HPS6_HUMAN
ID HPS6_HUMAN Reviewed; 775 AA.
AC Q86YV9; Q5VV69; Q9H685;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=BLOC-2 complex member HPS6 {ECO:0000305};
DE AltName: Full=Hermansky-Pudlak syndrome 6 protein;
DE AltName: Full=Ruby-eye protein homolog;
DE Short=Ru;
GN Name=HPS6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INVOLVEMENT IN HPS6.
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 GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 368-775.
RC TISSUE=Kidney;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH HPS3 AND HPS5.
RX PubMed=15030569; DOI=10.1111/j.1600-0854.2004.0171.x;
RA Di Pietro S.M., Falcon-Perez J.M., Dell'Angelica E.C.;
RT "Characterization of BLOC-2, a complex containing the Hermansky-Pudlak
RT syndrome proteins HPS3, HPS5 and HPS6.";
RL Traffic 5:276-283(2004).
RN [7]
RP INTERACTION WITH MNAT1.
RX PubMed=16169070; DOI=10.1016/j.cell.2005.08.029;
RA Stelzl U., Worm U., Lalowski M., Haenig C., Brembeck F.H., Goehler H.,
RA Stroedicke M., Zenkner M., Schoenherr A., Koeppen S., Timm J.,
RA Mintzlaff S., Abraham C., Bock N., Kietzmann S., Goedde A., Toksoez E.,
RA Droege A., Krobitsch S., Korn B., Birchmeier W., Lehrach H., Wanker E.E.;
RT "A human protein-protein interaction network: a resource for annotating the
RT proteome.";
RL Cell 122:957-968(2005).
RN [8]
RP FUNCTION, AND INVOLVEMENT IN HPS6.
RX PubMed=17041891; DOI=10.1002/humu.9463;
RA Schreyer-Shafir N., Huizing M., Anikster Y., Nusinker Z.,
RA Bejarano-Achache I., Maftzir G., Resnik L., Helip-Wooley A., Westbroek W.,
RA Gradstein L., Rosenmann A., Blumenfeld A.;
RT "A new genetic isolate with a unique phenotype of syndromic oculocutaneous
RT albinism: clinical, molecular, and cellular characteristics.";
RL Hum. Mutat. 27:1158-1158(2006).
RN [9]
RP INTERACTION WITH BLOC1 COMPLEX AND AP-3 COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=16837549; DOI=10.1091/mbc.e06-05-0379;
RA Di Pietro S.M., Falcon-Perez J.M., Tenza D., Setty S.R., Marks M.S.,
RA Raposo G., Dell'Angelica E.C.;
RT "BLOC-1 interacts with BLOC-2 and the AP-3 complex to facilitate protein
RT trafficking on endosomes.";
RL Mol. Biol. Cell 17:4027-4038(2006).
RN [10]
RP FUNCTION, INTERACTION WITH DCTN1; HPS3; HPS5 AND DYNEIN INTERMEDIATE CHAIN,
RP AND SUBCELLULAR LOCATION.
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 (PubMed:17041891). Acts as cargo adapter for the dynein-
CC dynactin motor complex to mediate the transport of lysosomes from the
CC cell periphery to the perinuclear region. Facilitates retrograde
CC lysosomal trafficking by linking the motor complex to lysosomes, and
CC perinuclear positioning of lysosomes is crucial for the delivery of
CC endocytic cargos to lysosomes, for lysosome maturation and functioning
CC (PubMed:25189619). {ECO:0000269|PubMed:17041891,
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 (PubMed:15030569, PubMed:25189619). Interacts with
CC biogenesis of lysosome-related organelles complex-1 (BLOC1). Interacts
CC with AP-3 complex (PubMed:16837549). Interacts with MNAT1 (Probable).
CC Interacts with DCTN1 and dynein intermediate chain (PubMed:25189619).
CC {ECO:0000269|PubMed:15030569, ECO:0000269|PubMed:16837549,
CC ECO:0000269|PubMed:25189619, ECO:0000305|PubMed:16169070}.
CC -!- SUBCELLULAR LOCATION: Microsome membrane {ECO:0000269|PubMed:15030569}.
CC Cytoplasm, cytosol {ECO:0000269|PubMed:15030569}. Early endosome
CC membrane {ECO:0000269|PubMed:16837549}. Lysosome membrane
CC {ECO:0000269|PubMed:25189619}.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DISEASE: Hermansky-Pudlak syndrome 6 (HPS6) [MIM:614075]: A form of
CC Hermansky-Pudlak syndrome, a genetically heterogeneous autosomal
CC recessive disorder characterized by oculocutaneous albinism, bleeding
CC due to platelet storage pool deficiency, and lysosomal storage defects.
CC This syndrome results from defects of diverse cytoplasmic organelles
CC including melanosomes, platelet dense granules and lysosomes. Ceroid
CC storage in the lungs is associated with pulmonary fibrosis, a common
CC cause of premature death in individuals with HPS.
CC {ECO:0000269|PubMed:12548288, ECO:0000269|PubMed:17041891}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15378.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF536238; AAO25965.1; -; mRNA.
DR EMBL; AL500527; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49726.1; -; Genomic_DNA.
DR EMBL; BC011594; AAH11594.2; -; mRNA.
DR EMBL; BC014993; AAH14993.2; -; mRNA.
DR EMBL; AK026154; BAB15378.1; ALT_INIT; mRNA.
DR CCDS; CCDS7527.1; -.
DR RefSeq; NP_079023.2; NM_024747.5.
DR AlphaFoldDB; Q86YV9; -.
DR BioGRID; 122900; 47.
DR ComplexPortal; CPX-5044; BLOC-2 complex.
DR CORUM; Q86YV9; -.
DR IntAct; Q86YV9; 17.
DR MINT; Q86YV9; -.
DR STRING; 9606.ENSP00000299238; -.
DR ChEMBL; CHEMBL4295884; -.
DR iPTMnet; Q86YV9; -.
DR PhosphoSitePlus; Q86YV9; -.
DR BioMuta; HPS6; -.
DR DMDM; 47115774; -.
DR EPD; Q86YV9; -.
DR jPOST; Q86YV9; -.
DR MassIVE; Q86YV9; -.
DR MaxQB; Q86YV9; -.
DR PaxDb; Q86YV9; -.
DR PeptideAtlas; Q86YV9; -.
DR PRIDE; Q86YV9; -.
DR ProteomicsDB; 70478; -.
DR Antibodypedia; 31371; 153 antibodies from 29 providers.
DR DNASU; 79803; -.
DR Ensembl; ENST00000299238.7; ENSP00000299238.5; ENSG00000166189.8.
DR GeneID; 79803; -.
DR KEGG; hsa:79803; -.
DR MANE-Select; ENST00000299238.7; ENSP00000299238.5; NM_024747.6; NP_079023.2.
DR UCSC; uc001kuj.4; human.
DR CTD; 79803; -.
DR DisGeNET; 79803; -.
DR GeneCards; HPS6; -.
DR GeneReviews; HPS6; -.
DR HGNC; HGNC:18817; HPS6.
DR HPA; ENSG00000166189; Low tissue specificity.
DR MalaCards; HPS6; -.
DR MIM; 607522; gene.
DR MIM; 614075; phenotype.
DR neXtProt; NX_Q86YV9; -.
DR OpenTargets; ENSG00000166189; -.
DR Orphanet; 231512; Hermansky-Pudlak syndrome due to BLOC-2 deficiency.
DR PharmGKB; PA134989637; -.
DR VEuPathDB; HostDB:ENSG00000166189; -.
DR eggNOG; ENOG502QSBH; Eukaryota.
DR GeneTree; ENSGT00390000001546; -.
DR HOGENOM; CLU_019081_0_0_1; -.
DR InParanoid; Q86YV9; -.
DR OMA; VWCEERQ; -.
DR OrthoDB; 287250at2759; -.
DR PhylomeDB; Q86YV9; -.
DR TreeFam; TF331635; -.
DR PathwayCommons; Q86YV9; -.
DR SignaLink; Q86YV9; -.
DR SIGNOR; Q86YV9; -.
DR BioGRID-ORCS; 79803; 17 hits in 1077 CRISPR screens.
DR ChiTaRS; HPS6; human.
DR GeneWiki; HPS6; -.
DR GenomeRNAi; 79803; -.
DR Pharos; Q86YV9; Tbio.
DR PRO; PR:Q86YV9; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q86YV9; protein.
DR Bgee; ENSG00000166189; Expressed in granulocyte and 157 other tissues.
DR Genevisible; Q86YV9; HS.
DR GO; GO:0031084; C:BLOC-2 complex; IPI:FlyBase.
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; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0030742; F:GTP-dependent protein binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0031267; F:small GTPase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0007596; P:blood coagulation; IEA:Ensembl.
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; IBA:GO_Central.
DR GO; GO:0060155; P:platelet dense granule organization; IC:ComplexPortal.
DR GO; GO:0072657; P:protein localization to membrane; IMP:ParkinsonsUK-UCL.
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 Albinism; Cytoplasm; Endoplasmic reticulum; Endosome;
KW Hermansky-Pudlak syndrome; Lysosome; Membrane; Microsome;
KW Reference proteome.
FT CHAIN 1..775
FT /note="BLOC-2 complex member HPS6"
FT /id="PRO_0000084056"
SQ SEQUENCE 775 AA; 82975 MW; B990A23DD0B00A30 CRC64;
MKRSGTLRLL SDLSAFGGAA RLRELVAGDS AVRVRGSPDG RHLLLLRPPG AVAPQLLVAS
RGPGAELERA WPAGQPSPLD AFFLPWPARP ALVLVWESGL AEVWGAGVGP GWRPLQSTEL
CPGGGARVVA VAALRGRLVW CEERQARAEG PSGSPAAAFS HCVCVRTLEP SGEASTSLGR
THVLLHHCPA FGLLASCRQL FLVPTATTWP GVAHVLLIWS PGKGKVMVAA PRLGLSYSKS
LNPGRGDTWD FRTLLRGLPG LLSPREPLAV HTWAPTPQGL LLLDFGGTVS LLQSHGGTRA
VGTLQEAPVG PWGSAALGTF QGTLACVLGS TLELLDMGSG QLLERKVLST DRVHLLEPPA
PGMEDEEELE TRGNLRLLSA LGLFCVGWEA PQGVELPSAK DLVFEEACGY YQRRSLRGAQ
LTPEELRHSS TFRAPQALAS ILQGHLPPSA LLTMLRTELR DYRGLEQLKA QLVAGDDEEA
GWTELAEQEV ARLLRTELIG DQLAQLNTVF QALPTAAWGA TLRALQLQLD GNGKLRSQAP
PDVWKKVLGG ITAGKEPPNG ILPPFELLCQ CLCQLEPRWL PPFVELAQQQ GGPGWGAGGP
GLPLYRRALA VLGEEGTRPE ALELELLLSS GRPKAVLQAV GQLVQKEQWD RALDAGLALG
PSSPLLRSEI FKLLLAEFAQ HRRLDAHLPL LCRLCPPELA PAELLLLLRT YLPDEVGPPT
PFPEPGAEPP LTVGLLKALL EQTGAQGWLS GPVLSPYEDI LWDPSTPPPT PPRDL
