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P04278 (SHBG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 151. 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) [Reference proteome]
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.

Post-translational modification

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

Sequence similarities

Contains 2 laminin G-like domains.

Sequence caution

The sequence CAA29309.1 differs from that shown. Reason: Frameshift at positions 47, 52 and 54.

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_processprimary spermatocyte growth

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentextracellular region

Non-traceable author statement PubMed 14718574. Source: UniProtKB

   Molecular_functionandrogen binding

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 5 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.
Isoform 3 (identifier: P04278-3)

The sequence of this isoform differs from the canonical sequence as follows:
     285-293: KVVLSSGSG → EKTLPPLFA
     294-402: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: P04278-4)

The sequence of this isoform differs from the canonical sequence as follows:
     239-353: Missing.
Isoform 5 (identifier: P04278-5)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929 Ref.10 Ref.11
Chain30 – 402373Sex hormone-binding globulin Ref.11
PRO_0000032557

Regions

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

Amino acid modifications

Glycosylation361O-linked (GalNAc...)
CAR_000174
Glycosylation3801N-linked (GlcNAc...) Ref.11 Ref.12 Ref.13
Glycosylation3961N-linked (GlcNAc...) Ref.11
Disulfide bond193 ↔ 217 Ref.11
Disulfide bond362 ↔ 390 Ref.11

Natural variations

Alternative sequence1 – 3737MESRG…VLPTQ → PRFKGSPAVLFKLTYAVITC FSLRLTHPPRPW in isoform 2.
VSP_006090
Alternative sequence186 – 20318Missing in isoform 5.
VSP_045376
Alternative sequence239 – 353115Missing in isoform 4.
VSP_045358
Alternative sequence285 – 2939KVVLSSGSG → EKTLPPLFA in isoform 2 and isoform 3.
VSP_006091
Alternative sequence294 – 402109Missing in isoform 2 and isoform 3.
VSP_006092
Natural variant221R → H.
Corresponds to variant rs9282845 [ dbSNP | Ensembl ].
VAR_022002
Natural variant251R → H. Ref.18
Corresponds to variant rs6260 [ dbSNP | Ensembl ].
VAR_013946
Natural variant1851P → L.
Corresponds to variant rs6258 [ dbSNP | Ensembl ].
VAR_016182
Natural variant3561D → N Polymorphism that generates a N-glycosylation site. Ref.14 Ref.17 Ref.18
Corresponds to variant rs6259 [ dbSNP | Ensembl ].
VAR_013129

Experimental info

Sequence conflict221R → Q in CAA28987. 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
Isoform 3 [UniParc].

Checksum: B88FA1CEE7F97A7E
Show »

FASTA29332,363
Isoform 4 [UniParc].

Checksum: 04D30318BC6B1191
Show »

FASTA28731,720
Isoform 5 [UniParc].

Checksum: ACAF2C28914C13D1
Show »

FASTA38441,712

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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
Tissue: Testis.
[3]"PCR isolation and cloning of novel splice variant mRNAs from known drug target genes."
Jin P., Fu G.K., Wilson A.D., Yang J., Chien D., Hawkins P.R., Au-Young J., Stuve L.L.
Genomics 83:566-571(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[4]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Liver.
[6]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-402 (ISOFORM 1).
Tissue: Liver.
[7]"Human sex hormone-binding globulin gene transcript expression in liver, prostate, breast, testis, and brain- multiple promoters and complex alternative splicing."
Kahn S.M., Nakhla A.M., Hryb D.J., Rosner W., Romas N.A.
Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 28-402 (ISOFORM 4).
Tissue: Liver.
[8]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 47-402 (ISOFORM 1).
Tissue: Liver.
[9]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 121-402 (ISOFORM 1).
Tissue: Liver.
[10]"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] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 30-54.
[11]"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] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 30-402.
[12]"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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-380.
Tissue: Plasma.
[13]"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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-380.
Tissue: Liver.
[14]"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] [Europe PMC] [Abstract]
Cited for: VARIANT ASN-356, CHARACTERIZATION OF VARIANT ASN-356, GLYCOSYLATION.
[15]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 42-211.
[16]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 42-218.
[17]"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] [Europe PMC] [Abstract]
Cited for: VARIANT ASN-356.
[18]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS HIS-25 AND ASN-356.
[19]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.

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.
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.
CCDSCCDS11117.1. [P04278-1]
CCDS54082.1. [P04278-3]
CCDS54083.1. [P04278-4]
CCDS58513.1. [P04278-5]
PIRBOHUS. S09606.
RefSeqNP_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.
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 32-391.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112359. 56 interactions.
IntActP04278. 2 interactions.
STRING9606.ENSP00000369816.

Chemistry

BindingDBP04278.
ChEMBLCHEMBL3305.
DrugBankDB01406. Danazol.
DB00858. Dromostanolone.
DB00783. Estradiol.
DB00655. Estrone.
DB01185. Fluoxymesterone.
DB00741. Hydrocortisone.
DB00648. Mitotane.
DB00717. Norethindrone.
DB00624. Testosterone.

PTM databases

UniCarbKBP04278.

Polymorphism databases

DMDM134907.

Proteomic databases

PaxDbP04278.
PeptideAtlasP04278.
PRIDEP04278.

Protocols and materials databases

DNASU6462.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000380450; ENSP00000369816; ENSG00000129214. [P04278-1]
ENST00000416273; ENSP00000388867; ENSG00000129214. [P04278-3]
ENST00000441599; ENSP00000393426; ENSG00000129214. [P04278-4]
ENST00000575903; ENSP00000458973; ENSG00000129214. [P04278-5]
ENST00000576830; ENSP00000460219; ENSG00000129214.
GeneID6462.
KEGGhsa:6462.
UCSCuc002gie.2. human. [P04278-1]

Organism-specific databases

CTD6462.
GeneCardsGC17P007519.
HGNCHGNC:10839. SHBG.
MIM182205. gene.
neXtProtNX_P04278.
PharmGKBPA35745.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39525.
HOGENOMHOG000285982.
HOVERGENHBG017800.
InParanoidP04278.
OMAEIQLHNH.
PhylomeDBP04278.
TreeFamTF334367.

Gene expression databases

ArrayExpressP04278.
BgeeP04278.
CleanExHS_SHBG.
GenevestigatorP04278.

Family and domain databases

Gene3D2.60.120.200. 2 hits.
InterProIPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
IPR001791. Laminin_G.
[Graphical view]
PfamPF00054. Laminin_G_1. 1 hit.
[Graphical view]
SMARTSM00282. LamG. 1 hit.
[Graphical view]
SUPFAMSSF49899. SSF49899. 2 hits.
PROSITEPS50025. LAM_G_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSHBG. human.
EvolutionaryTraceP04278.
GeneWikiSex_hormone-binding_globulin.
GenomeRNAi6462.
NextBio25109.
PROP04278.
SOURCESearch...

Entry information

Entry nameSHBG_HUMAN
AccessionPrimary (citable) accession number: P04278
Secondary accession number(s): B0FWH4 expand/collapse secondary AC list , E9PGW1, F5H5Z8, I3L1N7, P14689, Q16616, Q3MIL0, Q6ISD2
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: April 1, 1990
Last modified: July 9, 2014
This is version 151 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

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

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