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O43914 (TYOBP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
TYRO protein tyrosine kinase-binding protein
Alternative name(s):
DNAX-activation protein 12
Killer-activating receptor-associated protein
Short name=KAR-associated protein
Gene names
Name:TYROBP
Synonyms:DAP12, KARAP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length113 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Non-covalently associates with activating receptors of the CD300 family. Cross-linking of CD300-TYROBP complexes results in cellular activation. Involved for instance in neutrophil activation mediated by integrin.

Subunit structure

Homodimer; disulfide-linked. Interacts with SIRPB1 and TREM1. Interacts with CLECSF5. Interacts with SIGLEC14. Interacts with CD300LB and CD300E. Interacts with CD300D By similarity. Interacts (via ITAM domain) with SYK (via SH2 domains); activates SYK mediating neutrophils and macrophages integrin-mediated activation By similarity. Interacts with KLRC2 and KIR2DS3. Ref.10 Ref.12 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

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. Ref.14

Post-translational modification

Tyrosine phosphorylated.

Involvement in disease

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) [MIM:221770]: Recessively inherited disease characterized by a combination of psychotic symptoms rapidly progressing to presenile dementia and bone cysts restricted to wrists and ankles. PLOSL has a global distribution, although most of the patients have been diagnosed in Finland and Japan, with an estimated population prevalence of 2x10(-6) in the Finns.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.13

Sequence similarities

Belongs to the TYROBP family.

Contains 1 ITAM domain.

Ontologies

Keywords
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   PTMDisulfide bond
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaxon guidance

Traceable author statement. Source: Reactome

cellular defense response

Traceable author statement Ref.1. Source: ProtInc

innate immune response

Traceable author statement. Source: Reactome

integrin-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Traceable author statement Ref.1. Source: ProtInc

macrophage activation involved in immune response

Inferred from electronic annotation. Source: Ensembl

neutrophil activation involved in immune response

Inferred from electronic annotation. Source: Ensembl

regulation of immune response

Traceable author statement. Source: Reactome

regulation of osteoclast development

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentcell surface

Inferred from direct assay PubMed 15294961. Source: UniProtKB

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionidentical protein binding

Inferred from physical interaction Ref.20. Source: IntAct

receptor binding

Inferred from physical interaction PubMed 15294961. Source: UniProtKB

receptor signaling protein activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O43914-1)

Also known as: KARAP-a;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O43914-2)

Also known as: KARAP-b;

The sequence of this isoform differs from the canonical sequence as follows:
     77-77: Missing.
Isoform 3 (identifier: O43914-3)

The sequence of this isoform differs from the canonical sequence as follows:
     20-30: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 11392TYRO protein tyrosine kinase-binding protein
PRO_0000022603

Regions

Topological domain22 – 4019Extracellular Potential
Transmembrane41 – 6121Helical; Potential
Topological domain62 – 11352Cytoplasmic Potential
Domain80 – 10829ITAM

Sites

Site541Important for interaction with transmembrane receptors

Amino acid modifications

Modified residue911Phosphotyrosine By similarity
Modified residue1021Phosphotyrosine By similarity
Disulfide bond35Interchain Ref.20

Natural variations

Alternative sequence20 – 3011Missing in isoform 3.
VSP_046066
Alternative sequence771Missing in isoform 2.
VSP_012909
Natural variant1111Y → H.
Corresponds to variant rs14714 [ dbSNP | Ensembl ].
VAR_011985

Experimental info

Mutagenesis541T → A: Reduced interaction with KLRC2 and KIR2DS3. Ref.20

Secondary structure

... 113
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (KARAP-a) [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: 267CB1C1756F89F0

FASTA11312,179
        10         20         30         40         50         60 
MGGLEPCSRL LLLPLLLAVS GLRPVQAQAQ SDCSCSTVSP GVLAGIVMGD LVLTVLIALA 

        70         80         90        100        110 
VYFLGRLVPR GRGAAEAATR KQRITETESP YQELQGQRSD VYSDLNTQRP YYK 

« Hide

Isoform 2 (KARAP-b) [UniParc].

Checksum: D89003C4B50874D0
Show »

FASTA11212,108
Isoform 3 [UniParc].

Checksum: 4DB742FB830E8C48
Show »

FASTA10211,043

References

« Hide 'large scale' references
[1]"Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells."
Lanier L.L., Corliss B.C., Wu J., Leong C., Phillips J.H.
Nature 391:703-707(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[2]"Killer activating receptor associated protein isoform b."
Cantoni C., Biassoni R.
Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Lymphoid tissue.
[3]"Dendritic cells express two types of immunoreceptor DAP12 transcripts."
Begum N.A., Seya T.
Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Umbilical cord blood.
[6]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]"Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes."
Kimura K., Wakamatsu A., Suzuki Y., Ota T., Nishikawa T., Yamashita R., Yamamoto J., Sekine M., Tsuritani K., Wakaguri H., Ishii S., Sugiyama T., Saito K., Isono Y., Irie R., Kushida N., Yoneyama T., Otsuka R. expand/collapse author list , Kanda K., Yokoi T., Kondo H., Wagatsuma M., Murakawa K., Ishida S., Ishibashi T., Takahashi-Fujii A., Tanase T., Nagai K., Kikuchi H., Nakai K., Isogai T., Sugano S.
Genome Res. 16:55-65(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Macrophage.
[8]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[10]"Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells."
Bakker A.B.H., Baker E., Sutherland G.R., Phillips J.H., Lanier L.L.
Proc. Natl. Acad. Sci. U.S.A. 96:9792-9796(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CLECSF5.
[11]"Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts."
Paloneva J., Kestilae M., Wu J., Salminen A., Boehling T., Ruotsalainen V., Hakola P., Bakker A.B.H., Phillips J.H., Pekkarinen P., Lanier L.L., Timonen T., Peltonen L.
Nat. Genet. 25:357-361(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: DISEASE.
[12]"Inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes."
Bouchon A., Dietrich J., Colonna M.
J. Immunol. 164:4991-4995(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TREM1.
[13]"Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): three genetic forms."
Kondo T., Takahashi K., Kohara N., Takahashi Y., Hayashi S., Takahashi H., Matsuo H., Yamazaki M., Inoue K., Miyamoto K., Yamamura T.
Neurology 59:1105-1107(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: DISEASE.
[14]"TREM-1, MDL-1, and DAP12 expression is associated with a mature stage of myeloid development."
Gingras M.-C., Lapillonne H., Margolin J.F.
Mol. Immunol. 38:817-824(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[15]"Molecular characterization of a novel immune receptor restricted to the monocytic lineage."
Aguilar H., Alvarez-Errico D., Garcia-Montero A.C., Orfao A., Sayos J., Lopez-Botet M.
J. Immunol. 173:6703-6711(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CD300E.
[16]"Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates."
Angata T., Hayakawa T., Yamanaka M., Varki A., Nakamura M.
FASEB J. 20:1964-1973(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SIGLEC14.
[17]"Molecular and functional characterization of CD300b, a new activating immunoglobulin receptor able to transduce signals through two different pathways."
Martinez-Barriocanal A., Sayos J.
J. Immunol. 177:2819-2830(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CD300LB.
[18]"Analysis of mouse LMIR5/CLM-7 as an activating receptor: differential regulation of LMIR5/CLM-7 in mouse versus human cells."
Yamanishi Y., Kitaura J., Izawa K., Matsuoka T., Oki T., Lu Y., Shibata F., Yamazaki S., Kumagai H., Nakajima H., Maeda-Yamamoto M., Tybulewicz V.L.J., Takai T., Kitamura T.
Blood 111:688-698(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CD300LB.
[19]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"The structural basis for intramembrane assembly of an activating immunoreceptor complex."
Call M.E., Wucherpfennig K.W., Chou J.J.
Nat. Immunol. 11:1023-1029(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 35-67 IN COMPLEX WITH KLRC2, SUBUNIT, DISULFIDE BOND, MUTAGENESIS OF THR-54, INTERACTION WITH KLRC2 AND KIR2DS3.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001166985.1. NM_001173514.1.
NP_003323.1. NM_003332.3.
NP_937758.1. NM_198125.2.
UniGeneHs.515369.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2L34NMR-A/B35-67[»]
2L35NMR-A35-67[»]
B35-66[»]
ProteinModelPortalO43914.
SMRO43914. Positions 35-67.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113155. 7 interactions.
IntActO43914. 8 interactions.
STRING9606.ENSP00000262629.

PTM databases

PhosphoSiteO43914.

Proteomic databases

PaxDbO43914.
PRIDEO43914.

Protocols and materials databases

DNASU7305.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262629; ENSP00000262629; ENSG00000011600. [O43914-1]
ENST00000544690; ENSP00000445332; ENSG00000011600. [O43914-3]
ENST00000589517; ENSP00000468447; ENSG00000011600. [O43914-2]
GeneID7305.
KEGGhsa:7305.
UCSCuc002ocm.3. human. [O43914-1]
uc002ocn.3. human. [O43914-2]

Organism-specific databases

CTD7305.
GeneCardsGC19M036395.
HGNCHGNC:12449. TYROBP.
HPACAB009493.
HPA041899.
MIM221770. phenotype.
604142. gene.
neXtProtNX_O43914.
Orphanet2770. Nasu-Hakola disease.
PharmGKBPA37100.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG44707.
HOGENOMHOG000056440.
HOVERGENHBG061468.
InParanoidO43914.
KOK07992.
PhylomeDBO43914.
TreeFamTF336898.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111155. Cell-Cell communication.
REACT_6900. Immune System.
SignaLinkO43914.

Gene expression databases

ArrayExpressO43914.
BgeeO43914.
CleanExHS_TYROBP.
GenevestigatorO43914.

Family and domain databases

InterProIPR026200. Tyrobp.
[Graphical view]
PANTHERPTHR17554:SF0. PTHR17554:SF0. 1 hit.
ProtoNetSearch...

Other

ChiTaRSTYROBP. human.
EvolutionaryTraceO43914.
GeneWikiTYROBP.
GenomeRNAi7305.
NextBio28562.
PROO43914.
SOURCESearch...

Entry information

Entry nameTYOBP_HUMAN
AccessionPrimary (citable) accession number: O43914
Secondary accession number(s): A8K2X0 expand/collapse secondary AC list , F5H389, Q6FGA5, Q9UMT3
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: June 1, 1998
Last modified: April 16, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM