TNC

Protein identityUniProt · HPA

UniProt accession

P24821

Gene

TNC

Ensembl

ENSG00000041982

Chromosome

9

Canonical length

2201 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Secretome location

Secreted to extracellular matrix

Quaternary structure

Homohexamer

OverviewNCBI Gene

This gene encodes an extracellular matrix protein with a spatially and temporally restricted tissue distribution. This protein is homohexameric with disulfide-linked subunits, and contains multiple EGF-like and fibronectin type-III domains. It is implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity, and neuronal regeneration. [provided by RefSeq, Jul 2011]

Canonical amino-acid sequenceUniProt

2201 residues, UniProt reviewed canonical sequence.

>P24821|TNC
     1  MGAMTQLLAG VFLAFLALAT EGGVLKKVIR HKRQSGVNAT LPEENQPVVF NHVYNIKLPV
    61  GSQCSVDLES ASGEKDLAPP SEPSESFQEH TVDGENQIVF THRINIPRRA CGCAAAPDVK
   121  ELLSRLEELE NLVSSLREQC TAGAGCCLQP ATGRLDTRPF CSGRGNFSTE GCGCVCEPGW
   181  KGPNCSEPEC PGNCHLRGRC IDGQCICDDG FTGEDCSQLA CPSDCNDQGK CVNGVCICFE
   241  GYAGADCSRE ICPVPCSEEH GTCVDGLCVC HDGFAGDDCN KPLCLNNCYN RGRCVENECV
   301  CDEGFTGEDC SELICPNDCF DRGRCINGTC YCEEGFTGED CGKPTCPHAC HTQGRCEEGQ
   361  CVCDEGFAGV DCSEKRCPAD CHNRGRCVDG RCECDDGFTG ADCGELKCPN GCSGHGRCVN
   421  GQCVCDEGYT GEDCSQLRCP NDCHSRGRCV EGKCVCEQGF KGYDCSDMSC PNDCHQHGRC
   481  VNGMCVCDDG YTGEDCRDRQ CPRDCSNRGL CVDGQCVCED GFTGPDCAEL SCPNDCHGQG
   541  RCVNGQCVCH EGFMGKDCKE QRCPSDCHGQ GRCVDGQCIC HEGFTGLDCG QHSCPSDCNN
   601  LGQCVSGRCI CNEGYSGEDC SEVSPPKDLV VTEVTEETVN LAWDNEMRVT EYLVVYTPTH
   661  EGGLEMQFRV PGDQTSTIIQ ELEPGVEYFI RVFAILENKK SIPVSARVAT YLPAPEGLKF
   721  KSIKETSVEV EWDPLDIAFE TWEIIFRNMN KEDEGEITKS LRRPETSYRQ TGLAPGQEYE
   781  ISLHIVKNNT RGPGLKRVTT TRLDAPSQIE VKDVTDTTAL ITWFKPLAEI DGIELTYGIK
   841  DVPGDRTTID LTEDENQYSI GNLKPDTEYE VSLISRRGDM SSNPAKETFT TGLDAPRNLR
   901  RVSQTDNSIT LEWRNGKAAI DSYRIKYAPI SGGDHAEVDV PKSQQATTKT TLTGLRPGTE
   961  YGIGVSAVKE DKESNPATIN AATELDTPKD LQVSETAETS LTLLWKTPLA KFDRYRLNYS
  1021  LPTGQWVGVQ LPRNTTSYVL RGLEPGQEYN VLLTAEKGRH KSKPARVKAS TEQAPELENL
  1081  TVTEVGWDGL RLNWTAADQA YEHFIIQVQE ANKVEAARNL TVPGSLRAVD IPGLKAATPY
  1141  TVSIYGVIQG YRTPVLSAEA STGETPNLGE VVVAEVGWDA LKLNWTAPEG AYEYFFIQVQ
  1201  EADTVEAAQN LTVPGGLRST DLPGLKAATH YTITIRGVTQ DFSTTPLSVE VLTEEVPDMG
  1261  NLTVTEVSWD ALRLNWTTPD GTYDQFTIQV QEADQVEEAH NLTVPGSLRS MEIPGLRAGT
  1321  PYTVTLHGEV RGHSTRPLAV EVVTEDLPQL GDLAVSEVGW DGLRLNWTAA DNAYEHFVIQ
  1381  VQEVNKVEAA QNLTLPGSLR AVDIPGLEAA TPYRVSIYGV IRGYRTPVLS AEASTAKEPE
  1441  IGNLNVSDIT PESFNLSWMA TDGIFETFTI EIIDSNRLLE TVEYNISGAE RTAHISGLPP
  1501  STDFIVYLSG LAPSIRTKTI SATATTEALP LLENLTISDI NPYGFTVSWM ASENAFDSFL
  1561  VTVVDSGKLL DPQEFTLSGT QRKLELRGLI TGIGYEVMVS GFTQGHQTKP LRAEIVTEAE
  1621  PEVDNLLVSD ATPDGFRLSW TADEGVFDNF VLKIRDTKKQ SEPLEITLLA PERTRDITGL
  1681  REATEYEIEL YGISKGRRSQ TVSAIATTAM GSPKEVIFSD ITENSATVSW RAPTAQVESF
  1741  RITYVPITGG TPSMVTVDGT KTQTRLVKLI PGVEYLVSII AMKGFEESEP VSGSFTTALD
  1801  GPSGLVTANI TDSEALARWQ PAIATVDSYV ISYTGEKVPE ITRTVSGNTV EYALTDLEPA
  1861  TEYTLRIFAE KGPQKSSTIT AKFTTDLDSP RDLTATEVQS ETALLTWRPP RASVTGYLLV
  1921  YESVDGTVKE VIVGPDTTSY SLADLSPSTH YTAKIQALNG PLRSNMIQTI FTTIGLLYPF
  1981  PKDCSQAMLN GDTTSGLYTI YLNGDKAEAL EVFCDMTSDG GGWIVFLRRK NGRENFYQNW
  2041  KAYAAGFGDR REEFWLGLDN LNKITAQGQY ELRVDLRDHG ETAFAVYDKF SVGDAKTRYK
  2101  LKVEGYSGTA GDSMAYHNGR SFSTFDKDTD SAITNCALSY KGAFWYRNCH RVNLMGRYGD
  2161  NNHSQGVNWF HWKGHEHSIQ FAEMKLRPSN FRNLEGRRKR A

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TNC can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.32

Highest tissue expression

447 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TNC.

Disease | AllUniProt

Conditions TNC is implicated in, by any mechanism.

• Deafness, autosomal dominant, 56 (DFNA56) MIM:615629

Disease | GeneticClinVar

5 pathogenic / likely-pathogenic of 655 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal dominant nonsyndromic hearing loss 56
• TNC-related disorder

Disease | ImmuneIEDB

Conditions an epitope on TNC was assayed in.

• rheumatoid arthritis B and T cell
• glioblastoma T cell
• osteoarthritis B cell
• systemic juvenile rheumatoid arthritis T cell

ReferencesPubMed · IEDB

Publications for TNC from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.45

gnomAD pLI

0

gnomAD missense Z

-0.08

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• bud outgrowth involved in lung branching
• cell adhesion
• cellular response to prostaglandin D stimulus
• cellular response to retinoic acid
• cellular response to vitamin D
• mesenchymal-epithelial cell signaling involved in prostate gland development
• morphogenesis of an epithelium
• negative regulation of cell adhesion
• neuromuscular junction development
• odontogenesis of dentin-containing tooth
• osteoblast differentiation
• peripheral nervous system axon regeneration
• positive regulation of cell population proliferation
• positive regulation of gene expression
• prostate gland epithelium morphogenesis
• regulation of cell adhesion
• regulation of cell growth
• regulation of cell migration
• regulation of inflammatory response
• response to ethanol
• response to fibroblast growth factor
• response to mechanical stimulus
• response to wounding

Molecular functions

• extracellular matrix structural constituent
• integrin binding
• syndecan binding

Cellular components

• basement membrane
• endoplasmic reticulum lumen
• extracellular matrix
• extracellular matrix of synaptic cleft
• extracellular region
• extracellular space
• focal adhesion
• glutamatergic synapse
• interstitial matrix
• membrane
• tenascin complex
• perisynaptic extracellular matrix

Protein domainsUniProt · Pfam · InterPro

• EGF-like domain
• Fibrinogen, alpha/beta/gamma chain, C-terminal globular domain
• Fibronectin type III
• Epidermal growth factor-like domain, extracellular
• Immunoglobulin-like fold
• Fibrinogen, alpha/beta/gamma chain, C-terminal globular, subdomain 1
• Fibrinogen-like, C-terminal
• Fibronectin type III superfamily
• Tenascin, EGF-like domain
• Extracellular Matrix Regulatory Proteins
• Fibronectin type III domain
• Fibrinogen beta and gamma chains, C-terminal globular domain
• EGF-like domain
• Tenascin EGF domain
• Teneurin-like EGF domain
• Teneurin EGF domain

KeywordsUniProt

• Cell adhesion
• Coiled coil
• Deafness
• Disulfide bond
• EGF-like domain
• Extracellular matrix
• Glycoprotein
• Non-syndromic deafness
• Phosphoprotein
• Proteoglycan
• Repeat
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of TNC in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CSPG4
• TNR