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Protein

StAR-related lipid transfer protein 3

Gene

STARD3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Sterol-binding protein that mediates cholesterol transport from the endoplasmic reticulum to endosomes (PubMed:11053434, PubMed:15930133, PubMed:22514632, PubMed:28377464). Creates contact site between the endoplasmic reticulum and late endosomes: localizes to late endosome membranes and contacts the endoplasmic reticulum via interaction with VAPA and VAPB (PubMed:24105263, PubMed:28377464). Acts as a lipid transfer protein that redirects sterol to the endosome at the expense of the cell membrane and favors membrane formation inside endosomes (PubMed:28377464). May also mediate cholesterol transport between other membranes, such as mitochondria membrane or cell membrane (PubMed:12070139, PubMed:19965586). However, such results need additional experimental evidences; probably mainly mediates cholesterol transport from the endoplasmic reticulum to endosomes (PubMed:28377464). Does not activate transcriptional cholesterol sensing (PubMed:28377464). Able to bind other lipids, such as lutein, a xanthophyll carotenoids that form the macular pigment of the retina (PubMed:21322544).8 Publications

GO - Molecular functioni

  • cholesterol binding Source: UniProtKB
  • cholesterol transporter activity Source: InterPro
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

  • C21-steroid hormone biosynthetic process Source: Reactome
  • cholesterol metabolic process Source: ProtInc
  • cholesterol transport Source: UniProtKB
  • lipid metabolic process Source: ProtInc
  • mitochondrial transport Source: ProtInc
  • progesterone biosynthetic process Source: Ensembl
  • steroid metabolic process Source: ProtInc
  • vesicle tethering to endoplasmic reticulum Source: UniProtKB

Keywordsi

Biological processLipid transport, Transport
LigandLipid-binding

Enzyme and pathway databases

ReactomeiR-HSA-196108. Pregnenolone biosynthesis.

Protein family/group databases

TCDBi9.B.64.1.1. the putative cholesterol transporter (start1) family.

Chemistry databases

SwissLipidsiSLP:000000712.

Names & Taxonomyi

Protein namesi
Recommended name:
StAR-related lipid transfer protein 3Curated
Alternative name(s):
Metastatic lymph node gene 64 protein1 Publication
Short name:
MLN 641 Publication
Protein CAB11 Publication
START domain-containing protein 31 Publication
Short name:
StARD31 Publication
Gene namesi
Name:STARD3Imported
Synonyms:CAB11 Publication, MLN641 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000131748.15.
HGNCiHGNC:17579. STARD3.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 51Cytoplasmic1 PublicationAdd BLAST51
Transmembranei52 – 72HelicalPROSITE-ProRule annotationAdd BLAST21
Topological domaini73 – 94ExtracellularSequence analysisAdd BLAST22
Transmembranei95 – 115HelicalPROSITE-ProRule annotationAdd BLAST21
Topological domaini116 – 120CytoplasmicSequence analysis5
Transmembranei121 – 141HelicalPROSITE-ProRule annotationAdd BLAST21
Topological domaini142 – 148ExtracellularSequence analysis7
Transmembranei149 – 169HelicalPROSITE-ProRule annotationAdd BLAST21
Topological domaini170 – 445Cytoplasmic1 PublicationAdd BLAST276

Keywords - Cellular componenti

Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi66 – 67LL → AS: Abolishes localization to late endosomes and leads to mislocalization to the endoplasmic reticulum. 1 Publication2
Mutagenesisi89Y → V: Abolishes localization to late endosomes and leads to mislocalization to the endoplasmic reticulum. 1 Publication1
Mutagenesisi113Y → A: Does not affect localization to late endosomes. 1 Publication1
Mutagenesisi206 – 212Missing : Abolishes interaction with VAPA and VAPB, thereby preventing contact with the endoplasmic reticulum membrane. 1 Publication7
Mutagenesisi207 – 208FY → AA: Abolishes interaction with VAPA and VAPB, thereby preventing contact with the endoplasmic reticulum membrane. Abolishes cholesterol accumulation in endosomes. 1 Publication2
Mutagenesisi219N → A: Does not affect localization to late endosomes. 1 Publication1
Mutagenesisi307 – 311MVLWN → NVLWD: Abolishes ability to transfer cholesterol between membranes. 1 Publication5
Mutagenesisi311N → A: Does not affect localization to late endosomes. 1 Publication1

Organism-specific databases

DisGeNETi10948.
OpenTargetsiENSG00000131748.
PharmGKBiPA134981867.

Polymorphism and mutation databases

BioMutaiSTARD3.
DMDMi116242802.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002206531 – 445StAR-related lipid transfer protein 3Add BLAST445

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei209PhosphoserineBy similarity1
Modified residuei217PhosphoserineBy similarity1
Modified residuei221PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ14849.
PaxDbiQ14849.
PeptideAtlasiQ14849.
PRIDEiQ14849.

PTM databases

iPTMnetiQ14849.
PhosphoSitePlusiQ14849.

Expressioni

Tissue specificityi

Expressed in retina.1 Publication

Inductioni

Not regulated by increases in total cholesterol content, or by marked alterations in cholesterol flux.1 Publication

Gene expression databases

BgeeiENSG00000131748.
CleanExiHS_STARD3.
ExpressionAtlasiQ14849. baseline and differential.
GenevisibleiQ14849. HS.

Organism-specific databases

HPAiCAB017021.

Interactioni

Subunit structurei

Homodimer (PubMed:15718238, PubMed:16709157). Interacts (via the MENTAL domain) with STARD3NL (PubMed:15718238, PubMed:16709157). Interacts (via FFAT motif) with VAPA (PubMed:24105263, PubMed:28377464). Interacts (via FFAT motif) with VAPB (PubMed:24105263, PubMed:28377464).4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi116148. 17 interactors.
IntActiQ14849. 3 interactors.
STRINGi9606.ENSP00000337446.

Structurei

Secondary structure

1445
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi233 – 254Combined sources22
Helixi255 – 258Combined sources4
Beta strandi260 – 264Combined sources5
Beta strandi270 – 276Combined sources7
Turni277 – 279Combined sources3
Beta strandi280 – 291Combined sources12
Helixi293 – 300Combined sources8
Helixi304 – 310Combined sources7
Beta strandi314 – 323Combined sources10
Turni324 – 326Combined sources3
Beta strandi327 – 334Combined sources8
Beta strandi340 – 342Combined sources3
Beta strandi345 – 355Combined sources11
Beta strandi357 – 366Combined sources10
Beta strandi378 – 380Combined sources3
Beta strandi385 – 392Combined sources8
Beta strandi400 – 406Combined sources7
Beta strandi412 – 414Combined sources3
Helixi416 – 443Combined sources28

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EM2X-ray2.20A216-444[»]
2I92model-A230-443[»]
5I9JX-ray1.74A216-444[»]
ProteinModelPortaliQ14849.
SMRiQ14849.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ14849.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini46 – 217MENTALPROSITE-ProRule annotationAdd BLAST172
Domaini230 – 443STARTPROSITE-ProRule annotationAdd BLAST214

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi207 – 212FFAT1 Publication6

Domaini

The FFAT motif mediates interaction with VAPA and VAPB.1 Publication
The START domain mediates lipid-transfer between membranes. It contains a hydrophobic cavity able to accommodate one lipid molecule, thereby serving as a 'hydrophobic bridge' across the aqueous gap between donor and acceptor organelle membranes.1 Publication
The MENTAL domain anchors the protein in endosome membranes and exposes the START domain in the cytosol (PubMed:11053434). It binds cholesterol and mediates homotypic as well as heterotypic interactions between STARD3 and STARD3NL (PubMed:15718238, PubMed:16709157).3 Publications

Sequence similaritiesi

Belongs to the STARD3 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3845. Eukaryota.
ENOG41100B5. LUCA.
GeneTreeiENSGT00530000063139.
HOGENOMiHOG000015362.
HOVERGENiHBG052482.
InParanoidiQ14849.
PhylomeDBiQ14849.
TreeFamiTF313869.

Family and domain databases

CDDicd08906. START_STARD3-like. 1 hit.
Gene3Di3.30.530.20. 1 hit.
InterProiView protein in InterPro
IPR019498. MENTAL.
IPR000799. StAR-like.
IPR029867. STARD3_MLN64_C.
IPR023393. START-like_dom_sf.
IPR002913. START_lipid-bd_dom.
PfamiView protein in Pfam
PF10457. MENTAL. 1 hit.
PF01852. START. 1 hit.
PRINTSiPR00978. STARPROTEIN.
SMARTiView protein in SMART
SM00234. START. 1 hit.
PROSITEiView protein in PROSITE
PS51439. MENTAL. 1 hit.
PS50848. START. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q14849-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSKLPRELTR DLERSLPAVA SLGSSLSHSQ SLSSHLLPPP EKRRAISDVR
60 70 80 90 100
RTFCLFVTFD LLFISLLWII ELNTNTGIRK NLEQEIIQYN FKTSFFDIFV
110 120 130 140 150
LAFFRFSGLL LGYAVLRLRH WWVIAVTTLV SSAFLIVKVI LSELLSKGAF
160 170 180 190 200
GYLLPIVSFV LAWLETWFLD FKVLPQEAEE ERWYLAAQVA VARGPLLFSG
210 220 230 240 250
ALSEGQFYSP PESFAGSDNE SDEEVAGKKS FSAQEREYIR QGKEATAVVD
260 270 280 290 300
QILAQEENWK FEKNNEYGDT VYTIEVPFHG KTFILKTFLP CPAELVYQEV
310 320 330 340 350
ILQPERMVLW NKTVTACQIL QRVEDNTLIS YDVSAGAAGG VVSPRDFVNV
360 370 380 390 400
RRIERRRDRY LSSGIATSHS AKPPTHKYVR GENGPGGFIV LKSASNPRVC
410 420 430 440
TFVWILNTDL KGRLPRYLIH QSLAATMFEF AFHLRQRISE LGARA
Length:445
Mass (Da):50,502
Last modified:October 17, 2006 - v2
Checksum:i8EBFBAF013CFDC7E
GO
Isoform 2 (identifier: Q14849-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     126-143: Missing.

Note: No experimental confirmation available.
Show »
Length:427
Mass (Da):48,601
Checksum:i2B97748DBDD1C4CE
GO
Isoform 3 (identifier: Q14849-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     122-183: WVIAVTTLVS...LPQEAEEERW → SRRWCPVHSS...LKRSDSAPPG

Note: No experimental confirmation available.
Show »
Length:445
Mass (Da):49,960
Checksum:iF5A010E90FC97121
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_027877117R → Q5 PublicationsCorresponds to variant dbSNP:rs1877031Ensembl.1
Natural variantiVAR_027878216G → A1 PublicationCorresponds to variant dbSNP:rs11556624Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_045361122 – 183WVIAV…EEERW → SRRWCPVHSSLSRSSSLSCS AKGHLATCSPSSLLSSPGWR PGSLTSKSYPRKLKRSDSAP PG in isoform 3. 1 PublicationAdd BLAST62
Alternative sequenceiVSP_042710126 – 143Missing in isoform 2. 1 PublicationAdd BLAST18

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80198 mRNA. Translation: CAA56489.1.
D38255 mRNA. Translation: BAA22525.1.
BT006964 mRNA. Translation: AAP35610.1.
AK300176 mRNA. Translation: BAG61955.1.
AK300842 mRNA. Translation: BAG62493.1.
AC087491 Genomic DNA. No translation available.
BC008356 mRNA. Translation: AAH08356.1.
BC008747 mRNA. Translation: AAH08747.1.
BC025679 mRNA. Translation: AAH25679.1.
CCDSiCCDS11341.1. [Q14849-1]
CCDS54117.1. [Q14849-3]
CCDS54118.1. [Q14849-2]
PIRiI38027.
RefSeqiNP_001159409.1. NM_001165937.1. [Q14849-3]
NP_001159410.1. NM_001165938.1. [Q14849-2]
NP_006795.3. NM_006804.3. [Q14849-1]
XP_016879530.1. XM_017024041.1. [Q14849-1]
UniGeneiHs.728838.

Genome annotation databases

EnsembliENST00000336308; ENSP00000337446; ENSG00000131748. [Q14849-1]
ENST00000394250; ENSP00000377794; ENSG00000131748. [Q14849-2]
ENST00000544210; ENSP00000439869; ENSG00000131748. [Q14849-3]
GeneIDi10948.
KEGGihsa:10948.
UCSCiuc002hsd.4. human. [Q14849-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSTAR3_HUMAN
AccessioniPrimary (citable) accession number: Q14849
Secondary accession number(s): A8MXA4
, B4DUY1, F5H0G2, Q53Y53, Q96HM9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: October 17, 2006
Last modified: November 22, 2017
This is version 172 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Caution

STARD3 was reported to function in cholesterol transport to the mitochondria or to the cell membrane (PubMed:12070139, PubMed:19965586). Other reports however showed that it mediates cholesterol transport from the endoplasmic reticulum to endosomes (PubMed:11053434, PubMed:28377464). Discrepancies may be due to the different cell type used and the cellular physiological state (PubMed:28377464).4 Publications

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families