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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
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000123561-MONOMER.

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

HGNCiHGNC:11583. SERPINA7.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
  • extracellular space Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Thyroxine-binding globulin deficiency (TBG deficiency)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionMutations 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.
See also OMIM:314200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00710243S → T in TBG deficiency; San Diego; partial TBG deficiency. 1 PublicationCorresponds to variant rs72554662dbSNPEnsembl.1
Natural variantiVAR_007103116I → N in TBG deficiency; Gary; severe TBG deficiency. 1 PublicationCorresponds to variant rs28933689dbSNPEnsembl.1
Natural variantiVAR_007104133A → P in TBG deficiency; Montreal/TBG-M; partial TBG deficiency. 1 PublicationCorresponds to variant rs28933688dbSNPEnsembl.1
Natural variantiVAR_007107247L → P in TBG deficiency; CD5; complete TBG deficiency. 1 PublicationCorresponds to variant rs28937312dbSNPEnsembl.1
Natural variantiVAR_007109351H → Y in TBG deficiency; Quebec; partial TBG deficiency. 1 PublicationCorresponds to variant rs72554659dbSNPEnsembl.1
Natural variantiVAR_007110383P → L in TBG deficiency; Kumamoto. 1 PublicationCorresponds to variant rs72554658dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi6906.
MalaCardsiSERPINA7.
MIMi314200. gene+phenotype.
OpenTargetsiENSG00000123561.
Orphaneti209893. Congenital isolated thyroxine-binding globulin deficiency.
PharmGKBiPA36347.

Chemistry databases

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

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)2 Publications1
Glycosylationi99N-linked (GlcNAc...)1
Glycosylationi116N-linked (GlcNAc...); in variant GaryCurated1
Glycosylationi165N-linked (GlcNAc...)1 Publication1
Glycosylationi253N-linked (GlcNAc...)1

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.
OMAiFNLTDTP.
OrthoDBiEOG091G0ION.
PhylomeDBiP05543.
TreeFamiTF343201.

Family and domain databases

InterProiIPR023795. Serpin_CS.
IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view]
PANTHERiPTHR11461. PTHR11461. 1 hit.
PfamiPF00079. Serpin. 1 hit.
[Graphical view]
SMARTiSM00093. SERPIN. 1 hit.
[Graphical view]
SUPFAMiSSF56574. SSF56574. 1 hit.
PROSITEiPS00284. SERPIN. 1 hit.
[Graphical view]

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

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).2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00710243S → T in TBG deficiency; San Diego; partial TBG deficiency. 1 PublicationCorresponds to variant rs72554662dbSNPEnsembl.1
Natural variantiVAR_007103116I → N in TBG deficiency; Gary; severe TBG deficiency. 1 PublicationCorresponds to variant rs28933689dbSNPEnsembl.1
Natural variantiVAR_007104133A → P in TBG deficiency; Montreal/TBG-M; partial TBG deficiency. 1 PublicationCorresponds to variant rs28933688dbSNPEnsembl.1
Natural variantiVAR_007105191D → N in TBG-S/Slow. 1 PublicationCorresponds to variant rs1050086dbSNPEnsembl.1
Natural variantiVAR_007106211A → T in TBG-A/Aborigine. 1 PublicationCorresponds to variant rs2234036dbSNPEnsembl.1
Natural variantiVAR_007107247L → P in TBG deficiency; CD5; complete TBG deficiency. 1 PublicationCorresponds to variant rs28937312dbSNPEnsembl.1
Natural variantiVAR_007108303L → F Common polymorphism. Corresponds to variant rs1804495dbSNPEnsembl.1
Natural variantiVAR_007109351H → Y in TBG deficiency; Quebec; partial TBG deficiency. 1 PublicationCorresponds to variant rs72554659dbSNPEnsembl.1
Natural variantiVAR_007110383P → L in TBG deficiency; Kumamoto. 1 PublicationCorresponds to variant rs72554658dbSNPEnsembl.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. Translation: CAB06092.1.
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

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. Translation: CAB06092.1.
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.

Protein family/group databases

MEROPSiI04.955.

PTM databases

iPTMnetiP05543.
PhosphoSitePlusiP05543.

Polymorphism and mutation databases

BioMutaiSERPINA7.
DMDMi1351236.

Proteomic databases

MaxQBiP05543.
PaxDbiP05543.
PeptideAtlasiP05543.
PRIDEiP05543.

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.
GeneCardsiSERPINA7.
HGNCiHGNC:11583. SERPINA7.
HPAiHPA002803.
MalaCardsiSERPINA7.
MIMi314200. gene+phenotype.
neXtProtiNX_P05543.
OpenTargetsiENSG00000123561.
Orphaneti209893. Congenital isolated thyroxine-binding globulin deficiency.
PharmGKBiPA36347.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000123561-MONOMER.

Miscellaneous databases

EvolutionaryTraceiP05543.
GenomeRNAii6906.
PROiP05543.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000123561.
CleanExiHS_SERPINA7.
GenevisibleiP05543. HS.

Family and domain databases

InterProiIPR023795. Serpin_CS.
IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view]
PANTHERiPTHR11461. PTHR11461. 1 hit.
PfamiPF00079. Serpin. 1 hit.
[Graphical view]
SMARTiSM00093. SERPIN. 1 hit.
[Graphical view]
SUPFAMiSSF56574. SSF56574. 1 hit.
PROSITEiPS00284. SERPIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTHBG_HUMAN
AccessioniPrimary (citable) accession number: P05543
Secondary accession number(s): D3DUX1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: February 1, 1996
Last modified: November 30, 2016
This is version 181 of the entry and version 2 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.