TNFAIP6
entrez
7130
canonical
uniprot
P98066
canonical
ensembl
ENSG00000123610
resolver
ensp
ENSP00000243347
resolver
enst
ENST00000243347
resolver
genesymbol
TNFAIP6
resolver
genesymbol_syn
TSG6
resolver
hgnc
HGNC:11898
resolver
uniprot
Q53TI7
resolver
uniprot
Q8WWI9
resolver
uniprot_entry
TSG6_HUMAN
resolver
uniprot_sec
Q53TI7
resolver
uniprot_sec
Q8WWI9
resolver
amino_acid_sequence
MIILIYLFLLLWEDTQGWGFKDGIFHNSIWLERAAGVYHREARSGKYKLTYAEAKAVCEFEGGHLATYKQLEAARKIGFHVCAAGWMAKGRVGYPIVKPGPNCGFGKTGIIDYGIRLNRSERWDAYCYNPHAKECGGVFTDPKQIFKSPGFPNEYEDNQICYWHIRLKYGQRIHLSFLDFDLEDDPGCLADYVEIYDSYDDVHGFVGRYCGDELPDDIISTGNVMTLKFLSDASVTAGGFQIKYVAMDPVSKSSQGKNTSTTSTGNKNFLAGRFSHL
uniprot
proteins
ec_number
3.1.1.-
uniprot
proteins
function
FUNCTION: Major regulator of extracellular matrix organization during tissue remodeling (PubMed:15917224, PubMed:18042364, PubMed:26823460). Catalyzes the transfer of a heavy chain (HC) from inter-alpha-inhibitor (I-alpha-I) complex to hyaluronan. Cleaves the ester bond between the C-terminus of the HC and GalNAc residue of the chondroitin sulfate chain in I-alpha-I complex followed by transesterification of the HC to hyaluronan. In the process, potentiates the antiprotease function of I-alpha-I complex through release of free bikunin (PubMed:15917224, PubMed:16873769, PubMed:20463016). Acts as a catalyst in the formation of hyaluronan-HC oligomers and hyaluronan-rich matrix surrounding the cumulus cell-oocyte complex, a necessary step for oocyte fertilization (PubMed:26468290). Assembles hyaluronan in pericellular matrices that serve as platforms for receptor clustering and signaling. Enables binding of hyaluronan deposited on the surface of macrophages to LYVE1 on lymphatic endothelium and facilitates macrophage extravasation. Alters hyaluronan binding to functionally latent CD44 on vascular endothelium, switching CD44 into an active state that supports leukocyte rolling (PubMed:15060082, PubMed:26823460). Modulates the interaction of chemokines with extracellular matrix components and proteoglycans on endothelial cell surface, likely preventing chemokine gradient formation (PubMed:27044744). In a negative feedback mechanism, may limit excessive neutrophil recruitment at inflammatory sites by antagonizing the association of CXCL8 with glycosaminoglycans on vascular endothelium (PubMed:24501198). Has a role in osteogenesis and bone remodeling. Inhibits BMP2-dependent differentiation of mesenchymal stem cell to osteoblasts (PubMed:16771708, PubMed:18586671). Protects against bone erosion during inflammation by inhibiting TNFSF11/RANKL-dependent osteoclast activation (PubMed:18586671). {ECO:0000269|PubMed:15060082, ECO:0000269|PubMed:15917224, ECO:0000269|PubMed:16771708, ECO:0000269|PubMed:16873769, ECO:0000269|PubMed:18042364, ECO:0000269|PubMed:18586671, ECO:0000269|PubMed:20463016, ECO:0000269|PubMed:24501198, ECO:0000269|PubMed:26468290, ECO:0000269|PubMed:26823460, ECO:0000269|PubMed:27044744}.
uniprot
proteins
mass_dalton
31203
uniprot
proteins
mutagenesis
MUTAGEN 39; /note="H->K: Decreases binding of hyaluronan to CD44. Decreases hyaluronan-dependent lymphocyte rolling."; /evidence="ECO:0000269|PubMed:15060082"; MUTAGEN 41; /note="E->K: Has no significant effect on hyaluronan binding to CD44 or hyaluronan-dependent lymphocyte rolling."; /evidence="ECO:0000269|PubMed:15060082"; MUTAGEN 46; /note="K->Q: Abolishes binding to bikunin."; /evidence="ECO:0000269|PubMed:15917224"; MUTAGEN 47; /note="Y->F: Abolishes binding to bikunin. Impairs binding to hyaluronan. Retains the ability to bind heavy chains but cannot transfer them onto hyaluronan. Impairs binding of hyaluronan to CD44. Decreases hyaluronan-dependent lymphocyte rolling."; /evidence="ECO:0000269|PubMed:15060082, ECO:0000269|PubMed:15917224, ECO:0000269|PubMed:26468290"; MUTAGEN 48; /note="K->E: Decreases binding of hyaluronan to CD44. Decreases hyaluronan-dependent lymphocyte rolling."; /evidence="ECO:0000269|PubMed:15060082"; MUTAGEN 55; /note="K->A: Decreases binding to heparin. Has normal binding to bikunin. Impairs binding to heparin; when associated with A-69 and A-76. Has no effect on CXCL8-induced neutrophil transmigration; when associated with A-69 and A-76."; /evidence="ECO:0000269|PubMed:15917224, ECO:0000269|PubMed:24501198"; MUTAGEN 64; /note="H->K: Increases binding of hyaluronan to CD44. Has no significant effect on hyaluronan-dependent lymphocyte rolling."; /evidence="ECO:0000269|PubMed:15060082"; MUTAGEN 69; /note="K->A: Decreases binding to heparin. Has normal binding to bikunin. Impairs binding to heparin; when associated with A-55 and A-76. Has no effect on CXCL8-induced neutrophil transmigration; when associated with A-55 and A-76."; /evidence="ECO:0000269|PubMed:15917224, ECO:0000269|PubMed:24501198"; MUTAGEN 76; /note="K->A: Decreases binding to heparin. Has normal binding to bikunin. Impairs binding to heparin and decreases the potentiation effect toward bikunin antiprotease activity; when associated with A-55 and A-69. Has no effect on CXCL8-induced neutrophil transmigration; when associated with A-55 and A-69."; /evidence="ECO:0000269|PubMed:15917224, ECO:0000269|PubMed:24501198"; MUTAGEN 89; /note="K->A: Decreases binding to heparin. Has normal binding to bikunin."; /evidence="ECO:0000269|PubMed:15917224"; MUTAGEN 94; /note="Y->F: Abolishes binding to bikunin. Has no effect on transesterification reaction."; /evidence="ECO:0000269|PubMed:15917224, ECO:0000269|PubMed:26468290"; MUTAGEN 105; /note="F->V: Impairs binding of hyaluronan to CD44. Decreases hyaluronan-dependent lymphocyte rolling."; /evidence="ECO:0000269|PubMed:15060082"; MUTAGEN 113; /note="Y->F: Abolishes binding to bikunin. Impairs binding of hyaluronan to CD44. Decreases hyaluronan-dependent lymphocyte rolling. Has no effect on transesterification reaction."; /evidence="ECO:0000269|PubMed:15060082, ECO:0000269|PubMed:15917224, ECO:0000269|PubMed:26468290"; MUTAGEN 183; /note="E->S: Reduces the binding affinity to calcium ions. Abolishes the interaction with heavy chain ITIH1."; /evidence="ECO:0000269|PubMed:26468290
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000269|PubMed:1730767}.
uniprot
proteins
pubmed
11854277
uniprot
proteins
pubmed
15060082
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
15917224
uniprot
proteins
pubmed
16771708
uniprot
proteins
pubmed
16873769
uniprot
proteins
pubmed
1730767
uniprot
proteins
pubmed
18042364
uniprot
proteins
pubmed
18586671
uniprot
proteins
pubmed
20463016
uniprot
proteins
pubmed
24501198
uniprot
proteins
pubmed
26468290
uniprot
proteins
pubmed
26823460
uniprot
proteins
pubmed
27044744
uniprot
proteins
pubmed
7516184
uniprot
proteins
pubmed
8797823
uniprot
proteins
sequence_length
277
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1730767}.
uniprot
proteins