PKHF1_HUMAN
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 03-AUG-2022, entry version 160.
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 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; Q96S99; -.
DR PeptideAtlas; Q96S99; -.
DR PRIDE; Q96S99; -.
DR ProteomicsDB; 78093; -.
DR Antibodypedia; 15545; 130 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 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; VSWSAFH; -.
DR PhylomeDB; Q96S99; -.
DR TreeFam; TF315235; -.
DR PathwayCommons; Q96S99; -.
DR SignaLink; Q96S99; -.
DR BioGRID-ORCS; 79156; 11 hits in 1083 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 156 other tissues.
DR ExpressionAtlas; Q96S99; baseline and differential.
DR Genevisible; Q96S99; HS.
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; -; 1.
DR Gene3D; 3.30.40.10; -; 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 Pfam; PF01363; FYVE; 1.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00064; FYVE; 1.
DR SMART; SM00233; PH; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50178; ZF_FYVE; 1.
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
