ID   PKHF1_HUMAN             Reviewed;         279 AA.
AC   Q96S99; Q96K11; Q9BUB9;
DT   03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2006, sequence version 3.
DT   27-MAR-2024, entry version 168.
DE   RecName: Full=Pleckstrin homology domain-containing family F member 1;
DE            Short=PH domain-containing family F member 1;
DE   AltName: Full=Lysosome-associated apoptosis-inducing protein containing PH and FYVE domains;
DE            Short=Apoptosis-inducing protein;
DE   AltName: Full=PH and FYVE domain-containing protein 1;
DE   AltName: Full=Phafin-1;
DE   AltName: Full=Zinc finger FYVE domain-containing protein 15;
GN   Name=PLEKHF1; Synonyms=APPD, LAPF, ZFYVE15;
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], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=16188880; DOI=10.1074/jbc.m502190200;
RA   Chen W., Li N., Chen T., Han Y., Li C., Wang Y., He W., Zhang L., Wan T.,
RA   Cao X.;
RT   "The lysosome-associated apoptosis-inducing protein containing the
RT   pleckstrin homology (PH) and FYVE domains (LAPF), representative of a novel
RT   family of PH and FYVE domain-containing proteins, induces caspase-
RT   independent apoptosis via the lysosomal-mitochondrial pathway.";
RL   J. Biol. Chem. 280:40985-40995(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Shi H., Hong W.;
RT   "Phafin 1, PH and FYVE domain-containing protein 1.";
RL   Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Placenta;
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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).
CC   -!- FUNCTION: May induce apoptosis through the lysosomal-mitochondrial
CC       pathway. Translocates to the lysosome initiating the permeabilization
CC       of lysosomal membrane (LMP) and resulting in the release of CTSD and
CC       CTSL to the cytoplasm. Triggers the caspase-independent apoptosis by
CC       altering mitochondrial membrane permeabilization (MMP) resulting in the
CC       release of PDCD8. {ECO:0000269|PubMed:16188880}.
CC   -!- INTERACTION:
CC       Q96S99; O95810: CAVIN2; NbExp=3; IntAct=EBI-745767, EBI-742141;
CC       Q96S99; Q9UKJ5: CHIC2; NbExp=3; IntAct=EBI-745767, EBI-741528;
CC       Q96S99; Q96JM7: L3MBTL3; NbExp=3; IntAct=EBI-745767, EBI-2686809;
CC       Q96S99; Q96JM7-2: L3MBTL3; NbExp=3; IntAct=EBI-745767, EBI-11985629;
CC       Q96S99; Q86SE8-2: NPM2; NbExp=3; IntAct=EBI-745767, EBI-12193061;
CC       Q96S99; O95379: TNFAIP8; NbExp=3; IntAct=EBI-745767, EBI-1049336;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16188880}. Cytoplasm,
CC       perinuclear region {ECO:0000269|PubMed:16188880}. Lysosome
CC       {ECO:0000269|PubMed:16188880}. Note=Translocates to lysosome during
CC       apoptosis.
CC   -!- TISSUE SPECIFICITY: Highly expressed in heart and skeletal muscle.
CC       Weakly expressed in brain, thymus, spleen, kidney, liver, small
CC       intestine, placenta and lung. {ECO:0000269|PubMed:16188880}.
CC   -!- DOMAIN: PH and FYVE-type zinc finger domains are required for lysosomal
CC       location.
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DR   EMBL; AY037145; AAK67626.2; -; mRNA.
DR   EMBL; AF434818; AAL30773.1; -; mRNA.
DR   EMBL; AK027758; BAB55349.1; -; mRNA.
DR   EMBL; BC002744; AAH02744.1; -; mRNA.
DR   CCDS; CCDS12417.1; -.
DR   RefSeq; NP_077286.3; NM_024310.4.
DR   RefSeq; XP_011525611.1; XM_011527309.2.
DR   AlphaFoldDB; Q96S99; -.
DR   SMR; Q96S99; -.
DR   BioGRID; 122574; 9.
DR   IntAct; Q96S99; 7.
DR   STRING; 9606.ENSP00000389787; -.
DR   TCDB; 8.A.136.1.12; the alpha/beta-arrestin (arrb) family.
DR   iPTMnet; Q96S99; -.
DR   PhosphoSitePlus; Q96S99; -.
DR   BioMuta; PLEKHF1; -.
DR   DMDM; 115502559; -.
DR   EPD; Q96S99; -.
DR   jPOST; Q96S99; -.
DR   MassIVE; Q96S99; -.
DR   MaxQB; Q96S99; -.
DR   PaxDb; 9606-ENSP00000389787; -.
DR   PeptideAtlas; Q96S99; -.
DR   ProteomicsDB; 78093; -.
DR   Pumba; Q96S99; -.
DR   Antibodypedia; 15545; 146 antibodies from 22 providers.
DR   DNASU; 79156; -.
DR   Ensembl; ENST00000436066.4; ENSP00000389787.2; ENSG00000166289.6.
DR   Ensembl; ENST00000592810.1; ENSP00000466292.1; ENSG00000166289.6.
DR   GeneID; 79156; -.
DR   KEGG; hsa:79156; -.
DR   MANE-Select; ENST00000436066.4; ENSP00000389787.2; NM_024310.5; NP_077286.3.
DR   UCSC; uc002nsh.5; human.
DR   AGR; HGNC:20764; -.
DR   CTD; 79156; -.
DR   DisGeNET; 79156; -.
DR   GeneCards; PLEKHF1; -.
DR   HGNC; HGNC:20764; PLEKHF1.
DR   HPA; ENSG00000166289; Tissue enhanced (skeletal).
DR   MIM; 615200; gene.
DR   neXtProt; NX_Q96S99; -.
DR   OpenTargets; ENSG00000166289; -.
DR   PharmGKB; PA134928547; -.
DR   VEuPathDB; HostDB:ENSG00000166289; -.
DR   eggNOG; KOG1729; Eukaryota.
DR   GeneTree; ENSGT00940000160728; -.
DR   HOGENOM; CLU_064864_2_0_1; -.
DR   InParanoid; Q96S99; -.
DR   OMA; ICMRCTH; -.
DR   OrthoDB; 5385125at2759; -.
DR   PhylomeDB; Q96S99; -.
DR   TreeFam; TF315235; -.
DR   PathwayCommons; Q96S99; -.
DR   SignaLink; Q96S99; -.
DR   BioGRID-ORCS; 79156; 11 hits in 1160 CRISPR screens.
DR   ChiTaRS; PLEKHF1; human.
DR   GenomeRNAi; 79156; -.
DR   Pharos; Q96S99; Tbio.
DR   PRO; PR:Q96S99; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q96S99; Protein.
DR   Bgee; ENSG00000166289; Expressed in hindlimb stylopod muscle and 158 other cell types or tissues.
DR   ExpressionAtlas; Q96S99; baseline and differential.
DR   GO; GO:0005769; C:early endosome; IBA:GO_Central.
DR   GO; GO:0010008; C:endosome membrane; IC:BHF-UCL.
DR   GO; GO:0005765; C:lysosomal membrane; IC:BHF-UCL.
DR   GO; GO:0005764; C:lysosome; IDA:BHF-UCL.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0035091; F:phosphatidylinositol binding; IBA:GO_Central.
DR   GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IDA:BHF-UCL.
DR   GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:BHF-UCL.
DR   GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; IDA:BHF-UCL.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0007032; P:endosome organization; IMP:BHF-UCL.
DR   GO; GO:0008333; P:endosome to lysosome transport; IBA:GO_Central.
DR   GO; GO:0010508; P:positive regulation of autophagy; IDA:BHF-UCL.
DR   GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IBA:GO_Central.
DR   GO; GO:0072659; P:protein localization to plasma membrane; IMP:BHF-UCL.
DR   GO; GO:0016050; P:vesicle organization; IMP:BHF-UCL.
DR   CDD; cd15754; FYVE_PKHF1; 1.
DR   CDD; cd01218; PH_Phafin2-like; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR   Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR001849; PH_domain.
DR   InterPro; IPR037871; PH_Phafin.
DR   InterPro; IPR042762; PKHF1_FYVE.
DR   InterPro; IPR000306; Znf_FYVE.
DR   InterPro; IPR017455; Znf_FYVE-rel.
DR   InterPro; IPR011011; Znf_FYVE_PHD.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   PANTHER; PTHR46280:SF2; PLECKSTRIN HOMOLOGY DOMAIN-CONTAINING FAMILY F MEMBER 1; 1.
DR   PANTHER; PTHR46280; PLECKSTRIN HOMOLOGY DOMAIN-CONTAINING FAMILY F MEMBER 2-RELATED; 1.
DR   Pfam; PF01363; FYVE; 1.
DR   Pfam; PF00169; PH; 1.
DR   SMART; SM00064; FYVE; 1.
DR   SMART; SM00233; PH; 1.
DR   SUPFAM; SSF57903; FYVE/PHD zinc finger; 1.
DR   SUPFAM; SSF50729; PH domain-like; 1.
DR   PROSITE; PS50003; PH_DOMAIN; 1.
DR   PROSITE; PS50178; ZF_FYVE; 1.
DR   Genevisible; Q96S99; HS.
PE   1: Evidence at protein level;
KW   Apoptosis; Cytoplasm; Lysosome; Metal-binding; Nucleus; Reference proteome;
KW   Zinc; Zinc-finger.
FT   CHAIN           1..279
FT                   /note="Pleckstrin homology domain-containing family F
FT                   member 1"
FT                   /id="PRO_0000251597"
FT   DOMAIN          35..131
FT                   /note="PH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT   ZN_FING         152..212
FT                   /note="FYVE-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   REGION          218..264
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         158
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         161
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         175
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         178
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         183
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         186
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         204
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         207
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   CONFLICT        55
FT                   /note="F -> L (in Ref. 2; AAL30773 and 3; BAB55349)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        135
FT                   /note="R -> K (in Ref. 1; AAK67626)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        229
FT                   /note="G -> R (in Ref. 1; AAK67626)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   279 AA;  31195 MW;  ED2ADEBDE6BCF3BF CRC64;
     MVDHLANTEI NSQRIAAVES CFGASGQPLA LPGRVLLGEG VLTKECRKKA KPRIFFLFND
     ILVYGSIVLN KRKYRSQHII PLEEVTLELL PETLQAKNRW MIKTAKKSFV VSAASATERQ
     EWISHIEECV RRQLRATGRP PSTEHAAPWI PDKATDICMR CTQTRFSALT RRHHCRKCGF
     VVCAECSRQR FLLPRLSPKP VRVCSLCYRE LAAQQRQEEA EEQGAGSPGQ PAHLARPICG
     ASSGDDDDSD EDKEGSRDGD WPSSVEFYAS GVAWSAFHS
//