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Protein

Sex hormone-binding globulin

Gene

SHBG

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

Functioni

Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration.

GO - Molecular functioni

  • androgen binding Source: ProtInc
  • steroid binding Source: UniProtKB-KW
Complete GO annotation...

Keywords - Ligandi

Lipid-binding, Steroid-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000129214-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Sex hormone-binding globulin
Short name:
SHBG
Alternative name(s):
Sex steroid-binding protein
Short name:
SBP
Testis-specific androgen-binding protein
Short name:
ABP
Testosterone-estradiol-binding globulin
Short name:
TeBG
Testosterone-estrogen-binding globulin
Gene namesi
Name:SHBG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:10839. SHBG.

Subcellular locationi

  • Secreted By similarity

  • Note: In testis, it is synthesized by the Sertoli cells, secreted into the lumen of the seminiferous tubule and transported to the epididymis.By similarity

GO - Cellular componenti

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

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi6462.
OpenTargetsiENSG00000129214.
PharmGKBiPA35745.

Chemistry databases

ChEMBLiCHEMBL3305.
DrugBankiDB01406. Danazol.
DB00858. Drostanolone.
DB00783. Estradiol.
DB04574. Estropipate.
DB01185. Fluoxymesterone.
DB00741. Hydrocortisone.
DB06710. Methyltestosterone.
DB00648. Mitotane.
DB00717. Norethisterone.
DB06412. Oxymetholone.
DB00421. Spironolactone.
DB00624. Testosterone.
DB05275. transdermal testosterone gel.

Polymorphism and mutation databases

BioMutaiSHBG.
DMDMi134907.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 292 PublicationsAdd BLAST29
ChainiPRO_000003255730 – 402Sex hormone-binding globulin1 PublicationAdd BLAST373

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
GlycosylationiCAR_00017436O-linked (GalNAc...)1 Publication1
Disulfide bondi193 ↔ 217PROSITE-ProRule annotation1 Publication
Disulfide bondi362 ↔ 390PROSITE-ProRule annotation1 Publication
Glycosylationi380N-linked (GlcNAc...)3 Publications1
Glycosylationi396N-linked (GlcNAc...)2 Publications1

Post-translational modificationi

Variant Asn-356 contains one N-linked (GlcNAc...) at position 356.3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP04278.
PeptideAtlasiP04278.
PRIDEiP04278.

PTM databases

iPTMnetiP04278.
PhosphoSitePlusiP04278.
UniCarbKBiP04278.

Expressioni

Tissue specificityi

Isoform 1 and isoform 2 are present in liver and testis.

Gene expression databases

BgeeiENSG00000129214.
CleanExiHS_SHBG.
ExpressionAtlasiP04278. baseline and differential.
GenevisibleiP04278. HS.

Interactioni

Subunit structurei

Homodimer.

Protein-protein interaction databases

BioGridi112359. 58 interactors.
IntActiP04278. 2 interactors.
STRINGi9606.ENSP00000369816.

Chemistry databases

BindingDBiP04278.

Structurei

Secondary structure

1402
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi44 – 47Combined sources4
Beta strandi56 – 62Combined sources7
Helixi63 – 65Combined sources3
Beta strandi70 – 78Combined sources9
Beta strandi80 – 90Combined sources11
Turni91 – 93Combined sources3
Beta strandi94 – 101Combined sources8
Beta strandi104 – 113Combined sources10
Beta strandi115 – 119Combined sources5
Beta strandi126 – 128Combined sources3
Beta strandi130 – 137Combined sources8
Beta strandi140 – 145Combined sources6
Beta strandi148 – 153Combined sources6
Helixi160 – 162Combined sources3
Beta strandi167 – 174Combined sources8
Helixi179 – 181Combined sources3
Beta strandi182 – 184Combined sources3
Beta strandi192 – 200Combined sources9
Helixi202 – 204Combined sources3
Beta strandi205 – 209Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1D2SX-ray1.55A42-217[»]
1F5FX-ray1.70A30-234[»]
1KDKX-ray1.70A41-217[»]
1KDMX-ray2.35A41-217[»]
1LHNX-ray2.00A30-218[»]
1LHOX-ray2.00A30-218[»]
1LHUX-ray1.80A30-218[»]
1LHVX-ray2.00A30-218[»]
1LHWX-ray1.75A30-218[»]
ProteinModelPortaliP04278.
SMRiP04278.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04278.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini45 – 217Laminin G-like 1PROSITE-ProRule annotationAdd BLAST173
Domaini224 – 390Laminin G-like 2PROSITE-ProRule annotationAdd BLAST167

Sequence similaritiesi

Contains 2 laminin G-like domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IKW6. Eukaryota.
ENOG410YKMT. LUCA.
GeneTreeiENSGT00530000063339.
HOGENOMiHOG000285982.
HOVERGENiHBG017800.
InParanoidiP04278.
OMAiEIQLHNH.
OrthoDBiEOG091G0D6A.
PhylomeDBiP04278.
TreeFamiTF334367.

Family and domain databases

Gene3Di2.60.120.200. 2 hits.
InterProiIPR013320. ConA-like_dom.
IPR001791. Laminin_G.
[Graphical view]
PfamiPF00054. Laminin_G_1. 1 hit.
[Graphical view]
SMARTiSM00282. LamG. 1 hit.
[Graphical view]
SUPFAMiSSF49899. SSF49899. 2 hits.
PROSITEiPS50025. LAM_G_DOMAIN. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

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

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P04278-1) [UniParc]FASTAAdd to basket
Also known as: SHBG, SHBGr-1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MESRGPLATS RLLLLLLLLL LRHTRQGWAL RPVLPTQSAH DPPAVHLSNG
60 70 80 90 100
PGQEPIAVMT FDLTKITKTS SSFEVRTWDP EGVIFYGDTN PKDDWFMLGL
110 120 130 140 150
RDGRPEIQLH NHWAQLTVGA GPRLDDGRWH QVEVKMEGDS VLLEVDGEEV
160 170 180 190 200
LRLRQVSGPL TSKRHPIMRI ALGGLLFPAS NLRLPLVPAL DGCLRRDSWL
210 220 230 240 250
DKQAEISASA PTSLRSCDVE SNPGIFLPPG TQAEFNLRDI PQPHAEPWAF
260 270 280 290 300
SLDLGLKQAA GSGHLLALGT PENPSWLSLH LQDQKVVLSS GSGPGLDLPL
310 320 330 340 350
VLGLPLQLKL SMSRVVLSQG SKMKALALPP LGLAPLLNLW AKPQGRLFLG
360 370 380 390 400
ALPGEDSSTS FCLNGLWAQG QRLDVDQALN RSHEIWTHSC PQSPGNGTDA

SH
Length:402
Mass (Da):43,779
Last modified:April 1, 1990 - v2
Checksum:i5A3B1885E4E7A460
GO
Isoform 2 (identifier: P04278-2) [UniParc]FASTAAdd to basket
Also known as: Sex hormone binding globulin-gene-related protein (SHBGgrp), SHBGr-2

The sequence of this isoform differs from the canonical sequence as follows:
     1-37: MESRGPLATSRLLLLLLLLLLRHTRQGWALRPVLPTQ → PRFKGSPAVLFKLTYAVITCFSLRLTHPPRPW
     285-293: KVVLSSGSG → EKTLPPLFA
     294-402: Missing.

Note: Incomplete sequence.
Show »
Length:288
Mass (Da):31,829
Checksum:iF5BCCF800F560461
GO
Isoform 3 (identifier: P04278-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     285-293: KVVLSSGSG → EKTLPPLFA
     294-402: Missing.

Note: No experimental confirmation available.
Show »
Length:293
Mass (Da):32,363
Checksum:iB88FA1CEE7F97A7E
GO
Isoform 4 (identifier: P04278-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     239-353: Missing.

Show »
Length:287
Mass (Da):31,720
Checksum:i04D30318BC6B1191
GO
Isoform 5 (identifier: P04278-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     186-203: Missing.

Show »
Length:384
Mass (Da):41,712
Checksum:iACAF2C28914C13D1
GO

Sequence cautioni

The sequence CAA29309 differs from that shown. Reason: Frameshift at positions 47, 52 and 54.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti22R → Q in CAA28987 (PubMed:15489334).Curated1
Sequence conflicti334A → L in AAC18778 (PubMed:2608061).Curated1
Sequence conflicti336L → S in AAC18778 (PubMed:2608061).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02200222R → H.Corresponds to variant rs9282845dbSNPEnsembl.1
Natural variantiVAR_01394625R → H.1 PublicationCorresponds to variant rs6260dbSNPEnsembl.1
Natural variantiVAR_016182185P → L.Corresponds to variant rs6258dbSNPEnsembl.1
Natural variantiVAR_013129356D → N Polymorphism; generates a N-glycosylation site. 3 PublicationsCorresponds to variant rs6259dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0060901 – 37MESRG…VLPTQ → PRFKGSPAVLFKLTYAVITC FSLRLTHPPRPW in isoform 2. CuratedAdd BLAST37
Alternative sequenceiVSP_045376186 – 203Missing in isoform 5. CuratedAdd BLAST18
Alternative sequenceiVSP_045358239 – 353Missing in isoform 4. 1 PublicationAdd BLAST115
Alternative sequenceiVSP_006091285 – 293KVVLSSGSG → EKTLPPLFA in isoform 2 and isoform 3. 1 Publication9
Alternative sequenceiVSP_006092294 – 402Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST109

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X16349 Genomic DNA. Translation: CAA34398.1.
X16350 Genomic DNA. Translation: CAA34399.1.
X16351 mRNA. Translation: CAA34400.1.
M31651 Genomic DNA. Translation: AAC18778.1.
CD013955 mRNA. No translation available.
BC069597 mRNA. Translation: AAH69597.1.
BC101785 mRNA. Translation: AAI01786.1.
BC112186 mRNA. Translation: AAI12187.1.
AC007421 Genomic DNA. No translation available.
X05403 mRNA. Translation: CAA28987.1.
EU352661 mRNA. Translation: ABY67999.1.
X05885 mRNA. Translation: CAA29309.1. Frameshift.
X05792 mRNA. Translation: CAA29234.1.
CCDSiCCDS11117.1. [P04278-1]
CCDS54082.1. [P04278-3]
CCDS54083.1. [P04278-4]
CCDS58513.1. [P04278-5]
PIRiS09606. BOHUS.
RefSeqiNP_001031.2. NM_001040.4. [P04278-1]
NP_001139751.1. NM_001146279.2. [P04278-5]
NP_001139752.1. NM_001146280.2. [P04278-3]
NP_001139753.1. NM_001146281.2. [P04278-4]
NP_001276042.1. NM_001289113.1.
NP_001276043.1. NM_001289114.1.
NP_001276044.1. NM_001289115.1.
NP_001276045.1. NM_001289116.1.
UniGeneiHs.632235.

Genome annotation databases

EnsembliENST00000380450; ENSP00000369816; ENSG00000129214. [P04278-1]
ENST00000416273; ENSP00000388867; ENSG00000129214. [P04278-3]
ENST00000441599; ENSP00000393426; ENSG00000129214. [P04278-4]
ENST00000575903; ENSP00000458973; ENSG00000129214. [P04278-5]
GeneIDi6462.
KEGGihsa:6462.
UCSCiuc002gie.4. human. [P04278-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Androgen-binding protein entry

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X16349 Genomic DNA. Translation: CAA34398.1.
X16350 Genomic DNA. Translation: CAA34399.1.
X16351 mRNA. Translation: CAA34400.1.
M31651 Genomic DNA. Translation: AAC18778.1.
CD013955 mRNA. No translation available.
BC069597 mRNA. Translation: AAH69597.1.
BC101785 mRNA. Translation: AAI01786.1.
BC112186 mRNA. Translation: AAI12187.1.
AC007421 Genomic DNA. No translation available.
X05403 mRNA. Translation: CAA28987.1.
EU352661 mRNA. Translation: ABY67999.1.
X05885 mRNA. Translation: CAA29309.1. Frameshift.
X05792 mRNA. Translation: CAA29234.1.
CCDSiCCDS11117.1. [P04278-1]
CCDS54082.1. [P04278-3]
CCDS54083.1. [P04278-4]
CCDS58513.1. [P04278-5]
PIRiS09606. BOHUS.
RefSeqiNP_001031.2. NM_001040.4. [P04278-1]
NP_001139751.1. NM_001146279.2. [P04278-5]
NP_001139752.1. NM_001146280.2. [P04278-3]
NP_001139753.1. NM_001146281.2. [P04278-4]
NP_001276042.1. NM_001289113.1.
NP_001276043.1. NM_001289114.1.
NP_001276044.1. NM_001289115.1.
NP_001276045.1. NM_001289116.1.
UniGeneiHs.632235.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1D2SX-ray1.55A42-217[»]
1F5FX-ray1.70A30-234[»]
1KDKX-ray1.70A41-217[»]
1KDMX-ray2.35A41-217[»]
1LHNX-ray2.00A30-218[»]
1LHOX-ray2.00A30-218[»]
1LHUX-ray1.80A30-218[»]
1LHVX-ray2.00A30-218[»]
1LHWX-ray1.75A30-218[»]
ProteinModelPortaliP04278.
SMRiP04278.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112359. 58 interactors.
IntActiP04278. 2 interactors.
STRINGi9606.ENSP00000369816.

Chemistry databases

BindingDBiP04278.
ChEMBLiCHEMBL3305.
DrugBankiDB01406. Danazol.
DB00858. Drostanolone.
DB00783. Estradiol.
DB04574. Estropipate.
DB01185. Fluoxymesterone.
DB00741. Hydrocortisone.
DB06710. Methyltestosterone.
DB00648. Mitotane.
DB00717. Norethisterone.
DB06412. Oxymetholone.
DB00421. Spironolactone.
DB00624. Testosterone.
DB05275. transdermal testosterone gel.

PTM databases

iPTMnetiP04278.
PhosphoSitePlusiP04278.
UniCarbKBiP04278.

Polymorphism and mutation databases

BioMutaiSHBG.
DMDMi134907.

Proteomic databases

PaxDbiP04278.
PeptideAtlasiP04278.
PRIDEiP04278.

Protocols and materials databases

DNASUi6462.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000380450; ENSP00000369816; ENSG00000129214. [P04278-1]
ENST00000416273; ENSP00000388867; ENSG00000129214. [P04278-3]
ENST00000441599; ENSP00000393426; ENSG00000129214. [P04278-4]
ENST00000575903; ENSP00000458973; ENSG00000129214. [P04278-5]
GeneIDi6462.
KEGGihsa:6462.
UCSCiuc002gie.4. human. [P04278-1]

Organism-specific databases

CTDi6462.
DisGeNETi6462.
GeneCardsiSHBG.
HGNCiHGNC:10839. SHBG.
MIMi182205. gene.
neXtProtiNX_P04278.
OpenTargetsiENSG00000129214.
PharmGKBiPA35745.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IKW6. Eukaryota.
ENOG410YKMT. LUCA.
GeneTreeiENSGT00530000063339.
HOGENOMiHOG000285982.
HOVERGENiHBG017800.
InParanoidiP04278.
OMAiEIQLHNH.
OrthoDBiEOG091G0D6A.
PhylomeDBiP04278.
TreeFamiTF334367.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000129214-MONOMER.

Miscellaneous databases

ChiTaRSiSHBG. human.
EvolutionaryTraceiP04278.
GeneWikiiSex_hormone-binding_globulin.
GenomeRNAii6462.
PROiP04278.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000129214.
CleanExiHS_SHBG.
ExpressionAtlasiP04278. baseline and differential.
GenevisibleiP04278. HS.

Family and domain databases

Gene3Di2.60.120.200. 2 hits.
InterProiIPR013320. ConA-like_dom.
IPR001791. Laminin_G.
[Graphical view]
PfamiPF00054. Laminin_G_1. 1 hit.
[Graphical view]
SMARTiSM00282. LamG. 1 hit.
[Graphical view]
SUPFAMiSSF49899. SSF49899. 2 hits.
PROSITEiPS50025. LAM_G_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSHBG_HUMAN
AccessioniPrimary (citable) accession number: P04278
Secondary accession number(s): B0FWH4
, E9PGW1, F5H5Z8, I3L1N7, P14689, Q16616, Q3MIL0, Q6ISD2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: April 1, 1990
Last modified: November 2, 2016
This is version 172 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 17
    Human chromosome 17: 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.