Summary: START domain
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This is the Wikipedia entry entitled "StAR-related transfer domain". More...
StAR-related transfer domain Edit Wikipedia article
| START domain | |||||||||
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| Identifiers | |||||||||
| Symbol | START | ||||||||
| Pfam | PF01852 | ||||||||
| InterPro | IPR002913 | ||||||||
| SMART | START | ||||||||
| SCOP | 1em2 | ||||||||
| SUPERFAMILY | 1em2 | ||||||||
| TCDB | 9.B.64 | ||||||||
| OPM superfamily | 147 | ||||||||
| OPM protein | 1ln1 | ||||||||
| CDD | cd00177 | ||||||||
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| START | |||||||||
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star-related lipid transport domain of mln64
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| Identifiers | |||||||||
| Symbol | START | ||||||||
| Pfam | PF01852 | ||||||||
| Pfam clan | CL0209 | ||||||||
| InterPro | IPR002913 | ||||||||
| SMART | START | ||||||||
| SCOP | 1em2 | ||||||||
| SUPERFAMILY | 1em2 | ||||||||
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START (StAR-related lipid-transfer) is a lipid-binding domain in StAR, HD-ZIP and signalling proteins.[1] The archetypical domain is found in StAR (Steroidogenic acute regulatory protein), a mitochondrial protein that is synthesized in steroid-producing cells.[2] StAR initiates steroid production by mediating the delivery of cholesterol to the first enzyme in steroidogenic pathway. The START domain is critical for this activity, perhaps through the binding of cholesterol. Following the discovery of StAR, 15 START-domain-containing proteins (termed STARD1 through STARD15) were subsequently identified in vertebrates as well as other that are related.
Thousands of proteins containing at least one START domain have been determined in invertebrates, bacteria and plants to form a larger superfamily, variously known as START, Bet v1-like or SRPBCC (START/RHOalphaC/PITP/Bet v1/CoxG/CalC) domain proteins, all of which bind hydrophobic ligands. In the case of plants, many of the START proteins fall into the category of putative lipid/sterol-binding homeodomain (HD) transcription factors or HD-START proteins.[3]
Representatives of the START domain family bind different substances or ligands such as sterols (e.g., StAR or STARD1) and lipids like phosphatidylcholine (phosphatidylcholine transfer protein, also called PCTP or STARD2) and have enzymatic activities. Ligand binding by the START domain in multidomain proteins can also regulate the activities of the other domains, such as the RhoGAP domain, the homeodomain and the thioesterase domain.[1][4]
Contents
Structure
The crystal structure of START domain of human MLN64 shows an alpha/beta fold built around a U-shaped incomplete beta-barrel. Most importantly, the interior of the protein encompasses a 26 × 12 × 11-Angstrom hydrophobic tunnel that is apparently large enough to bind a single cholesterol molecule.[5] The START domain structure revealed an unexpected similarity to that of the birch pollen allergen Bet v 1 and to bacterial polyketide cyclases/aromatases.[4][5]
Human proteins containing the START domain
START domain-containing proteins in the human are divided into five subfamilies. An exception is StarD9 whose activity remains unknown. Other proteins also exist in the human with domains that are members of the START-based superfamily such as PITP, but are not part of the START domain itself.
Mutations in STAR D9 (KIF16A) have been associated with a syndrome which includes severe ID, characteristic features, epilepsy, acquired microcephaly and blindness.[6] The STAR D9 gene encodes a 4.7 kiloDalton amino acid protein which is a member of the kinesin superfamily. C-terminally truncated STAR D9 mutants are known from experimtal work to induce spindle assembly defects. In the reported case, several mitotic defects including multipolar spindle formation, fragmentation of pericentriolar materials and centrosome amplification were found.
Cholesterol/oxysterol binding StarD1/D3 subfamily
These proteins are primarily concerned with cholesterol transport
- StAR (STARD1)
- MLN64 (STARD3)
StarD4 subfamily
These proteins are involved in cholesterol and oxysterol transport
Phospholipid/sphingolipid binding StarD2 subfamily
SAM-RhoGAP-START subfamily
These proteins contain both the START domain and Rho-GTPase signaling activity
Acyl-CoA thioesterase subfamily
The members of this subfamily possess the START domain and thioesterase activity
See also
References
- ^ a b Ponting CP, Aravind L (1999). "START: a lipid-binding domain in StAR, HD-ZIP and signalling proteins". Trends Biochem. Sci. 24 (4): 130–132. doi:10.1016/S0968-0004(99)01362-6. PMID 10322415.
- ^ Clark BJ, Wells J, King SR, Stocco DM (1994). "The purification, cloning, and expression of a novel luteinizing hormone-induced mitochondrial protein in MA-10 mouse Leydig tumor cells. Characterization of the steroidogenic acute regulatory protein (StAR)". J. Biol. Chem. 269 (45): 28314–28322. PMID 7961770.
- ^ Schrick K, Nguyen D, Karlowski WM, Mayer KF (2004). "START lipid/sterol-binding domains are amplified in plants and are predominantly associated with homeodomain transcription factors". Genome Biol. 5: R41. doi:10.1186/gb-2004-5-6-r41. PMC 463074
. PMID 15186492. - ^ a b Koonin EV, Aravind L, Iyer LM (2001). "Adaptations of the helix-grip fold for ligand binding and catalysis in the START domain superfamily". Proteins. 43 (2): 134–144. doi:10.1002/1097-0134(20010501)43:2<134::AID-PROT1025>3.0.CO;2-I. PMID 11276083.
- ^ a b Hurley JH, Tsujishita Y (2000). "Structure and lipid transport mechanism of a StAR-related domain". Nat. Struct. Biol. 7 (5): 408–414. doi:10.1038/75192. PMID 10802740.
- ^ Okamoto N, Tsuchiya Y, Miya F, Tsunoda T, Yamashita K, Boroevich KA, Kato M, Saitoh S, Yamasaki M, Kanemura Y, Kosaki K, Kitagawa D (2017) A novel genetic syndrome with STARD9 mutation and abnormal spindle morphology. Am J Med Genet
This article incorporates text from the public domain Pfam and InterPro IPR002913
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START domain Provide feedback
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Literature references
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Ponting CP, Aravind L; , Trends Biochem Sci 1999;24:130-132.: START: a lipid-binding domain in StAR, HD-ZIP and signalling proteins. PUBMED:10322415 EPMC:10322415
Internal database links
| SCOOP: | DUF3074 Polyketide_cyc Polyketide_cyc2 |
| Similarity to PfamA using HHSearch: | DUF3074 |
External database links
| SCOP: | 1em2 |
| SMART: | START |
This tab holds annotation information from the InterPro database.
InterPro entry IPR002913
START (StAR-related lipid-transfer) is a lipid-binding domain in StAR, HD-ZIP and signalling proteins [PUBMED:10322415]. StAR (Steroidogenic Acute Regulatory protein) is a mitochondrial protein that is synthesised in response to luteinising hormone stimulation [PUBMED:7961770]. Expression of the protein in the absence of hormone stimulation is sufficient to induce steroid production, suggesting that this protein is required in the acute regulation of steroidogenesis. Representatives of the START domain family have been shown to bind different ligands such as sterols (StAR protein) and phosphatidylcholine (PC-TP). Ligand binding by the START domain can also regulate the activities of other domains that co-occur with the START domain in multidomain proteins such as Rho-gap, the homeodomain, and the thioesterase domain [PUBMED:10322415, PUBMED:11276083].
The crystal structure of START domain of human MLN64 shows an alpha/beta fold built around an U-shaped incomplete beta-barrel. Most importantly, the interior of the protein encompasses a 26 x 12 x 11 Angstroms hydrophobic tunnel that is apparently large enough to bind a single cholesterol molecule [PUBMED:10802740]. The START domain structure revealed an unexpected similarity to that of the birch pollen allergen Bet v 1 and to bacterial polyketide cyclases/aromatases [PUBMED:11276083, PUBMED:10802740].
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
| Molecular function | lipid binding (GO:0008289) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan Bet_V_1_like (CL0209), which has the following description:
The Bet_V_I family is composed of sequences related to the major Birch (Betula verrucose) pollen antigen Betv1. This allergen is known to cause hayfever, dermatitis, asthma and occasionally anaphylactic shock. The other families in this clan share the same structure as Betv1 which is composed of antiparallel beta sheets and alpha helices. There is a cavity between the beta sheet and a long C terminal helix. The cavity appears to play roles in the binding of lipid molecules [1][2][3] which seems a common feature of the families in this clan.
The clan contains the following 19 members:
AHSA1 Aromatic_hydrox Bet_v_1 COXG DAPG_hydrolase DUF1857 DUF2505 DUF3074 DUF3211 DUF3284 Fungal_KA1 IP_trans Lipoprotein_18 Polyketide_cyc Polyketide_cyc2 PRELI Ring_hydroxyl_A START VAStAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
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| Seed (16) |
Full (8486) |
Representative proteomes | UniProt (13603) |
NCBI (20869) |
Meta (54) |
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| RP15 (2104) |
RP35 (4542) |
RP55 (6615) |
RP75 (7890) |
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| HTML | |||||||||
| PP/heatmap | 1 | ||||||||
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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| Seed (16) |
Full (8486) |
Representative proteomes | UniProt (13603) |
NCBI (20869) |
Meta (54) |
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|---|---|---|---|---|---|---|---|---|---|
| RP15 (2104) |
RP35 (4542) |
RP55 (6615) |
RP75 (7890) |
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| Raw Stockholm | |||||||||
| Gzipped | |||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
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Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Alignment kindly provided by SMART |
| Previous IDs: | none |
| Type: | Domain |
| Sequence Ontology: | SO:0000417 |
| Author: | SMART |
| Number in seed: | 16 |
| Number in full: | 8486 |
| Average length of the domain: | 187.60 aa |
| Average identity of full alignment: | 16 % |
| Average coverage of the sequence by the domain: | 31.30 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 209 | ||||||||||||
| Family (HMM) version: | 19 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Colour assignments
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Interactions
There is 1 interaction for this family. More...
STARTStructures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the START domain has been found. There are 45 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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