ID   HPS5_MOUSE              Reviewed;        1126 AA.
AC   P59438; G3X8S7;
DT   28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2012, sequence version 2.
DT   24-JAN-2024, entry version 140.
DE   RecName: Full=BLOC-2 complex member HPS5 {ECO:0000305};
DE   AltName: Full=Hermansky-Pudlak syndrome 5 protein homolog;
DE   AltName: Full=Ruby-eye protein 2;
DE            Short=Ru2;
GN   Name=Hps5; Synonyms=Ru2;
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] (ISOFORMS 1; 2 AND 3), AND INVOLVEMENT IN
RP   HERMANSKY-PUDLAK-LIKE SYNDROME.
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 GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 174-1126.
RC   STRAIN=FVB/N; 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   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA   Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA   Thibault P.;
RT   "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL   Immunity 30:143-154(2009).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Kidney, Lung, Spleen, and Testis;
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).
CC   -!- FUNCTION: May regulate the synthesis and function of lysosomes and of
CC       highly specialized organelles, such as melanosomes and platelet dense
CC       granules. Regulates intracellular vesicular trafficking in fibroblasts.
CC       May be involved in the regulation of general functions of integrins.
CC       {ECO:0000250|UniProtKB:Q9UPZ3}.
CC   -!- SUBUNIT: Component of the biogenesis of lysosome-related organelles
CC       complex-2 (or BLOC2) composed of HPS3, HPS5 and HPS6. Interacts with
CC       HPS6 and HPS3. May interact with all alpha-integrin chains that have an
CC       aromatic residue before the first lysine of the conserved KXGFFKR
CC       motif, including ITGA2, ITGA3, ITGA5 and ITGA6.
CC       {ECO:0000250|UniProtKB:Q9UPZ3}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:Q9UPZ3}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P59438-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P59438-2; Sequence=VSP_007036;
CC       Name=3;
CC         IsoId=P59438-3; Sequence=VSP_007037, VSP_007038;
CC   -!- TISSUE SPECIFICITY: Widely expressed, with lowest expression in
CC       skeletal muscle and spleen.
CC   -!- DISEASE: Note=Defects in Hps5 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}.
CC   -!- SIMILARITY: Belongs to the HPS5 family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AF534396; AAO25958.1; -; mRNA.
DR   EMBL; AF534397; AAO25959.1; -; mRNA.
DR   EMBL; AF534398; AAO25960.1; -; mRNA.
DR   EMBL; AF534399; AAO25961.1; -; mRNA.
DR   EMBL; AC090122; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH466603; EDL22941.1; -; Genomic_DNA.
DR   EMBL; CH466603; EDL22942.1; -; Genomic_DNA.
DR   EMBL; CH466603; EDL22943.1; -; Genomic_DNA.
DR   EMBL; BC046405; AAH46405.1; -; mRNA.
DR   CCDS; CCDS21286.1; -. [P59438-1]
DR   RefSeq; NP_001005247.2; NM_001005247.2. [P59438-1]
DR   RefSeq; NP_001005248.2; NM_001005248.2. [P59438-1]
DR   RefSeq; NP_001161336.1; NM_001167864.1.
DR   RefSeq; XP_006540967.1; XM_006540904.2. [P59438-1]
DR   RefSeq; XP_006540968.1; XM_006540905.3. [P59438-1]
DR   AlphaFoldDB; P59438; -.
DR   SMR; P59438; -.
DR   BioGRID; 232927; 1.
DR   ComplexPortal; CPX-5084; BLOC-2 complex.
DR   CORUM; P59438; -.
DR   STRING; 10090.ENSMUSP00000014562; -.
DR   iPTMnet; P59438; -.
DR   PhosphoSitePlus; P59438; -.
DR   EPD; P59438; -.
DR   jPOST; P59438; -.
DR   MaxQB; P59438; -.
DR   PaxDb; 10090-ENSMUSP00000014562; -.
DR   PeptideAtlas; P59438; -.
DR   ProteomicsDB; 267154; -. [P59438-1]
DR   ProteomicsDB; 267155; -. [P59438-2]
DR   ProteomicsDB; 267156; -. [P59438-3]
DR   Pumba; P59438; -.
DR   Antibodypedia; 25002; 136 antibodies from 23 providers.
DR   DNASU; 246694; -.
DR   Ensembl; ENSMUST00000014562.14; ENSMUSP00000014562.8; ENSMUSG00000014418.17. [P59438-1]
DR   Ensembl; ENSMUST00000107654.8; ENSMUSP00000103281.2; ENSMUSG00000014418.17. [P59438-1]
DR   Ensembl; ENSMUST00000142663.8; ENSMUSP00000122887.2; ENSMUSG00000014418.17. [P59438-3]
DR   GeneID; 246694; -.
DR   KEGG; mmu:246694; -.
DR   UCSC; uc009gzh.2; mouse. [P59438-1]
DR   AGR; MGI:2180307; -.
DR   CTD; 11234; -.
DR   MGI; MGI:2180307; Hps5.
DR   VEuPathDB; HostDB:ENSMUSG00000014418; -.
DR   eggNOG; KOG3621; Eukaryota.
DR   GeneTree; ENSGT00940000155818; -.
DR   HOGENOM; CLU_039180_0_0_1; -.
DR   InParanoid; P59438; -.
DR   OMA; MCLLCYQ; -.
DR   OrthoDB; 2881230at2759; -.
DR   PhylomeDB; P59438; -.
DR   TreeFam; TF323607; -.
DR   BioGRID-ORCS; 246694; 5 hits in 77 CRISPR screens.
DR   ChiTaRS; Hps5; mouse.
DR   PRO; PR:P59438; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   RNAct; P59438; Protein.
DR   Bgee; ENSMUSG00000014418; Expressed in humerus cartilage element and 227 other cell types or tissues.
DR   ExpressionAtlas; P59438; baseline and differential.
DR   GO; GO:0031084; C:BLOC-2 complex; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005769; C:early endosome; NAS:ComplexPortal.
DR   GO; GO:0007596; P:blood coagulation; IMP:MGI.
DR   GO; GO:0048066; P:developmental pigmentation; IBA:GO_Central.
DR   GO; GO:0046907; P:intracellular transport; NAS:ComplexPortal.
DR   GO; GO:1903232; P:melanosome assembly; NAS: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; NAS:ComplexPortal.
DR   Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1.
DR   InterPro; IPR035431; HPS5.
DR   InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR   InterPro; IPR036322; WD40_repeat_dom_sf.
DR   PANTHER; PTHR23287:SF18; HERMANSKY-PUDLAK SYNDROME 5 PROTEIN; 1.
DR   PANTHER; PTHR23287; RUBY-EYE2-LIKE PROTEIN; 1.
DR   PIRSF; PIRSF037475; BLOC-2_complex_Hps5; 1.
DR   SUPFAM; SSF50978; WD40 repeat-like; 1.
DR   Genevisible; P59438; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cytoplasm; Phosphoprotein; Reference proteome.
FT   CHAIN           1..1126
FT                   /note="BLOC-2 complex member HPS5"
FT                   /id="PRO_0000084055"
FT   REGION          461..514
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          560..579
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        471..497
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        498..512
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         532
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UPZ3"
FT   MOD_RES         534
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UPZ3"
FT   MOD_RES         693
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UPZ3"
FT   VAR_SEQ         1..165
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:12548288"
FT                   /id="VSP_007036"
FT   VAR_SEQ         504..526
FT                   /note="ESASHSPVMSEVDKSEAFLPFSI -> GMKDGSRFGSHCLPFSMLQHSCD
FT                   (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:12548288"
FT                   /id="VSP_007037"
FT   VAR_SEQ         527..1126
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:12548288"
FT                   /id="VSP_007038"
FT   CONFLICT        442
FT                   /note="E -> V (in Ref. 1;
FT                   AAO25958/AAO25959/AAO25960/AAO25961)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1126 AA;  126337 MW;  31B715FE32DAE699 CRC64;
     MTFVPVIPEA YSHVLAEFES LDPLLTALRL DSSRLRCTSI AVSRKWLALG STGGGLNLIQ
     KDGWKQRLFL SHREGAISQI ACCSHDDDYV AVATSQGLVV VWELNQERRG KPERIHVSSE
     HKGRKVTALC WDTAVLRVFV GDHVGKVSAI KLNTLKQAKA AAAFVMFPVQ TVLTVDSCVV
     QLDYLDGRLL VSSLTRSFLC DTEREKFWKI GNKERHGEYG ACFFPGRCAG GQQPVIYCAR
     PGSRMWEVNF DGEVLSTHQF KKLLSMPPLP VITARSEPQY DHTVGSSQSL AFPKLLHLSE
     HCVLTWTEKG IYIFIPQNVQ VLLWSEVKDI QDVAVYKNEL FCLHFNGKIS HLSLLSVERC
     VERLLRRGLW DLAARTCCLF QNSIITSRAR KTLTADKLEH LKSQLDLTAC SELISQLDDL
     ILRFEPLESA CSSRRSSISS HESFSILDSG IYRIISSRRG SQSDEDSCSL HSQTFSEDER
     LKEFASHQEE EQPEQGCGAN RNEESASHSP VMSEVDKSEA FLPFSIALPF RSPSPLVSLQ
     AVKDSVSSFV RKTTEKIGTL HGSPELKEPF ESKDADRAHE EEVSAVTCPL EEDTEEKEIH
     QPPKEDRLQE LTAATAEAMT KLLDPLVLFE PKVLRMVLLE WLSQLEKTFA MKDFPGISNT
     SSPTVKSNLG AHLLGETEKR VLDEESGEGR RVSLVTEEAG GQITCDPVSN LSEPSADRFR
     VCSPYAITNS LQRDLAELTT LCLELNVLTS AMESVGGHVD RASQQLSPEI LACRFLKKYF
     FLLDLKRAKE SIKLTYDSPC VWDTFVEGLK EMARSNPAYT ELEEGDLPTG LQLLDGSVPS
     DSPLLIAFAT RLYDRFGESA LRACIKFYPS ISPSDIAQLC RHHPAQFLAY LDSLVKSRPE
     DQWPSFLEFL LQPESLRLEW LLLAVSHDAP PSTSTVDDEG HPRPHSHLLS WGYSQLILLL
     IKLPADFTTK EKMTDICRSY GFWPGYLTLC LELERRREAF TNIVYLNDIS LMEGDNGWIP
     ETLEEWKLLL HLLQTKSTRP APQESLNGSL SDGPAPINVE NVALLLAKAM GPDRAWSLLQ
     ECGLALELSE KFTRTCDILR IAERRQRALI QGMLEKCDRF LWSQQA
//