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P05543 (THBG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Thyroxine-binding globulin
Alternative name(s):
Serpin A7
T4-binding globulin
Gene names
Name:SERPINA7
Synonyms:TBG
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length415 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Major thyroid hormone transport protein in serum.

Subcellular location

Secreted.

Tissue specificity

Expressed by the liver and secreted in plasma.

Polymorphism

Two qualitative TBG variants occur in particular populations. TBG-A is found in 40% of Australian aborigines, it has reduced affinity for thyroxine and triiodothyroxine and increased susceptibility to inactivation by heat or acid. TBG-S ('s' for slow shift on isoelectic focusing) is found in blacks, Eskimos, Melanesians, Polynesians and Indonesians, but not in Caucasians; TBG-S is slightly more thermolabile.

Involvement in disease

Thyroxine-binding globulin deficiency (TBG deficiency) [MIM:314200]: Mutations in the SERPINA7 gene can result as a whole spectrum of deficiencies, characterized by either reduced or increased TBG levels in the serum. Patients show, respectively, reduced or elevated protein-bound iodine but are euthyroid.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Sequence similarities

Belongs to the serpin family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Ref.7
Chain21 – 415395Thyroxine-binding globulin
PRO_0000032436

Sites

Binding site2931Thyroxine
Binding site3981Thyroxine

Amino acid modifications

Glycosylation361N-linked (GlcNAc...) (complex) Ref.8 Ref.9
Glycosylation991N-linked (GlcNAc...)
Glycosylation1161N-linked (GlcNAc...); in variant Gary Probable
Glycosylation1651N-linked (GlcNAc...) Ref.8
Glycosylation2531N-linked (GlcNAc...)

Natural variations

Natural variant431S → T in TBG deficiency; San Diego; partial TBG deficiency. Ref.18
VAR_007102
Natural variant1161I → N in TBG deficiency; Gary; severe TBG deficiency. Ref.14
Corresponds to variant rs28933689 [ dbSNP | Ensembl ].
VAR_007103
Natural variant1331A → P in TBG deficiency; Montreal/TBG-M; partial TBG deficiency. Ref.16
Corresponds to variant rs28933688 [ dbSNP | Ensembl ].
VAR_007104
Natural variant1911D → N in TBG-S/Slow. Ref.20
Corresponds to variant rs1050086 [ dbSNP | Ensembl ].
VAR_007105
Natural variant2111A → T in TBG-A/Aborigine. Ref.19
Corresponds to variant rs2234036 [ dbSNP | Ensembl ].
VAR_007106
Natural variant2471L → P in TBG deficiency; CD5; complete TBG deficiency. Ref.13
Corresponds to variant rs28937312 [ dbSNP | Ensembl ].
VAR_007107
Natural variant3031L → F Common polymorphism.
Corresponds to variant rs1804495 [ dbSNP | Ensembl ].
VAR_007108
Natural variant3511H → Y in TBG deficiency; Quebec; partial TBG deficiency. Ref.17
VAR_007109
Natural variant3831P → L in TBG deficiency; Kumamoto. Ref.15
VAR_007110

Experimental info

Sequence conflict30 – 312CH → DS AA sequence Ref.7
Sequence conflict381T → S AA sequence Ref.7
Sequence conflict1971I → T in AAA60616. Ref.1

Secondary structure

......................................................... 415
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P05543 [UniParc].

Last modified February 1, 1996. Version 2.
Checksum: 8B24EF8C7CEF8F0A

FASTA41546,325
        10         20         30         40         50         60 
MSPFLYLVLL VLGLHATIHC ASPEGKVTAC HSSQPNATLY KMSSINADFA FNLYRRFTVE 

        70         80         90        100        110        120 
TPDKNIFFSP VSISAALVML SFGACCSTQT EIVETLGFNL TDTPMVEIQH GFQHLICSLN 

       130        140        150        160        170        180 
FPKKELELQI GNALFIGKHL KPLAKFLNDV KTLYETEVFS TDFSNISAAK QEINSHVEMQ 

       190        200        210        220        230        240 
TKGKVVGLIQ DLKPNTIMVL VNYIHFKAQW ANPFDPSKTE DSSSFLIDKT TTVQVPMMHQ 

       250        260        270        280        290        300 
MEQYYHLVDM ELNCTVLQMD YSKNALALFV LPKEGQMESV EAAMSSKTLK KWNRLLQKGW 

       310        320        330        340        350        360 
VDLFVPKFSI SATYDLGATL LKMGIQHAYS ENADFSGLTE DNGLKLSNAA HKAVLHIGEK 

       370        380        390        400        410 
GTEAAAVPEV ELSDQPENTF LHPIIQIDRS FMLLILERST RSILFLGKVV NPTEA 

« Hide

References

« Hide 'large scale' references
[1]"Complete amino acid sequence of human thyroxine-binding globulin deduced from cloned DNA: close homology to the serine antiproteases."
Flink I.L., Bayley T.J., Gustafson T.A., Markham B.E., Morkin E.
Proc. Natl. Acad. Sci. U.S.A. 83:7708-7712(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]"The structure of the human thyroxine binding globulin (TBG) gene."
Akbari M.T., Kapadi A., Farmer M.J., Fitch N.J.S., McCann K.P., Kordestani S., Flink I.L., Sheppard M.C., Ramsden D.B.
Biochim. Biophys. Acta 1216:446-454(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Human thyroxine-binding globulin gene: complete sequence and transcriptional regulation."
Hayashi Y., Mori Y., Janssen O.E., Sunthornthepvarakul T., Weiss R.E., Takeda K., Weinberg M., Seo H., Bell G.I., Refetoff S.
Mol. Endocrinol. 7:1049-1060(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]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. expand/collapse author list , 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].
[6]"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: Liver.
[7]"Partial amino acid sequence of human thyroxine-binding globulin. Further evidence for a single polypeptide chain."
Cheng S.-Y.
Biochem. Biophys. Res. Commun. 79:1212-1218(1977) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 21-40.
[8]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-36 AND ASN-165.
Tissue: Plasma.
[9]"Enrichment of glycopeptides for glycan structure and attachment site identification."
Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G.
Nat. Methods 6:809-811(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-36, STRUCTURE OF CARBOHYDRATES.
Tissue: Cerebrospinal fluid.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Structural mechanism for the carriage and release of thyroxine in the blood."
Zhou A., Wei Z., Read R.J., Carrell R.W.
Proc. Natl. Acad. Sci. U.S.A. 103:13321-13326(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 39-415 IN COMPLEX WITH THYROXINE.
[12]"Molecular basis of inherited thyroxine-binding globulin defects."
Janssen O.E., Bertenshaw R., Takeda K., Weiss R., Refetoff S.
Trends Endocrinol. Metab. 3:49-53(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[13]"Replacement of Leu227 by Pro in thyroxine-binding globulin (TBG) is associated with complete TBG deficiency in three of eight families with this inherited defect."
Mori Y., Takeda K., Charbonneau M., Refetoff S.
J. Clin. Endocrinol. Metab. 70:804-809(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TBG DEFICIENCY PRO-247.
[14]"A mutation causing reduced biological activity and stability of thyroxine-binding globulin probably as a result of abnormal glycosylation of the molecule."
Mori Y., Seino S., Takeda K., Flink I.L., Murata Y., Bell G.I., Refetoff S.
Mol. Endocrinol. 3:575-579(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TBG DEFICIENCY ASN-116.
[15]"Thyroxine-binding globulin variant (TBG-Kumamoto): identification of a point mutation and genotype analysis of its family."
Shirotani T., Kishikawa H., Wake N., Miyamura N., Hashimoto Y., Motoyoshi S., Yamaguchi K., Shichiri M.
Endocrinol. Jpn. 39:577-584(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TBG DEFICIENCY LEU-383.
[16]"Sequence of the variant thyroxine-binding globulin (TBG) in a Montreal family with partial TBG deficiency."
Janssen O.E., Takeda K., Refetoff S.
Hum. Genet. 87:119-122(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TBG DEFICIENCY PRO-133.
[17]"Sequencing of the variant thyroxine-binding globulin (TBG)-Quebec reveals two nucleotide substitutions."
Bertenshaw R., Takeda K., Refetoff S.
Am. J. Hum. Genet. 48:741-744(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TBG DEFICIENCY TYR-351.
[18]"Sequencing of the variant thyroxine-binding globulin (TBG)-San Diego reveals two nucleotide substitutions."
Bertenshaw R., Sarne D., Tornari J., Weinberg M., Refetoff S.
Biochim. Biophys. Acta 1139:307-310(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TBG DEFICIENCY THR-43.
[19]"Sequence of the variant thyroxine-binding globulin of Australian aborigines. Only one of two amino acid replacements is responsible for its altered properties."
Takeda K., Mori Y., Sobieszczyk S., Seo H., Dick M., Watson F., Flink I.L., Seino S., Bell G.I., Refetoff S.
J. Clin. Invest. 83:1344-1348(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TBG-A THR-211.
[20]"Molecular basis for the properties of the thyroxine-binding globulin-slow variant in American blacks."
Waltz M.R., Pullman T.N., Takeda K., Sobieszczyk P., Refetoff S.
J. Endocrinol. Invest. 13:343-349(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TBG-S ASN-191.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M14091 mRNA. Translation: AAA60616.1.
X64171 Genomic DNA. Translation: CAA45509.1.
L13470 Genomic DNA. Translation: AAA16067.1.
Z83850 Genomic DNA. Translation: CAB06092.1.
CH471120 Genomic DNA. Translation: EAX02747.1.
CH471120 Genomic DNA. Translation: EAX02748.1.
BC020747 mRNA. Translation: AAH20747.1.
PIRA47224.
RefSeqNP_000345.2. NM_000354.5.
UniGeneHs.76838.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CEOX-ray2.80A/B39-415[»]
2RIVX-ray1.50A33-365[»]
B377-415[»]
2RIWX-ray2.04A39-365[»]
B377-415[»]
2XN3X-ray2.09A33-365[»]
B377-415[»]
2XN5X-ray1.70A32-365[»]
B381-415[»]
2XN6X-ray1.29A32-365[»]
B381-415[»]
2XN7X-ray1.43A32-365[»]
B381-415[»]
ProteinModelPortalP05543.
SMRP05543. Positions 37-415.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112769. 1 interaction.
STRING9606.ENSP00000329374.

Chemistry

ChEMBLCHEMBL3843.
DrugBankDB00451. Levothyroxine.
DB00279. Liothyronine.

Protein family/group databases

MEROPSI04.955.

PTM databases

PhosphoSiteP05543.

Polymorphism databases

DMDM1351236.

Proteomic databases

PaxDbP05543.
PeptideAtlasP05543.
PRIDEP05543.

Protocols and materials databases

DNASU6906.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000327674; ENSP00000329374; ENSG00000123561.
ENST00000372563; ENSP00000361644; ENSG00000123561.
GeneID6906.
KEGGhsa:6906.
UCSCuc004eme.2. human.

Organism-specific databases

CTD6906.
GeneCardsGC0XM105277.
HGNCHGNC:11583. SERPINA7.
HPAHPA002803.
MIM314200. gene+phenotype.
neXtProtNX_P05543.
Orphanet209893. Congenital isolated thyroxine-binding globulin deficiency.
PharmGKBPA36347.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4826.
HOGENOMHOG000238521.
HOVERGENHBG005957.
InParanoidP05543.
OMAFNLTDTP.
OrthoDBEOG7QC7W9.
PhylomeDBP05543.
TreeFamTF343201.

Gene expression databases

BgeeP05543.
CleanExHS_SERPINA7.
GenevestigatorP05543.

Family and domain databases

InterProIPR023795. Serpin_CS.
IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view]
PANTHERPTHR11461. PTHR11461. 1 hit.
PfamPF00079. Serpin. 1 hit.
[Graphical view]
SMARTSM00093. SERPIN. 1 hit.
[Graphical view]
SUPFAMSSF56574. SSF56574. 1 hit.
PROSITEPS00284. SERPIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP05543.
GenomeRNAi6906.
NextBio27007.
PROP05543.
SOURCESearch...

Entry information

Entry nameTHBG_HUMAN
AccessionPrimary (citable) accession number: P05543
Secondary accession number(s): D3DUX1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: February 1, 1996
Last modified: April 16, 2014
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM