HPS3_HUMAN
ID HPS3_HUMAN Reviewed; 1004 AA.
AC Q969F9; A8K6G6; Q8WTV6; Q96AP1; Q96MR3; Q9H608;
DT 10-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=BLOC-2 complex member HPS3 {ECO:0000305};
DE AltName: Full=Hermansky-Pudlak syndrome 3 protein;
GN Name=HPS3;
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 [GENOMIC DNA / MRNA] (ISOFORM 1), AND INVOLVEMENT IN
RP HPS3.
RX PubMed=11455388; DOI=10.1038/ng576;
RA Anikster Y., Huizing M., White J.G., Shevchenko Y.O., Fitzpatrick D.L.,
RA Touchman J.W., Comptom J.G., Bale S.J., Swank R.T., Gahl W.A., Toro J.R.;
RT "Mutation of a new gene causes a unique form of Hermansky-Pudlak syndrome
RT in a genetic isolate of central Puerto Rico.";
RL Nat. Genet. 28:376-380(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 199-1004 (ISOFORMS 1 AND 2).
RC TISSUE=Placenta, Small intestine, and Tongue;
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 [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] (ISOFORM 1).
RC TISSUE=Kidney, and Lymph;
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 INTERACTION WITH HPS6 AND HPS5, AND SUBCELLULAR LOCATION.
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 [6]
RP INTERACTION WITH HPS6.
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).
RN [7]
RP VARIANT HPS3 TRP-397.
RX PubMed=11590544; DOI=10.1086/324168;
RA Huizing M., Anikster Y., Fitzpatrick D.L., Jeong A.B., D'Souza M.,
RA Rausche M., Toro J.R., Kaiser-Kupfer M.I., White J.G., Gahl W.A.;
RT "Hermansky-Pudlak syndrome type 3 in Ashkenazi Jews and other non-Puerto
RT Rican patients with hypopigmentation and platelet storage-pool
RT deficiency.";
RL Am. J. Hum. Genet. 69:1022-1032(2001).
RN [8]
RP VARIANT [LARGE SCALE ANALYSIS] GLN-397.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Involved in early stages of melanosome biogenesis and
CC maturation. {ECO:0000250|UniProtKB:Q91VB4}.
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 (PubMed:15030569). Interacts with HPS6 (PubMed:15030569,
CC PubMed:25189619). {ECO:0000269|PubMed:15030569,
CC ECO:0000269|PubMed:25189619}.
CC -!- INTERACTION:
CC Q969F9; A0A0H3NFP4: sifA; Xeno; NbExp=3; IntAct=EBI-16781620, EBI-27055396;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q91VB4}.
CC Cytoplasm, cytosol {ECO:0000269|PubMed:15030569}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q969F9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q969F9-2; Sequence=VSP_003878, VSP_003879;
CC -!- TISSUE SPECIFICITY: Widely expressed. Higher levels of expression are
CC observed in kidney, liver and placenta.
CC -!- DISEASE: Hermansky-Pudlak syndrome 3 (HPS3) [MIM:614072]: 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:11455388, ECO:0000269|PubMed:11590544}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH16901.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH22062.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAB71221.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Mutations of the HPS3 gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/hps3mut.htm";
CC -!- WEB RESOURCE: Name=Albinism database (ADB); Note=HPS3 mutations;
CC URL="http://www.ifpcs.org/albinism/hps3mut.html";
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DR EMBL; AF375663; AAK84131.1; -; Genomic_DNA.
DR EMBL; AY033141; AAK53457.1; -; mRNA.
DR EMBL; AK026357; BAB15459.1; -; mRNA.
DR EMBL; AK056575; BAB71221.1; ALT_INIT; mRNA.
DR EMBL; AK291631; BAF84320.1; -; mRNA.
DR EMBL; CH471052; EAW78886.1; -; Genomic_DNA.
DR EMBL; BC016901; AAH16901.1; ALT_INIT; mRNA.
DR EMBL; BC022062; AAH22062.2; ALT_INIT; mRNA.
DR EMBL; BC040359; AAH40359.1; -; mRNA.
DR CCDS; CCDS3140.1; -. [Q969F9-1]
DR RefSeq; NP_001295187.1; NM_001308258.1.
DR RefSeq; NP_115759.2; NM_032383.4. [Q969F9-1]
DR AlphaFoldDB; Q969F9; -.
DR BioGRID; 124064; 72.
DR ComplexPortal; CPX-5044; BLOC-2 complex.
DR CORUM; Q969F9; -.
DR IntAct; Q969F9; 5.
DR MINT; Q969F9; -.
DR STRING; 9606.ENSP00000296051; -.
DR iPTMnet; Q969F9; -.
DR PhosphoSitePlus; Q969F9; -.
DR BioMuta; HPS3; -.
DR DMDM; 20532121; -.
DR EPD; Q969F9; -.
DR jPOST; Q969F9; -.
DR MassIVE; Q969F9; -.
DR MaxQB; Q969F9; -.
DR PaxDb; Q969F9; -.
DR PeptideAtlas; Q969F9; -.
DR PRIDE; Q969F9; -.
DR ProteomicsDB; 75751; -. [Q969F9-1]
DR ProteomicsDB; 75752; -. [Q969F9-2]
DR Antibodypedia; 33559; 173 antibodies from 30 providers.
DR DNASU; 84343; -.
DR Ensembl; ENST00000296051.7; ENSP00000296051.2; ENSG00000163755.9. [Q969F9-1]
DR GeneID; 84343; -.
DR KEGG; hsa:84343; -.
DR MANE-Select; ENST00000296051.7; ENSP00000296051.2; NM_032383.5; NP_115759.2.
DR UCSC; uc003ewu.2; human. [Q969F9-1]
DR CTD; 84343; -.
DR DisGeNET; 84343; -.
DR GeneCards; HPS3; -.
DR GeneReviews; HPS3; -.
DR HGNC; HGNC:15597; HPS3.
DR HPA; ENSG00000163755; Low tissue specificity.
DR MalaCards; HPS3; -.
DR MIM; 606118; gene.
DR MIM; 614072; phenotype.
DR neXtProt; NX_Q969F9; -.
DR OpenTargets; ENSG00000163755; -.
DR Orphanet; 231512; Hermansky-Pudlak syndrome due to BLOC-2 deficiency.
DR PharmGKB; PA29433; -.
DR VEuPathDB; HostDB:ENSG00000163755; -.
DR eggNOG; ENOG502QRQB; Eukaryota.
DR GeneTree; ENSGT00390000015458; -.
DR InParanoid; Q969F9; -.
DR OMA; SPSTYRH; -.
DR OrthoDB; 85118at2759; -.
DR PhylomeDB; Q969F9; -.
DR TreeFam; TF324432; -.
DR PathwayCommons; Q969F9; -.
DR SignaLink; Q969F9; -.
DR SIGNOR; Q969F9; -.
DR BioGRID-ORCS; 84343; 9 hits in 1077 CRISPR screens.
DR ChiTaRS; HPS3; human.
DR GeneWiki; HPS3; -.
DR GenomeRNAi; 84343; -.
DR Pharos; Q969F9; Tbio.
DR PRO; PR:Q969F9; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q969F9; protein.
DR Bgee; ENSG00000163755; Expressed in ileal mucosa and 174 other tissues.
DR ExpressionAtlas; Q969F9; baseline and differential.
DR Genevisible; Q969F9; HS.
DR GO; GO:0031084; C:BLOC-2 complex; IPI:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005769; C:early endosome; IC:ComplexPortal.
DR GO; GO:0046907; P:intracellular transport; IC:ComplexPortal.
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 InterPro; IPR017216; HPS3.
DR InterPro; IPR029438; HPS3_C.
DR InterPro; IPR028167; HPS3_central_dom.
DR InterPro; IPR029437; HPS3_N.
DR PANTHER; PTHR28633; PTHR28633; 1.
DR Pfam; PF14763; HPS3_C; 1.
DR Pfam; PF14762; HPS3_Mid; 1.
DR Pfam; PF14761; HPS3_N; 1.
DR PIRSF; PIRSF037473; BLOC-2_complex_Hps3; 1.
PE 1: Evidence at protein level;
KW Albinism; Alternative splicing; Cytoplasm; Disease variant;
KW Hermansky-Pudlak syndrome; Reference proteome.
FT CHAIN 1..1004
FT /note="BLOC-2 complex member HPS3"
FT /id="PRO_0000084050"
FT MOTIF 172..176
FT /note="Clathrin-binding"
FT /evidence="ECO:0000255"
FT VAR_SEQ 864..890
FT /note="SLICGPSFDIASIIPFLEPLSEDTIAG -> LPLFRSWSHFQKTLLPASVSM
FT FCVVHA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_003878"
FT VAR_SEQ 891..1004
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_003879"
FT VARIANT 275
FT /note="E -> K (in dbSNP:rs34388030)"
FT /id="VAR_038379"
FT VARIANT 397
FT /note="R -> Q (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs747708121)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035928"
FT VARIANT 397
FT /note="R -> W (in HPS3; mild; dbSNP:rs121908316)"
FT /evidence="ECO:0000269|PubMed:11590544"
FT /id="VAR_013251"
FT CONFLICT 144..145
FT /note="VK -> AR (in Ref. 4; AAH22062)"
FT /evidence="ECO:0000305"
FT CONFLICT 556
FT /note="G -> E (in Ref. 2; BAB71221)"
FT /evidence="ECO:0000305"
FT CONFLICT 563
FT /note="S -> T (in Ref. 4; AAH22062)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1004 AA; 113736 MW; ECA8FDF6AE37B47A CRC64;
MVQLYNLHPF GSQQVVPCKL EPDRFCGGGR DALFVAAGCK VEAFAVAGQE LCQPRCAFST
LGRVLRLAYS EAGDYLVAIE EKNKATFLRA YVNWRNKRTE NSRVCIRMIG HNVEGPFSKA
FRDQMYIIEM PLSEAPLCIS CCPVKGDLLV GCTNKLVLFS LKYQIINEEF SLLDFERSLI
IHIDNITPVE VSFCVGYVAV MSDLEVLIVK LESGPKNGER VHHHPHKTNN RIRRTEEGIS
NEISQLESDD FVICQKPLEL LGEKSEQSGL SVTLESTGLA DEKRKYSHFQ HLLYRRFAPD
ISSYVLSDDI KLHSLQLLPI YQTGSLTSDG KNLSQEKELL SLFCFFSLPH VGYLYMVVKS
VELMSVYQYP EKSQQAVLTP QFLHVITSNN LQCFTVRCSA AAAREEDPYM DTTLKACPPV
SMDVCALRIQ LFIGLKAICH FKNHIILLTK AEPEAIPERR QSPKRLLSRK DTSVKIKIPP
VAEAGWNLYI VNTISPVQLY KEMVDYSNTY KTVKTQSCIH LLSEAHLLVR AALMDASQLE
PGEKAELLEA FKESCGHLGD CYSRLDSQHS HLTLPYYKMS GLSMAEVLAR TDWTVEDGLQ
KYERGLIFYI NHSLYENLDE ELNEELAAKV VQMFYVAEPK QVPHILCSPS MKNINPLTAM
SYLRKLDTSG FSSILVTLTK AAVALKMGDL DMHRNEMKSH SEMKLVCGFI LEPRLLIQQR
KGQIVPTELA LHLKETQPGL LVASVLGLQK NNKIGIEEAD SFFKVLCAKD EDTIPQLLVD
FWEAQLVACL PDVVLQELFF KLTSQYIWRL SKRQPPDTTP LRTSEDLINA CSHYGLIYPW
VHVVISSDSL ADKNYTEDLS KLQSLICGPS FDIASIIPFL EPLSEDTIAG LSVHVLCRTR
LKEYEQCIDI LLERCPEAVI PYANHELKEE NRTLWWKKLL PELCQRIKCG GEKYQLYLSS
LKETLSIVAV ELELKDFMNV LPEDGTATFF LPYLLYCSRK KPLT
