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40  structures 457  species 1  interaction 2507  sequences 50  architectures

Family: START (PF01852)

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
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
START
PDB 1em2 EBI.jpg
star-related lipid transport domain of mln64
Identifiers
Symbol START
Pfam PF01852
Pfam clan CL0209
InterPro IPR002913
SMART START
SCOP 1em2
SUPERFAMILY 1em2

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 and 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]

Structure[edit]

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[disambiguation needed]/aromatases.[4][5]

Human proteins containing the START domain[edit]

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.

Cholesterol/oxysterol binding StarD1/D3 subfamily[edit]

These proteins are primarily concerned with cholesterol transport

StAR (STARD1)
MLN64 (STARD3)

StarD4 subfamily[edit]

These proteins are involved in cholesterol and oxysterol transport

STARD4
STARD5
STARD6

Phospholipid/sphingolipid binding StarD2 subfamily[edit]

PCTP (STARD2)
STARD7
STARD10
COL4A3BP (STARD11)

SAM-RhoGAP-START subfamily[edit]

These proteins contain both the START domain and Rho-GTPase signaling activity

STARD8 (DLC-3)
DLC1 (STARD12)
STARD13 (DLC-2)

Acyl-CoA thioesterase subfamily[edit]

The members of this subfamily possess the START domain and thioesterase activity

ACOT11 (STARD14)
ACOT12 (STARD15)

See also[edit]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 

This article incorporates text from the public domain Pfam and InterPro IPR002913

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Literature references

  1. 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

External database links

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].

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 14 members:

AHSA1 Aromatic_hydrox Bet_v_1 COXG DUF1857 DUF2505 DUF3074 DUF3211 DUF3284 IP_trans Polyketide_cyc Polyketide_cyc2 Ring_hydroxyl_A START

Alignments

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(18)
Full
(2507)
Representative proteomes NCBI
(2394)
Meta
(50)
RP15
(408)
RP35
(676)
RP55
(997)
RP75
(1330)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(18)
Full
(2507)
Representative proteomes NCBI
(2394)
Meta
(50)
RP15
(408)
RP35
(676)
RP55
(997)
RP75
(1330)
Alignment:
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Sequence:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(18)
Full
(2507)
Representative proteomes NCBI
(2394)
Meta
(50)
RP15
(408)
RP35
(676)
RP55
(997)
RP75
(1330)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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 View help on the curation process

Seed source: Alignment kindly provided by SMART
Previous IDs: none
Type: Domain
Author: SMART
Number in seed: 18
Number in full: 2507
Average length of the domain: 186.50 aa
Average identity of full alignment: 16 %
Average coverage of the sequence by the domain: 33.31 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.6 20.6
Trusted cut-off 20.7 20.6
Noise cut-off 20.5 20.5
Model length: 206
Family (HMM) version: 14
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

START

Structures

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 40 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 seqence.

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