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UniProt SwissProt/TrEMBL Protein Annotations   (All Genes and Gene Predictions tracks)

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 SwissProt Aln.  UCSC alignment of SwissProt proteins to genome (dark blue: main isoform, light blue: alternative isoforms)   Schema 
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 TrEMBL Aln.  UCSC alignment of TrEMBL proteins to genome   Schema 
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 Signal Peptide  UniProt Signal Peptides   Schema 
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 Extracellular  UniProt Extracellular Domain   Schema 
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 Interest  UniProt Regions of Interest   Schema 
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 Transmembrane  UniProt Transmembrane Domains   Schema 
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 Cytoplasmic  UniProt Cytoplasmic Domains   Schema 
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 Chains  UniProt Mature Protein Products (Polypeptide Chains)   Schema 
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 Disulf. Bonds  UniProt Disulfide Bonds   Schema 
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 Domains  UniProt Domains   Schema 
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 AA Modifications  UniProt Amino Acid Modifications   Schema 
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 Mutations  UniProt Amino Acid Mutations   Schema 
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 Other Annot.  UniProt Other Annotations   Schema 
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 Structure  UniProt Protein Primary/Secondary Structure Annotations   Schema 
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 Repeats  UniProt Repeats   Schema 
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 Seq. Conflicts  UniProt Sequence Conflicts   Schema 
    
Source data version: UniProt Knowledgebase Release 2020_06

Description

This track shows protein sequences and annotations on them from the UniProt/SwissProt database, mapped to genomic coordinates.

UniProt/SwissProt data has been curated from scientific publications by the UniProt staff, UniProt/TrEMBL data has been predicted by various computational algorithms. The annotations are divided into multiple subtracks, based on their "feature type" in UniProt. The first two subtracks below - one for SwissProt, one for TrEMBL - show the alignments of protein sequences to the genome, all other tracks below are the protein annotations mapped through these alignments to the genome.

Track Name Description
UCSC Alignment, SwissProt = curated protein sequences Protein sequences from SwissProt mapped to the genome. All other tracks are (start,end) SwissProt annotations on these sequences mapped through this alignment. Even protein sequences without a single curated annotation (splice isoforms) are visible in this track. Each UniProt protein has one main isoform, which is colored in dark. Alternative isoforms are sequences that do not have annotations on them and are colored in light-blue. They can be hidden with the TrEMBL/Isoform filter (see below).
UCSC Alignment, TrEMBL = predicted protein sequences Protein sequences from TrEMBL mapped to the genome. All other tracks below are (start,end) TrEMBL annotations mapped to the genome using this track. This track is hidden by default. To show it, click its checkbox on the track configuration page.
UniProt Signal Peptides Regions found in proteins destined to be secreted, generally cleaved from mature protein.
UniProt Extracellular Domains Protein domains with the comment "Extracellular".
UniProt Transmembrane Domains Protein domains of the type "Transmembrane".
UniProt Cytoplasmic Domains Protein domains with the comment "Cytoplasmic".
UniProt Polypeptide Chains Polypeptide chain in mature protein after post-processing.
UniProt Regions of Interest Regions that have been experimentally defined, such as the role of a region in mediating protein-protein interactions or some other biological process.
UniProt Domains Protein domains, zinc finger regions and topological domains.
UniProt Disulfide Bonds Disulfide bonds.
UniProt Amino Acid Modifications Glycosylation sites, modified residues and lipid moiety-binding regions.
UniProt Amino Acid Mutations Mutagenesis sites and sequence variants.
UniProt Protein Primary/Secondary Structure Annotations Beta strands, helices, coiled-coil regions and turns.
UniProt Sequence Conflicts Differences between Genbank sequences and the UniProt sequence.
UniProt Repeats Regions of repeated sequence motifs or repeated domains.
UniProt Other Annotations All other annotations, e.g. compositional bias

For consistency and convenience for users of mutation-related tracks, the subtrack "UniProt/SwissProt Variants" is a copy of the track "UniProt Variants" in the track group "Phenotype and Literature", or "Variation and Repeats", depending on the assembly.

Display Conventions and Configuration

Genomic locations of UniProt/SwissProt annotations are labeled with a short name for the type of annotation (e.g. "glyco", "disulf bond", "Signal peptide" etc.). A click on them shows the full annotation and provides a link to the UniProt/SwissProt record for more details. TrEMBL annotations are always shown in light blue, except in the Signal Peptides, Extracellular Domains, Transmembrane Domains, and Cytoplamsic domains subtracks.

Mouse over a feature to see the full UniProt annotation comment. For variants, the mouse over will show the full name of the UniProt disease acronym.

The subtracks for domains related to subcellular location are sorted from outside to inside of the cell: Signal peptide, extracellular, transmembrane, and cytoplasmic.

In the "UniProt Modifications" track, lipoification sites are highlighted in dark blue, glycosylation sites in dark green, and phosphorylation in light green.

Duplicate annotations are removed as far as possible: if a TrEMBL annotation has the same genome position and same feature type, comment, disease and mutated amino acids as a SwissProt annotation, it is not shown again. Two annotations mapped through different protein sequence alignments but with the same genome coordinates are only shown once.

On the configuration page of this track, you can choose to hide any TrEMBL annotations. This filter will also hide the UniProt alternative isoform protein sequences because both types of information are less relevant to most users. Please contact us if you want more detailed filtering features.

Note that for the human hg38 assembly and SwissProt annotations, there also is a public track hub prepared by UniProt itself, with genome annotations maintained by UniProt using their own mapping method based on those Gencode/Ensembl gene models that are annotated in UniProt for a given protein. For proteins that differ from the genome, UniProt's mapping method will, in most cases, map a protein and its annotations to an unexpected location (see below for details on UCSC's mapping method).

Methods

Briefly, UniProt protein sequences were aligned to the transcripts associated with the protein, the top-scoring alignments were retained, and the result was projected to the genome through a transcript-to-genome alignment. Depending on the genome, the transcript-genome alignments was either provided by the source database (NBCI RefSeq), created at UCSC (UCSC RefSeq) or derived from the transcripts (Ensembl/Augustus). The transcript set is NCBI RefSeq for hg38, UCSC RefSeq for hg19 (due to alt/fix haplotype misplacements in the NCBI RefSeq set on hg19). For other genomes, RefSeq, Ensembl and Augustus are tried, in this order. The resulting protein-genome alignments of this process are available in the file formats for liftOver or pslMap from our data archive (see "Data Access" section below).

An important step of the mapping process is filtering the alignment from protein to transcript. Due to differences between the UniProt proteins and the transcripts and the genome, the best matching transcript is not always the correct transcript. Therefore, only for organisms that have a RefSeq transcript track, proteins are only aligned to the RefSeq transcripts that are annotated by UniProt for this protein. If no transcripts are annotated on the protein, or the annotated ones do not exist anymore, but a NCBI Gene ID is annotated, the RefSeq transcripts for the gene are used. If no NCBI Gene is annotated, then the best matching alignment is used. Only a handful of edge cases (pseudogenes, very recently added proteins) on hg38 remain where the global transcriptome-wide matches have to be used. The details page of the protein alignments shows the transcripts used for the mapping and how these transcripts were found. There can be multiple transcripts for one protein, as their coding sequences can be identical or several of them do not differ by more than 1% in alignment score.

In other words, when an NCBI or UCSC RefSeq track is used for the mapping and to align a protein sequence to the correct transcript, we use a three stage process:

  1. If UniProt has annotated a given RefSeq transcript for a given protein sequence, the protein is aligned to this transcript. Any difference in the version suffix is tolerated in this comparison.
  2. If no transcript is annotated or the transcript cannot be found in the NCBI/UCSC RefSeq track, the UniProt-annotated NCBI Gene ID is resolved to a set of NCBI RefSeq transcript IDs via the most current version of NCBI genes tables. Only the top match of the resulting alignments and all others within 1% of its score are used for the mapping.
  3. If no transcript can be found after step (2), the protein is aligned to all transcripts, the top match, and all others within 1% of its score are used.

This system was designed to resolve the problem of incorrect mappings of proteins, mostly on hg38, due to differences between the SwissProt sequences and the genome reference sequence, which has changed since the proteins were defined. The problem is most pronounced for gene families composed of either very repetitive or very similar proteins. To make sure that the alignments always go to the best chromosome location, all _alt and _fix reference patch sequences are ignored for the alignment, so the patches are entirely free of UniProt annotations. Please contact us if you have feedback on this process or example edge cases. We are not aware of a way to evaluate the results completely and in an automated manner.

Proteins were aligned to transcripts with TBLASTN, converted to PSL, filtered with pslReps (93% query coverage, keep alignments within top 1% score), lifted to genome positions with pslMap and filtered again with pslReps. UniProt annotations were obtained from the UniProt XML file. The UniProt annotations were then mapped to the genome through the alignment described above using the pslMap program. This approach draws heavily on the LS-SNP pipeline by Mark Diekhans. Like all Genome Browser source code, the main script used to build this track can be found on Github.

Automated data updates and release history

This track is automatically updated on an ongoing basis, every 2-3 months. The current version is always shown on the track details page, it includes the release of UniProt, the version of the transcript set and a unique MD5 that is based on the protein sequences, the transcript sequences, the mapping file between both and the transcript-genome alignment. The exact transcript that was used for the alignment is shown when clicking a protein alignment in one of the two alignment tracks.

For reproducibility of older analysis results, previous versions of this track are available for browsing in the form of the UCSC UniProt Archive Track Hub. The underlying data of all releases of this track (past and current) can be obtained from our downloads server, including the UniProt protein-to-genome alignment. The file formats available are in the command line programs liftOver or pslMap, which can be used to map coordinates on protein sequences to genome coordinates. The filenames are unipToGenome.over.chain.gz (liftOver) and unipToGenomeLift.psl.gz (pslMap).

Data Access

The raw data of the current track can be explored interactively with the Table Browser, or the Data Integrator. For automated analysis, the genome annotation is stored in a bigBed file that can be downloaded from the download server. The exact filenames can be found in the track configuration file. Annotations can be converted to ASCII text by our tool bigBedToBed which can be compiled from the source code or downloaded as a precompiled binary for your system. Instructions for downloading source code and binaries can be found here. The tool can also be used to obtain only features within a given range, for example:

bigBedToBed http://hgdownload.soe.ucsc.edu/gbdb/hg19/uniprot/unipStruct.bb -chrom=chr6 -start=0 -end=1000000 stdout

Please refer to our mailing list archives for questions, or our Data Access FAQ for more information.

Credits

This track was created by Maximilian Haeussler at UCSC, with a lot of input from Chris Lee, Mark Diekhans and Brian Raney, feedback from the UniProt staff, Alejo Mujica, Regeneron Pharmaceuticals and Pia Riestra, GeneDx. Thanks to UniProt for making all data available for download.

References

UniProt Consortium. Reorganizing the protein space at the Universal Protein Resource (UniProt). Nucleic Acids Res. 2012 Jan;40(Database issue):D71-5. PMID: 22102590; PMC: PMC3245120

Yip YL, Scheib H, Diemand AV, Gattiker A, Famiglietti LM, Gasteiger E, Bairoch A. The Swiss-Prot variant page and the ModSNP database: a resource for sequence and structure information on human protein variants. Hum Mutat. 2004 May;23(5):464-70. PMID: 15108278