Skip Header

Contribute Send feedback
Read comments (?) or add your own

P04278 (SHBG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 125. 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·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SHBG
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length402 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Homodimer.

Subcellular location

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.

Tissue specificity

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

Sequence similarities

Contains 2 laminin G-like domains.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
Signal
   LigandLipid-binding
Steroid-binding
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological processhormone transport

Non-traceable author statement. Source: UniProtKB

   Cellular componentextracellular region

Non-traceable author statement. Source: UniProtKB

   Molecular functionandrogen binding

Traceable author statement. Source: ProtInc

protein homodimerization activity

Non-traceable author statement. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P04278-1)

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.
Isoform 2 (identifier: P04278-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929 Ref.7 Ref.8
Chain30 – 402373Sex hormone-binding globulin Ref.8
PRO_0000032557

Regions

Domain45 – 217173Laminin G-like 1
Domain224 – 390167Laminin G-like 2

Amino acid modifications

Glycosylation361O-linked (GalNAc...)
CAR_000174
Glycosylation3561N-linked (GlcNAc...); when associated with variant N-356 Ref.11
Glycosylation3801N-linked (GlcNAc...) Ref.8 Ref.9 Ref.10
Glycosylation3961N-linked (GlcNAc...) Ref.8
Disulfide bond193 ↔ 217 Ref.8
Disulfide bond362 ↔ 390 Ref.8

Natural variations

Alternative sequence1 – 3737MESRG…VLPTQ → PRFKGSPAVLFKLTYAVITC FSLRLTHPPRPW in isoform 2.
VSP_006090
Alternative sequence285 – 2939KVVLSSGSG → EKTLPPLFA in isoform 2.
VSP_006091
Alternative sequence294 – 402109Missing in isoform 2.
VSP_006092
Natural variant221R → H.
Corresponds to variant rs9282845 [ dbSNP | Ensembl ].
VAR_022002
Natural variant251R → H. Ref.15
Corresponds to variant rs6260 [ dbSNP | Ensembl ].
VAR_013946
Natural variant1851P → L.
Corresponds to variant rs6258 [ dbSNP | Ensembl ].
VAR_016182
Natural variant3561D → N. Ref.11 Ref.14 Ref.15
Corresponds to variant rs6259 [ dbSNP | Ensembl ].
VAR_013129

Experimental info

Sequence conflict221R → Q in CAA28987. Ref.4
Sequence conflict47 – 559LSNGPGQEP → VHSAAQTTL in CAA29309. Ref.5
Sequence conflict3341A → L in AAC18778. Ref.2
Sequence conflict3361L → S in AAC18778. Ref.2

Secondary structure

.................................. 402
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (SHBG) (SHBGr-1) [UniParc].

Last modified April 1, 1990. Version 2.
Checksum: 5A3B1885E4E7A460

FASTA40243,779
        10         20         30         40         50         60 
MESRGPLATS RLLLLLLLLL LRHTRQGWAL RPVLPTQSAH DPPAVHLSNG PGQEPIAVMT 

        70         80         90        100        110        120 
FDLTKITKTS SSFEVRTWDP EGVIFYGDTN PKDDWFMLGL RDGRPEIQLH NHWAQLTVGA 

       130        140        150        160        170        180 
GPRLDDGRWH QVEVKMEGDS VLLEVDGEEV LRLRQVSGPL TSKRHPIMRI ALGGLLFPAS 

       190        200        210        220        230        240 
NLRLPLVPAL DGCLRRDSWL DKQAEISASA PTSLRSCDVE SNPGIFLPPG TQAEFNLRDI 

       250        260        270        280        290        300 
PQPHAEPWAF SLDLGLKQAA GSGHLLALGT PENPSWLSLH LQDQKVVLSS GSGPGLDLPL 

       310        320        330        340        350        360 
VLGLPLQLKL SMSRVVLSQG SKMKALALPP LGLAPLLNLW AKPQGRLFLG ALPGEDSSTS 

       370        380        390        400 
FCLNGLWAQG QRLDVDQALN RSHEIWTHSC PQSPGNGTDA SH 

« Hide

Isoform 2 (Sex hormone binding globulin-gene-related protein (SHBGgrp)) (SHBGr-2) [UniParc].

Checksum: F5BCCF800F560461
Show »

FASTA28831,829

References

« Hide 'large scale' references
[1]"Characterization of the human sex hormone binding globulin (SHBG) gene and demonstration of two transcripts in both liver and testis."
Gershagen S., Lundwall A., Fernlund P.
Nucleic Acids Res. 17:9245-9258(1989) [PubMed: 2587256] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING.
Tissue: Testis.
[2]"The human sex hormone-binding globulin gene contains exons for androgen-binding protein and two other testicular messenger RNAs."
Hammond G.L., Underhill D.A., Rykse H.M., Smith C.L.
Mol. Endocrinol. 3:1869-1876(1989) [PubMed: 2608061] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
Tissue: Testis.
[3]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Liver.
[4]"The cDNA-deduced primary structure of human sex hormone-binding globulin and location of its steroid-binding domain."
Hammond G.L., Underhill D.A., Smith C.L., Goping I.S., Harley M.J., Musto N.A., Cheng C.Y., Bardin C.W.
FEBS Lett. 215:100-104(1987) [PubMed: 3569533] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-402 (ISOFORM 1).
Tissue: Liver.
[5]"A cDNA coding for human sex hormone binding globulin. Homology to vitamin K-dependent protein S."
Gershagen S., Fernlund P., Lundwall A.
FEBS Lett. 220:129-135(1987) [PubMed: 2956126] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 47-402 (ISOFORM 1).
Tissue: Liver.
[6]"Characterization of a cDNA coding for sex steroid-binding protein of human plasma."
Que B.G., Petra P.H.
FEBS Lett. 219:405-409(1987) [PubMed: 2956125] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 121-402 (ISOFORM 1).
Tissue: Liver.
[7]"Physicochemical characteristics of human sex hormone binding globulin: evidence for two identical subunits."
Hammond G.L., Robinson P.A., Sugino H., Ward D.N., Finne J.
J. Steroid Biochem. 24:815-824(1986) [PubMed: 3702459] [Abstract]
Cited for: PROTEIN SEQUENCE OF 30-54.
[8]"Amino acid sequence of the sex steroid binding protein of human blood plasma."
Walsh K.A., Titani K., Takio K., Kumar S., Hayes R., Petra P.H.
Biochemistry 25:7584-7590(1986) [PubMed: 3542030] [Abstract]
Cited for: PROTEIN SEQUENCE OF 30-402.
[9]"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: 16335952] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-380, MASS SPECTROMETRY.
Tissue: Plasma.
[10]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-380, MASS SPECTROMETRY.
Tissue: Liver.
[11]"Molecular analyses of a human sex hormone-binding globulin variant: evidence for an additional carbohydrate chain."
Power S.G.A., Bocchinfuso W.P., Pallesen M., Warmels-Rodenhiser S., Van Baelen H., Hammond G.L.
J. Clin. Endocrinol. Metab. 75:1066-1070(1992) [PubMed: 1400872] [Abstract]
Cited for: VARIANT ASN-356, GLYCOSYLATION AT ASN-356.
[12]"Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain."
Grishkovskaya I., Avvakumov G.V., Sklenar G., Dales D., Hammond G.L., Muller Y.A.
EMBO J. 19:504-512(2000) [PubMed: 10675319] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 42-211.
[13]"Steroid ligands bind human sex hormone-binding globulin in specific orientations and produce distinct changes in protein conformation."
Grishkovskaya I., Avvakumov G.V., Hammond G.L., Catalano M.G., Muller Y.A.
J. Biol. Chem. 277:32086-32093(2002) [PubMed: 12065592] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 42-218.
[14]"Molecular characterization of a genetic variant of the steroid hormone-binding globulin gene in heterozygous subjects."
Hardy D.O., Carino C., Catterall J.F., Larrea F.
J. Clin. Endocrinol. Metab. 80:1253-1256(1995) [PubMed: 7714097] [Abstract]
Cited for: VARIANT ASN-356.
[15]"Characterization of single-nucleotide polymorphisms in coding regions of human genes."
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 22:231-238(1999) [PubMed: 10391209] [Abstract]
Cited for: VARIANTS HIS-25 AND ASN-356.
[16]Erratum
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 23:373-373(1999)
+Additional computationally mapped references.

Web resources

Wikipedia

Androgen-binding protein entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X16349 Genomic DNA. Translation: CAA34398.1.
X16350 Genomic DNA. Translation: CAA34399.1.
X16351 mRNA. Translation: CAA34400.1.
M31651 Genomic DNA. Translation: AAC18778.1.
BC069597 mRNA. Translation: AAH69597.1.
BC101785 mRNA. Translation: AAI01786.1.
BC112186 mRNA. Translation: AAI12187.1.
X05403 mRNA. Translation: CAA28987.1.
X05885 mRNA. Translation: CAA29309.1.
X05792 mRNA. Translation: CAA29234.1.
IPIIPI00023019.
IPI00940099.
PIRBOHUS. S09606.
RefSeqNP_001031.2. NM_001040.3.
UniGeneHs.632235.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP04278.
SMRP04278. Positions 32-394.
ModBaseSearch...

Protein-protein interaction databases

IntActP04278. 2 interactions.
STRINGP04278.

PTM databases

GlycoSuiteDBP04278.

Polymorphism databases

DMDM134907.

Proteomic databases

PeptideAtlasP04278.
PRIDEP04278.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000380450; ENSP00000369816; ENSG00000129214.
GeneID6462.
KEGGhsa:6462.
UCSCuc002gid.2. human.
uc002gie.1. human.

Organism-specific databases

CTD6462.
GeneCardsGC17P007519.
H-InvDBHIX0039213.
HGNCHGNC:10839. SHBG.
MIM182205. gene.
neXtProtNX_P04278.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG19266.
GeneTreeENSGT00530000063339.
HOGENOMHBG125136.
HOVERGENHBG017800.
InParanoidP04278.
OMAQSPGNGT.
OrthoDBEOG4RFKTB.
PhylomeDBP04278.

Gene expression databases

ArrayExpressP04278.
BgeeP04278.
CleanExHS_SHBG.
GenevestigatorP04278.
GermOnlineENSG00000129214. Homo sapiens.

Family and domain databases

InterProIPR008985. ConA-like_lec_gl.
IPR013320. ConA-like_subgrp.
IPR001791. Laminin_G.
IPR012679. Laminin_G_1.
[Graphical view]
Gene3DG3DSA:2.60.120.200. ConA_like_subgrp. 2 hits.
PfamPF00054. Laminin_G_1. 1 hit.
[Graphical view]
SMARTSM00282. LamG. 1 hit.
[Graphical view]
SUPFAMSSF49899. ConA_like_lec_gl. 2 hits.
PROSITEPS50025. LAM_G_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

DrugBankDB01406. Danazol.
DB00858. Dromostanolone.
DB00783. Estradiol.
DB00655. Estrone.
DB01185. Fluoxymesterone.
DB00741. Hydrocortisone.
DB00648. Mitotane.
DB00717. Norethindrone.
DB00624. Testosterone.
NextBio25109.
SOURCESearch...

Entry information

Entry nameSHBG_HUMAN
AccessionPrimary (citable) accession number: P04278
Secondary accession number(s): P14689 expand/collapse secondary AC list , Q16616, Q3MIL0, Q6ISD2
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: April 1, 1990
Last modified: January 25, 2012
This is version 125 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

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families