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P49675 (STAR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length285 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processLipid transport
Steroidogenesis
Transport
   Cellular componentMitochondrion
   Coding sequence diversityPolymorphism
   DiseaseCongenital adrenal hyperplasia
Disease mutation
   DomainTransit peptide
   LigandLipid-binding
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processC21-steroid hormone biosynthetic process

Traceable author statement. Source: Reactome

bile acid biosynthetic process

Inferred from electronic annotation. Source: Ensembl

biphenyl metabolic process

Inferred from electronic annotation. Source: Ensembl

brain development

Inferred from electronic annotation. Source: Ensembl

cellular response to alkaloid

Inferred from electronic annotation. Source: Ensembl

cellular response to antibiotic

Inferred from electronic annotation. Source: Ensembl

cellular response to cAMP

Inferred from electronic annotation. Source: Ensembl

cellular response to cadmium ion

Inferred from electronic annotation. Source: Ensembl

cellular response to dexamethasone stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to epinephrine stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to fibroblast growth factor stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to follicle-stimulating hormone stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to glucose stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to growth hormone stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to insulin stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to interferon-alpha

Inferred from electronic annotation. Source: Ensembl

cellular response to interferon-gamma

Inferred from electronic annotation. Source: Ensembl

cellular response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

cellular response to luteinizing hormone stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to transforming growth factor beta stimulus

Inferred from electronic annotation. Source: Ensembl

cholesterol metabolic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

circadian sleep/wake cycle, REM sleep

Inferred from electronic annotation. Source: Ensembl

dibenzo-p-dioxin metabolic process

Inferred from electronic annotation. Source: Ensembl

diterpenoid metabolic process

Inferred from electronic annotation. Source: Ensembl

estrogen biosynthetic process

Inferred from electronic annotation. Source: Ensembl

fractalkine metabolic process

Inferred from electronic annotation. Source: Ensembl

glucocorticoid metabolic process

Inferred from electronic annotation. Source: Ensembl

insecticide metabolic process

Inferred from electronic annotation. Source: Ensembl

intracellular cholesterol transport

Inferred from electronic annotation. Source: Ensembl

male gonad development

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

phenol-containing compound metabolic process

Inferred from electronic annotation. Source: Ensembl

phthalate metabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

positive regulation of neurogenesis

Inferred from electronic annotation. Source: Ensembl

progesterone biosynthetic process

Inferred from electronic annotation. Source: Ensembl

regulation of neuronal synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

regulation of steroid biosynthetic process

Inferred from electronic annotation. Source: Ensembl

response to activity

Inferred from electronic annotation. Source: Ensembl

response to corticosterone

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to estrogen

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to fungicide

Inferred from electronic annotation. Source: Ensembl

response to herbicide

Inferred from electronic annotation. Source: Ensembl

response to hydrogen peroxide

Inferred from electronic annotation. Source: Ensembl

response to ionizing radiation

Inferred from electronic annotation. Source: Ensembl

response to lead ion

Inferred from electronic annotation. Source: Ensembl

response to leptin

Inferred from electronic annotation. Source: Ensembl

response to nicotine

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

steroid biosynthetic process

Traceable author statement Ref.1. Source: ProtInc

steroid metabolic process

Traceable author statement. Source: Reactome

testosterone biosynthetic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Inferred from electronic annotation. Source: Ensembl

mitochondrial crista

Inferred from electronic annotation. Source: Ensembl

mitochondrial intermembrane space

Traceable author statement. Source: Reactome

neuron projection

Inferred from electronic annotation. Source: Ensembl

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

   Molecular_functioncholesterol binding

Inferred from electronic annotation. Source: Ensembl

cholesterol transporter activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 6363Mitochondrion By similarity
Chain64 – 285222Steroidogenic acute regulatory protein, mitochondrial
PRO_0000033316

Regions

Domain67 – 280214START

Amino acid modifications

Modified residue571Phosphoserine; by PKA Ref.6
Modified residue1951Phosphoserine; by PKA Ref.6

Natural variations

Natural variant1211R → W.
Corresponds to variant rs34908868 [ dbSNP | Ensembl ].
VAR_034520
Natural variant1691E → G in AH1; partial loss of activity. Ref.8
VAR_014236
Natural variant1691E → K in AH1; partial loss of activity. Ref.8
VAR_014237
Natural variant1821R → L in AH1; partial loss of activity. Ref.8
VAR_005627
Natural variant2031A → D. Ref.1 Ref.2 Ref.10
Corresponds to variant rs1042854 [ dbSNP | Ensembl ].
VAR_005628
Natural variant2171R → T in AH1. Ref.11
Corresponds to variant rs28938471 [ dbSNP | Ensembl ].
VAR_014238
Natural variant2181A → V in AH1; partial loss of activity. Ref.8 Ref.9 Ref.11
VAR_014239
Natural variant2251M → T in AH1. Ref.9
VAR_014240
Natural variant2721Missing in AH1; partial loss of activity. Ref.8
VAR_014241
Natural variant2751L → P in AH1; partial loss of activity. Ref.8
VAR_014242

Secondary structure

............................... 285
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P49675 [UniParc].

Last modified July 19, 2005. Version 2.
Checksum: 2683086C20DE88AB

FASTA28531,914
        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 

« Hide

References

« Hide '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

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U17280 mRNA. Translation: AAC50141.1.
U29105 expand/collapse EMBL AC list , 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.
CCDSCCDS6102.1.
PIRI38248.
RefSeqNP_000340.2. NM_000349.2.
UniGeneHs.521535.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IMGmodel-A67-280[»]
2I93model-A67-280[»]
3P0LX-ray3.40A/B/C/D66-284[»]
ProteinModelPortalP49675.
SMRP49675. Positions 66-276.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112647. 3 interactions.
IntActP49675. 1 interaction.
MINTMINT-1403878.
STRING9606.ENSP00000276449.

PTM databases

PhosphoSiteP49675.

Polymorphism databases

DMDM71152974.

Proteomic databases

MaxQBP49675.
PaxDbP49675.
PRIDEP49675.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000276449; ENSP00000276449; ENSG00000147465.
GeneID6770.
KEGGhsa:6770.
UCSCuc003xkv.1. human.

Organism-specific databases

CTD6770.
GeneCardsGC08M038018.
HGNCHGNC:11359. STAR.
HPACAB032598.
HPA023644.
HPA027318.
MIM201710. phenotype.
600617. gene.
neXtProtNX_P49675.
Orphanet325524. Classic congenital lipoid adrenal hyperplasia due to STAR deficency.
361. Familial glucocorticoid deficiency.
325529. Non-classic congenital lipoid adrenal hyperplasia due to STAR deficency.
PharmGKBPA36181.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG239518.
HOGENOMHOG000142452.
HOVERGENHBG010529.
InParanoidP49675.
KOK16931.
OMALATFKLC.
OrthoDBEOG74FF0Z.
PhylomeDBP49675.
TreeFamTF313869.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_15493. Steroid hormones.
UniPathwayUPA00296.

Gene expression databases

ArrayExpressP49675.
BgeeP49675.
CleanExHS_STAR.
GenevestigatorP49675.

Family and domain databases

Gene3D3.30.530.20. 1 hit.
InterProIPR000799. StAR.
IPR023393. START-like_dom.
IPR002913. START_lipid-bd_dom.
[Graphical view]
PfamPF01852. START. 1 hit.
[Graphical view]
PRINTSPR00978. STARPROTEIN.
SMARTSM00234. START. 1 hit.
[Graphical view]
PROSITEPS50848. START. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSTAR. human.
EvolutionaryTraceP49675.
GenomeRNAi6770.
NextBio26420.
PROP49675.
SOURCESearch...

Entry information

Entry nameSTAR_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 148 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

PATHWAY comments

Index of metabolic and biosynthesis pathways

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 8

Human chromosome 8: entries, gene names and cross-references to MIM