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Protein

Thyroxine-binding globulin

Gene

SERPINA7

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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: GO_Central

GO - Biological processi

  • negative regulation of endopeptidase activity Source: GO_Central
  • 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
MIMi314200 gene
neXtProtiNX_P05543

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 NON RARE IN EUROPE: 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

EPDiP05543
MaxQBiP05543
PaxDbiP05543
PeptideAtlasiP05543
PRIDEiP05543
ProteomicsDBi51845

PTM databases

GlyConnecti750
iPTMnetiP05543
PhosphoSitePlusiP05543

Expressioni

Tissue specificityi

Expressed by the liver and secreted in plasma.

Gene expression databases

BgeeiENSG00000123561 Expressed in 35 organ(s), highest expression level in liver
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

3D structure databases

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
OMAiELQMGNA
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:rs28933689EnsemblClinVar.1
Natural variantiVAR_007104133A → P Polymorphism; Montreal/TBG-M; partial thyroxine-binding globulin deficiency. 1 PublicationCorresponds to variant dbSNP:rs28933688EnsemblClinVar.1
Natural variantiVAR_007105191D → N Polymorphism; TBG-S/Slow. 1 PublicationCorresponds to variant dbSNP:rs1050086EnsemblClinVar.1
Natural variantiVAR_007106211A → T Polymorphism; TBG-A/Aborigine. 1 PublicationCorresponds to variant dbSNP:rs2234036EnsemblClinVar.1
Natural variantiVAR_007107247L → P Polymorphism; CD5; complete thyroxine-binding globulin deficiency. 1 PublicationCorresponds to variant dbSNP:rs28937312EnsemblClinVar.1
Natural variantiVAR_007108303L → F Common polymorphism; associated with T-43 in San Diego. 1 PublicationCorresponds to variant dbSNP:rs1804495EnsemblClinVar.1
Natural variantiVAR_007109351H → Y Polymorphism; Quebec; partial thyroxine-binding globulin deficiency. 1 PublicationCorresponds to variant dbSNP:rs72554659EnsemblClinVar.1
Natural variantiVAR_007110383P → L Polymorphism; Kumamoto; partial thyroxine-binding globulin deficiency. 1 PublicationCorresponds to variant dbSNP:rs72554658EnsemblClinVar.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

Cross-referencesi

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

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...

Protein-protein interaction databases

BioGridi112769, 5 interactors
IntActiP05543, 1 interactor
STRINGi9606.ENSP00000329374

Chemistry databases

ChEMBLiCHEMBL3843
DrugBankiDB00451 Levothyroxine
DB00279 Liothyronine
DB01583 Liotrix
DB05235 NRP409

Protein family/group databases

MEROPSiI04.955

PTM databases

GlyConnecti750
iPTMnetiP05543
PhosphoSitePlusiP05543

Polymorphism and mutation databases

BioMutaiSERPINA7
DMDMi1351236

Proteomic databases

EPDiP05543
MaxQBiP05543
PaxDbiP05543
PeptideAtlasiP05543
PRIDEiP05543
ProteomicsDBi51845

Protocols and materials databases

DNASUi6906
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi6906
DisGeNETi6906
EuPathDBiHostDB:ENSG00000123561.14
GeneCardsiSERPINA7
HGNCiHGNC:11583 SERPINA7
HPAiHPA002803
MalaCardsiSERPINA7
MIMi300932 phenotype
314200 gene
neXtProtiNX_P05543
OpenTargetsiENSG00000123561
Orphaneti209893 NON RARE IN EUROPE: Congenital isolated thyroxine-binding globulin deficiency
PharmGKBiPA36347
GenAtlasiSearch...

Phylogenomic databases

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

Miscellaneous databases

EvolutionaryTraceiP05543
GenomeRNAii6906
PROiPR:P05543
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000123561 Expressed in 35 organ(s), highest expression level in liver
CleanExiHS_SERPINA7
GenevisibleiP05543 HS

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
ProtoNetiSearch...

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 7, 2018
This is version 194 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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