HPS4_MOUSE
ID HPS4_MOUSE Reviewed; 671 AA.
AC Q99KG7;
DT 06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 06-JUN-2002, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=BLOC-3 complex member HPS4 {ECO:0000305};
DE AltName: Full=Hermansky-Pudlak syndrome 4 protein homolog;
DE AltName: Full=Light-ear protein;
DE Short=Le protein;
GN Name=Hps4; Synonyms=Le;
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 [GENOMIC DNA], VARIANT LE, AND DISEASE.
RC STRAIN=129/SvJ;
RX PubMed=11836498; DOI=10.1038/ng835;
RA Suzuki T., Li W., Zhang Q., Karim A., Novak E.K., Sviderskaya E.V.,
RA Hill S.P., Bennett D.C., Levin A.V., Nieuwenhuis H.K., Fong C.-T.,
RA Castellan C., Miterski B., Swank R.T., Spritz R.A.;
RT "Hermansky-Pudlak syndrome is caused by mutations in HPS4, the human
RT homolog of the mouse light-ear gene.";
RL Nat. Genet. 30:321-324(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 287-671.
RC TISSUE=Mammary gland;
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 [3]
RP INTERACTION WITH RAB9A, AND ABSENCE OF INTERACTION WITH RAB4A AND RAB7A.
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 [4]
RP INTERACTION WITH RAB9A.
RX PubMed=26620560; DOI=10.1074/jbc.m115.684043;
RA Marubashi S., Shimada H., Fukuda M., Ohbayashi N.;
RT "RUTBC1 functions as a GTPase-activating protein for Rab32/38 and regulates
RT melanogenic enzyme trafficking in melanocytes.";
RL J. Biol. Chem. 291:1427-1440(2016).
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 {ECO:0000250|UniProtKB:Q9NQG7}.
CC -!- SUBUNIT: Component of the biogenesis of lysosome-related organelles
CC complex-3 (or BLOC-3), a heterodimer of HPS1 and HPS4. HPS4 and the
CC BLOC-3 complex interact with the GTP-bound form of RAB9B but not with
CC the GDP-bound form of RAB9B (By similarity). HPS4 and the BLOC-3
CC complex interact with the GTP-bound form of RAB9A but not with the GDP-
CC bound form of RAB9A (PubMed:20048159, PubMed:26620560,). HPS4 does not
CC interact RAB4A and RAB7A (PubMed:26620560).
CC {ECO:0000250|UniProtKB:Q9NQG7, ECO:0000269|PubMed:20048159,
CC ECO:0000269|PubMed:26620560}.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, brain, liver and testis.
CC Expressed at lower level in skeletal muscle.
CC -!- DISEASE: Note=Defects in Hps4 are the cause of the light ear (le)
CC mutant which exhibits hypopigmentation associated with defects of
CC multiple cytoplasmic organelles, including melanosomes, lysosomes, and
CC granular elements of platelets (PubMed:11836498).
CC {ECO:0000269|PubMed:11836498}.
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DR EMBL; AY043414; AAK95331.1; -; Genomic_DNA.
DR EMBL; AY043402; AAK95331.1; JOINED; Genomic_DNA.
DR EMBL; AY043403; AAK95331.1; JOINED; Genomic_DNA.
DR EMBL; AY043404; AAK95331.1; JOINED; Genomic_DNA.
DR EMBL; AY043405; AAK95331.1; JOINED; Genomic_DNA.
DR EMBL; AY043406; AAK95331.1; JOINED; Genomic_DNA.
DR EMBL; AY043407; AAK95331.1; JOINED; Genomic_DNA.
DR EMBL; AY043408; AAK95331.1; JOINED; Genomic_DNA.
DR EMBL; AY043409; AAK95331.1; JOINED; Genomic_DNA.
DR EMBL; AY043410; AAK95331.1; JOINED; Genomic_DNA.
DR EMBL; AY043411; AAK95331.1; JOINED; Genomic_DNA.
DR EMBL; AY043412; AAK95331.1; JOINED; Genomic_DNA.
DR EMBL; AY043413; AAK95331.1; JOINED; Genomic_DNA.
DR EMBL; AY043415; AAK95332.1; -; mRNA.
DR EMBL; BC004668; AAH04668.1; -; mRNA.
DR CCDS; CCDS19540.1; -.
DR RefSeq; NP_619587.3; NM_138646.3.
DR RefSeq; XP_006534893.1; XM_006534830.2.
DR RefSeq; XP_006534894.1; XM_006534831.3.
DR RefSeq; XP_006534895.1; XM_006534832.3.
DR AlphaFoldDB; Q99KG7; -.
DR BioGRID; 228683; 1.
DR ComplexPortal; CPX-5083; BLOC-3 complex.
DR IntAct; Q99KG7; 1.
DR STRING; 10090.ENSMUSP00000047920; -.
DR iPTMnet; Q99KG7; -.
DR PhosphoSitePlus; Q99KG7; -.
DR MaxQB; Q99KG7; -.
DR PaxDb; Q99KG7; -.
DR PRIDE; Q99KG7; -.
DR ProteomicsDB; 267015; -.
DR Antibodypedia; 54828; 53 antibodies from 16 providers.
DR Ensembl; ENSMUST00000035279; ENSMUSP00000047920; ENSMUSG00000042328.
DR Ensembl; ENSMUST00000112359; ENSMUSP00000107978; ENSMUSG00000042328.
DR GeneID; 192232; -.
DR KEGG; mmu:192232; -.
DR UCSC; uc008ytd.2; mouse.
DR CTD; 89781; -.
DR MGI; MGI:2177742; Hps4.
DR VEuPathDB; HostDB:ENSMUSG00000042328; -.
DR eggNOG; ENOG502QSIZ; Eukaryota.
DR GeneTree; ENSGT00390000007349; -.
DR HOGENOM; CLU_028579_0_0_1; -.
DR InParanoid; Q99KG7; -.
DR OMA; FYNGPVR; -.
DR OrthoDB; 359138at2759; -.
DR PhylomeDB; Q99KG7; -.
DR TreeFam; TF332819; -.
DR Reactome; R-MMU-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR BioGRID-ORCS; 192232; 3 hits in 74 CRISPR screens.
DR PRO; PR:Q99KG7; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q99KG7; protein.
DR Bgee; ENSMUSG00000042328; Expressed in internal carotid artery and 256 other tissues.
DR ExpressionAtlas; Q99KG7; baseline and differential.
DR Genevisible; Q99KG7; MM.
DR GO; GO:0031085; C:BLOC-3 complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR GO; GO:0005765; C:lysosomal membrane; IBA:GO_Central.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0042470; C:melanosome; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0042827; C:platelet dense granule; ISO:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:MGI.
DR GO; GO:0046983; F:protein dimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB.
DR GO; GO:0007596; P:blood coagulation; IMP:MGI.
DR GO; GO:0046907; P:intracellular transport; IC:ComplexPortal.
DR GO; GO:0007040; P:lysosome organization; ISS:UniProtKB.
DR GO; GO:0030318; P:melanocyte differentiation; IMP:MGI.
DR GO; GO:1903232; P:melanosome assembly; ISS:UniProtKB.
DR GO; GO:0006996; P:organelle organization; IMP:MGI.
DR GO; GO:0060155; P:platelet dense granule organization; IC:ComplexPortal.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0006605; P:protein targeting; ISS:UniProtKB.
DR GO; GO:0016192; P:vesicle-mediated transport; IEA:InterPro.
DR InterPro; IPR043987; CCZ1/INTU/HSP4_longin_1.
DR InterPro; IPR043989; CCZ1/INTU/HSP4_longin_3.
DR InterPro; IPR026091; HPS4.
DR PANTHER; PTHR14407; PTHR14407; 2.
DR Pfam; PF19031; Intu_longin_1; 1.
DR Pfam; PF19033; Intu_longin_3; 1.
PE 1: Evidence at protein level;
KW Albinism; Disease variant; Guanine-nucleotide releasing factor;
KW Reference proteome.
FT CHAIN 1..671
FT /note="BLOC-3 complex member HPS4"
FT /id="PRO_0000084053"
FT REGION 269..291
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 417..497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 269..289
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 420..434
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 437..451
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 465..482
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 51..671
FT /note="Missing (in Le)"
FT CONFLICT 287..290
FT /note="AEDA -> PRVR (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 671 AA; 72662 MW; 3167737195F7F3BD CRC64;
MATTTPPETK SAAWWNYFFL YDGSKVKGEG DPTRAGICYF YPPQTLLDQQ ELLCGQLAGV
VRCLWDLSGT PPMLIRMRNL KFAIRADGDY LWALGCGVEI SDASCRQFLD QLIGFFHFYM
GPVSLAYKSH PQEELSLQWD TSITQVLRST SESHRIFNAL WNLDRTKVEP LLLLKAALIL
QTCQRSPHVL AGCILYKGLI VNSQLLPSLT AKVLLHQTVP ADQRLPGAGA APQETGAALP
PDVQITSVFL SEEEVASLHE FPVEHETRLQ GSSVQYPPWD QSSPTQAEDA WASAAIPEPT
PHDGACPSGS GADERLPRLE QECAGPTGLC TTACGQGSGL SSRLQKELCL SREELDSSEM
HVSEAQEAFP PLPALGDLET LHSSHSAPTL PEDTAICSCL HPCPLERLPE SGRLGQLADL
PLTNGQTQVP GTDPLPSSMP VALPPQHPVG VEPSVEPYGN GAQESHSALP RSSRSPDSPG
PSPSADRTGF KPSPSGRHAG LVPMNLYTHS VNGLVLSLLA EETLLSDTAA IEEVYHSSLA
SLNGLEVHLK ETLPRDEASL TSSTYNFLHY DRIQSVLSAN LPLVTAPQDR RFLQAVNLMH
SDFALLPMLY EMTIRNASTA VYACSSPAQE TYFQQLAPTA RSSGFPNPQD CAFSLAGKAK
QKLLKHGVNL L
