P98066 (TSG6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tumor necrosis factor-inducible gene 6 protein

Alternative name(s):
Hyaluronate-binding protein
TNF-stimulated gene 6 protein
Short name=TSG-6
Tumor necrosis factor alpha-induced protein 6
Short name=TNF alpha-induced protein 6

Gene names

Name:	TNFAIP6
Synonyms:	TSG6

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	277 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	Possibly involved in cell-cell and cell-matrix interactions during inflammation and tumorigenesis.
Subunit structure	Interacts with inter-alpha-inhibitor (I-alpha-I). Chondroitin sulfate may be required for the stability of the complex. Ref.6
Tissue specificity	Found in the synovial fluid of patients with rheumatoid arthritis. Ref.6
Induction	By TNF.
Sequence similarities	Contains 1 CUB domain. Contains 1 Link domain.

Ontologies

Keywords
Biological process	Cell adhesion
Coding sequence diversity	Polymorphism
Domain	Signal
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW cell-cell signaling Traceable author statement Ref.1. Source: ProtInc inflammatory response Traceable author statement Ref.1. Source: ProtInc signal transduction Traceable author statement Ref.1. Source: ProtInc
Molecular_function	hyaluronic acid binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Ref.6

Chain

18 – 277

260

Tumor necrosis factor-inducible gene 6 protein

PRO_0000026692

Regions

Domain

36 – 129

94

Link

Domain

135 – 247

113

CUB

Amino acid modifications

Glycosylation

118

1

N-linked (GlcNAc...) Potential

Glycosylation

258

1

N-linked (GlcNAc...) Potential

Disulfide bond

58 ↔ 127

Disulfide bond

82 ↔ 103

Disulfide bond

135 ↔ 161

By similarity

Disulfide bond

188 ↔ 210

By similarity

Natural variations

Natural variant

144

1

Q → R. Ref.1 Ref.5
Corresponds to variant rs1046668 [ dbSNP | Ensembl ].

VAR_013005

Secondary structure

1

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277

Helix Strand Turn

Details...

Beta strand

37 – 40

4

Beta strand

42 – 44

3

Beta strand

45 – 47

3

Helix

51 – 60

10

Helix

68 – 76

9

Beta strand

85 – 87

3

Helix

88 – 90

3

Beta strand

91 – 97

7

Turn

101 – 103

3

Beta strand

109 – 115

7

Beta strand

123 – 128

6

Beta strand

137 – 139

3

Beta strand

141 – 147

7

Turn

149 – 152

4

Beta strand

160 – 166

7

Beta strand

172 – 181

10

Beta strand

190 – 209

20

Beta strand

211 – 213

3

Beta strand

221 – 230

10

Beta strand

239 – 247

9

Sequences

	Sequence		Length	Mass (Da)
	P98066 [UniParc]. Last modified June 21, 2005. Version 2. Checksum: E2B3AEB76353A782	FASTA	277	31,203
	10 20 30 40 50 60 MIILIYLFLL LWEDTQGWGF KDGIFHNSIW LERAAGVYHR EARSGKYKLT YAEAKAVCEF 70 80 90 100 110 120 EGGHLATYKQ LEAARKIGFH VCAAGWMAKG RVGYPIVKPG PNCGFGKTGI IDYGIRLNRS 130 140 150 160 170 180 ERWDAYCYNP HAKECGGVFT DPKQIFKSPG FPNEYEDNQI CYWHIRLKYG QRIHLSFLDF 190 200 210 220 230 240 DLEDDPGCLA DYVEIYDSYD DVHGFVGRYC GDELPDDIIS TGNVMTLKFL SDASVTAGGF 250 260 270 QIKYVAMDPV SKSSQGKNTS TTSTGNKNFL AGRFSHL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel secretory tumor necrosis factor-inducible protein (TSG-6) is a member of the family of hyaluronate binding proteins, closely related to the adhesion receptor CD44." Lee T.H., Wisniewski H.-G., Vilcek J. J. Cell Biol. 116:545-557(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-144. Tissue: Fibroblast.
[2]	"A novel allelic variant of the human TSG-6 gene encoding an amino acid difference in the CUB module. Chromosomal localization, frequency analysis, modeling, and expression." Nentwich H.A., Mustafa Z., Rugg M.S., Marsden B.D., Cordell M.R., Mahoney D.J., Jenkins S.C., Dowling B., Fries E., Milner C.M., Loughlin J., Day A.J. J. Biol. Chem. 277:15354-15362(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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], VARIANT ARG-144. Tissue: Lung and Spleen.
[6]	"TSG-6, an arthritis-associated hyaluronan binding protein, forms a stable complex with the serum protein inter-alpha-inhibitor." Wisniewski H.-G., Burgess W.H., Oppenheim J.D., Vilcek J. Biochemistry 33:7423-7429(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-27, TISSUE SPECIFICITY, INTERACTION WITH INTER-ALPHA-INHIBITOR.
[7]	"Solution structure of the link module: a hyaluronan-binding domain involved in extracellular matrix stability and cell migration." Kohda D., Morton C.J., Parkar A.A., Hatanaka H., Inagaki F.M., Campbell I.D., Day A.J. Cell 86:767-775(1996) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 36-133.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M31165 mRNA. Translation: AAB00792.1.
AJ421518 mRNA. Translation: CAD13434.1.
AJ419936 mRNA. Translation: CAD12353.1.
AC009311 Genomic DNA. Translation: AAY15067.1.
CH471058 Genomic DNA. Translation: EAX11511.1.
BC030205 mRNA. Translation: AAH30205.1.

IPI

IPI00303341.

PIR

A41735.

RefSeq

NP_009046.2. NM_007115.3.

UniGene

Hs.437322.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1O7B	NMR	-	T	36-133	[»]
1O7C	NMR	-	T	36-133	[»]
2PF5	X-ray	1.90	A/B/C/D/E	36-133	[»]
2WNO	X-ray	2.30	A	129-277	[»]

ProteinModelPortal

P98066.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000243347.

PTM databases

PhosphoSite

P98066.

Polymorphism databases

DMDM

68067717.

Proteomic databases

PaxDb

P98066.

PRIDE

P98066.

Protocols and materials databases

DNASU

7130.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000243347; ENSP00000243347; ENSG00000123610.

GeneID

7130.

KEGG

hsa:7130.

UCSC

uc002txk.3. human.

Organism-specific databases

CTD

7130.

GeneCards

GC02P152178.

HGNC

HGNC:11898. TNFAIP6.

HPA

CAB032719.

MIM

600410. gene.

neXtProt

NX_P98066.

PharmGKB

PA36595.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG237473.

HOGENOM

HOG000043074.

HOVERGEN

HBG006669.

InParanoid

P98066.

OMA

PNEYDDN.

OrthoDB

EOG4WWRK3.

PhylomeDB

P98066.

Gene expression databases

Bgee

P98066.

CleanEx

HS_TNFAIP6.

Genevestigator

P98066.

GermOnline

ENSG00000123610. Homo sapiens.

Family and domain databases

Gene3D

2.60.120.290. 1 hit.
3.10.100.10. 1 hit.

InterPro

IPR016186. C-type_lectin-like.
IPR016187. C-type_lectin_fold.
IPR000859. CUB_dom.
IPR000538. Link.
[Graphical view]

Pfam

PF00431. CUB. 1 hit.
PF00193. Xlink. 1 hit.
[Graphical view]

PRINTS

PR01265. LINKMODULE.

SMART

SM00042. CUB. 1 hit.
SM00445. LINK. 1 hit.
[Graphical view]

SUPFAM

SSF56436. C-type_lectin_fold. 1 hit.
SSF49854. CUB. 1 hit.

PROSITE

PS01180. CUB. 1 hit.
PS01241. LINK_1. 1 hit.
PS50963. LINK_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P98066.

GenomeRNAi

7130.

NextBio

27899.

SOURCE

Search...

Entry information

Entry name

TSG6_HUMAN

Accession

Primary (citable) accession number: P98066
Secondary accession number(s): Q53TI7, Q8WWI9

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	June 21, 2005
Last modified:	May 1, 2013
This is version 129 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.