HPS6_MOUSE
ID HPS6_MOUSE Reviewed; 805 AA.
AC Q8BLY7; Q3TWQ8; Q8BML5; Q8CIA3;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=BLOC-2 complex member HPS6 {ECO:0000305};
DE AltName: Full=Hermansky-Pudlak syndrome 6 protein homolog;
DE AltName: Full=Ruby-eye protein;
DE Short=Ru;
GN Name=Hps6; Synonyms=Ru;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT RU 187-HIS--PRO-189 DEL, AND DISEASE.
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=12548288; DOI=10.1038/ng1087;
RA Zhang Q., Zhao B., Li W., Oiso N., Novak E.K., Rusiniak M.E., Gautam R.,
RA Chintala S., O'Brien E.P., Zhang Y., Roe B.A., Elliott R.W., Eicher E.M.,
RA Liang P., Kratz C., Legius E., Spritz R.A., O'Sullivan T.N., Copeland N.G.,
RA Jenkins N.A., Swank R.T.;
RT "Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-
RT Pudlak syndrome types 5 and 6.";
RL Nat. Genet. 33:145-153(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Aorta, Pituitary, and Vein;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH AP-3 COMPLEX.
RX PubMed=19010779; DOI=10.1074/jbc.m805991200;
RA Salazar G., Zlatic S., Craige B., Peden A.A., Pohl J., Faundez V.;
RT "Hermansky-Pudlak syndrome protein complexes associate with
RT phosphatidylinositol 4-kinase type II alpha in neuronal and non-neuronal
RT cells.";
RL J. Biol. Chem. 284:1790-1802(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, AND INTERACTION WITH DCTN1.
RX PubMed=25189619; DOI=10.1242/jcs.141978;
RA Li K., Yang L., Zhang C., Niu Y., Li W., Liu J.J.;
RT "HPS6 interacts with dynactin p150Glued to mediate retrograde trafficking
RT and maturation of lysosomes.";
RL J. Cell Sci. 127:4574-4588(2014).
CC -!- FUNCTION: May regulate the synthesis and function of lysosomes and of
CC highly specialized organelles, such as melanosomes and platelet dense
CC granules (By similarity). Acts as cargo adapter for the dynein-dynactin
CC motor complex to mediate the transport of lysosomes from the cell
CC periphery to the perinuclear region. Facilitates retrograde lysosomal
CC trafficking by linking the motor complex to lysosomes, and perinuclear
CC positioning of lysosomes is crucial for the delivery of endocytic
CC cargos to lysosomes, for lysosome maturation and functioning
CC (PubMed:25189619). {ECO:0000250|UniProtKB:Q86YV9,
CC ECO:0000269|PubMed:25189619}.
CC -!- SUBUNIT: Component of the biogenesis of lysosome-related organelles
CC complex-2 (or BLOC2) composed of HPS3, HPS5 and HPS6. Interacts with
CC HPS5 and HPS3. Interacts with biogenesis of lysosome-related organelles
CC complex-1 (BLOC1). Interacts with dynein intermediate chain (By
CC similarity). Interacts with AP-3 complex (PubMed:19010779). Interacts
CC with DCTN1 (PubMed:25189619). {ECO:0000250|UniProtKB:Q86YV9,
CC ECO:0000269|PubMed:19010779, ECO:0000269|PubMed:25189619}.
CC -!- SUBCELLULAR LOCATION: Microsome membrane
CC {ECO:0000250|UniProtKB:Q86YV9}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q86YV9}. Early endosome membrane
CC {ECO:0000250|UniProtKB:Q86YV9}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q86YV9}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with lowest expression in
CC skeletal muscle.
CC -!- DISEASE: Note=Defects in Hps6 are the cause of Hermansky-Pudlak-like
CC syndrome, a syndrome characterized by hypopigmented eyes and coat,
CC melanosomes greatly reduced in number and morphologically bizarre,
CC kidney proximal tubules secreting lysosomal enzymes into urine at
CC greatly reduced rates, platelet dense granules deficient in critical
CC components, such as serotonin and adenine nucleotides, leading to
CC functionally abnormal platelets and prolonged bleeding times, and mast
CC cell granules undergoing unregulated 'kiss-and-run' fusion at the
CC plasma membrane. {ECO:0000269|PubMed:12548288}.
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DR EMBL; AF536239; AAO25966.1; -; mRNA.
DR EMBL; AK030582; BAC27030.1; -; mRNA.
DR EMBL; AK040849; BAC30719.1; -; mRNA.
DR EMBL; AK159588; BAE35208.1; -; mRNA.
DR EMBL; BC034055; AAH34055.1; -; mRNA.
DR CCDS; CCDS29869.1; -.
DR RefSeq; NP_789742.2; NM_176785.3.
DR AlphaFoldDB; Q8BLY7; -.
DR BioGRID; 203035; 1.
DR ComplexPortal; CPX-5084; BLOC-2 complex.
DR CORUM; Q8BLY7; -.
DR STRING; 10090.ENSMUSP00000096991; -.
DR iPTMnet; Q8BLY7; -.
DR PhosphoSitePlus; Q8BLY7; -.
DR EPD; Q8BLY7; -.
DR MaxQB; Q8BLY7; -.
DR PaxDb; Q8BLY7; -.
DR PeptideAtlas; Q8BLY7; -.
DR PRIDE; Q8BLY7; -.
DR ProteomicsDB; 273169; -.
DR Antibodypedia; 31371; 153 antibodies from 29 providers.
DR Ensembl; ENSMUST00000099393; ENSMUSP00000096991; ENSMUSG00000074811.
DR GeneID; 20170; -.
DR KEGG; mmu:20170; -.
DR UCSC; uc008hrx.2; mouse.
DR CTD; 79803; -.
DR MGI; MGI:2181763; Hps6.
DR VEuPathDB; HostDB:ENSMUSG00000074811; -.
DR eggNOG; ENOG502QSBH; Eukaryota.
DR GeneTree; ENSGT00390000001546; -.
DR HOGENOM; CLU_019081_0_0_1; -.
DR InParanoid; Q8BLY7; -.
DR OMA; VWCEERQ; -.
DR OrthoDB; 287250at2759; -.
DR TreeFam; TF331635; -.
DR BioGRID-ORCS; 20170; 4 hits in 72 CRISPR screens.
DR PRO; PR:Q8BLY7; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q8BLY7; protein.
DR Bgee; ENSMUSG00000074811; Expressed in primary oocyte and 110 other tissues.
DR Genevisible; Q8BLY7; MM.
DR GO; GO:0031084; C:BLOC-2 complex; ISO:MGI.
DR GO; GO:0005769; C:early endosome; IC:ComplexPortal.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0030742; F:GTP-dependent protein binding; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0007596; P:blood coagulation; IMP:MGI.
DR GO; GO:0046907; P:intracellular transport; IC:ComplexPortal.
DR GO; GO:0032418; P:lysosome localization; IMP:UniProtKB.
DR GO; GO:0030318; P:melanocyte differentiation; IBA:GO_Central.
DR GO; GO:1903232; P:melanosome assembly; IC:ComplexPortal.
DR GO; GO:0006996; P:organelle organization; IMP:MGI.
DR GO; GO:0043473; P:pigmentation; IMP:MGI.
DR GO; GO:0060155; P:platelet dense granule organization; IC:ComplexPortal.
DR GO; GO:0072657; P:protein localization to membrane; ISO:MGI.
DR InterPro; IPR017218; BLOC-2_complex_Hps6_subunit.
DR PANTHER; PTHR14696; PTHR14696; 1.
DR Pfam; PF15702; HPS6; 1.
DR PIRSF; PIRSF037476; BLOC-2_complex_Hps6; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Disease variant; Endoplasmic reticulum; Endosome; Lysosome;
KW Membrane; Microsome; Reference proteome.
FT CHAIN 1..805
FT /note="BLOC-2 complex member HPS6"
FT /id="PRO_0000084057"
FT REGION 743..805
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 763..777
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 187..189
FT /note="Missing (in allele ru; HPS-like mutant)"
FT /evidence="ECO:0000269|PubMed:12548288"
FT CONFLICT 137
FT /note="R -> S (in Ref. 2; BAC27030)"
FT /evidence="ECO:0000305"
FT CONFLICT 384
FT /note="F -> L (in Ref. 3; AAH34055)"
FT /evidence="ECO:0000305"
FT CONFLICT 667
FT /note="R -> G (in Ref. 2; BAC27030)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 805 AA; 87341 MW; 503BCD0B3760D95A CRC64;
MKRAGTLRLL SDLSNFTGAA RLRELLAGDP AVLVRCSPDG RHLLLLRPPG SPAPQLLVAV
RGPGLPLERA WPEGDPSPLD VFFVPWLARP ALILVWESGL AEVWGVGMEP GWKLLQSTEL
CPDGGARVMA VAATRGRLVW CEERQPGVKD QPEQLSTAFS HRVCFKTLET SGEAGTKLGC
THILLHHCPL FGLIASRKDL FLVPTTNTWS GVAHLLLIWS PSKGKVIVAA PSLGLSHSKS
LNPKQGDTWD FRTLLRGLPG FLSPREPLAV HTWAPSSQGL LLLDLKGKVS LVQCHGGTRT
VGILQEAPVS LKGSAALGTF HGTLACVLGS TLELLDMSSG RLLEKKVLST DRVHLLEPPA
PGMKNEEELE TRGALRLLSA LGLFCVCWET PQGLELPSDK DLVFEEACGY YQRRSLRGTQ
LTPEELRHNS MFRAPQALAS ILQGHLPPST LLTTLRAELR DYRSIEQLKA QLVAGDDEEA
GWTELAEHEV ARLLRTQLTG DQLAQFNTIF QALPTAAWGA TLQALQLQPD RSGRLRSQAP
PDVWKKVLRA PTAGKEHPNG ILPPFELLCQ CLGQLEPQWL PPFVKLAQQQ GGPGWGAEGP
SLPLYRRALA VLGEEGKRPE ALELELLLGS GRPKAVLQAV RQLIKKEEWE RALEAGLALD
ASSPLLRSEI FKLLLAEFAQ HRRLDAHLPL LCRLCPPEVA PHELLLLLRT HLPDDEGTTP
FPEPGAEPPL TVGLVRALLE QTGAQGRPSG PVQSTYEDIL WDPGTPPPTP PRGPTASLPA
SDHPGQEAWV PPGQGLGAAD VGVHL
