O43914 (TYOBP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	113 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon guidance Traceable author statement. Source: Reactome cellular defense response Traceable author statement Ref.1. Source: ProtInc integrin-mediated signaling pathway Inferred from electronic annotation. Source: Compara intracellular signal transduction Traceable author statement Ref.1. Source: ProtInc macrophage activation involved in immune response Inferred from electronic annotation. Source: Compara neutrophil activation involved in immune response Inferred from electronic annotation. Source: Compara regulation of immune response Traceable author statement. Source: Reactome
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	receptor signaling protein activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-2214794,EBI-2214794
KLRC2	P26717	2	EBI-2214794,EBI-3862171
SIRPB1	O00241	4	EBI-2214794,EBI-2615458

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Potential

Chain

22 – 113

92

TYRO protein tyrosine kinase-binding protein

PRO_0000022603

Regions

Topological domain

22 – 40

19

Extracellular Potential

Transmembrane

41 – 61

21

Helical; Potential

Topological domain

62 – 113

52

Cytoplasmic Potential

Domain

80 – 108

29

ITAM

Sites

Site

54

1

Important for interaction with transmembrane receptors

Amino acid modifications

Modified residue

91

1

Phosphotyrosine By similarity

Modified residue

102

1

Phosphotyrosine By similarity

Disulfide bond

35

Interchain Ref.20

Natural variations

Alternative sequence

20 – 30

11

Missing in isoform 3.

VSP_046066

Alternative sequence

77

1

Missing in isoform 2.

VSP_012909

Natural variant

111

1

Y → H.
Corresponds to variant rs14714 [ dbSNP | Ensembl ].

VAR_011985

Experimental info

Mutagenesis

54

1

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

Secondary structure

1

.

.

.

113

Helix Strand Turn

Details...

Helix

41 – 64

24

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (KARAP-a) [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 267CB1C1756F89F0	FASTA	113	12,179
	10 20 30 40 50 60 MGGLEPCSRL LLLPLLLAVS GLRPVQAQAQ SDCSCSTVSP GVLAGIVMGD LVLTVLIALA 70 80 90 100 110 VYFLGRLVPR GRGAAEAATR KQRITETESP YQELQGQRSD VYSDLNTQRP YYK
	Isoform 2 (KARAP-b) [UniParc]. Checksum: D89003C4B50874D0	FASTA	112	12,108
	10 20 30 40 50 60 MGGLEPCSRL LLLPLLLAVS GLRPVQAQAQ SDCSCSTVSP GVLAGIVMGD LVLTVLIALA 70 80 90 100 110 VYFLGRLVPR GRGAAEATRK QRITETESPY QELQGQRSDV YSDLNTQRPY YK
	Isoform 3 [UniParc]. Checksum: 4DB742FB830E8C48	FASTA	102	11,043
	10 20 30 40 50 60 MGGLEPCSRL LLLPLLLAVS DCSCSTVSPG VLAGIVMGDL VLTVLIALAV YFLGRLVPRG 70 80 90 100 RGAAEAATRK QRITETESPY QELQGQRSDV YSDLNTQRPY YK

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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

GeneReviews

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.

IPI

IPI00015144.
IPI00384633.
IPI00956488.

RefSeq

NP_001166985.1. NM_001173514.1.
NP_003323.1. NM_003332.3.
NP_937758.1. NM_198125.2.

UniGene

Hs.515369.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2L34	NMR	-	A/B	35-67	[»]
2L35	NMR	-	A	35-67	[»]
			B	35-66	[»]

ProteinModelPortal

O43914.

ModBase

Search...

Protein-protein interaction databases

IntAct

O43914. 8 interactions.

STRING

9606.ENSP00000262629.

PTM databases

PhosphoSite

O43914.

Proteomic databases

PaxDb

O43914.

PRIDE

O43914.

Protocols and materials databases

DNASU

7305.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262629; ENSP00000262629; ENSG00000011600.
ENST00000544690; ENSP00000445332; ENSG00000011600.
ENST00000589517; ENSP00000468447; ENSG00000011600.

GeneID

7305.

KEGG

hsa:7305.

UCSC

uc002ocm.3. human.
uc002ocn.3. human.

Organism-specific databases

CTD

7305.

GeneCards

GC19M036395.

HGNC

HGNC:12449. TYROBP.

HPA

CAB009493.
HPA041899.

MIM

221770. phenotype.
604142. gene.

neXtProt

NX_O43914.

Orphanet

2770. Polycystic lipomembranous osteodysplasia - sclerosing leukoencephalopathy.

PharmGKB

PA37100.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG44707.

HOGENOM

HOG000056440.

HOVERGEN

HBG061468.

InParanoid

O43914.

KO

K07992.

OMA

NTQRPYY.

PhylomeDB

O43914.

Enzyme and pathway databases

Reactome

REACT_111045. Developmental Biology.
REACT_111155. Cell-Cell communication.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

O43914.

Bgee

O43914.

CleanEx

HS_TYROBP.

Genevestigator

O43914.

GermOnline

ENSG00000011600. Homo sapiens.

Family and domain databases

InterPro

IPR026200. Tyrobp.
[Graphical view]

PANTHER

PTHR17554. PTHR17554. 1 hit.

PROSITE

PS51055. ITAM_1. False negative.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

TYROBP. human.

EvolutionaryTrace

O43914.

GenomeRNAi

7305.

NextBio

28562.

SOURCE

Search...

Entry information

Entry name

TYOBP_HUMAN

Accession

Primary (citable) accession number: O43914
Secondary accession number(s): A8K2X0 , F5H389, Q6FGA5, Q9UMT3

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	June 1, 1998
Last modified:	May 1, 2013
This is version 112 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.