HPS1_HUMAN
ID HPS1_HUMAN Reviewed; 700 AA.
AC Q92902; A8MRT2; O15402; O15502; Q5TAA3; Q8WXE5;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=BLOC-3 complex member HPS1 {ECO:0000305};
DE AltName: Full=Hermansky-Pudlak syndrome 1 protein;
GN Name=HPS1; Synonyms=HPS;
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] (ISOFORM I), AND VARIANTS.
RX PubMed=8896559; DOI=10.1038/ng1196-300;
RA Oh J., Bailin T., Fukai K., Feng G.H., Ho L., Mao J.-I., Frenk E.,
RA Tamura N., Spritz R.A.;
RT "Positional cloning of a gene for Hermansky-Pudlak syndrome, a disorder of
RT cytoplasmic organelles.";
RL Nat. Genet. 14:300-306(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS I; II AND IV), AND VARIANTS.
RX PubMed=9182823; DOI=10.1111/1523-1747.ep12294634;
RA Bailin T., Oh J., Feng G.H., Fukai K., Spritz R.A.;
RT "Organization and nucleotide sequence of the human Hermansky-Pudlak
RT syndrome (HPS) gene.";
RL J. Invest. Dermatol. 108:923-927(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM III).
RX PubMed=9579545; DOI=10.1046/j.1523-1747.1998.00183.x;
RA Wildenberg S.C., Fryer J.P., Gardner J.M., Oetting W.S., Brilliant M.H.,
RA King R.A.;
RT "Identification of a novel transcript produced by the gene responsible for
RT the Hermansky-Pudlak syndrome in Puerto Rico.";
RL J. Invest. Dermatol. 110:777-781(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10798370; DOI=10.1007/s004390051053;
RA Huizing M., Anikster Y., Gahl W.A.;
RT "Characterization of a partial pseudogene homologous to the Hermansky-
RT Pudlak syndrome gene HPS-1; relevance for mutation detection.";
RL Hum. Genet. 106:370-373(2000).
RN [5]
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 [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM III).
RC TISSUE=Placenta;
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 [8]
RP REVIEW ON HPS1 VARIANTS.
RX PubMed=10094567;
RX DOI=10.1002/(sici)1098-1004(1999)13:2<99::aid-humu2>3.0.co;2-c;
RA Oetting W.S., King R.A.;
RT "Molecular basis of albinism: mutations and polymorphisms of pigmentation
RT genes associated with albinism.";
RL Hum. Mutat. 13:99-115(1999).
RN [9]
RP SUBUNIT, AND LACK OF INTERACTION WITH RAB9A.
RX PubMed=20048159; DOI=10.1074/jbc.m109.069088;
RA Kloer D.P., Rojas R., Ivan V., Moriyama K., van Vlijmen T., Murthy N.,
RA Ghirlando R., van der Sluijs P., Hurley J.H., Bonifacino J.S.;
RT "Assembly of the biogenesis of lysosome-related organelles complex-3 (BLOC-
RT 3) and its interaction with Rab9.";
RL J. Biol. Chem. 285:7794-7804(2010).
RN [10]
RP FUNCTION, AND SUBUNIT.
RX PubMed=23084991; DOI=10.1016/j.cub.2012.09.020;
RA Gerondopoulos A., Langemeyer L., Liang J.R., Linford A., Barr F.A.;
RT "BLOC-3 mutated in Hermansky-Pudlak syndrome is a Rab32/38 guanine
RT nucleotide exchange factor.";
RL Curr. Biol. 22:2135-2139(2012).
RN [11]
RP VARIANT HPS1 ILE-55 DEL.
RX PubMed=9497254; DOI=10.1086/301757;
RA Oh J., Ho L., Ala-Mello S., Amato D., Armstrong L., Bellucci S.,
RA Carakushansky G., Ellis J.P., Fong C.-T., Green J.S., Heon E., Legius E.,
RA Levin A.V., Nieuwenhuis H.K., Pinckers A., Tamura N., Whiteford M.L.,
RA Yamasaki H., Spritz R.A.;
RT "Mutation analysis of patients with Hermansky-Pudlak syndrome: a frameshift
RT hot spot in the HPS gene and apparent locus heterogeneity.";
RL Am. J. Hum. Genet. 62:593-598(1998).
CC -!- FUNCTION: Component of the BLOC-3 complex, a complex that acts as a
CC guanine exchange factor (GEF) for RAB32 and RAB38, promotes the
CC exchange of GDP to GTP, converting them from an inactive GDP-bound form
CC into an active GTP-bound form. The BLOC-3 complex plays an important
CC role in the control of melanin production and melanosome biogenesis and
CC promotes the membrane localization of RAB32 and RAB38
CC (PubMed:23084991). {ECO:0000269|PubMed:23084991}.
CC -!- SUBUNIT: Component of the biogenesis of lysosome-related organelles
CC complex-3 (or BLOC-3), a heterodimer of HPS1 and HPS4 (PubMed:20048159,
CC PubMed:23084991). HPS1 cannot but BLOC-3 complex (heterodimer of HPS1
CC and HPS4) can interact with the GTP-bound form of RAB9A and RAB9B. HPS1
CC and BLOC-3 complex do not interact with the GDP-bound form of RAB9A and
CC RAB9B (PubMed:20048159). {ECO:0000269|PubMed:20048159,
CC ECO:0000269|PubMed:23084991}.
CC -!- INTERACTION:
CC Q92902; Q9NQG7: HPS4; NbExp=17; IntAct=EBI-704347, EBI-704377;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Additional isoforms seem to exist.;
CC Name=I;
CC IsoId=Q92902-1; Sequence=Displayed;
CC Name=II;
CC IsoId=Q92902-2; Sequence=VSP_004289;
CC Name=III;
CC IsoId=Q92902-3; Sequence=VSP_004290, VSP_004291;
CC Name=IV;
CC IsoId=Q92902-4; Sequence=VSP_004288;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DISEASE: Hermansky-Pudlak syndrome 1 (HPS1) [MIM:203300]: 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:9497254}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- WEB RESOURCE: Name=Mutations of the HPS gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/epmut.htm";
CC -!- WEB RESOURCE: Name=Albinism database (ADB); Note=HPS1 mutations;
CC URL="http://www.ifpcs.org/albinism/hps1mut.html";
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DR EMBL; U65676; AAB17869.1; -; mRNA.
DR EMBL; U79136; AAB70662.1; -; Genomic_DNA.
DR EMBL; U79123; AAB70662.1; JOINED; Genomic_DNA.
DR EMBL; U79124; AAB70662.1; JOINED; Genomic_DNA.
DR EMBL; U79125; AAB70662.1; JOINED; Genomic_DNA.
DR EMBL; U79126; AAB70662.1; JOINED; Genomic_DNA.
DR EMBL; U79127; AAB70662.1; JOINED; Genomic_DNA.
DR EMBL; U79128; AAB70662.1; JOINED; Genomic_DNA.
DR EMBL; U79129; AAB70662.1; JOINED; Genomic_DNA.
DR EMBL; U79130; AAB70662.1; JOINED; Genomic_DNA.
DR EMBL; U79131; AAB70662.1; JOINED; Genomic_DNA.
DR EMBL; U79132; AAB70662.1; JOINED; Genomic_DNA.
DR EMBL; U79133; AAB70662.1; JOINED; Genomic_DNA.
DR EMBL; U79134; AAB70662.1; JOINED; Genomic_DNA.
DR EMBL; U79135; AAB70662.1; JOINED; Genomic_DNA.
DR EMBL; U96721; AAC52074.1; -; mRNA.
DR EMBL; AF450133; AAL50684.1; -; Genomic_DNA.
DR EMBL; AL139243; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49882.1; -; Genomic_DNA.
DR EMBL; BC000175; AAH00175.1; -; mRNA.
DR CCDS; CCDS7475.1; -. [Q92902-1]
DR CCDS; CCDS7476.1; -. [Q92902-3]
DR RefSeq; NP_000186.2; NM_000195.4. [Q92902-1]
DR RefSeq; NP_001309405.1; NM_001322476.1. [Q92902-1]
DR RefSeq; NP_001309406.1; NM_001322477.1. [Q92902-1]
DR RefSeq; NP_001309407.1; NM_001322478.1. [Q92902-2]
DR RefSeq; NP_001309408.1; NM_001322479.1. [Q92902-2]
DR RefSeq; NP_872577.1; NM_182639.3. [Q92902-3]
DR RefSeq; XP_005269814.1; XM_005269757.4. [Q92902-1]
DR AlphaFoldDB; Q92902; -.
DR BioGRID; 109494; 11.
DR ComplexPortal; CPX-5043; BLOC-3 complex.
DR CORUM; Q92902; -.
DR IntAct; Q92902; 9.
DR STRING; 9606.ENSP00000326649; -.
DR iPTMnet; Q92902; -.
DR PhosphoSitePlus; Q92902; -.
DR BioMuta; HPS1; -.
DR DMDM; 68067891; -.
DR EPD; Q92902; -.
DR MassIVE; Q92902; -.
DR MaxQB; Q92902; -.
DR PaxDb; Q92902; -.
DR PeptideAtlas; Q92902; -.
DR PRIDE; Q92902; -.
DR ProteomicsDB; 75584; -. [Q92902-1]
DR ProteomicsDB; 75585; -. [Q92902-2]
DR ProteomicsDB; 75586; -. [Q92902-3]
DR ProteomicsDB; 75587; -. [Q92902-4]
DR Antibodypedia; 45895; 124 antibodies from 28 providers.
DR DNASU; 3257; -.
DR Ensembl; ENST00000325103.10; ENSP00000326649.6; ENSG00000107521.20. [Q92902-1]
DR Ensembl; ENST00000338546.9; ENSP00000343638.5; ENSG00000107521.20. [Q92902-3]
DR Ensembl; ENST00000361490.9; ENSP00000355310.4; ENSG00000107521.20. [Q92902-1]
DR GeneID; 3257; -.
DR KEGG; hsa:3257; -.
DR MANE-Select; ENST00000361490.9; ENSP00000355310.4; NM_000195.5; NP_000186.2.
DR UCSC; uc001kpl.4; human. [Q92902-1]
DR CTD; 3257; -.
DR DisGeNET; 3257; -.
DR GeneCards; HPS1; -.
DR GeneReviews; HPS1; -.
DR HGNC; HGNC:5163; HPS1.
DR HPA; ENSG00000107521; Low tissue specificity.
DR MalaCards; HPS1; -.
DR MIM; 203300; phenotype.
DR MIM; 604982; gene.
DR neXtProt; NX_Q92902; -.
DR OpenTargets; ENSG00000107521; -.
DR Orphanet; 231500; Hermansky-Pudlak syndrome due to BLOC-3 deficiency.
DR PharmGKB; PA35101; -.
DR VEuPathDB; HostDB:ENSG00000107521; -.
DR eggNOG; ENOG502QW8U; Eukaryota.
DR GeneTree; ENSGT00390000015298; -.
DR HOGENOM; CLU_016960_1_0_1; -.
DR InParanoid; Q92902; -.
DR OMA; TATCAVE; -.
DR OrthoDB; 568288at2759; -.
DR PhylomeDB; Q92902; -.
DR TreeFam; TF324374; -.
DR PathwayCommons; Q92902; -.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR SignaLink; Q92902; -.
DR SIGNOR; Q92902; -.
DR BioGRID-ORCS; 3257; 12 hits in 1073 CRISPR screens.
DR ChiTaRS; HPS1; human.
DR GeneWiki; HPS1; -.
DR GenomeRNAi; 3257; -.
DR Pharos; Q92902; Tbio.
DR PRO; PR:Q92902; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q92902; protein.
DR Bgee; ENSG00000107521; Expressed in granulocyte and 155 other tissues.
DR ExpressionAtlas; Q92902; baseline and differential.
DR Genevisible; Q92902; HS.
DR GO; GO:0031085; C:BLOC-3 complex; IPI:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:ComplexPortal.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005764; C:lysosome; TAS:ProtInc.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:UniProtKB-KW.
DR GO; GO:0046983; F:protein dimerization activity; IPI:UniProtKB.
DR GO; GO:0046907; P:intracellular transport; IC:ComplexPortal.
DR GO; GO:0007040; P:lysosome organization; TAS:ProtInc.
DR GO; GO:1903232; P:melanosome assembly; IDA:UniProtKB.
DR GO; GO:0060155; P:platelet dense granule organization; IC:ComplexPortal.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0016192; P:vesicle-mediated transport; IEA:InterPro.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR InterPro; IPR043972; FUZ/MON1/HPS1_longin_1.
DR InterPro; IPR043971; FUZ/MON1/HPS1_longin_2.
DR InterPro; IPR043970; FUZ/MON1/HPS1_longin_3.
DR InterPro; IPR026053; HPS1.
DR PANTHER; PTHR12761; PTHR12761; 1.
DR Pfam; PF19036; Fuz_longin_1; 1.
DR Pfam; PF19037; Fuz_longin_2; 1.
DR Pfam; PF19038; Fuz_longin_3; 1.
PE 1: Evidence at protein level;
KW Albinism; Alternative splicing; Disease variant;
KW Guanine-nucleotide releasing factor; Hermansky-Pudlak syndrome;
KW Reference proteome; Repeat; Sensory transduction; Vision.
FT CHAIN 1..700
FT /note="BLOC-3 complex member HPS1"
FT /id="PRO_0000084047"
FT REPEAT 45..51
FT /note="[DE]-X(4)-L-L 1"
FT REPEAT 147..153
FT /note="[DE]-X(4)-L-L 2"
FT REPEAT 516..522
FT /note="[DE]-X(4)-L-L 3"
FT REPEAT 644..650
FT /note="[DE]-X(4)-L-L 4"
FT REGION 249..317
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 698..700
FT /note="Melanosome targeting signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 260..296
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 114..133
FT /note="Missing (in isoform IV)"
FT /evidence="ECO:0000305"
FT /id="VSP_004288"
FT VAR_SEQ 257..289
FT /note="Missing (in isoform II)"
FT /evidence="ECO:0000305"
FT /id="VSP_004289"
FT VAR_SEQ 314..324
FT /note="STIWLEGGTPP -> EDRRKAGGNNS (in isoform III)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9579545"
FT /id="VSP_004290"
FT VAR_SEQ 325..700
FT /note="Missing (in isoform III)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9579545"
FT /id="VSP_004291"
FT VARIANT 55
FT /note="Missing (in HPS1; mild)"
FT /evidence="ECO:0000269|PubMed:9497254"
FT /id="VAR_007950"
FT VARIANT 100
FT /note="E -> D (in dbSNP:rs1801285)"
FT /id="VAR_014887"
FT VARIANT 186
FT /note="A -> V (in dbSNP:rs1801286)"
FT /id="VAR_014888"
FT VARIANT 283
FT /note="G -> W (in dbSNP:rs11592273)"
FT /id="VAR_005290"
FT VARIANT 480
FT /note="A -> T (in dbSNP:rs17109853)"
FT /id="VAR_038378"
FT VARIANT 491
FT /note="P -> R (in dbSNP:rs2296434)"
FT /id="VAR_005291"
FT VARIANT 603
FT /note="Q -> R (in dbSNP:rs2296436)"
FT /id="VAR_005292"
FT VARIANT 630
FT /note="V -> I (in dbSNP:rs139061260)"
FT /id="VAR_005293"
FT CONFLICT 254
FT /note="D -> H (in Ref. 3; AAC52074)"
FT /evidence="ECO:0000305"
FT CONFLICT 533..537
FT /note="SYLED -> Y (in Ref. 2; AAB70662)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 700 AA; 79292 MW; 0885D3E2D64B3248 CRC64;
MKCVLVATEG AEVLFYWTDQ EFEESLRLKF GQSENEEEEL PALEDQLSTL LAPVIISSMT
MLEKLSDTYT CFSTENGNFL YVLHLFGECL FIAINGDHTE SEGDLRRKLY VLKYLFEVHF
GLVTVDGHLI RKELRPPDLA QRVQLWEHFQ SLLWTYSRLR EQEQCFAVEA LERLIHPQLC
ELCIEALERH VIQAVNTSPE RGGEEALHAF LLVHSKLLAF YSSHSASSLR PADLLALILL
VQDLYPSEST AEDDIQPSPR RARSSQNIPV QQAWSPHSTG PTGGSSAETE TDSFSLPEEY
FTPAPSPGDQ SSGSTIWLEG GTPPMDALQI AEDTLQTLVP HCPVPSGPRR IFLDANVKES
YCPLVPHTMY CLPLWQGINL VLLTRSPSAP LALVLSQLMD GFSMLEKKLK EGPEPGASLR
SQPLVGDLRQ RMDKFVKNRG AQEIQSTWLE FKAKAFSKSE PGSSWELLQA CGKLKRQLCA
IYRLNFLTTA PSRGGPHLPQ HLQDQVQRLM REKLTDWKDF LLVKSRRNIT MVSYLEDFPG
LVHFIYVDRT TGQMVAPSLN CSQKTSSELG KGPLAAFVKT KVWSLIQLAR RYLQKGYTTL
LFQEGDFYCS YFLWFENDMG YKLQMIEVPV LSDDSVPIGM LGGDYYRKLL RYYSKNRPTE
AVRCYELLAL HLSVIPTDLL VQQAGQLARR LWEASRIPLL
