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0  structures 217  species 0  interactions 253  sequences 7  architectures

Family: HPS6 (PF15702)

Summary: Hermansky-Pudlak syndrome 6 protein N-terminal domain

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This is the Wikipedia entry entitled "HPS6". More...

HPS6 Edit Wikipedia article

AliasesHPS6, BLOC2S3, biogenesis of lysosomal organelles complex 2 subunit 3, HPS6 biogenesis of lysosomal organelles complex 2 subunit 3
External IDsOMIM: 607522 MGI: 2181763 HomoloGene: 11691 GeneCards: HPS6
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 10: 102.07 – 102.07 MbChr 19: 46 – 46.01 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Hermansky–Pudlak syndrome 6 (HPS6), also known as ruby-eye protein homolog (Ru), is a protein that in humans is encoded by the HPS6 gene.[5]


This intronless gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes.[6] HPS6 along with HPS3 and HPS5 form a stable protein complex named Biogenesis of Lysosome-related Organelles Complex-2 (BLOC-2).[7]

Clinical significance

Mutations in this gene are associated with Hermansky–Pudlak syndrome type 6 characterized by albinism and prolonged bleeding.[5][8]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000166189 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000074811 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Zhang Q, Zhao B, Li W, Oiso N, Novak EK, Rusiniak ME, Gautam R, Chintala S, O'Brien EP, Zhang Y, Roe BA, Elliott RW, Eicher EM, Liang P, Kratz C, Legius E, Spritz RA, O'Sullivan TN, Copeland NG, Jenkins NA, Swank RT (February 2003). "Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky–Pudlak syndrome types 5 and 6". Nat. Genet. 33 (2): 145–53. doi:10.1038/ng1087. PMID 12548288. S2CID 23938527.
  6. ^ "Entrez Gene: HPS6 Hermansky–Pudlak syndrome 6".
  7. ^ Di Pietro SM, Falcón-Pérez JM, Dell'Angelica EC (April 2004). "Characterization of BLOC-2, a complex containing the Hermansky–Pudlak syndrome proteins HPS3, HPS5 and HPS6". Traffic. 5 (4): 276–83. doi:10.1111/j.1600-0854.2004.0171.x. PMID 15030569. S2CID 20584286.
  8. ^ Wei ML (February 2006). "Hermansky–Pudlak syndrome: a disease of protein trafficking and organelle function". Pigment Cell Res. 19 (1): 19–42. doi:10.1111/j.1600-0749.2005.00289.x. PMID 16420244.

Further reading

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Hermansky-Pudlak syndrome 6 protein N-terminal domain Provide feedback

This entry represents the N-terminal beta propeller domain of the HPS6 protein.

Literature references

  1. Zhang Q, Zhao B, Li W, Oiso N, Novak EK, Rusiniak ME, Gautam R, Chintala S, O'Brien EP, Zhang Y, Roe BA, Elliott RW, Eicher EM, Liang P, Kratz C, Legius E, Spritz RA, O'Sullivan TN, Copeland NG, Jenkins NA, Swank RT;, Nat Genet. 2003;33:145-153.: Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-Pudlak syndrome types 5 and 6. PUBMED:12548288 EPMC:12548288

This tab holds annotation information from the InterPro database.

InterPro entry IPR017218

Lysosome-related organelles comprise a group of specialised intracellular compartments that include melanosomes and platelet dense granules in mammals and eye pigment granules in insects. Genes associated with HPS encode subunits of three complexes of unknown function; (BLOC)-1, -2 and -3 [ PUBMED:17156100 ]. Hermansky-Pudlak syndrome (HPS) is a disorder of lysosome-related organelle biogenesis. There are eight known HPS proteins of the BLOCs (Biogenesis of Lysosome-related Organelles Complex) [ PUBMED:17365864 ]. Organelles affected in HPS include the melanosome, resulting in hypopigmentation, and the platelet delta (dense) granule, resulting in prolonged bleeding times.

HPS in humans or mice is caused by mutations in any of 15 genes, five of which encode subunits BLOC-1. BLOC-1 and BLOC-2 act sequentially in the same pathway. Melanosome maturation requires at least two cargo transport pathways directly from early endosomes to melanosomes. One pathway mediated by AP-3, and one pathway mediated by BLOC-1 and BLOC-2 [ PUBMED:17182842 ]. The adaptor protein AP-3 complex is a component of the cellular machinery that controls protein sorting from endosomes to lysosomes and melanosomes. BLOC-1 interacts physically and functionally with AP-3 to facilitate the trafficking of a known AP-3 cargo, CD63, and of tyrosinase-related protein 1 (Tyrp1). BLOC-1 also interacts with BLOC-2 to facilitate Tyrp1 trafficking by a mechanism apparently independent of AP-3 function. Both BLOC-1 and -2 predominantly localise to early endosome-associated tubules [ PUBMED:16837549 ].

Complex-2 (BLOC-2) contains the HPS3, HPS5 and HPS6 proteins as subunits. Fibroblasts deficient in the BLOC-2 subunits HPS3 or HPS6 have normal basal secretion function of the lysosomal enzyme beta-hexosaminidase [ PUBMED:15030569 ].

This group represents a BLOC-2 complex, Hps6 subunit.

Domain organisation

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Pfam Clan

This family is a member of clan Beta_propeller (CL0186), which has the following description:

This large clan contains proteins that contain beta propellers. These are composed of between 6 and 8 repeats. The individual repeats are composed of a four stranded sheet. The clan includes families such as WD40 Pfam:PF00400 where the individual repeats are modeled. The clan also includes families where the entire propeller is modeled such as Pfam:PF02239 usually because the individual repeats are not discernible. These proteins carry out a very wide diversity of functions including catalysis.

The clan contains the following 112 members:

ANAPC1 ANAPC4_WD40 Arylesterase Arylsulfotran_2 Arylsulfotrans B_lectin BBS2_Mid BBS2_N Beta_propel Coatomer_WDAD CPSF_A CyRPA Cytochrom_D1 DCAF17 Dpp_8_9_N DPPIV_N DPPIV_rep DUF1513 DUF1668 DUF2415 DUF346 DUF3466 DUF3616 DUF3748 DUF4221 DUF4374 DUF4394 DUF4623 DUF4784 DUF4915 DUF4933 DUF4934 DUF5046 DUF5050 DUF5122 DUF5128 DUF5711 DUF839 eIF2A FG-GAP FG-GAP_2 FG-GAP_3 Frtz Ge1_WD40 Glu_cyclase_2 Glyoxal_oxid_N Gmad1 GSDH Helveticin_J HPS3_N HPS6 Hyd_WA IKI3 Itfg2 Kelch_1 Kelch_2 Kelch_3 Kelch_4 Kelch_5 Kelch_6 Lactonase Ldl_recept_b LGFP Lgl_C LVIVD Me-amine-dh_H MgpC MRJP Nbas_N NBCH_WD40 Neisseria_PilC NHL nos_propeller nos_propeller_2 Nucleoporin_N Nup160 Nup88 P1_N PALB2_WD40 PD40 Pectate_lyase22 Peptidase_S9_N PHTB1_N Phytase-like PQQ PQQ_2 PQQ_3 RAB3GAP2_N RAG2 RCC1 RCC1_2 Reg_prop RPE65 SBBP SBP56 SdiA-regulated Sema SGL SSL_N Str_synth TcdB_toxin_midN Tectonin TolB_like VID27 Vps16_N WD40 WD40_2 WD40_3 WD40_4 WD40_like WDCP YmzC


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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Curation and family details

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Seed source: Jackhmmer:Q7M733
Previous IDs: none
Type: Repeat
Sequence Ontology: SO:0001068
Author: Eberhardt R
Number in seed: 8
Number in full: 253
Average length of the domain: 346.80 aa
Average identity of full alignment: 42 %
Average coverage of the sequence by the domain: 45.32 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 27.0
Trusted cut-off 27.0 32.7
Noise cut-off 26.2 25.2
Model length: 378
Family (HMM) version: 8
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Viroids Viroids Unclassified sequence Unclassified sequence


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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
Q7M733 View 3D Structure Click here
Q86YV9 View 3D Structure Click here
Q8BLY7 View 3D Structure Click here

trRosetta Structure

The structural model below was generated by the Baker group with the trRosetta software using the Pfam UniProt multiple sequence alignment.

The InterPro website shows the contact map for the Pfam SEED alignment. Hovering or clicking on a contact position will highlight its connection to other residues in the alignment, as well as on the 3D structure.

Improved protein structure prediction using predicted inter-residue orientations. Jianyi Yang, Ivan Anishchenko, Hahnbeom Park, Zhenling Peng, Sergey Ovchinnikov, David Baker Proceedings of the National Academy of Sciences Jan 2020, 117 (3) 1496-1503; DOI: 10.1073/pnas.1914677117;