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B2RUP2 (UN13D_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 51. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein unc-13 homolog D
Alternative name(s):
Munc13-4
Gene names
Name:Unc13d
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1085 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse. Regulates assembly of recycling and late endosomal structures, leading to the formation of an endosomal exocytic compartment that fuses with perforin-containing granules at the immunologic synapse and licences them for exocytosis By similarity. Regulates Ca2+-dependent secretory lysosome exocytosis in mast cells. Ref.7

Subunit structure

Interacts with RAB27A and DOC2A. Both RAB27A and DOC2A can simultaneously bind UNC13D. Ref.7

Subcellular location

Cytoplasm By similarity. Membrane; Peripheral membrane protein By similarity. Late endosome By similarity. Recycling endosome By similarity. Lysosome. Note: Colocalizes with cytotoxic granules at the plasma membrane By similarity. Localizes to endosomal exocytic vesicles By similarity. Ref.7

Tissue specificity

Mast cells. Ref.7

Domain

The MHD1 and MHD2 domains mediate localization on recycling endosomes and lysosome By similarity.

Disruption phenotype

A truncating mutation is the cause of the jinxed phenotype (jinx), a chemically-induced mutation that make mice susceptible to murine cytomegalovirus (MCMV). It is a mouse model of human type 3 familial hemophagocytic lymphohistiocytosis. Affected mice produce a truncated protein that lack the second of the C2 domains and part of the second MHD domain. In jinx homozygotes, activated NK cells and cytotoxic T-lymphocytes (CTLs) fail to degranulate, although they retain the ability to produce cytokines. Mice do not spontaneously develop clinical features of hemophagocytic lymphohistiocytosis (HLH), but do so when infected with lymphocytic choriomeningitis virus (LCMV), exhibiting hyperactivation of CTLs and antigen-presenting cells, and inadequate restriction of viral proliferation. In contrast, neither Listeria monocytogenes nor MCMV induce the syndrome. Ref.1

Sequence similarities

Belongs to the unc-13 family.

Contains 2 C2 domains.

Contains 1 MHD1 (MUNC13 homology domain 1) domain.

Contains 1 MHD2 (MUNC13 homology domain 2) domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: B2RUP2-1)

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: B2RUP2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     480-481: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10851085Protein unc-13 homolog D
PRO_0000382950

Regions

Domain97 – 220124C2 1
Domain554 – 674121MHD1
Domain785 – 892108MHD2
Domain909 – 1016108C2 2
Region239 – 542304Interaction with RAB27A By similarity
Compositional bias21 – 266Poly-Arg

Amino acid modifications

Modified residue1491Phosphoserine Ref.6

Natural variations

Alternative sequence480 – 4812Missing in isoform 2.
VSP_037950

Experimental info

Sequence conflict7921P → F in ABO15440. Ref.1
Sequence conflict7961F → N in ABO15440. Ref.1

Sequences

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

Last modified September 1, 2009. Version 2.
Checksum: BA46A15BBF62B8B7

FASTA1,085123,119
        10         20         30         40         50         60 
MATHLSHPQR RPLLRQAIKI RRRRVRDLQD PPPQATQEVQ VQSHHFSPEE RDLLYEEALY 

        70         80         90        100        110        120 
TVLHRLGQPE PNHVKEASEL LSYLQEAFQV QPEEHQQMLR RVRELEKPVF CLKATVKQAK 

       130        140        150        160        170        180 
GILGKDVSGF SDPYCLLGIE QKVGVAEGSP VSRRRQKAVV KHTIPEEETH RTQVKSQTLN 

       190        200        210        220        230        240 
PVWDETFILE FEDIANASFH LDMWDLDTVE SVRQKLGELT DLHGLRRIFK EARKDKGQDD 

       250        260        270        280        290        300 
FLGNVVLRLQ DLRCREDQWF PLEPCTETYP DRGQCHLQFQ FIHKRRATAA SRSQPSYTVH 

       310        320        330        340        350        360 
FHLLQQLVSH EVTQHQAGST SWDASLSPQA VTILFLHATQ KDLSDFHQSM AQWLAYSRLY 

       370        380        390        400        410        420 
QSLEFPSSCL LHPITSIEYQ WIQGRLKAEQ REELATSFTS LLAYGLSLIR KFRSVFPLSV 

       430        440        450        460        470        480 
SDSPSRLQSL LRVLVQMCKM KAFGELCPDS APLSQLVSEA LRMGTVEWFH LMQQHHQPMV 

       490        500        510        520        530        540 
QGILEAGKAL LNLVQDVMGD LYQCRRTWNK IFHNVLKIDL FSMAFLELQW LVAKRVQDHT 

       550        560        570        580        590        600 
VAAGNLVSPD IGESLFQLYV SLKELCQLGP VPSDSREVLA LDGFHRWFQP AIPSWLQKTY 

       610        620        630        640        650        660 
SVALERVQRA VQMDTLVPLG ELTKHSTSAV DLSTCFAQIS HTARQLDWPD PEEAFMITVK 

       670        680        690        700        710        720 
FVEDTCRLAL VYCSLIKARA RELSAVQKDQ SQAADMLCVV VNNMEQLRLI IDKLPTQLAW 

       730        740        750        760        770        780 
EALEQRVGAV LEEGQLQNTL HAQLQGALAG LGHEIRTGVR TLAEQLEVGI ATHIQKLIGV 

       790        800        810        820        830        840 
KESVLPEDAI LPLMKFLEVK LCYMNTNLVQ ENFSSLLTLL WTHTLTVLVE VASSQRSSSL 

       850        860        870        880        890        900 
ASGRLKVALQ NLEVCFHAEG CGLPPEALHT DTFQALQNDL ELQAASSREL IQKYFCSRIQ 

       910        920        930        940        950        960 
QQAETTSERL GAVTVKVSYR ASEQRLRVEL LSASSLLPLD SNGSSDPFVQ LTLEPRHEFP 

       970        980        990       1000       1010       1020 
EVAPRETQKH KKELHPLFDE TFEFLVPAEP CQKAWACLLL TVLDHDRLGA DDLEGEAFLP 

      1030       1040       1050       1060       1070       1080 
LCRVPGLTDC AEPGEAPQMR LPLTYPAPNG DPILRLLESR KGDREAQAFV KLRRQRAKQA 


SQHAP 

« Hide

Isoform 2 [UniParc].

Checksum: C0AF2730D27FA497
Show »

FASTA1,083122,892

References

« Hide 'large scale' references
[1]"Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis."
Crozat K., Hoebe K., Ugolini S., Hong N.A., Janssen E., Rutschmann S., Mudd S., Sovath S., Vivier E., Beutler B.
J. Exp. Med. 204:853-863(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 792-814, DISRUPTION PHENOTYPE.
Strain: C57BL/6.
[2]Erratum
Crozat K., Hoebe K., Ugolini S., Hong N.A., Janssen E., Rutschmann S., Mudd S., Sovath S., Vivier E., Beutler B.
J. Exp. Med. 205:737-737(2008)
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]"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 2).
Tissue: Brain.
[5]"Prediction of the coding sequences of mouse homologues of KIAA gene. The complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O., Koga H.
Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 193-1085 (ISOFORM 2).
Tissue: Spleen.
[6]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-149, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[7]"Doc2 alpha and Munc13-4 regulate Ca(2+) -dependent secretory lysosome exocytosis in mast cells."
Higashio H., Nishimura N., Ishizaki H., Miyoshi J., Orita S., Sakane A., Sasaki T.
J. Immunol. 180:4774-4784(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RAB27A AND DOC2A, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
EF127645 mRNA. Translation: ABO15439.1.
EF127646 Genomic DNA. Translation: ABO15440.1.
AL607108 Genomic DNA. Translation: CAM24043.1.
BC141289 mRNA. Translation: AAI41290.1.
AK220199 mRNA. Translation: BAD90124.1.
RefSeqNP_001009573.2. NM_001009573.2.
XP_006534251.1. XM_006534188.1.
XP_006534252.1. XM_006534189.1.
XP_006534253.1. XM_006534190.1.
XP_006534254.1. XM_006534191.1.
UniGeneMm.259460.

3D structure databases

ProteinModelPortalB2RUP2.
SMRB2RUP2. Positions 587-882, 911-1019.
ModBaseSearch...
MobiDBSearch...

Proteomic databases

PaxDbB2RUP2.
PRIDEB2RUP2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000075036; ENSMUSP00000074549; ENSMUSG00000057948. [B2RUP2-2]
ENSMUST00000106450; ENSMUSP00000102058; ENSMUSG00000057948. [B2RUP2-1]
ENSMUST00000106451; ENSMUSP00000102059; ENSMUSG00000057948. [B2RUP2-1]
ENSMUST00000173345; ENSMUSP00000133679; ENSMUSG00000057948.
ENSMUST00000174822; ENSMUSP00000134260; ENSMUSG00000057948. [B2RUP2-2]
GeneID70450.
KEGGmmu:70450.
UCSCuc007mjt.1. mouse. [B2RUP2-2]

Organism-specific databases

CTD201294.
MGIMGI:1917700. Unc13d.

Phylogenomic databases

eggNOGNOG290002.
GeneTreeENSGT00730000110939.
HOGENOMHOG000060231.
InParanoidA3R4M5.
OMAPYCLLGI.
OrthoDBEOG7XPZ4S.
PhylomeDBB2RUP2.
TreeFamTF315526.

Gene expression databases

BgeeB2RUP2.
GenevestigatorB2RUP2.

Family and domain databases

Gene3D2.60.40.150. 2 hits.
InterProIPR000008. C2_dom.
IPR014770. Munc13_1.
IPR014772. Munc13_dom-2.
IPR019558. Munc13_subgr_dom-2.
[Graphical view]
PfamPF00168. C2. 2 hits.
PF10540. Membr_traf_MHD. 1 hit.
[Graphical view]
SMARTSM00239. C2. 2 hits.
[Graphical view]
SUPFAMSSF49562. SSF49562. 4 hits.
PROSITEPS50004. C2. 2 hits.
PS51258. MHD1. 1 hit.
PS51259. MHD2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio331645.
PROB2RUP2.
SOURCESearch...

Entry information

Entry nameUN13D_MOUSE
AccessionPrimary (citable) accession number: B2RUP2
Secondary accession number(s): A2A856 expand/collapse secondary AC list , A3R4M4, A3R4M5, Q571J0
Entry history
Integrated into UniProtKB/Swiss-Prot: September 1, 2009
Last sequence update: September 1, 2009
Last modified: April 16, 2014
This is version 51 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot