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Entry version 164 (18 Sep 2019)
Sequence version 1 (01 Jun 1998)
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Protein

TYRO protein tyrosine kinase-binding protein

Gene

TYROBP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Adapter protein which non-covalently associates with activating receptors found on the surface of a variety of immune cells to mediate signaling and cell activation following ligand binding by the receptors (PubMed:9490415, PubMed:9655483, PubMed:10604985). TYROBP is tyrosine-phosphorylated in the ITAM domain following ligand binding by the associated receptors which leads to activation of additional tyrosine kinases and subsequent cell activation (PubMed:9490415). Also has an inhibitory role in some cells (PubMed:21727189). Non-covalently associates with activating receptors of the CD300 family to mediate cell activation (PubMed:15557162, PubMed:16920917, PubMed:17928527; PubMed:26221034). Also mediates cell activation through association with activating receptors of the CD200R family (By similarity). Required for neutrophil activation mediated by integrin (By similarity). Required for the activation of myeloid cells mediated by the CLEC5A/MDL1 receptor (PubMed:10449773). Associates with natural killer (NK) cell receptors such as KIR2DS2 and the KLRD1/KLRC2 heterodimer to mediate NK cell activation (PubMed:9490415, PubMed:9655483, PubMed:23715743). Also enhances trafficking and cell surface expression of NK cell receptors KIR2DS1, KIR2DS2 and KIR2DS4 and ensures their stability at the cell surface (PubMed:23715743). Associates with SIRPB1 to mediate activation of myeloid cells such as monocytes and dendritic cells (PubMed:10604985). Associates with TREM1 to mediate activation of neutrophils and monocytes (PubMed:10799849). Associates with TREM2 on monocyte-derived dendritic cells to mediate up-regulation of chemokine receptor CCR7 and dendritic cell maturation and survival (PubMed:11602640). Association with TREM2 mediates cytokine-induced formation of multinucleated giant cells which are formed by the fusion of macrophages (PubMed:18957693). Stabilizes the TREM2 C-terminal fragment (TREM2-CTF) produced by TREM2 ectodomain shedding which suppresses the release of pro-inflammatory cytokines (PubMed:25957402). In microglia, required with TREM2 for phagocytosis of apoptotic neurons (By similarity). Required with ITGAM/CD11B in microglia to control production of microglial superoxide ions which promote the neuronal apoptosis that occurs during brain development (By similarity). Promotes proinflammatory responses in microglia following nerve injury which accelerates degeneration of injured neurons (By similarity). Positively regulates the expression of the IRAK3/IRAK-M kinase and IL10 production by liver dendritic cells and inhibits their T cell allostimulatory ability (By similarity). Negatively regulates B cell proliferation (PubMed:21727189). Required for CSF1-mediated osteoclast cytoskeletal organization (By similarity). Positively regulates multinucleation during osteoclast development (By similarity).By similarity14 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi50Metal cation; shared with neighboring subunit in homooligomer1 Publication1
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections (‘Function’, ‘PTM / Processing’, ‘Pathology and Biotech’) according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei54Important for interaction with transmembrane receptors1 Publication1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Biological processImmunity
LigandMetal-binding

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-2172127 DAP12 interactions
R-HSA-2424491 DAP12 signaling
R-HSA-391160 Signal regulatory protein family interactions
R-HSA-416700 Other semaphorin interactions
R-HSA-6798695 Neutrophil degranulation

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...
SignaLinki
O43914

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
TYRO protein tyrosine kinase-binding proteinImported
Alternative name(s):
DNAX-activation protein 121 Publication
Killer-activating receptor-associated protein
Short name:
KAR-associated protein
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:TYROBPImported
Synonyms:DAP121 Publication, KARAPBy similarity
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 19

Organism-specific databases

Human Gene Nomenclature Database

More...
HGNCi
HGNC:12449 TYROBP

Online Mendelian Inheritance in Man (OMIM)

More...
MIMi
604142 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_O43914

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini22 – 40Extracellular1 PublicationAdd BLAST19
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei41 – 61Helical1 PublicationAdd BLAST21
Topological domaini62 – 113Cytoplasmic1 PublicationAdd BLAST52

Keywords - Cellular componenti

Cell membrane, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 (PLOSL1)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA recessively inherited disease characterized by presenile dementia along with large-scale destruction of cancellous bones. Initial symptoms, starting in the twenties, are pain and swelling resulting from cysts in the wrists and ankles. Extremity bone fractures could occur with minor trauma. At around 30 years of age, patients gradually develop neuropsychiatric symptoms, including epileptic seizures, agnosia, apraxia, speech disorder, memory disturbance, euphoria, and loss of social inhibitions. The disorder usuallly leads to death in the fifth decade of life.
Related information in OMIM

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi41G → L: Does not significantly alter the formation of homotrimers or homotetramers; when associated with L-45 and L-49. 1 Publication1
Mutagenesisi45G → L: Does not significantly alter the formation of homotrimers or homotetramers; when associated with L-41 and L-49. 1 Publication1
Mutagenesisi49G → L: Does not significantly alter the formation of homotrimers or homotetramers; when associated with L-41 and L-45. 1 Publication1
Mutagenesisi50D → A: Reduced cell surface expression of KIR2DS1. Severely impairs formation of homotrimers and homotetramers. Abolishes interaction with TREM2 and stabilization of TREM2-CTF. 3 Publications1
Mutagenesisi50D → E or Q: Severely impairs formation of homotrimers and homotetramers. 1 Publication1
Mutagenesisi50D → N: Reduces formation of homotrimers and homotetramers. 1 Publication1
Mutagenesisi54T → A: Reduced interaction with KLRC2 and KIR2DS3. Reduces homotrimer formation and increases homotetramer formation. 2 Publications1

Organism-specific databases

DisGeNET

More...
DisGeNETi
7305

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...
GeneReviewsi
TYROBP

MalaCards human disease database

More...
MalaCardsi
TYROBP
MIMi221770 phenotype

Open Targets

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OpenTargetsi
ENSG00000011600

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
2770 Nasu-Hakola disease

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...
PharmGKBi
PA37100

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

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Pharosi
O43914

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
TYROBP

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 21Sequence analysisAdd BLAST21
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000002260322 – 113TYRO protein tyrosine kinase-binding proteinAdd BLAST92

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi35InterchainCombined sources2 Publications
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei91PhosphotyrosineBy similarity1
Modified residuei102PhosphotyrosineBy similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Following ligand binding by associated receptors, tyrosine phosphorylated in the ITAM domain which leads to activation of additional tyrosine kinases and subsequent cell activation.1 Publication

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
O43914

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
O43914

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
O43914

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
O43914

PeptideAtlas

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PeptideAtlasi
O43914

PRoteomics IDEntifications database

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PRIDEi
O43914

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
26198
49229 [O43914-1]
49230 [O43914-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
O43914

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
O43914

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed at low levels in the early development of the hematopoietic system and in the promonocytic stage and at high levels in mature monocytes. Expressed in hematological cells and tissues such as peripheral blood leukocytes and spleen. Also found in bone marrow, lymph nodes, placenta, lung and liver. Expressed at lower levels in different parts of the brain especially in the basal ganglia and corpus callosum.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000011600 Expressed in 216 organ(s), highest expression level in blood

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
O43914 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
O43914 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
CAB009493
HPA041899

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer; disulfide-linked (PubMed:20890284). Homotrimer; disulfide-linked (PubMed:25981043). Homotetramer; disulfide-linked (PubMed:25981043). Homotrimers and homotetramers form when low levels of partner receptors are available and are competitive with assembly with interacting receptors (PubMed:25981043). They may represent alternative oligomerization states or may be intermediates in the receptor assembly process (PubMed:25981043). Binding of a metal cation aids in homooligomerization through coordination of the metal ion by the subunits of the oligomer (PubMed:25981043).

Interacts with TREM1 (PubMed:10799849).

Interacts with TREM2 (PubMed:11602640, PubMed:25957402).

Interacts with SIRPB1 (PubMed:10604985).

Interacts with CLECSF5 (PubMed:10449773).

Interacts with SIGLEC14 (PubMed:17012248).

Interacts with CD300LB and CD300E (PubMed:15557162, PubMed:16920917, PubMed:17928527).

Interacts with CD300C2 (By similarity).

Interacts (via ITAM domain) with SYK (via SH2 domains); activates SYK mediating neutrophil and macrophage integrin-mediated activation (By similarity).

Interacts with KLRC2, KIR2DS3 and KIR2DS5 (PubMed:18624290, PubMed:20890284).

Interacts with CD300H (PubMed:26221034).

Interacts with KIR2DS1 (PubMed:23715743).

Interacts with KLRD1 (PubMed:9655483).

By similarity15 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
113155, 19 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
O43914

Protein interaction database and analysis system

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IntActi
O43914, 14 interactors

STRING: functional protein association networks

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STRINGi
9606.ENSP00000262629

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1113
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
O43914

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
O43914

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini80 – 108ITAMAdd BLAST29

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the TYROBP family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
ENOG410J1XS Eukaryota
ENOG410Z4TN LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00390000016786

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000056440

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
O43914

KEGG Orthology (KO)

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KOi
K07992

Database of Orthologous Groups

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OrthoDBi
1508977at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
O43914

TreeFam database of animal gene trees

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TreeFami
TF336898

Family and domain databases

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR026200 Tyrobp

The PANTHER Classification System

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PANTHERi
PTHR17554 PTHR17554, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O43914-1) [UniParc]FASTAAdd to basket
Also known as: KARAP-a

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MGGLEPCSRL LLLPLLLAVS GLRPVQAQAQ SDCSCSTVSP GVLAGIVMGD
60 70 80 90 100
LVLTVLIALA VYFLGRLVPR GRGAAEAATR KQRITETESP YQELQGQRSD
110
VYSDLNTQRP YYK
Length:113
Mass (Da):12,179
Last modified:June 1, 1998 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i267CB1C1756F89F0
GO
Isoform 2 (identifier: O43914-2) [UniParc]FASTAAdd to basket
Also known as: KARAP-b

The sequence of this isoform differs from the canonical sequence as follows:
     77-77: Missing.

Show »
Length:112
Mass (Da):12,108
Checksum:iD89003C4B50874D0
GO
Isoform 3 (identifier: O43914-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     20-30: Missing.

Note: No experimental confirmation available.
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Length:102
Mass (Da):11,043
Checksum:i4DB742FB830E8C48
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
X6RGC9X6RGC9_HUMAN
TYRO protein tyrosine kinase-bindin...
TYROBP
101Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
K7ES93K7ES93_HUMAN
TYRO protein tyrosine kinase-bindin...
TYROBP
144Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
K7EKK0K7EKK0_HUMAN
TYRO protein tyrosine kinase-bindin...
TYROBP
35Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_0813982G → E Found in patients with early-onset Alzheimer disease; unknown pathological significance; associated in cis with L-55 in some patients. 1 PublicationCorresponds to variant dbSNP:rs200649978Ensembl.1
Natural variantiVAR_08139923R → C Found in patients with early-onset Alzheimer disease; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs769635655Ensembl.1
Natural variantiVAR_08140047V → A Found in patients with early-onset Alzheimer disease; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs372140827Ensembl.1
Natural variantiVAR_08140150D → DPADGRLVLGDRDGR Found in patients with early-onset Alzheimer disease; unknown pathological significance; causes reduced expression; also leads to reduced expression of TREM2. 1 Publication1
Natural variantiVAR_08140255V → L Found in patients with early-onset Alzheimer disease; unknown pathological significance; associated in cis with E-2 in some patients. 2 PublicationsCorresponds to variant dbSNP:rs77782321EnsemblClinVar.1
Natural variantiVAR_08140380R → W Found in patients with early-onset Alzheimer disease; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs140188939EnsemblClinVar.1
Natural variantiVAR_08140484I → V Found in patients with early-onset Alzheimer disease; unknown pathological significance. 1 Publication1
Natural variantiVAR_08140589S → L Found in patients with early-onset Alzheimer disease; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs557854792Ensembl.1
Natural variantiVAR_011985111Y → H. Corresponds to variant dbSNP:rs14714Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_04606620 – 30Missing in isoform 3. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_01290977Missing in isoform 2. 3 Publications1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
AF019562 mRNA Translation: AAD09436.1
AF019563 Genomic DNA Translation: AAD09437.1
AJ010098 mRNA Translation: CAB52288.1
AY074782 mRNA Translation: AAL74017.1
BT009851 mRNA Translation: AAP88853.1
AK290385 mRNA Translation: BAF83074.1
CR450342 mRNA Translation: CAG29338.1
CR542202 mRNA Translation: CAG46999.1
BP295666 mRNA No translation available.
AD000833 Genomic DNA No translation available.
AD000864 Genomic DNA No translation available.
BC011175 mRNA Translation: AAH11175.1

The Consensus CDS (CCDS) project

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CCDSi
CCDS12482.1 [O43914-1]
CCDS46058.1 [O43914-2]
CCDS54255.1 [O43914-3]

NCBI Reference Sequences

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RefSeqi
NP_001166985.1, NM_001173514.1 [O43914-3]
NP_003323.1, NM_003332.3 [O43914-1]
NP_937758.1, NM_198125.2 [O43914-2]

Genome annotation databases

Ensembl eukaryotic genome annotation project

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Ensembli
ENST00000262629; ENSP00000262629; ENSG00000011600 [O43914-1]
ENST00000544690; ENSP00000445332; ENSG00000011600 [O43914-3]
ENST00000589517; ENSP00000468447; ENSG00000011600 [O43914-2]

Database of genes from NCBI RefSeq genomes

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GeneIDi
7305

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:7305

UCSC genome browser

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UCSCi
uc002ocm.4 human [O43914-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF019562 mRNA Translation: AAD09436.1
AF019563 Genomic DNA Translation: AAD09437.1
AJ010098 mRNA Translation: CAB52288.1
AY074782 mRNA Translation: AAL74017.1
BT009851 mRNA Translation: AAP88853.1
AK290385 mRNA Translation: BAF83074.1
CR450342 mRNA Translation: CAG29338.1
CR542202 mRNA Translation: CAG46999.1
BP295666 mRNA No translation available.
AD000833 Genomic DNA No translation available.
AD000864 Genomic DNA No translation available.
BC011175 mRNA Translation: AAH11175.1
CCDSiCCDS12482.1 [O43914-1]
CCDS46058.1 [O43914-2]
CCDS54255.1 [O43914-3]
RefSeqiNP_001166985.1, NM_001173514.1 [O43914-3]
NP_003323.1, NM_003332.3 [O43914-1]
NP_937758.1, NM_198125.2 [O43914-2]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2L34NMR-A/B35-67[»]
2L35NMR-A35-67[»]
B35-66[»]
4WO1X-ray2.14A/B/C/D35-67[»]
4WOLX-ray1.77A/B/C35-67[»]
SMRiO43914
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGridi113155, 19 interactors
CORUMiO43914
IntActiO43914, 14 interactors
STRINGi9606.ENSP00000262629

PTM databases

iPTMnetiO43914
PhosphoSitePlusiO43914

Polymorphism and mutation databases

BioMutaiTYROBP

Proteomic databases

EPDiO43914
jPOSTiO43914
MassIVEiO43914
PaxDbiO43914
PeptideAtlasiO43914
PRIDEiO43914
ProteomicsDBi26198
49229 [O43914-1]
49230 [O43914-2]

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
7305

Genome annotation databases

EnsembliENST00000262629; ENSP00000262629; ENSG00000011600 [O43914-1]
ENST00000544690; ENSP00000445332; ENSG00000011600 [O43914-3]
ENST00000589517; ENSP00000468447; ENSG00000011600 [O43914-2]
GeneIDi7305
KEGGihsa:7305
UCSCiuc002ocm.4 human [O43914-1]

Organism-specific databases

Comparative Toxicogenomics Database

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CTDi
7305
DisGeNETi7305

GeneCards: human genes, protein and diseases

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GeneCardsi
TYROBP
GeneReviewsiTYROBP
HGNCiHGNC:12449 TYROBP
HPAiCAB009493
HPA041899
MalaCardsiTYROBP
MIMi221770 phenotype
604142 gene
neXtProtiNX_O43914
OpenTargetsiENSG00000011600
Orphaneti2770 Nasu-Hakola disease
PharmGKBiPA37100

GenAtlas: human gene database

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GenAtlasi
Search...

Phylogenomic databases

eggNOGiENOG410J1XS Eukaryota
ENOG410Z4TN LUCA
GeneTreeiENSGT00390000016786
HOGENOMiHOG000056440
InParanoidiO43914
KOiK07992
OrthoDBi1508977at2759
PhylomeDBiO43914
TreeFamiTF336898

Enzyme and pathway databases

ReactomeiR-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-2172127 DAP12 interactions
R-HSA-2424491 DAP12 signaling
R-HSA-391160 Signal regulatory protein family interactions
R-HSA-416700 Other semaphorin interactions
R-HSA-6798695 Neutrophil degranulation
SignaLinkiO43914

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

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ChiTaRSi
TYROBP human
EvolutionaryTraceiO43914

The Gene Wiki collection of pages on human genes and proteins

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GeneWikii
TYROBP

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

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GenomeRNAii
7305
PharosiO43914

Protein Ontology

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PROi
PR:O43914

The Stanford Online Universal Resource for Clones and ESTs

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SOURCEi
Search...

Gene expression databases

BgeeiENSG00000011600 Expressed in 216 organ(s), highest expression level in blood
ExpressionAtlasiO43914 baseline and differential
GenevisibleiO43914 HS

Family and domain databases

InterProiView protein in InterPro
IPR026200 Tyrobp
PANTHERiPTHR17554 PTHR17554, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

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ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiTYOBP_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: O43914
Secondary accession number(s): A8K2X0
, F5H389, Q6FGA5, Q9UMT3
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: June 1, 1998
Last modified: September 18, 2019
This is version 164 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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