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UniProtKB - Q14849 (STAR3_HUMAN)

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Protein

StAR-related lipid transfer protein 3

Gene

STARD3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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

GO - Molecular functioni

  • cholesterol binding Source: UniProtKB
  • cholesterol transporter activity Source: InterPro
  • protein homodimerization activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

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
View the complete GO annotation on QuickGO ...

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000131748.15
HGNCiHGNC:17579 STARD3
MIMi607048 gene
neXtProtiNX_Q14849

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
ProteomicsDBi60208
60209 [Q14849-2]

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
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi116148, 19 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
KOiK22291
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: June 20, 2018
This is version 176 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

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

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