P49675 (STAR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Steroidogenic acute regulatory protein, mitochondrial
Short name=StAR

Alternative name(s):
START domain-containing protein 1
Short name=StARD1

Gene names

Name:	STAR
Synonyms:	STARD1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	285 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	Plays a key role in steroid hormone synthesis by enhancing the metabolism of cholesterol into pregnenolone. Mediates the transfer of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane where it is cleaved to pregnenolone.
Pathway	Steroid metabolism; cholesterol metabolism.
Subunit structure	May interact with TSPO By similarity.
Subcellular location	Mitochondrion.
Tissue specificity	Expressed in gonads, adrenal cortex and kidney.
Involvement in disease	Adrenal hyperplasia 1 (AH1) [MIM:201710]: The most severe form of adrenal hyperplasia. It is a condition characterized by onset of profound adrenocortical insufficiency shortly after birth, hyperpigmentation reflecting increased production of pro-opiomelanocortin, elevated plasma renin activity as a consequence of reduced aldosterone synthesis, and male pseudohermaphroditism resulting from deficient fetal testicular testosterone synthesis. Affected individuals are phenotypic females irrespective of gonadal sex, and frequently die in infancy if mineralocorticoid and glucocorticoid replacement are not instituted. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.11
Sequence similarities	Contains 1 START domain.

Ontologies

Keywords
Biological process	Lipid transport Steroidogenesis Transport
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Congenital adrenal hyperplasia Disease mutation
Domain	Transit peptide
Ligand	Lipid-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	C21-steroid hormone biosynthetic process Traceable author statement. Source: Reactome bile acid biosynthetic process Inferred from electronic annotation. Source: Compara biphenyl metabolic process Inferred from electronic annotation. Source: Compara brain development Inferred from electronic annotation. Source: Compara cellular response to alkaloid Inferred from electronic annotation. Source: Compara cellular response to antibiotic Inferred from electronic annotation. Source: Compara cellular response to cAMP Inferred from electronic annotation. Source: Compara cellular response to cadmium ion Inferred from electronic annotation. Source: Compara cellular response to dexamethasone stimulus Inferred from electronic annotation. Source: Compara cellular response to epinephrine stimulus Inferred from electronic annotation. Source: Compara cellular response to fibroblast growth factor stimulus Inferred from electronic annotation. Source: Compara cellular response to follicle-stimulating hormone stimulus Inferred from electronic annotation. Source: Compara cellular response to glucose stimulus Inferred from electronic annotation. Source: Compara cellular response to growth hormone stimulus Inferred from electronic annotation. Source: Compara cellular response to insulin stimulus Inferred from electronic annotation. Source: Compara cellular response to interferon-alpha Inferred from electronic annotation. Source: Compara cellular response to interferon-gamma Inferred from electronic annotation. Source: Compara cellular response to lipopolysaccharide Inferred from electronic annotation. Source: Compara cellular response to luteinizing hormone stimulus Inferred from electronic annotation. Source: Compara cellular response to transforming growth factor beta stimulus Inferred from electronic annotation. Source: Compara cholesterol metabolic process Inferred from electronic annotation. Source: UniProtKB-UniPathway circadian sleep/wake cycle, REM sleep Inferred from electronic annotation. Source: Compara dibenzo-p-dioxin metabolic process Inferred from electronic annotation. Source: Compara diterpenoid metabolic process Inferred from electronic annotation. Source: Compara estrogen biosynthetic process Inferred from electronic annotation. Source: Compara fractalkine metabolic process Inferred from electronic annotation. Source: Compara glucocorticoid metabolic process Inferred from electronic annotation. Source: Compara insecticide metabolic process Inferred from electronic annotation. Source: Compara intracellular cholesterol transport Inferred from electronic annotation. Source: Compara male gonad development Inferred from electronic annotation. Source: Compara phenol-containing compound metabolic process Inferred from electronic annotation. Source: Compara phthalate metabolic process Inferred from electronic annotation. Source: Compara positive regulation of gene expression Inferred from electronic annotation. Source: Compara positive regulation of neurogenesis Inferred from electronic annotation. Source: Compara progesterone biosynthetic process Inferred from electronic annotation. Source: Compara regulation of neuronal synaptic plasticity Inferred from electronic annotation. Source: Compara regulation of steroid biosynthetic process Inferred from electronic annotation. Source: Compara response to corticosterone stimulus Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to estrogen stimulus Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara response to fungicide Inferred from electronic annotation. Source: Compara response to herbicide Inferred from electronic annotation. Source: Compara response to hydrogen peroxide Inferred from electronic annotation. Source: Compara response to ionizing radiation Inferred from electronic annotation. Source: Compara response to lead ion Inferred from electronic annotation. Source: Compara response to leptin stimulus Inferred from electronic annotation. Source: Compara response to nicotine Inferred from electronic annotation. Source: Compara response to nutrient Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome testosterone biosynthetic process Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from electronic annotation. Source: Compara mitochondrial crista Inferred from electronic annotation. Source: Compara mitochondrial intermembrane space Traceable author statement. Source: Reactome neuron projection Inferred from electronic annotation. Source: Compara neuronal cell body Inferred from electronic annotation. Source: Compara
Molecular_function	cholesterol binding Inferred from electronic annotation. Source: Compara cholesterol transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 63

63

Mitochondrion By similarity

Chain

64 – 285

222

Steroidogenic acute regulatory protein, mitochondrial

PRO_0000033316

Regions

Domain

67 – 280

214

START

Amino acid modifications

Modified residue

57

1

Phosphoserine; by PKA Ref.6

Modified residue

195

1

Phosphoserine; by PKA Ref.6

Natural variations

Natural variant

121

1

R → W.
Corresponds to variant rs34908868 [ dbSNP | Ensembl ].

VAR_034520

Natural variant

169

1

E → G in AH1; partial loss of activity. Ref.8

VAR_014236

Natural variant

169

1

E → K in AH1; partial loss of activity. Ref.8

VAR_014237

Natural variant

182

1

R → L in AH1; partial loss of activity. Ref.8

VAR_005627

Natural variant

203

1

A → D. Ref.1 Ref.2 Ref.10
Corresponds to variant rs1042854 [ dbSNP | Ensembl ].

VAR_005628

Natural variant

217

1

R → T in AH1. Ref.11
Corresponds to variant rs28938471 [ dbSNP | Ensembl ].

VAR_014238

Natural variant

218

1

A → V in AH1; partial loss of activity. Ref.8 Ref.9 Ref.11

VAR_014239

Natural variant

225

1

M → T in AH1. Ref.9

VAR_014240

Natural variant

272

1

Missing in AH1; partial loss of activity. Ref.8

VAR_014241

Natural variant

275

1

L → P in AH1; partial loss of activity. Ref.8

VAR_014242

Secondary structure

1

.

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.

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.

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285

Helix Strand Turn

Details...

Helix

70 – 91

22

Beta strand

97 – 101

5

Beta strand

107 – 112

6

Beta strand

114 – 116

3

Beta strand

118 – 128

11

Helix

130 – 137

8

Turn

138 – 140

3

Helix

141 – 143

3

Beta strand

152 – 159

8

Beta strand

161 – 171

11

Beta strand

182 – 192

11

Beta strand

197 – 199

3

Beta strand

215 – 217

3

Beta strand

224 – 230

7

Beta strand

233 – 243

11

Helix

253 – 274

22

Sequences

	Sequence		Length	Mass (Da)
	P49675 [UniParc]. Last modified July 19, 2005. Version 2. Checksum: 2683086C20DE88AB	FASTA	285	31,914
	10 20 30 40 50 60 MLLATFKLCA GSSYRHMRNM KGLRQQAVMA ISQELNRRAL GGPTPSTWIN QVRRRSSLLG 70 80 90 100 110 120 SRLEETLYSD QELAYLQQGE EAMQKALGIL SNQEGWKKES QQDNGDKVMS KVVPDVGKVF 130 140 150 160 170 180 RLEVVVDQPM ERLYEELVER MEAMGEWNPN VKEIKVLQKI GKDTFITHEL AAEAAGNLVG 190 200 210 220 230 240 PRDFVSVRCA KRRGSTCVLA GMATDFGNMP EQKGVIRAEH GPTCMVLHPL AGSPSKTKLT 250 260 270 280 WLLSIDLKGW LPKSIINQVL SQTQVDFANH LRKRLESHPA SEARC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human steroidogenic acute regulatory protein: functional activity in COS-1 cells, tissue-specific expression, and mapping of the structural gene to 8p11.2 and a pseudogene to chromosome 13." Sugawara T., Holt J.A., Driscoll D., Strauss J.F. III, Lin D., Miller W.L., Patterson D., Clancy K.P., Hart I.M., Clark B.J., Stocco D.M. Proc. Natl. Acad. Sci. U.S.A. 92:4778-4782(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASP-203. Tissue: Adrenal cortex.
[2]	"Structure of the human steroidogenic acute regulatory protein (StAR) gene: StAR stimulates mitochondrial cholesterol 27-hydroxylase activity." Sugawara T., Lin D., Holt J.A., Martin K.O., Javitt N.B., Miller W.L., Strauss J.F. III Biochemistry 34:12506-12512(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASP-203. Tissue: Placenta.
[3]	"The human steroidogenic acute regulatory (StAR) gene is expressed in the urogenital system and encodes a mitochondrial polypeptide." Gradi A., Tang-Wai R., McBride H.M., Chu L.L., Shore G.C., Pelletier J. Biochim. Biophys. Acta 1258:228-233(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	Yu W., Sarginson J., Gibbs R.A. Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[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]. Tissue: Brain.
[6]	"The steroidogenic acute regulatory protein (StAR): a window into the complexities of intracellular cholesterol trafficking." Strauss J.F. III, Kallen C.B., Christenson L.K., Watari H., Devoto L., Arakane F., Kiriakidou M., Sugawara T. Recent Prog. Horm. Res. 54:369-394(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-57 AND SER-195.
[7]	"Comparative structural analysis of lipid binding START domains." Thorsell A.G., Lee W.H., Persson C., Siponen M.I., Nilsson M., Busam R.D., Kotenyova T., Schuler H., Lehtio L. PLoS ONE 6:E19521-E19521(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.40 ANGSTROMS) OF 66-284.
[8]	"The pathophysiology and genetics of congenital lipoid adrenal hyperplasia." Bose H.S., Sugawara T., Strauss J.F. III, Miller W.L. N. Engl. J. Med. 335:1870-1878(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS AH1 GLY-169; LYS-169; LEU-182; VAL-218; ARG-272 DEL AND PRO-275, CHARACTERIZATION OF VARIANTS.
[9]	"Analysis of the steroidogenic acute regulatory protein (StAR) gene in Japanese patients with congenital lipoid adrenal hyperplasia." Nakae J., Tajima T., Sugawara T., Arakane F., Hanaki K., Hotsubo T., Igarashi N., Igarashi Y., Ishii T., Koda N., Kondo T., Kohno H., Nakagawa Y., Tachibana K., Takeshima Y., Tsubouchi K., Strauss J.F. III, Fujieda K. Hum. Mol. Genet. 6:571-576(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS AH1 VAL-218 AND THR-225.
[10]	"A novel frameshift mutation 840delA and a novel polymorphism D203A in the steroidogenic acute regulatory protein gene in a Japanese patient with congenital lipoid adrenal hyperplasia." Katsumata N., Tanae A., Shinagawa T., Nagashima-Miyokawa A., Shimizu M., Yasunaga T., Tanaka T., Hibi I. Hum. Mutat. Suppl. 1:S304-S307(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ASP-203.
[11]	"A novel compound heterozygous mutation in the steroidogenic acute regulatory protein gene in a patient with congenital lipoid adrenal hyperplasia." Katsumata N., Kawada Y., Yamamoto Y., Noda M., Nimura A., Horikawa R., Tanaka T. J. Clin. Endocrinol. Metab. 84:3983-3987(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS AH1 THR-217 AND VAL-218.
+	Additional computationally mapped references.

Web resources

Wikipedia

Steroidogenic acute regulatory protein entry

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U17280 mRNA. Translation: AAC50141.1.
U29105 , U29099, U29100, U29101, U29102, U29103, U29104 Genomic DNA. Translation: AAC50234.1.
S79669 mRNA. Translation: AAB35726.1.
AF035277 mRNA. Translation: AAB88174.1.
BC010550 mRNA. Translation: AAH10550.1.

IPI

IPI00027730.

PIR

I38248.

RefSeq

NP_000340.2. NM_000349.2.

UniGene

Hs.521535.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IMG	model	-	A	67-280	[»]
2I93	model	-	A	67-280	[»]
3P0L	X-ray	3.40	A/B/C/D	66-284	[»]

ProteinModelPortal

P49675.

ModBase

Search...

Protein-protein interaction databases

IntAct

P49675. 1 interaction.

MINT

MINT-1403878.

STRING

9606.ENSP00000276449.

PTM databases

PhosphoSite

P49675.

Polymorphism databases

DMDM

71152974.

Proteomic databases

PaxDb

P49675.

PRIDE

P49675.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000276449; ENSP00000276449; ENSG00000147465.

GeneID

6770.

KEGG

hsa:6770.

UCSC

uc003xkv.1. human.

Organism-specific databases

CTD

6770.

GeneCards

GC08M038018.

HGNC

HGNC:11359. STAR.

HPA

CAB032598.
HPA023644.
HPA027318.

MIM

201710. phenotype.
600617. gene.

neXtProt

NX_P49675.

Orphanet

90790. Congenital lipoid adrenal hyperplasia.

PharmGKB

PA36181.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG239518.

HOGENOM

HOG000142452.

HOVERGEN

HBG010529.

InParanoid

P49675.

OMA

ATFKLCA.

OrthoDB

EOG4JWVF2.

PhylomeDB

P49675.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.
REACT_15493. Steroid hormones.

UniPathway

UPA00296.

Gene expression databases

ArrayExpress

P49675.

Bgee

P49675.

CleanEx

HS_STAR.

Genevestigator

P49675.

GermOnline

ENSG00000147465. Homo sapiens.

Family and domain databases

Gene3D

3.30.530.20. 1 hit.

InterPro

IPR000799. StAR.
IPR023393. START-like_dom.
IPR002913. START_lipid-bd_dom.
[Graphical view]

Pfam

PF01852. START. 1 hit.
[Graphical view]

PRINTS

PR00978. STARPROTEIN.

SMART

SM00234. START. 1 hit.
[Graphical view]

PROSITE

PS50848. START. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

STAR. human.

EvolutionaryTrace

P49675.

GenomeRNAi

6770.

NextBio

26420.

SOURCE

Search...

Entry information

Entry name

STAR_HUMAN

Accession

Primary (citable) accession number: P49675
Secondary accession number(s): Q16396

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	July 19, 2005
Last modified:	May 1, 2013
This is version 137 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.