STAR_HUMAN
ID STAR_HUMAN Reviewed; 285 AA.
AC P49675; Q16396;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Steroidogenic acute regulatory protein, mitochondrial;
DE Short=StAR;
DE AltName: Full=START domain-containing protein 1;
DE Short=StARD1;
DE Flags: Precursor;
GN Name=STAR; Synonyms=STARD1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASP-203, FUNCTION, AND CATALYTIC
RP ACTIVITY.
RC TISSUE=Adrenal cortex;
RX PubMed=7761400; DOI=10.1073/pnas.92.11.4778;
RA Sugawara T., Holt J.A., Driscoll D., Strauss J.F. III, Lin D., Miller W.L.,
RA Patterson D., Clancy K.P., Hart I.M., Clark B.J., Stocco D.M.;
RT "Human steroidogenic acute regulatory protein: functional activity in COS-1
RT cells, tissue-specific expression, and mapping of the structural gene to
RT 8p11.2 and a pseudogene to chromosome 13.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:4778-4782(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASP-203.
RC TISSUE=Placenta;
RX PubMed=7547998; DOI=10.1021/bi00039a004;
RA Sugawara T., Lin D., Holt J.A., Martin K.O., Javitt N.B., Miller W.L.,
RA Strauss J.F. III;
RT "Structure of the human steroidogenic acute regulatory protein (StAR) gene:
RT StAR stimulates mitochondrial cholesterol 27-hydroxylase activity.";
RL Biochemistry 34:12506-12512(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7548191; DOI=10.1016/0005-2760(95)00140-8;
RA Gradi A., Tang-Wai R., McBride H.M., Chu L.L., Shore G.C., Pelletier J.;
RT "The human steroidogenic acute regulatory (StAR) gene is expressed in the
RT urogenital system and encodes a mitochondrial polypeptide.";
RL Biochim. Biophys. Acta 1258:228-233(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Yu W., Sarginson J., Gibbs R.A.;
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PHOSPHORYLATION AT SER-57 AND SER-195.
RX PubMed=10548884;
RA Strauss J.F. III, Kallen C.B., Christenson L.K., Watari H., Devoto L.,
RA Arakane F., Kiriakidou M., Sugawara T.;
RT "The steroidogenic acute regulatory protein (StAR): a window into the
RT complexities of intracellular cholesterol trafficking.";
RL Recent Prog. Horm. Res. 54:369-394(1999).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (3.40 ANGSTROMS) OF 66-284.
RX PubMed=21738568; DOI=10.1371/journal.pone.0019521;
RA Thorsell A.G., Lee W.H., Persson C., Siponen M.I., Nilsson M., Busam R.D.,
RA Kotenyova T., Schuler H., Lehtio L.;
RT "Comparative structural analysis of lipid binding START domains.";
RL PLoS ONE 6:E19521-E19521(2011).
RN [8]
RP CATALYTIC ACTIVITY, INVOLVEMENT IN AH1, AND FUNCTION.
RX PubMed=7892608; DOI=10.1126/science.7892608;
RA Lin D., Sugawara T., Strauss J.F. III, Clark B.J., Stocco D.M., Saenger P.,
RA Rogol A., Miller W.L.;
RT "Role of steroidogenic acute regulatory protein in adrenal and gonadal
RT steroidogenesis.";
RL Science 267:1828-1831(1995).
RN [9]
RP VARIANTS AH1 GLY-169; LYS-169; LEU-182; VAL-218; ARG-272 DEL AND PRO-275,
RP CHARACTERIZATION OF VARIANTS AH1 GLY-169; LYS-169; LEU-182; VAL-218;
RP ARG-272 DEL AND PRO-275, AND CATALYTIC ACTIVITY.
RX PubMed=8948562; DOI=10.1056/nejm199612193352503;
RA Bose H.S., Sugawara T., Strauss J.F. III, Miller W.L.;
RT "The pathophysiology and genetics of congenital lipoid adrenal
RT hyperplasia.";
RL N. Engl. J. Med. 335:1870-1878(1996).
RN [10]
RP VARIANTS AH1 VAL-218 AND THR-225.
RX PubMed=9097960; DOI=10.1093/hmg/6.4.571;
RA Nakae J., Tajima T., Sugawara T., Arakane F., Hanaki K., Hotsubo T.,
RA Igarashi N., Igarashi Y., Ishii T., Koda N., Kondo T., Kohno H.,
RA Nakagawa Y., Tachibana K., Takeshima Y., Tsubouchi K., Strauss J.F. III,
RA Fujieda K.;
RT "Analysis of the steroidogenic acute regulatory protein (StAR) gene in
RT Japanese patients with congenital lipoid adrenal hyperplasia.";
RL Hum. Mol. Genet. 6:571-576(1997).
RN [11]
RP VARIANT ASP-203.
RX PubMed=9452116; DOI=10.1002/humu.1380110195;
RA Katsumata N., Tanae A., Shinagawa T., Nagashima-Miyokawa A., Shimizu M.,
RA Yasunaga T., Tanaka T., Hibi I.;
RT "A novel frameshift mutation 840delA and a novel polymorphism D203A in the
RT steroidogenic acute regulatory protein gene in a Japanese patient with
RT congenital lipoid adrenal hyperplasia.";
RL Hum. Mutat. Suppl. 1:S304-S307(1998).
RN [12]
RP VARIANTS AH1 THR-217 AND VAL-218.
RX PubMed=10566637; DOI=10.1210/jcem.84.11.6118;
RA Katsumata N., Kawada Y., Yamamoto Y., Noda M., Nimura A., Horikawa R.,
RA Tanaka T.;
RT "A novel compound heterozygous mutation in the steroidogenic acute
RT regulatory protein gene in a patient with congenital lipoid adrenal
RT hyperplasia.";
RL J. Clin. Endocrinol. Metab. 84:3983-3987(1999).
CC -!- FUNCTION: Plays a key role in steroid hormone synthesis by enhancing
CC the metabolism of cholesterol into pregnenolone. Mediates the transfer
CC of cholesterol from the outer mitochondrial membrane to the inner
CC mitochondrial membrane where it is cleaved to pregnenolone.
CC {ECO:0000269|PubMed:7761400, ECO:0000269|PubMed:7892608,
CC ECO:0000269|PubMed:8948562}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol(in) = cholesterol(out); Xref=Rhea:RHEA:39747,
CC ChEBI:CHEBI:16113; Evidence={ECO:0000269|PubMed:7761400,
CC ECO:0000269|PubMed:7892608};
CC -!- PATHWAY: Steroid metabolism; cholesterol metabolism.
CC {ECO:0000305|PubMed:7761400}.
CC -!- SUBUNIT: May interact with TSPO. {ECO:0000250|UniProtKB:P79245}.
CC -!- INTERACTION:
CC P49675; Q6RW13-2: AGTRAP; NbExp=3; IntAct=EBI-722932, EBI-11522760;
CC P49675; Q8IZR5-2: CMTM4; NbExp=3; IntAct=EBI-722932, EBI-17278014;
CC P49675; Q6ZPD8: DGAT2L6; NbExp=3; IntAct=EBI-722932, EBI-12831978;
CC P49675; P42858: HTT; NbExp=3; IntAct=EBI-722932, EBI-466029;
CC P49675; G5E962: MAGEA11; NbExp=3; IntAct=EBI-722932, EBI-11525615;
CC P49675; P43364: MAGEA11; NbExp=6; IntAct=EBI-722932, EBI-739552;
CC P49675; P43364-2: MAGEA11; NbExp=3; IntAct=EBI-722932, EBI-10178634;
CC P49675; Q15276: RABEP1; NbExp=3; IntAct=EBI-722932, EBI-447043;
CC P49675; O60906: SMPD2; NbExp=3; IntAct=EBI-722932, EBI-12828299;
CC P49675; Q9UNK0: STX8; NbExp=3; IntAct=EBI-722932, EBI-727240;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P51557}.
CC -!- TISSUE SPECIFICITY: Expressed in gonads, adrenal cortex and kidney.
CC -!- DISEASE: Adrenal hyperplasia 1 (AH1) [MIM:201710]: The most severe form
CC of adrenal hyperplasia. It is a condition characterized by onset of
CC profound adrenocortical insufficiency shortly after birth,
CC hyperpigmentation reflecting increased production of pro-
CC opiomelanocortin, elevated plasma renin activity as a consequence of
CC reduced aldosterone synthesis, and male pseudohermaphroditism resulting
CC from deficient fetal testicular testosterone synthesis. Affected
CC individuals are phenotypic females irrespective of gonadal sex, and
CC frequently die in infancy if mineralocorticoid and glucocorticoid
CC replacement are not instituted. {ECO:0000269|PubMed:10566637,
CC ECO:0000269|PubMed:7892608, ECO:0000269|PubMed:8948562,
CC ECO:0000269|PubMed:9097960}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Steroidogenic acute regulatory
CC protein entry;
CC URL="https://en.wikipedia.org/wiki/Steroidogenic_acute_regulatory_protein";
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DR EMBL; U17280; AAC50141.1; -; mRNA.
DR EMBL; U29105; AAC50234.1; -; Genomic_DNA.
DR EMBL; U29099; AAC50234.1; JOINED; Genomic_DNA.
DR EMBL; U29100; AAC50234.1; JOINED; Genomic_DNA.
DR EMBL; U29101; AAC50234.1; JOINED; Genomic_DNA.
DR EMBL; U29102; AAC50234.1; JOINED; Genomic_DNA.
DR EMBL; U29103; AAC50234.1; JOINED; Genomic_DNA.
DR EMBL; U29104; AAC50234.1; JOINED; Genomic_DNA.
DR EMBL; S79669; AAB35726.1; -; mRNA.
DR EMBL; AF035277; AAB88174.1; -; mRNA.
DR EMBL; BC010550; AAH10550.1; -; mRNA.
DR CCDS; CCDS6102.1; -.
DR PIR; I38248; I38248.
DR RefSeq; NP_000340.2; NM_000349.2.
DR PDB; 3P0L; X-ray; 3.40 A; A/B/C/D=66-284.
DR PDB; 5OMA; X-ray; 3.90 A; A/B/C/D=54-62.
DR PDB; 6T5F; X-ray; 2.63 A; E/F/G/H=192-200.
DR PDB; 6T5H; X-ray; 2.04 A; A/B=54-62.
DR PDBsum; 3P0L; -.
DR PDBsum; 5OMA; -.
DR PDBsum; 6T5F; -.
DR PDBsum; 6T5H; -.
DR AlphaFoldDB; P49675; -.
DR SMR; P49675; -.
DR BioGRID; 112647; 11.
DR IntAct; P49675; 11.
DR STRING; 9606.ENSP00000276449; -.
DR SwissLipids; SLP:000000714; -.
DR SwissLipids; SLP:000000716; -.
DR iPTMnet; P49675; -.
DR PhosphoSitePlus; P49675; -.
DR BioMuta; STAR; -.
DR DMDM; 71152974; -.
DR EPD; P49675; -.
DR MassIVE; P49675; -.
DR PaxDb; P49675; -.
DR PeptideAtlas; P49675; -.
DR PRIDE; P49675; -.
DR ProteomicsDB; 56046; -.
DR Antibodypedia; 23510; 337 antibodies from 35 providers.
DR DNASU; 6770; -.
DR Ensembl; ENST00000276449.9; ENSP00000276449.3; ENSG00000147465.12.
DR GeneID; 6770; -.
DR KEGG; hsa:6770; -.
DR MANE-Select; ENST00000276449.9; ENSP00000276449.3; NM_000349.3; NP_000340.2.
DR CTD; 6770; -.
DR DisGeNET; 6770; -.
DR GeneCards; STAR; -.
DR HGNC; HGNC:11359; STAR.
DR HPA; ENSG00000147465; Tissue enriched (adrenal).
DR MalaCards; STAR; -.
DR MIM; 201710; phenotype.
DR MIM; 600617; gene.
DR neXtProt; NX_P49675; -.
DR OpenTargets; ENSG00000147465; -.
DR Orphanet; 325524; Classic congenital lipoid adrenal hyperplasia due to STAR deficency.
DR Orphanet; 361; Familial glucocorticoid deficiency.
DR Orphanet; 325529; Non-classic congenital lipoid adrenal hyperplasia due to STAR deficency.
DR PharmGKB; PA36181; -.
DR VEuPathDB; HostDB:ENSG00000147465; -.
DR eggNOG; KOG3845; Eukaryota.
DR GeneTree; ENSGT00940000155477; -.
DR HOGENOM; CLU_093200_1_0_1; -.
DR InParanoid; P49675; -.
DR OMA; KMPEQKG; -.
DR OrthoDB; 1437203at2759; -.
DR PhylomeDB; P49675; -.
DR TreeFam; TF313869; -.
DR PathwayCommons; P49675; -.
DR Reactome; R-HSA-196108; Pregnenolone biosynthesis.
DR SignaLink; P49675; -.
DR SIGNOR; P49675; -.
DR UniPathway; UPA00296; -.
DR BioGRID-ORCS; 6770; 7 hits in 1073 CRISPR screens.
DR ChiTaRS; STAR; human.
DR EvolutionaryTrace; P49675; -.
DR GenomeRNAi; 6770; -.
DR Pharos; P49675; Tbio.
DR PRO; PR:P49675; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P49675; protein.
DR Bgee; ENSG00000147465; Expressed in right adrenal gland and 113 other tissues.
DR ExpressionAtlas; P49675; baseline and differential.
DR Genevisible; P49675; HS.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IBA:GO_Central.
DR GO; GO:0015485; F:cholesterol binding; IDA:BHF-UCL.
DR GO; GO:0120020; F:cholesterol transfer activity; IEA:InterPro.
DR GO; GO:0044255; P:cellular lipid metabolic process; IEA:Ensembl.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0008211; P:glucocorticoid metabolic process; IEA:Ensembl.
DR GO; GO:0032367; P:intracellular cholesterol transport; IBA:GO_Central.
DR GO; GO:0070859; P:positive regulation of bile acid biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0050810; P:regulation of steroid biosynthetic process; IBA:GO_Central.
DR GO; GO:0006694; P:steroid biosynthetic process; IBA:GO_Central.
DR CDD; cd08905; START_STARD1-like; 1.
DR Gene3D; 3.30.530.20; -; 1.
DR InterPro; IPR029866; StAR.
DR InterPro; IPR000799; StAR-like.
DR InterPro; IPR023393; START-like_dom_sf.
DR InterPro; IPR002913; START_lipid-bd_dom.
DR PANTHER; PTHR46489; PTHR46489; 1.
DR Pfam; PF01852; START; 1.
DR PRINTS; PR00978; STARPROTEIN.
DR SMART; SM00234; START; 1.
DR PROSITE; PS50848; START; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Congenital adrenal hyperplasia; Disease variant;
KW Lipid transport; Lipid-binding; Mitochondrion; Phosphoprotein;
KW Reference proteome; Steroidogenesis; Transit peptide; Transport.
FT TRANSIT 1..63
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 64..285
FT /note="Steroidogenic acute regulatory protein,
FT mitochondrial"
FT /id="PRO_0000033316"
FT DOMAIN 67..280
FT /note="START"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00197"
FT MOD_RES 57
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:10548884"
FT MOD_RES 195
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:10548884"
FT VARIANT 121
FT /note="R -> W (in dbSNP:rs34908868)"
FT /id="VAR_034520"
FT VARIANT 169
FT /note="E -> G (in AH1; partial loss of activity;
FT dbSNP:rs1254559989)"
FT /evidence="ECO:0000269|PubMed:8948562"
FT /id="VAR_014236"
FT VARIANT 169
FT /note="E -> K (in AH1; partial loss of activity;
FT dbSNP:rs747169620)"
FT /evidence="ECO:0000269|PubMed:8948562"
FT /id="VAR_014237"
FT VARIANT 182
FT /note="R -> L (in AH1; partial loss of activity;
FT dbSNP:rs104894086)"
FT /evidence="ECO:0000269|PubMed:8948562"
FT /id="VAR_005627"
FT VARIANT 203
FT /note="A -> D (in dbSNP:rs1042854)"
FT /evidence="ECO:0000269|PubMed:7547998,
FT ECO:0000269|PubMed:7761400, ECO:0000269|PubMed:9452116"
FT /id="VAR_005628"
FT VARIANT 217
FT /note="R -> T (in AH1; dbSNP:rs137852689)"
FT /evidence="ECO:0000269|PubMed:10566637"
FT /id="VAR_014238"
FT VARIANT 218
FT /note="A -> V (in AH1; partial loss of activity;
FT dbSNP:rs137852690)"
FT /evidence="ECO:0000269|PubMed:10566637,
FT ECO:0000269|PubMed:8948562, ECO:0000269|PubMed:9097960"
FT /id="VAR_014239"
FT VARIANT 225
FT /note="M -> T (in AH1; dbSNP:rs1446362214)"
FT /evidence="ECO:0000269|PubMed:9097960"
FT /id="VAR_014240"
FT VARIANT 272
FT /note="Missing (in AH1; partial loss of activity)"
FT /evidence="ECO:0000269|PubMed:8948562"
FT /id="VAR_014241"
FT VARIANT 275
FT /note="L -> P (in AH1; partial loss of activity;
FT dbSNP:rs762245736)"
FT /evidence="ECO:0000269|PubMed:8948562"
FT /id="VAR_014242"
FT HELIX 70..91
FT /evidence="ECO:0007829|PDB:3P0L"
FT STRAND 97..101
FT /evidence="ECO:0007829|PDB:3P0L"
FT STRAND 107..112
FT /evidence="ECO:0007829|PDB:3P0L"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:3P0L"
FT STRAND 118..128
FT /evidence="ECO:0007829|PDB:3P0L"
FT HELIX 130..137
FT /evidence="ECO:0007829|PDB:3P0L"
FT TURN 138..140
FT /evidence="ECO:0007829|PDB:3P0L"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:3P0L"
FT STRAND 152..159
FT /evidence="ECO:0007829|PDB:3P0L"
FT STRAND 161..171
FT /evidence="ECO:0007829|PDB:3P0L"
FT STRAND 182..192
FT /evidence="ECO:0007829|PDB:3P0L"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:3P0L"
FT STRAND 215..217
FT /evidence="ECO:0007829|PDB:3P0L"
FT STRAND 224..230
FT /evidence="ECO:0007829|PDB:3P0L"
FT STRAND 233..243
FT /evidence="ECO:0007829|PDB:3P0L"
FT HELIX 253..274
FT /evidence="ECO:0007829|PDB:3P0L"
SQ SEQUENCE 285 AA; 31914 MW; 2683086C20DE88AB CRC64;
MLLATFKLCA GSSYRHMRNM KGLRQQAVMA ISQELNRRAL GGPTPSTWIN QVRRRSSLLG
SRLEETLYSD QELAYLQQGE EAMQKALGIL SNQEGWKKES QQDNGDKVMS KVVPDVGKVF
RLEVVVDQPM ERLYEELVER MEAMGEWNPN VKEIKVLQKI GKDTFITHEL AAEAAGNLVG
PRDFVSVRCA KRRGSTCVLA GMATDFGNMP EQKGVIRAEH GPTCMVLHPL AGSPSKTKLT
WLLSIDLKGW LPKSIINQVL SQTQVDFANH LRKRLESHPA SEARC
