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Protein

Thyroxine-binding globulin

Gene

SERPINA7

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Major thyroid hormone transport protein in serum.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei293Thyroxine1 Publication1
Binding sitei398Thyroxine1 Publication1

GO - Molecular functioni

  • serine-type endopeptidase inhibitor activity Source: ProtInc

GO - Biological processi

  • thyroid hormone transport Source: UniProtKB

Protein family/group databases

MEROPSiI04.955.

Names & Taxonomyi

Protein namesi
Recommended name:
Thyroxine-binding globulin
Alternative name(s):
Serpin A7
T4-binding globulin
Gene namesi
Name:SERPINA7
Synonyms:TBG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000123561.14.
HGNCiHGNC:11583. SERPINA7.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi6906.
MalaCardsiSERPINA7.
MIMi300932. phenotype.
OpenTargetsiENSG00000123561.
Orphaneti209893. Congenital isolated thyroxine-binding globulin deficiency.
PharmGKBiPA36347.

Chemistry databases

ChEMBLiCHEMBL3843.
DrugBankiDB00451. Levothyroxine.
DB00279. Liothyronine.
DB01583. Liotrix.
DB05235. NRP409.

Polymorphism and mutation databases

BioMutaiSERPINA7.
DMDMi1351236.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 201 PublicationAdd BLAST20
ChainiPRO_000003243621 – 415Thyroxine-binding globulinAdd BLAST395

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi36N-linked (GlcNAc...) (complex) asparagine2 Publications1
Glycosylationi99N-linked (GlcNAc...) asparagine1
Glycosylationi116N-linked (GlcNAc...) asparagine; in variant GaryCurated1
Glycosylationi165N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi253N-linked (GlcNAc...) asparagine1

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiP05543.
PaxDbiP05543.
PeptideAtlasiP05543.
PRIDEiP05543.

PTM databases

iPTMnetiP05543.
PhosphoSitePlusiP05543.

Expressioni

Tissue specificityi

Expressed by the liver and secreted in plasma.

Gene expression databases

BgeeiENSG00000123561.
CleanExiHS_SERPINA7.
GenevisibleiP05543. HS.

Organism-specific databases

HPAiHPA002803.

Interactioni

Protein-protein interaction databases

BioGridi112769. 5 interactors.
IntActiP05543. 1 interactor.
STRINGi9606.ENSP00000329374.

Structurei

Secondary structure

1415
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi40 – 60Combined sources21
Beta strandi66 – 68Combined sources3
Helixi70 – 82Combined sources13
Helixi86 – 95Combined sources10
Turni100 – 102Combined sources3
Helixi105 – 120Combined sources16
Beta strandi126 – 137Combined sources12
Helixi144 – 153Combined sources10
Beta strandi156 – 161Combined sources6
Helixi166 – 180Combined sources15
Turni181 – 183Combined sources3
Beta strandi198 – 212Combined sources15
Helixi216 – 218Combined sources3
Beta strandi220 – 228Combined sources9
Beta strandi231 – 249Combined sources19
Turni250 – 253Combined sources4
Beta strandi254 – 272Combined sources19
Helixi277 – 283Combined sources7
Helixi286 – 295Combined sources10
Beta strandi297 – 306Combined sources10
Beta strandi308 – 315Combined sources8
Helixi317 – 323Combined sources7
Helixi327 – 329Combined sources3
Turni336 – 338Combined sources3
Beta strandi339 – 342Combined sources4
Beta strandi344 – 357Combined sources14
Beta strandi359 – 374Combined sources16
Beta strandi384 – 386Combined sources3
Beta strandi391 – 397Combined sources7
Turni398 – 401Combined sources4
Beta strandi402 – 410Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CEOX-ray2.80A/B39-415[»]
2RIVX-ray1.50A33-386[»]
B376-415[»]
2RIWX-ray2.04A39-386[»]
B376-415[»]
2XN3X-ray2.09A33-386[»]
B377-415[»]
2XN5X-ray1.70A32-380[»]
B381-415[»]
2XN6X-ray1.29A32-380[»]
B381-415[»]
2XN7X-ray1.43A32-380[»]
B381-415[»]
4X30X-ray1.55A21-415[»]
4YIAX-ray1.58A1-386[»]
B382-415[»]
ProteinModelPortaliP05543.
SMRiP05543.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05543.

Family & Domainsi

Sequence similaritiesi

Belongs to the serpin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG2392. Eukaryota.
COG4826. LUCA.
GeneTreeiENSGT00760000118839.
HOGENOMiHOG000238521.
HOVERGENiHBG005957.
InParanoidiP05543.
KOiK20734.
OMAiCSLNFPK.
OrthoDBiEOG091G0ION.
PhylomeDBiP05543.
TreeFamiTF343201.

Family and domain databases

InterProiView protein in InterPro
IPR023795. Serpin_CS.
IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
IPR036186. Serpin_sf.
PANTHERiPTHR11461. PTHR11461. 1 hit.
PfamiView protein in Pfam
PF00079. Serpin. 1 hit.
SMARTiView protein in SMART
SM00093. SERPIN. 1 hit.
SUPFAMiSSF56574. SSF56574. 1 hit.
PROSITEiView protein in PROSITE
PS00284. SERPIN. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P05543-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSPFLYLVLL VLGLHATIHC ASPEGKVTAC HSSQPNATLY KMSSINADFA
60 70 80 90 100
FNLYRRFTVE TPDKNIFFSP VSISAALVML SFGACCSTQT EIVETLGFNL
110 120 130 140 150
TDTPMVEIQH GFQHLICSLN FPKKELELQI GNALFIGKHL KPLAKFLNDV
160 170 180 190 200
KTLYETEVFS TDFSNISAAK QEINSHVEMQ TKGKVVGLIQ DLKPNTIMVL
210 220 230 240 250
VNYIHFKAQW ANPFDPSKTE DSSSFLIDKT TTVQVPMMHQ MEQYYHLVDM
260 270 280 290 300
ELNCTVLQMD YSKNALALFV LPKEGQMESV EAAMSSKTLK KWNRLLQKGW
310 320 330 340 350
VDLFVPKFSI SATYDLGATL LKMGIQHAYS ENADFSGLTE DNGLKLSNAA
360 370 380 390 400
HKAVLHIGEK GTEAAAVPEV ELSDQPENTF LHPIIQIDRS FMLLILERST
410
RSILFLGKVV NPTEA
Length:415
Mass (Da):46,325
Last modified:February 1, 1996 - v2
Checksum:i8B24EF8C7CEF8F0A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti30 – 31CH → DS AA sequence (PubMed:414747).Curated2
Sequence conflicti38T → S AA sequence (PubMed:414747).Curated1
Sequence conflicti197I → T in AAA60616 (PubMed:3094014).Curated1

Polymorphismi

Genetic variants in SERPINA7 influence the serum levels of thyroxine-binding globulin and define the thyroxine-binding globulin quantitaive trait locus (TBGQTL) [MIMi:300932]. Individuals with low or high serum levels of thyroxine-binding globulin show, respectively, reduced or elevated protein-bound iodine but are euthyroid and do not manifest major metabolic alterations (PubMed:1294376, PubMed:1515456, PubMed:1901689, PubMed:1906047, PubMed:2155256, PubMed:2501669). 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 (PubMed:2495303). 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 (PubMed:2115061).8 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00710243S → T Polymorphism; associated with F-303 in San Diego; partial thyroxine-binding globulin deficiency. 1 PublicationCorresponds to variant dbSNP:rs72554662Ensembl.1
Natural variantiVAR_007103116I → N Polymorphism; Gary; severe thyroxine-binding globulin deficiency. 1 PublicationCorresponds to variant dbSNP:rs28933689Ensembl.1
Natural variantiVAR_007104133A → P Polymorphism; Montreal/TBG-M; partial thyroxine-binding globulin deficiency. 1 PublicationCorresponds to variant dbSNP:rs28933688Ensembl.1
Natural variantiVAR_007105191D → N Polymorphism; TBG-S/Slow. 1 PublicationCorresponds to variant dbSNP:rs1050086Ensembl.1
Natural variantiVAR_007106211A → T Polymorphism; TBG-A/Aborigine. 1 PublicationCorresponds to variant dbSNP:rs2234036Ensembl.1
Natural variantiVAR_007107247L → P Polymorphism; CD5; complete thyroxine-binding globulin deficiency. 1 PublicationCorresponds to variant dbSNP:rs28937312Ensembl.1
Natural variantiVAR_007108303L → F Common polymorphism; associated with T-43 in San Diego. 1 PublicationCorresponds to variant dbSNP:rs1804495Ensembl.1
Natural variantiVAR_007109351H → Y Polymorphism; Quebec; partial thyroxine-binding globulin deficiency. 1 PublicationCorresponds to variant dbSNP:rs72554659Ensembl.1
Natural variantiVAR_007110383P → L Polymorphism; Kumamoto; partial thyroxine-binding globulin deficiency. 1 PublicationCorresponds to variant dbSNP:rs72554658Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14091 mRNA. Translation: AAA60616.1.
X64171 Genomic DNA. Translation: CAA45509.1.
L13470 Genomic DNA. Translation: AAA16067.1.
Z83850 Genomic DNA. No translation available.
CH471120 Genomic DNA. Translation: EAX02747.1.
CH471120 Genomic DNA. Translation: EAX02748.1.
BC020747 mRNA. Translation: AAH20747.1.
CCDSiCCDS14518.1.
PIRiA47224.
RefSeqiNP_000345.2. NM_000354.5.
UniGeneiHs.76838.

Genome annotation databases

EnsembliENST00000327674; ENSP00000329374; ENSG00000123561.
ENST00000372563; ENSP00000361644; ENSG00000123561.
GeneIDi6906.
KEGGihsa:6906.
UCSCiuc004eme.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTHBG_HUMAN
AccessioniPrimary (citable) accession number: P05543
Secondary accession number(s): D3DUX1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: February 1, 1996
Last modified: November 22, 2017
This is version 188 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families