Q9H1C4 (UN93B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein unc-93 homolog B1
Short name=Unc-93B1
Short name=hUNC93B1

Gene names

Name:	UNC93B1
Synonyms:	UNC93, UNC93B

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	597 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays an important role in innate and adaptive immunity by regulating nucleotide-sensing Toll-like receptor (TLR) signaling. Required for the transport of a subset of TLRs (including TLR3, TLR7 and TLR9) from the endoplasmic reticulum to endolysosomes where they can engage pathogen nucleotides and activate signaling cascades. May play a role in autoreactive B-cells removal. Ref.8
Subunit structure	Interacts with TLR3, TLR7, and TLR9 (probably via transmembrane domain) By similarity.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein By similarity. Endosome By similarity. Lysosome By similarity. Cytoplasmic vesicle › phagosome By similarity. Note: Relocalizes from endoplasmic reticulum to endosome and lysosome upon cell-stimulation with CpG dinucleotides By similarity. Colocalizes with LAMP5 in large endosomal intracellular vesicles. Ref.7 Ref.11
Tissue specificity	Expressed in plasmocytoid dendritic cells (at protein level). Highly expressed in antigen-presenting cells. Expressed in heart, and at lower level in kidney. Expressed at low level in other tissues. Ref.1 Ref.7 Ref.11
Induction	Up-regulated by TLRs agonists. Ref.7
Post-translational modification	N-glycosylated By similarity.
Involvement in disease	Herpes simplex encephalitis 1 (HSE1) [MIM:610551]: A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Mutations in UNC93B1 resulting in autosomal recessive UNC93B1 deficieny predispose otherwise healthy individuals to isolated herpes simplex encephalitis due to impaired IFNs production. UNC93B1 deficieny, however, does not compromise immunity to most pathogens, unlike most known primary immunodeficiencies. Ref.6
Sequence similarities	Belongs to the unc-93 family.
Sequence caution	The sequence AAD15416.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Adaptive immunity Antiviral defense Immunity Innate immunity
Cellular component	Cytoplasmic vesicle Endoplasmic reticulum Endosome Lysosome Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Traceable author statement. Source: Reactome intracellular protein transport Inferred from sequence or structural similarity. Source: UniProtKB toll-like receptor 3 signaling pathway Inferred from mutant phenotype Ref.7. Source: UniProtKB toll-like receptor 7 signaling pathway Inferred from mutant phenotype Ref.8. Source: UniProtKB toll-like receptor 9 signaling pathway Inferred from mutant phenotype Ref.8. Source: UniProtKB
Cellular_component	Golgi membrane Traceable author statement. Source: Reactome early phagosome Inferred from sequence or structural similarity. Source: UniProtKB endoplasmic reticulum membrane Traceable author statement. Source: Reactome endosome Inferred from direct assay Ref.11. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW lysosome Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 597	597	Protein unc-93 homolog B1		PRO_0000190040
Regions
	Transmembrane	64 – 84	21	Helical; Potential
	Transmembrane	110 – 130	21	Helical; Potential
	Transmembrane	132 – 152	21	Helical; Potential
	Transmembrane	160 – 180	21	Helical; Potential
	Transmembrane	223 – 243	21	Helical; Potential
	Transmembrane	285 – 305	21	Helical; Potential
	Transmembrane	343 – 363	21	Helical; Potential
	Transmembrane	378 – 398	21	Helical; Potential
	Transmembrane	403 – 423	21	Helical; Potential
	Transmembrane	428 – 448	21	Helical; Potential
	Transmembrane	469 – 489	21	Helical; Potential
	Transmembrane	491 – 511	21	Helical; Potential
	Compositional bias	45 – 49	5	Poly-Glu
Amino acid modifications
	Modified residue	547	1	Phosphoserine Ref.9
	Modified residue	550	1	Phosphoserine Ref.5 Ref.9 Ref.10
	Glycosylation	251	1	N-linked (GlcNAc...) Potential
	Glycosylation	272	1	N-linked (GlcNAc...) Potential
	Glycosylation	449	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	436	1	Y → C. Corresponds to variant rs3175471 [ dbSNP | Ensembl ].		VAR_059850
Experimental info
	Sequence conflict	514	1	M → I in CAC19791. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9H1C4 [UniParc]. Last modified June 7, 2005. Version 2. Checksum: 8CAAB41678095157	FASTA	597	66,631
	10 20 30 40 50 60 MEAEPPLYPM AGAAGPQGDE DLLGVPDGPE APLDELVGAY PNYNEEEEER RYYRRKRLGV 70 80 90 100 110 120 LKNVLAASAG GMLTYGVYLG LLQMQLILHY DETYREVKYG NMGLPDIDSK MLMGINVTPI 130 140 150 160 170 180 AALLYTPVLI RFFGTKWMMF LAVGIYALFV STNYWERYYT LVPSAVALGM AIVPLWASMG 190 200 210 220 230 240 NYITRMAQKY HEYSHYKEQD GQGMKQRPPR GSHAPYLLVF QAIFYSFFHL SFACAQLPMI 250 260 270 280 290 300 YFLNHYLYDL NHTLYNVQSC GTNSHGILSG FNKTVLRTLP RSGNLIVVES VLMAVAFLAM 310 320 330 340 350 360 LLVLGLCGAA YRPTEEIDLR SVGWGNIFQL PFKHVRDYRL RHLVPFFIYS GFEVLFACTG 370 380 390 400 410 420 IALGYGVCSV GLERLAYLLV AYSLGASAAS LLGLLGLWLP RPVPLVAGAG VHLLLTFILF 430 440 450 460 470 480 FWAPVPRVLQ HSWILYVAAA LWGVGSALNK TGLSTLLGIL YEDKERQDFI FTIYHWWQAV 490 500 510 520 530 540 AIFTVYLGSS LHMKAKLAVL LVTLVAAAVS YLRMEQKLRR GVAPRQPRIP RPQHKVRGYR 550 560 570 580 590 YLEEDNSDES DAEGEHGDGA EEEAPPAGPR PGPEPAGLGR RPCPYEQAQG GDGPEEQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"hUNC93B1: a novel human gene representing a new gene family and encoding an unc-93-like protein." Kashuba V.I., Protopopov A.I., Kvasha S.M., Gizatullin R.Z., Wahlestedt C., Kisselev L.L., Klein G., Zabarovsky E.R. Gene 283:209-217(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Kidney.
[2]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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]. Tissue: Brain and Placenta.
[4]	"Cloning and characterization of mammalian homologs of unc-93 from Caenorhabditis elegans, a protein relevant for muscle contraction." Kollewe A. Thesis (2001), University of Hannover, Germany Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-497. Tissue: Uterus.
[5]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-550, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[6]	"Herpes simplex virus encephalitis in human UNC-93B deficiency." Casrouge A., Zhang S.-Y., Eidenschenk C., Jouanguy E., Puel A., Yang K., Alcais A., Picard C., Mahfoufi N., Nicolas N., Lorenzo L., Plancoulaine S., Senechal B., Geissmann F., Tabeta K., Hoebe K., Du X., Miller R.L. , Heron B., Mignot C., de Villemeur T.B., Lebon P., Dulac O., Rozenberg F., Beutler B., Tardieu M., Abel L., Casanova J.-L. Science 314:308-312(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN HSE1.
[7]	"Assessing the function of human UNC-93B in Toll-like receptor signaling and major histocompatibility complex II response." Koehn J., Huesken D., Jaritz M., Rot A., Zurini M., Dwertmann A., Beutler B., Korthaeuer U. Hum. Immunol. 68:871-878(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
[8]	"IRAK-4- and MyD88-dependent pathways are essential for the removal of developing autoreactive B cells in humans." Isnardi I., Ng Y.S., Srdanovic I., Motaghedi R., Rudchenko S., von Bernuth H., Zhang S.Y., Puel A., Jouanguy E., Picard C., Garty B.Z., Camcioglu Y., Doffinger R., Kumararatne D., Davies G., Gallin J.I., Haraguchi S., Day N.K., Casanova J.L., Meffre E. Immunity 29:746-757(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-547 AND SER-550, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-550, MASS SPECTROMETRY.
[11]	"BAD-LAMP is a novel biomarker of nonactivated human plasmacytoid dendritic cells." Defays A., David A., de Gassart A., De Angelis Rigotti F., Wenger T., Camossetto V., Brousset P., Petrella T., Dalod M., Gatti E., Pierre P. Blood 118:609-617(2011) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[12]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

UNC93B1base

UNC93B1 mutation db

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ271326 mRNA. Translation: CAC19791.1. AC004923 Genomic DNA. Translation: AAD15416.1. Sequence problems. BC092472 mRNA. Translation: AAH92472.1. BC101568 mRNA. Translation: AAI01569.1. BC105104 mRNA. Translation: AAI05105.1. AJ422142 mRNA. Translation: CAD19522.1.
IPI	IPI00008490.
RefSeq	NP_112192.2. NM_030930.2.
UniGene	Hs.502989.
3D structure databases
ProteinModelPortal	Q9H1C4.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H1C4. 1 interaction.
STRING	9606.ENSP00000227471.
PTM databases
PhosphoSite	Q9H1C4.
Polymorphism databases
DMDM	67462081.
Proteomic databases
PaxDb	Q9H1C4.
PRIDE	Q9H1C4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000227471; ENSP00000227471; ENSG00000110057.
GeneID	81622.
KEGG	hsa:81622.
UCSC	uc001omw.1. human.
Organism-specific databases
CTD	81622.
GeneCards	GC11M067759.
HGNC	HGNC:13481. UNC93B1.
HPA	HPA038717. HPA042803.
MIM	608204. gene. 610551. phenotype.
neXtProt	NX_Q9H1C4.
Orphanet	1930. Herpetic encephalitis.
PharmGKB	PA37781.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG294869.
HOGENOM	HOG000132956.
HOVERGEN	HBG084638.
InParanoid	Q9H1C4.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q9H1C4.
Bgee	Q9H1C4.
CleanEx	HS_UNC93B1.
Genevestigator	Q9H1C4.
GermOnline	ENSG00000110057. Homo sapiens.
Family and domain databases
InterPro	IPR010291. Ion_channel_UNC-93. [Graphical view]
Pfam	PF05978. UNC-93. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	UNC93B1. human.
GenomeRNAi	81622.
NextBio	71988.
SOURCE	Search...

Entry information

Entry name

UN93B_HUMAN

Accession

Primary (citable) accession number: Q9H1C4
Secondary accession number(s): O95764, Q569H6, Q710D4

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2005
Last sequence update:	June 7, 2005
Last modified:	May 1, 2013
This is version 79 of the entry and version 2 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.