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Using organism:"Homo sapiens (Human) [9606]" as a query in uniprot returns about 146,000 proteins. I was under the impression that there were only 20-25,000 protein coding genes in the human genome. Is this something to do with splice isoforms, like those from SpliceProt, or another splice isoform database or tool?

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Well you are assuming one sequenced genome/proteome per NCBI tax id. That is no longer true. So if you click on the proteome filter it decreases by half. Which gets you into the 60,000 range. Now not all of these are "different" conceptual proteins, many are artifacts from the way GenBank/EMBL/DDBJ interact with the TrEMBL section of UniProtKB i.e. they are not normalized in db speak.

So for the human case you also want to add the Swiss-Prot filter to get a decent proteome that gives you about 20,000 proteins. Corresponding to the predicted/confirmed human gene count.

In all bioinformatics databases you need to pay attention to difference between database records and biological concepts. They rarely map cleanly one to one. In this case an UniProt record is not a protein, but information about a protein and a different record could have information about the same "protein". Or at least the same under some definitions of "same".

See the announcement of the draft human proteome in UniProtKB

The known isoforms are most often stored in the alternative products section of an UniProt entry. In some rare cases when the splice variant has a completly different biological function they are described in separate UniProt entries. For UniProtKB/Swiss-Prot Human there is a near 1 to 1 relation between genes and proteins. Cases as above and fusion proteins are the exceptions to this rule.

TrEMBL tries to automatically reduce redundancy in INSDC by auto merging entries in the same taxid and now proteome that have an identical reported sequence. However, variations of single gene products due to mutations and or limit what auto merging can do. For example there are 8 records for the P53 gene in TrEMBL today. Many of them from mutants, i.e. cancer genomes etc...

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    $\begingroup$ Since most proteins exist in more than one isoform, the number should be higher than 20.000. $\endgroup$ – Chris Jul 22 '15 at 14:25
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    $\begingroup$ @chris in UniProtKB isoforms do not get an independent record. See neXtProt for an isoform centric database of human proteins. $\endgroup$ – Jerven Jul 22 '15 at 14:27
  • $\begingroup$ Very insightful answer, thanks. To be clear, these some 100,000 isoforms and artefacts are coming from GenBank, EMBL and DDBJ and are presented as TrEMBL entries? $\endgroup$ – James Jul 22 '15 at 14:33
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    $\begingroup$ The key point is that there are more proteins than genes because so many genes exist in multiple splice forms. You should not expect number of genes and number of proteins to match up. $\endgroup$ – Jack Aidley Jul 23 '15 at 9:13
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There are 20+ thousand genes in the genome, but each of these can produce multiple proteins. In addition to this, you have protein fragments and cleavage products further increasing the number of entries.

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  • $\begingroup$ I was also hoping to find out specifically where or how uniprot finds the information on those additional products. $\endgroup$ – James Jul 22 '15 at 14:24
  • $\begingroup$ @GoodGravy Proteomics data I presume $\endgroup$ – WYSIWYG Jul 23 '15 at 9:28
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    $\begingroup$ @GoodGravy A lot of them come directly from papers and other databases like NCBI. For example, B7U540 is an entry originating from me (via NCBI, since I never submitted it directly to UniProt). $\endgroup$ – Devon Ryan Jul 23 '15 at 9:49

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