Uniprot release 2014 08 brain anoxia

Headline ubiquitin caught at its own game

Ubiquitination is a widely used post-translational modification (PTM) in eukaryotic cells. It is involved in a plethora of cellular activities ranging from removal of misfolded and unwanted proteins to signaling in innate immunity, from transcriptional regulation to membrane trafficking. Ubiquitination is the covalent attachment of the small 76-residue protein ubiquitin onto a target protein, most often via an isopeptide bond between the amino group of a lysine side chain and ubiquitin C-terminus. This process occurs in several steps: an ubiquitin-activation step catalyzed by E1 enzymes, an ubiquitin-conjugation step catalyzed by E2 enzymes, and a step ensuring the target specificity involving E3 ligases.Brain anoxia


many different types of ubiquitination exist, monoubiquitination, multi(mono)ubiquitination and polyubiquitination, each type conveying a different signal. Polyubiquitination occurs via further ubiquitination of a single lysine residue on the substrate protein. Ubiquitin contains 7 ubiquitin lysines; each can serve as an acceptor for further elongation and each defines a distinct fate for the modified protein. The classic example is the lys-48-linked chain which targets the protein bearing it to degradation via the proteasome.

An additional step of complexity has been unveiled in 3 recent publications: ubiquitin was discovered to be itself subjected to another PTM, namely phosphorylation, which confers on it the ability to activate the E3 ubiquitin-protein ligase parkin ( PARK2).Brain anoxia

Parkin and the PINK1 kinase are involved in the signaling pathway leading to mitophagy, a specialized program which eliminates damaged mitochondria and hence maintains health. Indeed, defects in any of these proteins cause early-onset parkinson disease.

Under normal conditions, PINK1 is imported into mitochondria, where it is processed and rapidly degraded. When mitochondria lose membrane potential or amass unfolded proteins, PINK1 accumulates on the outer membrane where it recruits cytosolic parkin and activates its latent E3 activity. As a result, mitochondrial outer membrane proteins are ubiquitinated and the defective organelle is targeted for destruction.

It is in the parkin activation step that phosphorylated ubiquitin comes into play.Brain anoxia PINK1 directly phosphorylates ubiquitin at ser-65. Of note, parkin itself contains a ubiquitin-like domain that is also phosphorylated by PINK1 at ser-65. All three publications agree that phosphorylated ubiquitin is involved in the PINK1/PARK2 pathway. Nevertheless koyano and colleagues found that both ubiquitin and parkin ser-65 phosphorylations are needed for full parkin activation, whereas kane et al. Observed parkin activation with phospho-ubiquitin alone. While phospho-ubiquitin can be used by parkin as a substrate for ubiquitination, its parkin-binding and -activating abilities seem to be separated from its role as a substrate.

As of this release, human parkin, PINK1 and ubiquitin entries have been updated accordingly and annotations have been transferred to orthologous entries based on sequence similarity.Brain anoxia proteins known to undergo ubiquitination can be retrieved with the keyword ubl conjugation and proteins involved in the ubiquitination pathway, such as E1, E2 or E3 enzymes, with the keyword ubl conjugation pathway. UniProtKB news new variant types in homo_sapiens_variation.Txt.Gz on the uniprot FTP site

UniProt would like to announce the addition of two variant types, stop lost and stop gained, to the set of protein altering variants from the 1000 genomes project available in the homo_sapiens_variation.Txt.Gz file. Stop lost and stop gained variants have been selected as the first structural variants to be added to the uniprot variant catalogue because they are two of the most commonly occurring variant types.Brain anoxia uniprot expects to add further structural variant types and somatic variants to the available variant types and to include additional species. This file, along with the humsavar.Txt file, can now be found in the new dedicated variants directory in the uniprot FTP site. We very much welcome the feedback of the community on our efforts. Changes to the controlled vocabulary of human diseases

New diseases:

• abdominal obesity-metabolic syndrome 3

• aicardi-goutieres syndrome 7

• atrial fibrillation, familial, 15

• atrial standstill 2

• bardet-biedl syndrome 17

• bardet-biedl syndrome 18

• bosch-boonstra optic atrophy syndrome

• cone-rod dystrophy 19

• congenital anomalies of the kidney and urinary tract

• congenital heart defects, multiple types, 4

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• cortical dysplasia, complex, with other brain malformations 5

• cortical dysplasia, complex, with other brain malformations 6

• deafness, autosomal recessive, 101

• desbuquois dysplasia 2

• diarrhea 7

• epilepsy, idiopathic generalized 13

• epileptic encephalopathy, early infantile, 19

• epileptic encephalopathy, early infantile, 21

• epileptic encephalopathy, early infantile, 23

• hyperammonemia due to carbonic anhydrase VA deficiency

• ichthyosis, congenital, autosomal recessive 11

• immunodeficiency 22

• immunodeficiency 23

• immunodeficiency, common variable, 11

• melanocytic nevus syndrome, congenital

• melanosis, neurocutaneous

• mental retardation, autosomal dominant 24

• mental retardation, autosomal dominant 25

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• mental retardation, autosomal dominant 26

• mental retardation, autosomal dominant 27

• mental retardation, autosomal recessive 42

• mental retardation, autosomal recessive 43

• mental retardation, X-linked 99

• microcephaly, progressive, with seizures and cerebral and cerebellar atrophy

• microhydranencephaly

• mitochondrial complex III deficiency, nuclear 7

• mitochondrial complex III deficiency, nuclear 8

• moyamoya disease 6 with achalasia

• myasthenic syndrome, congenital, with pre- and postsynaptic defects

• nemaline myopathy 9

• nephronophthisis 18

• nephrotic syndrome 10

• olmsted syndrome, X-linked

• oocyte maturation defect

• pachyonychia congenita 3

• pachyonychia congenita 4

• pallister-hall syndrome 2

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• palmoplantar keratoderma, non-epidermolytic, focal or diffuse

• partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome

• polymicrogyria, bilateral perisylvian, autosomal recessive

• pontocerebellar hypoplasia 2E

• pontocerebellar hypoplasia 9

• pontocerebellar hypoplasia 10

• premature ovarian failure 8

• premature ovarian failure 9

• primary pigmented nodular adrenocortical disease 4

• pseudohyperkalemia, familial, 2, due to red cell leak

• renal hypodysplasia/aplasia 2

• sacral agenesis with vertebral anomalies

• seckel syndrome 8

• spermatogenic failure 13

• spermatogenic failure 14

• short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities

• short stature with microcephaly and distinctive facies

brain anoxia

• spinocerebellar ataxia, autosomal recessive, 16

• visceral myopathy

• white sponge nevus 2

Modified diseases:

• atrial standstill – atrial standstill 1

• dendritic cell monocyte lymphocyte B and natural killer lymphocyte deficiency – immunodeficiency 21

• desbuquois dysplasia – desbuquois dysplasia 1

• loeys-dietz syndrome 1A – loeys-dietz syndrome 1

• loeys-dietz syndrome 1B – loeys-dietz syndrome 2

• myopathy, distal, 2 – amyotrophic lateral sclerosis 21

• renal adysplasia – renal hypodysplasia/aplasia 1

• renal-coloboma syndrome – papillorenal syndrome

• severe myoclonic epilepsy in infancy – epileptic encephalopathy, early infantile, 6

• white sponge nevus of cannon – white sponge nevus 1

Deleted diseases:

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• ichthyosis, autosomal recessive, with hypotrichosis

• loeys-dietz syndrome 2A

• loeys-dietz syndrome 2B

Changes to the controlled vocabulary for ptms

New terms for the feature key ‘cross-link’ (‘CROSSLNK’ in the flat file):

• isoaspartyl glycine isopeptide (asn-gly)

• isoaspartyl glycine isopeptide (asp-gly)

Deleted terms:

• aspartyl isopeptide (asn)

• aspartyl isopeptide (asp)

Changes to keywords

Modified keyword:

• viral base plate protein – viral baseplate protein

Website news the uniprot website is changing

We would like to introduce you to the new uniprot website! We have been working on this site behind the scenes for a while and we’re glad it’s finally time to share it with you.

We redesigned the uniprot website following a user centered design process, involving over 250 users worldwide with varied research backgrounds and use cases.Brain anoxia user centered design is a design approach that is grounded in the requirements and expectations of users. They are included at every stage of the process, from gathering requirements to testing the end product.

Some highlights of the changes and improvements:

• A new homepage and advanced search functionality

• A new results page interface with easy to use filters

• A basket to store your favorite proteins and build up your own set

• new protein entry page content classification and navigation bar

• new tool output interfaces (e.G. BLAST results)

• new ‘proteomes’ pages for full protein sets from completely sequenced organisms

Contextual help is available on the site as well as uniprot help videos from the uniprot youtube channel.Brain anoxia we look forward to feedback from the scientific community to help improve the site further. This will take you to the BLAST page where you can edit options more.. Tools

• BLAST

• align

• retrieve/ID mapping

• peptide search

Core data

• protein knowledgebase (uniprotkb)

• sequence clusters (uniref)

• sequence archive (uniparc)

• proteomes

Supporting data

• literature citations

• taxonomy

• keywords

• subcellular locations

• cross-referenced databases

• diseases

Information

• about uniprot

• help

• FAQ

• uniprotkb manual

• technical corner

• expert biocuration