P04278 (SHBG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

SHBG

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	402 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal
Ligand	Lipid-binding Steroid-binding
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	hormone transport Non-traceable author statement. Source: UniProtKB
Cellular component	extracellular region Non-traceable author statement. Source: UniProtKB
Molecular function	androgen 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 29

29

Ref.7 Ref.8

Chain

30 – 402

373

Sex hormone-binding globulin Ref.8

PRO_0000032557

Regions

Domain

45 – 217

173

Laminin G-like 1

Domain

224 – 390

167

Laminin G-like 2

Amino acid modifications

Glycosylation

36

1

O-linked (GalNAc...)

CAR_000174

Glycosylation

356

1

N-linked (GlcNAc...); when associated with variant N-356 Ref.11

Glycosylation

380

1

N-linked (GlcNAc...) Ref.8 Ref.9 Ref.10

Glycosylation

396

1

N-linked (GlcNAc...) Ref.8

Disulfide bond

193 ↔ 217

Ref.8

Disulfide bond

362 ↔ 390

Ref.8

Natural variations

Alternative sequence

1 – 37

37

MESRG…VLPTQ → PRFKGSPAVLFKLTYAVITC FSLRLTHPPRPW in isoform 2.

VSP_006090

Alternative sequence

285 – 293

9

KVVLSSGSG → EKTLPPLFA in isoform 2.

VSP_006091

Alternative sequence

294 – 402

109

Missing in isoform 2.

VSP_006092

Natural variant

22

1

R → H.
Corresponds to variant rs9282845 [ dbSNP | Ensembl ].

VAR_022002

Natural variant

25

1

R → H. Ref.15
Corresponds to variant rs6260 [ dbSNP | Ensembl ].

VAR_013946

Natural variant

185

1

P → L.
Corresponds to variant rs6258 [ dbSNP | Ensembl ].

VAR_016182

Natural variant

356

1

D → N. Ref.11 Ref.14 Ref.15
Corresponds to variant rs6259 [ dbSNP | Ensembl ].

VAR_013129

Experimental info

Sequence conflict

22

1

R → Q in CAA28987. Ref.4

Sequence conflict

47 – 55

9

LSNGPGQEP → VHSAAQTTL in CAA29309. Ref.5

Sequence conflict

334

1

A → L in AAC18778. Ref.2

Sequence conflict

336

1

L → S in AAC18778. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

402

Helix Strand Turn

Details...

Beta strand

44 – 47

4

Beta strand

56 – 62

7

Helix

63 – 65

3

Beta strand

70 – 78

9

Beta strand

80 – 90

11

Turn

91 – 93

3

Beta strand

94 – 101

8

Beta strand

104 – 113

10

Beta strand

115 – 121

7

Beta strand

126 – 128

3

Beta strand

130 – 137

8

Beta strand

140 – 145

6

Beta strand

148 – 154

7

Beta strand

167 – 174

8

Helix

179 – 181

3

Beta strand

182 – 184

3

Beta strand

192 – 200

9

Helix

202 – 204

3

Beta strand

205 – 209

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (SHBG) (SHBGr-1) [UniParc]. Last modified April 1, 1990. Version 2. Checksum: 5A3B1885E4E7A460	FASTA	402	43,779
	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
	Isoform 2 (Sex hormone binding globulin-gene-related protein (SHBGgrp)) (SHBGr-2) [UniParc]. Checksum: F5BCCF800F560461	FASTA	288	31,829
	10 20 30 40 50 60 PRFKGSPAVL FKLTYAVITC FSLRLTHPPR PWSAHDPPAV HLSNGPGQEP IAVMTFDLTK 70 80 90 100 110 120 ITKTSSSFEV RTWDPEGVIF YGDTNPKDDW FMLGLRDGRP EIQLHNHWAQ LTVGAGPRLD 130 140 150 160 170 180 DGRWHQVEVK MEGDSVLLEV DGEEVLRLRQ VSGPLTSKRH PIMRIALGGL LFPASNLRLP 190 200 210 220 230 240 LVPALDGCLR RDSWLDKQAE ISASAPTSLR SCDVESNPGI FLPPGTQAEF NLRDIPQPHA 250 260 270 280 EPWAFSLDLG LKQAAGSGHL LALGTPENPS WLSLHLQDQE KTLPPLFA

References

	« Hide 'large scale' referencesShow '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.

IPI

IPI00023019.
IPI00940099.

PIR

BOHUS. S09606.

RefSeq

NP_001031.2. NM_001040.3.

UniGene

Hs.632235.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1D2S	X-ray	1.55	A	42-217	[»]
1F5F	X-ray	1.70	A	30-234	[»]
1KDK	X-ray	1.70	A	41-217	[»]
1KDM	X-ray	2.35	A	41-217	[»]
1LHN	X-ray	2.00	A	30-218	[»]
1LHO	X-ray	2.00	A	30-218	[»]
1LHU	X-ray	1.80	A	30-218	[»]
1LHV	X-ray	2.00	A	30-218	[»]
1LHW	X-ray	1.75	A	30-218	[»]

ProteinModelPortal

P04278.

SMR

P04278. Positions 32-394.

ModBase

Search...

Protein-protein interaction databases

IntAct

P04278. 2 interactions.

STRING

P04278.

PTM databases

GlycoSuiteDB

P04278.

Polymorphism databases

DMDM

134907.

Proteomic databases

PeptideAtlas

P04278.

PRIDE

P04278.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000380450; ENSP00000369816; ENSG00000129214.

GeneID

6462.

KEGG

hsa:6462.

UCSC

uc002gid.2. human.
uc002gie.1. human.

Organism-specific databases

CTD

6462.

GeneCards

GC17P007519.

H-InvDB

HIX0039213.

HGNC

HGNC:10839. SHBG.

MIM

182205. gene.

neXtProt

NX_P04278.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19266.

GeneTree

ENSGT00530000063339.

HOGENOM

HBG125136.

HOVERGEN

HBG017800.

InParanoid

P04278.

OMA

QSPGNGT.

OrthoDB

EOG4RFKTB.

PhylomeDB

P04278.

Gene expression databases

ArrayExpress

P04278.

Bgee

P04278.

CleanEx

HS_SHBG.

Genevestigator

P04278.

GermOnline

ENSG00000129214. Homo sapiens.

Family and domain databases

InterPro

IPR008985. ConA-like_lec_gl.
IPR013320. ConA-like_subgrp.
IPR001791. Laminin_G.
IPR012679. Laminin_G_1.
[Graphical view]

Gene3D

G3DSA:2.60.120.200. ConA_like_subgrp. 2 hits.

Pfam

PF00054. Laminin_G_1. 1 hit.
[Graphical view]

SMART

SM00282. LamG. 1 hit.
[Graphical view]

SUPFAM

SSF49899. ConA_like_lec_gl. 2 hits.

PROSITE

PS50025. LAM_G_DOMAIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB01406. Danazol.
DB00858. Dromostanolone.
DB00783. Estradiol.
DB00655. Estrone.
DB01185. Fluoxymesterone.
DB00741. Hydrocortisone.
DB00648. Mitotane.
DB00717. Norethindrone.
DB00624. Testosterone.

NextBio

25109.

SOURCE

Search...

Entry information

Entry name

SHBG_HUMAN

Accession

Primary (citable) accession number: P04278
Secondary accession number(s): P14689 , 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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.