: InterPro signal transduction Traceable author statement. Source: ProtInc
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	cytokine activity Inferred from electronic annotation. Source: UniProtKB-KW tumor necrosis factor receptor binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 199

199

Tumor necrosis factor ligand superfamily member 18

PRO_0000185506

Regions

Topological domain

23 – 50

28

Cytoplasmic Potential

Transmembrane

51 – 71

21

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

72 – 199

128

Extracellular Potential

Amino acid modifications

Glycosylation

151

1

N-linked (GlcNAc...) Potential

Glycosylation

183

1

N-linked (GlcNAc...) Potential

Disulfide bond

80 ↔ 100

Secondary structure

1

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199

Helix Strand Turn

Details...

Helix

42 – 68

27

Beta strand

81 – 84

4

Beta strand

91 – 94

4

Beta strand

100 – 105

6

Beta strand

108 – 111

4

Beta strand

115 – 123

9

Beta strand

137 – 141

5

Beta strand

144 – 149

6

Beta strand

152 – 154

3

Beta strand

160 – 164

5

Beta strand

169 – 176

8

Helix

177 – 179

3

Beta strand

186 – 193

8

Sequences

	Sequence		Length	Mass (Da)
	Q9UNG2 [UniParc]. Last modified March 8, 2011. Version 2. Checksum: C83A94645745DA58	FASTA	199	22,724
	10 20 30 40 50 60 MTLHPSPITC EFLFSTALIS PKMCLSHLEN MPLSHSRTQG AQRSSWKLWL FCSIVMLLFL 70 80 90 100 110 120 CSFSWLIFIF LQLETAKEPC MAKFGPLPSK WQMASSEPPC VNKVSDWKLE ILQNGLYLIY 130 140 150 160 170 180 GQVAPNANYN DVAPFEVRLY KNKDMIQTLT NKSKIQNVGG TYELHVGDTI DLIFNSEHQV 190 LKNNTYWGII LLANPQFIS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-199.
[5]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 17-199.
[6]	"Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of mouse GITR." Gurney A.L., Marsters S.A., Huang R.M., Pitti R.M., Mark D.T., Baldwin D.T., Gray A.M., Dowd A.D., Brush A.D., Heldens A.D., Schow A.D., Goddard A.D., Wood W.I., Baker K.P., Godowski P.J., Ashkenazi A. Curr. Biol. 9:215-218(1999) [PubMed: 10074428] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 23-199. Tissue: Umbilical vein.
[7]	"Identification of a novel activation-inducible protein of the tumor necrosis factor receptor superfamily and its ligand." Kwon B., Yu K.-Y., Ni J., Yu G.-L., Jang I.-K., Kim Y.-J., Xing L., Liu D., Wang S.-X., Kwon B.S. J. Biol. Chem. 274:6056-6061(1999) [PubMed: 10037686] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 31-199. Tissue: Brain.
[8]	"Expression of human GITRL on myeloid dendritic cells enhances their immunostimulatory function but does not abrogate the suppressive effect of CD4+CD25+ regulatory T cells." Tuyaerts S., Van Meirvenne S., Bonehill A., Heirman C., Corthals J., Waldmann H., Breckpot K., Thielemans K., Aerts J.L. J. Leukoc. Biol. 82:93-105(2007) [PubMed: 17449724] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[9]	"Assembly and structural properties of glucocorticoid-induced TNF receptor ligand: implications for function." Chattopadhyay K., Ramagopal U.A., Mukhopadhaya A., Malashkevich V.N., Dilorenzo T.P., Brenowitz M., Nathenson S.G., Almo S.C. Proc. Natl. Acad. Sci. U.S.A. 104:19452-19457(2007) [PubMed: 18040044] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 74-199, FUNCTION, SUBUNIT, DISULFIDE BOND.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AL031599 Genomic DNA. Translation: CAP58846.1.
CH471067 Genomic DNA. Translation: EAW90937.1. Different initiation.
BC069111 mRNA. Translation: AAH69111.1.
BC069319 mRNA. Translation: AAH69319.1.
BC093986 mRNA. Translation: AAH93986.1. Different initiation.
BC112032 mRNA. Translation: AAI12033.1. Different initiation.
AK313273 mRNA. Translation: BAG36082.1. Different initiation.
AY358868 mRNA. Translation: AAQ89227.1. Different initiation.
AF125303 mRNA. Translation: AAD22634.1.
AF117713 mRNA. Translation: AAD19695.1.

IPI

IPI00935899.

RefSeq

NP_005083.2. NM_005092.3.

UniGene

Hs.248197.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Q1M	X-ray	2.30	A	74-199	[»]
2R30	X-ray	3.20	A	74-199	[»]
2R32	X-ray	1.95	A	74-199	[»]
3B93	X-ray	2.20	A/B/C	72-199	[»]
3B94	X-ray	2.50	A/B/C/D	72-199	[»]

ProteinModelPortal

Q9UNG2.

SMR

Q9UNG2. Positions 77-199.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29882N.
DIP-6243N.

STRING

Q9UNG2.

Polymorphism databases

DMDM

13124621.

Proteomic databases

PRIDE

Q9UNG2.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000239468; ENSP00000239468; ENSG00000120337.
ENST00000404377; ENSP00000385470; ENSG00000120337.

GeneID

8995.

KEGG

hsa:8995.

Organism-specific databases

CTD

8995.

GeneCards

GC01M173009.

H-InvDB

HIX0028550.

HGNC

HGNC:11932. TNFSF18.

HPA

HPA012699.

MIM

603898. gene.

neXtProt

NX_Q9UNG2.

PharmGKB

PA36624.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13005.

GeneTree

ENSGT00390000002560.

HOVERGEN

HBG061857.

InParanoid

Q9UNG2.

OMA

FEVRLYK.

OrthoDB

EOG40GCRS.

Gene expression databases

ArrayExpress

Q9UNG2.

Bgee

Q9UNG2.

CleanEx

HS_TNFSF18.

Genevestigator

Q9UNG2.

GermOnline

ENSG00000120337. Homo sapiens.

Family and domain databases

InterPro

IPR006052. TNF.
IPR008983. Tumour_necrosis_fac-like.
[Graphical view]

Gene3D

G3DSA:2.60.120.40. Tumour_necrosis_fac-like. 1 hit.

KO

K05479.

Pfam

PF00229. TNF. 1 hit.
[Graphical view]

SUPFAM

SSF49842. TNF_like. 1 hit.

PROSITE

PS00251. TNF_1. False negative.
PS50049. TNF_2. False negative.
[Graphical view]

ProtoNet

Search...

Other

SOURCE

Search...

Entry information

Entry name

TNF18_HUMAN

Accession

Primary (citable) accession number: Q9UNG2
Secondary accession number(s): A9IQG8, O95852, Q6ISV1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	March 8, 2011
Last modified:	January 25, 2012
This is version 88 of the entry and version 2 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.