Full text data of PLEKHF2
PLEKHF2
(ZFYVE18)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Pleckstrin homology domain-containing family F member 2; PH domain-containing family F member 2 (Endoplasmic reticulum-associated apoptosis-involved protein containing PH and FYVE domains; EAPF; PH and FYVE domain-containing protein 2; Phafin-2; Phafin2; Zinc finger FYVE domain-containing protein 18)
Pleckstrin homology domain-containing family F member 2; PH domain-containing family F member 2 (Endoplasmic reticulum-associated apoptosis-involved protein containing PH and FYVE domains; EAPF; PH and FYVE domain-containing protein 2; Phafin-2; Phafin2; Zinc finger FYVE domain-containing protein 18)
UniProt
Q9H8W4
ID PKHF2_HUMAN Reviewed; 249 AA.
AC Q9H8W4;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 110.
DE RecName: Full=Pleckstrin homology domain-containing family F member 2;
DE Short=PH domain-containing family F member 2;
DE AltName: Full=Endoplasmic reticulum-associated apoptosis-involved protein containing PH and FYVE domains;
DE Short=EAPF;
DE AltName: Full=PH and FYVE domain-containing protein 2;
DE AltName: Full=Phafin-2;
DE Short=Phafin2;
DE AltName: Full=Zinc finger FYVE domain-containing protein 18;
GN Name=PLEKHF2; Synonyms=ZFYVE18;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Shi H., Hong W.;
RT "Phafin 2, PH and FYVE domain-containing protein 2.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 MRNA].
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=B-cell;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, AND
RP DOMAIN.
RX PubMed=18288467; DOI=10.1007/s00109-007-0298-7;
RA Li C., Liu Q., Li N., Chen W., Wang L., Wang Y., Yu Y., Cao X.;
RT "EAPF/Phafin-2, a novel endoplasmic reticulum-associated protein,
RT facilitates TNF-alpha-triggered cellular apoptosis through endoplasmic
RT reticulum-mitochondrial apoptotic pathway.";
RL J. Mol. Med. 86:471-484(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-44, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19995552; DOI=10.1016/j.bbrc.2009.12.016;
RA Lin W.J., Yang C.Y., Lin Y.C., Tsai M.C., Yang C.W., Tung C.Y.,
RA Ho P.Y., Kao F.J., Lin C.H.;
RT "Phafin2 modulates the structure and function of endosomes by a Rab5-
RT dependent mechanism.";
RL Biochem. Biophys. Res. Commun. 391:1043-1048(2010).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239 AND SER-248, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239 AND SER-248, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [12]
RP FUNCTION, INTERACTION WITH EEA1, AND SUBCELLULAR LOCATION.
RX PubMed=22816767; DOI=10.1111/j.1600-0854.2012.01400.x;
RA Pedersen N.M., Raiborg C., Brech A., Skarpen E., Roxrud I.,
RA Platta H.W., Liestol K., Stenmark H.;
RT "The PtdIns3P-binding protein Phafin 2 mediates epidermal growth
RT factor receptor degradation by promoting endosome fusion.";
RL Traffic 13:1547-1563(2012).
CC -!- FUNCTION: May play a role in early endosome fusion upstream of
CC RAB5, hence regulating receptor trafficking and fluid-phase
CC transport. Enhances cellular sensitivity to TNF-induced apoptosis
CC (PubMed:18288467).
CC -!- SUBUNIT: May interact with EEA1.
CC -!- INTERACTION:
CC Q9UKJ5:CHIC2; NbExp=3; IntAct=EBI-742388, EBI-741528;
CC Q9NS73:MBIP; NbExp=3; IntAct=EBI-742388, EBI-741953;
CC P10644:PRKAR1A; NbExp=3; IntAct=EBI-742388, EBI-476431;
CC Q9UI14:RABAC1; NbExp=3; IntAct=EBI-742388, EBI-712367;
CC -!- SUBCELLULAR LOCATION: Early endosome membrane; Peripheral membrane
CC protein. Endoplasmic reticulum. Note=Colocalizes with EEA1 and
CC RAB5 at endosomal membrane fusion hot spots. May translocate to
CC the endoplasmic reticulum in the early phase of apoptosis
CC (PubMed:18288467).
CC -!- TISSUE SPECIFICITY: Expressed in placenta, ovary and small
CC intestine, as well as in heart and pancreas. Also expressed in
CC peripheral blood mononuclear cells and dendritic cells.
CC -!- INDUCTION: Up-regulated by TNF, bacterial lipopolysaccharides
CC (LPS) and phorbol myristate acetate (PMA) (at protein level).
CC -!- DOMAIN: The PH and FYVE domains may be important for TNF-induced
CC localization to the endoplasmic reticulum and for enhanced
CC cellular sensitivity to TNF-induced apoptosis (PubMed:18288467).
CC The FYVE domain is important for binding to the endosomal
CC membrane.
CC -!- SIMILARITY: Contains 1 FYVE-type zinc finger.
CC -!- SIMILARITY: Contains 1 PH domain.
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DR EMBL; AF434819; AAL30774.1; -; mRNA.
DR EMBL; AK023249; BAB14486.1; -; mRNA.
DR EMBL; AL834473; CAD39132.1; -; mRNA.
DR EMBL; BC011806; AAH11806.1; -; mRNA.
DR RefSeq; NP_078889.1; NM_024613.3.
DR UniGene; Hs.29724; -.
DR ProteinModelPortal; Q9H8W4; -.
DR SMR; Q9H8W4; 26-137, 149-212.
DR IntAct; Q9H8W4; 35.
DR MINT; MINT-1468345; -.
DR STRING; 9606.ENSP00000322373; -.
DR PhosphoSite; Q9H8W4; -.
DR DMDM; 74762744; -.
DR PaxDb; Q9H8W4; -.
DR PRIDE; Q9H8W4; -.
DR DNASU; 79666; -.
DR Ensembl; ENST00000315367; ENSP00000322373; ENSG00000175895.
DR Ensembl; ENST00000519516; ENSP00000427792; ENSG00000175895.
DR GeneID; 79666; -.
DR KEGG; hsa:79666; -.
DR UCSC; uc003yhn.2; human.
DR CTD; 79666; -.
DR GeneCards; GC08P096215; -.
DR HGNC; HGNC:20757; PLEKHF2.
DR HPA; HPA024829; -.
DR MIM; 615208; gene.
DR neXtProt; NX_Q9H8W4; -.
DR PharmGKB; PA128394715; -.
DR eggNOG; NOG308864; -.
DR HOGENOM; HOG000231519; -.
DR HOVERGEN; HBG059973; -.
DR InParanoid; Q9H8W4; -.
DR OMA; GEHAAVW; -.
DR OrthoDB; EOG7PK90K; -.
DR PhylomeDB; Q9H8W4; -.
DR GeneWiki; PLEKHF2; -.
DR GenomeRNAi; 79666; -.
DR NextBio; 68872; -.
DR PRO; PR:Q9H8W4; -.
DR Bgee; Q9H8W4; -.
DR CleanEx; HS_PLEKHF2; -.
DR Genevestigator; Q9H8W4; -.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0030133; C:transport vesicle; IDA:LIFEdb.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR001849; Pleckstrin_homology.
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 Acetylation; Complete proteome; Endoplasmic reticulum; Endosome;
KW Membrane; Metal-binding; Phosphoprotein; Protein transport;
KW Reference proteome; Transport; Zinc; Zinc-finger.
FT CHAIN 1 249 Pleckstrin homology domain-containing
FT family F member 2.
FT /FTId=PRO_0000251600.
FT DOMAIN 35 131 PH.
FT ZN_FING 152 212 FYVE-type.
FT MOD_RES 44 44 N6-acetyllysine.
FT MOD_RES 239 239 Phosphoserine.
FT MOD_RES 248 248 Phosphoserine.
SQ SEQUENCE 249 AA; 27798 MW; F5E3F84595A98886 CRC64;
MVDRLANSEA NTRRISIVEN CFGAAGQPLT IPGRVLIGEG VLTKLCRKKP KARQFFLFND
ILVYGNIVIQ KKKYNKQHII PLENVTIDSI KDEGDLRNGW LIKTPTKSFA VYAATATEKS
EWMNHINKCV TDLLSKSGKT PSNEHAAVWV PDSEATVCMR CQKAKFTPVN RRHHCRKCGF
VVCGPCSEKR FLLPSQSSKP VRICDFCYDL LSAGDMATCQ PARSDSYSQS LKSPLNDMSD
DDDDDDSSD
//
ID PKHF2_HUMAN Reviewed; 249 AA.
AC Q9H8W4;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 110.
DE RecName: Full=Pleckstrin homology domain-containing family F member 2;
DE Short=PH domain-containing family F member 2;
DE AltName: Full=Endoplasmic reticulum-associated apoptosis-involved protein containing PH and FYVE domains;
DE Short=EAPF;
DE AltName: Full=PH and FYVE domain-containing protein 2;
DE AltName: Full=Phafin-2;
DE Short=Phafin2;
DE AltName: Full=Zinc finger FYVE domain-containing protein 18;
GN Name=PLEKHF2; Synonyms=ZFYVE18;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Shi H., Hong W.;
RT "Phafin 2, PH and FYVE domain-containing protein 2.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 MRNA].
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=B-cell;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, AND
RP DOMAIN.
RX PubMed=18288467; DOI=10.1007/s00109-007-0298-7;
RA Li C., Liu Q., Li N., Chen W., Wang L., Wang Y., Yu Y., Cao X.;
RT "EAPF/Phafin-2, a novel endoplasmic reticulum-associated protein,
RT facilitates TNF-alpha-triggered cellular apoptosis through endoplasmic
RT reticulum-mitochondrial apoptotic pathway.";
RL J. Mol. Med. 86:471-484(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-44, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19995552; DOI=10.1016/j.bbrc.2009.12.016;
RA Lin W.J., Yang C.Y., Lin Y.C., Tsai M.C., Yang C.W., Tung C.Y.,
RA Ho P.Y., Kao F.J., Lin C.H.;
RT "Phafin2 modulates the structure and function of endosomes by a Rab5-
RT dependent mechanism.";
RL Biochem. Biophys. Res. Commun. 391:1043-1048(2010).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239 AND SER-248, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239 AND SER-248, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [12]
RP FUNCTION, INTERACTION WITH EEA1, AND SUBCELLULAR LOCATION.
RX PubMed=22816767; DOI=10.1111/j.1600-0854.2012.01400.x;
RA Pedersen N.M., Raiborg C., Brech A., Skarpen E., Roxrud I.,
RA Platta H.W., Liestol K., Stenmark H.;
RT "The PtdIns3P-binding protein Phafin 2 mediates epidermal growth
RT factor receptor degradation by promoting endosome fusion.";
RL Traffic 13:1547-1563(2012).
CC -!- FUNCTION: May play a role in early endosome fusion upstream of
CC RAB5, hence regulating receptor trafficking and fluid-phase
CC transport. Enhances cellular sensitivity to TNF-induced apoptosis
CC (PubMed:18288467).
CC -!- SUBUNIT: May interact with EEA1.
CC -!- INTERACTION:
CC Q9UKJ5:CHIC2; NbExp=3; IntAct=EBI-742388, EBI-741528;
CC Q9NS73:MBIP; NbExp=3; IntAct=EBI-742388, EBI-741953;
CC P10644:PRKAR1A; NbExp=3; IntAct=EBI-742388, EBI-476431;
CC Q9UI14:RABAC1; NbExp=3; IntAct=EBI-742388, EBI-712367;
CC -!- SUBCELLULAR LOCATION: Early endosome membrane; Peripheral membrane
CC protein. Endoplasmic reticulum. Note=Colocalizes with EEA1 and
CC RAB5 at endosomal membrane fusion hot spots. May translocate to
CC the endoplasmic reticulum in the early phase of apoptosis
CC (PubMed:18288467).
CC -!- TISSUE SPECIFICITY: Expressed in placenta, ovary and small
CC intestine, as well as in heart and pancreas. Also expressed in
CC peripheral blood mononuclear cells and dendritic cells.
CC -!- INDUCTION: Up-regulated by TNF, bacterial lipopolysaccharides
CC (LPS) and phorbol myristate acetate (PMA) (at protein level).
CC -!- DOMAIN: The PH and FYVE domains may be important for TNF-induced
CC localization to the endoplasmic reticulum and for enhanced
CC cellular sensitivity to TNF-induced apoptosis (PubMed:18288467).
CC The FYVE domain is important for binding to the endosomal
CC membrane.
CC -!- SIMILARITY: Contains 1 FYVE-type zinc finger.
CC -!- SIMILARITY: Contains 1 PH domain.
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DR EMBL; AF434819; AAL30774.1; -; mRNA.
DR EMBL; AK023249; BAB14486.1; -; mRNA.
DR EMBL; AL834473; CAD39132.1; -; mRNA.
DR EMBL; BC011806; AAH11806.1; -; mRNA.
DR RefSeq; NP_078889.1; NM_024613.3.
DR UniGene; Hs.29724; -.
DR ProteinModelPortal; Q9H8W4; -.
DR SMR; Q9H8W4; 26-137, 149-212.
DR IntAct; Q9H8W4; 35.
DR MINT; MINT-1468345; -.
DR STRING; 9606.ENSP00000322373; -.
DR PhosphoSite; Q9H8W4; -.
DR DMDM; 74762744; -.
DR PaxDb; Q9H8W4; -.
DR PRIDE; Q9H8W4; -.
DR DNASU; 79666; -.
DR Ensembl; ENST00000315367; ENSP00000322373; ENSG00000175895.
DR Ensembl; ENST00000519516; ENSP00000427792; ENSG00000175895.
DR GeneID; 79666; -.
DR KEGG; hsa:79666; -.
DR UCSC; uc003yhn.2; human.
DR CTD; 79666; -.
DR GeneCards; GC08P096215; -.
DR HGNC; HGNC:20757; PLEKHF2.
DR HPA; HPA024829; -.
DR MIM; 615208; gene.
DR neXtProt; NX_Q9H8W4; -.
DR PharmGKB; PA128394715; -.
DR eggNOG; NOG308864; -.
DR HOGENOM; HOG000231519; -.
DR HOVERGEN; HBG059973; -.
DR InParanoid; Q9H8W4; -.
DR OMA; GEHAAVW; -.
DR OrthoDB; EOG7PK90K; -.
DR PhylomeDB; Q9H8W4; -.
DR GeneWiki; PLEKHF2; -.
DR GenomeRNAi; 79666; -.
DR NextBio; 68872; -.
DR PRO; PR:Q9H8W4; -.
DR Bgee; Q9H8W4; -.
DR CleanEx; HS_PLEKHF2; -.
DR Genevestigator; Q9H8W4; -.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0030133; C:transport vesicle; IDA:LIFEdb.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR001849; Pleckstrin_homology.
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 Acetylation; Complete proteome; Endoplasmic reticulum; Endosome;
KW Membrane; Metal-binding; Phosphoprotein; Protein transport;
KW Reference proteome; Transport; Zinc; Zinc-finger.
FT CHAIN 1 249 Pleckstrin homology domain-containing
FT family F member 2.
FT /FTId=PRO_0000251600.
FT DOMAIN 35 131 PH.
FT ZN_FING 152 212 FYVE-type.
FT MOD_RES 44 44 N6-acetyllysine.
FT MOD_RES 239 239 Phosphoserine.
FT MOD_RES 248 248 Phosphoserine.
SQ SEQUENCE 249 AA; 27798 MW; F5E3F84595A98886 CRC64;
MVDRLANSEA NTRRISIVEN CFGAAGQPLT IPGRVLIGEG VLTKLCRKKP KARQFFLFND
ILVYGNIVIQ KKKYNKQHII PLENVTIDSI KDEGDLRNGW LIKTPTKSFA VYAATATEKS
EWMNHINKCV TDLLSKSGKT PSNEHAAVWV PDSEATVCMR CQKAKFTPVN RRHHCRKCGF
VVCGPCSEKR FLLPSQSSKP VRICDFCYDL LSAGDMATCQ PARSDSYSQS LKSPLNDMSD
DDDDDDSSD
//
MIM
615208
*RECORD*
*FIELD* NO
615208
*FIELD* TI
*615208 PLECKSTRIN HOMOLOGY DOMAIN-CONTAINING PROTEIN, FAMILY F, MEMBER 2;
PLEKHF2
read more;;ENDOPLASMIC RETICULUM-ASSOCIATED APOPTOSIS-INVOLVED PROTEIN CONTAINING
PH AND FYVE DOMAINS; EAPF;;
PH AND FYVE DOMAINS-CONTAINING PROTEIN 2; PHAFIN2;;
PHAFIN 2
*FIELD* TX
DESCRIPTION
PLEKHF2 has roles in biogenesis of early endosomes (Pedersen et al.,
2012) and apoptosis (Li et al., 2008).
CLONING
By database analysis to identify genes similar to phafin-1 (PLEKHF1;
615200), followed by RT-PCR of bone marrow stromal cells, Li et al.
(2008) cloned PLEKHF2, which they designated EAPF, or phafin-2. The
deduced 249-amino acid protein has a calculated molecular mass of 27.8
kD. It has an N-terminal pleckstrin (PLEK; 173570) homology (PH) domain
and a C-terminal FYVE domain and shares 97.6% identity with mouse
phafin-2. RT-PCR analysis of 16 human tissues detected abundant
expression in placenta, ovary, and small intestine, with weaker
expression in heart and pancreas, and no expression in other tissues.
Phafin-2 was also expressed in dendritic cells and in most leukemia and
solid tumor cell lines examined. Among mouse tissues, highest Phafin2
expression was detected in brain, stomach, and thymus, with weaker
expression in spleen, kidney, and skeletal muscle. Fluorescence-tagged
mouse or human phafin-2 was expressed in both the cytosol and nucleus of
transfected mouse L929 cells.
GENE FUNCTION
Using mouse and human constructs and cell lines, Li et al. (2008) found
that TNF-alpha (191160), lysophosphatidic acid, and phorbol esters
induced phafin-2 expression. Overexpression of phafin-2 enhanced
cellular sensitivity to TNF-alpha-induced apoptosis, concomitant with
partial translocation of phafin-2 to the endoplasmic reticulum (ER).
Knockdown of mouse or human phafin-2 protected cells from
TNF-alpha-induced apoptosis. Phafin-2 also suppressed the
TNF-alpha-induced unfolded protein response in the ER. Mutation analysis
revealed that both the PH and FYVE domains of phafin-2 contributed to ER
translocation and phafin-2-enhanced apoptosis.
Using a lipid-binding assay, Lin et al. (2010) found that PHAFIN2 bound
strongly to phosphatidylinositol 3-phosphate, an abundant endosomal
lipid. Overexpression of human PHAFIN2 or its isolated FYVE domain
caused the formation of enlarged EEA1 (605070)-positive endosomes in
human cell lines. Endosome swelling involved PHAFIN2-mediated activation
of the small GTP-binding protein RAB5 (179512) and, most likely, its
downstream regulator PI3 kinase (PI3K; see 601232), as inhibition of
RAB5 signaling abolished PHAFIN2-dependent endosome swelling.
Overexpression of PHAFIN2 decreased insulin receptor (INSR; 147670)
internalization, resulting in increased cell surface INSR density and
downstream activation of AP1 (see 165160).
Using a library of small interfering RNAs, Pedersen et al. (2012)
identified PHAFIN2 among a group of proteins that interfered with EGF
(131530) degradation in HeLa cells. Knockdown of PHAFIN2 inhibited
endosome fusion, resulting in reduced size of vesicles that were
positive for early endosome markers. Knockdown of PHAFIN2 also delayed,
but did not block, fluid-phase transport. Conversely, overexpression of
PHAFIN2 resulted in enlarged early endosomes that were positive for
internalized EGF and transferrin (TF; 190000). Epitope-tagged PHAFIN2
localized close to the plasma membrane in spots negative for EEA1,
suggesting that PHAFIN2 is recruited to early endocytic vesicles prior
to EEA1. Pedersen et al. (2012) concluded that PHAFIN2 has a role in
fusion of early endosomes.
MAPPING
Hartz (2013) mapped the PLEKHF2 gene to chromosome 8q22.1 based on an
alignment of the PLEKHF2 sequence (GenBank GENBANK AK023249) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Hartz, P. A.: Personal Communication. Baltimore, Md. 4/29/2013.
2. Li, C.; Liu, Q.; Li, N.; Chen, W.; Wang, L.; Wang, Y.; Yu, Y.;
Cao, X.: EAPF/phafin-2, a novel endoplasmic reticulum-associated
protein, facilitates TNF-alpha-triggered cellular apoptosis through
endoplasmic reticulum-mitochondrial apoptotic pathway. J. Molec.
Med. 86: 471-484, 2008.
3. Lin, W.-J.; Yang, C.-Y.; Lin, Y.-C.; Tsai, M.-C.; Yang, C.-W.;
Tung, C.-Y.; Ho, P.-Y.; Kao, F.-J.; Lin, C.-H.: Phafin2 modulates
the structure and function of endosomes by a Rab5-dependent mechanism. Biochem.
Biophys. Res. Commun. 391: 1043-1048, 2010.
4. Pedersen, N. M.; Raiborg, C.; Brech, A.; Skarpen, E.; Roxrud, I.;
Platta, H. W.; Liestol, K.; Stenmark, H.: The PtdIns3P-binding protein
Phafin 2 mediates epidermal growth factor receptor degradation by
promoting endosome fusion. Traffic 13: 1547-1563, 2012.
*FIELD* CD
Patricia A. Hartz: 4/29/2013
*FIELD* ED
joanna: 05/07/2013
mgross: 4/29/2013
*RECORD*
*FIELD* NO
615208
*FIELD* TI
*615208 PLECKSTRIN HOMOLOGY DOMAIN-CONTAINING PROTEIN, FAMILY F, MEMBER 2;
PLEKHF2
read more;;ENDOPLASMIC RETICULUM-ASSOCIATED APOPTOSIS-INVOLVED PROTEIN CONTAINING
PH AND FYVE DOMAINS; EAPF;;
PH AND FYVE DOMAINS-CONTAINING PROTEIN 2; PHAFIN2;;
PHAFIN 2
*FIELD* TX
DESCRIPTION
PLEKHF2 has roles in biogenesis of early endosomes (Pedersen et al.,
2012) and apoptosis (Li et al., 2008).
CLONING
By database analysis to identify genes similar to phafin-1 (PLEKHF1;
615200), followed by RT-PCR of bone marrow stromal cells, Li et al.
(2008) cloned PLEKHF2, which they designated EAPF, or phafin-2. The
deduced 249-amino acid protein has a calculated molecular mass of 27.8
kD. It has an N-terminal pleckstrin (PLEK; 173570) homology (PH) domain
and a C-terminal FYVE domain and shares 97.6% identity with mouse
phafin-2. RT-PCR analysis of 16 human tissues detected abundant
expression in placenta, ovary, and small intestine, with weaker
expression in heart and pancreas, and no expression in other tissues.
Phafin-2 was also expressed in dendritic cells and in most leukemia and
solid tumor cell lines examined. Among mouse tissues, highest Phafin2
expression was detected in brain, stomach, and thymus, with weaker
expression in spleen, kidney, and skeletal muscle. Fluorescence-tagged
mouse or human phafin-2 was expressed in both the cytosol and nucleus of
transfected mouse L929 cells.
GENE FUNCTION
Using mouse and human constructs and cell lines, Li et al. (2008) found
that TNF-alpha (191160), lysophosphatidic acid, and phorbol esters
induced phafin-2 expression. Overexpression of phafin-2 enhanced
cellular sensitivity to TNF-alpha-induced apoptosis, concomitant with
partial translocation of phafin-2 to the endoplasmic reticulum (ER).
Knockdown of mouse or human phafin-2 protected cells from
TNF-alpha-induced apoptosis. Phafin-2 also suppressed the
TNF-alpha-induced unfolded protein response in the ER. Mutation analysis
revealed that both the PH and FYVE domains of phafin-2 contributed to ER
translocation and phafin-2-enhanced apoptosis.
Using a lipid-binding assay, Lin et al. (2010) found that PHAFIN2 bound
strongly to phosphatidylinositol 3-phosphate, an abundant endosomal
lipid. Overexpression of human PHAFIN2 or its isolated FYVE domain
caused the formation of enlarged EEA1 (605070)-positive endosomes in
human cell lines. Endosome swelling involved PHAFIN2-mediated activation
of the small GTP-binding protein RAB5 (179512) and, most likely, its
downstream regulator PI3 kinase (PI3K; see 601232), as inhibition of
RAB5 signaling abolished PHAFIN2-dependent endosome swelling.
Overexpression of PHAFIN2 decreased insulin receptor (INSR; 147670)
internalization, resulting in increased cell surface INSR density and
downstream activation of AP1 (see 165160).
Using a library of small interfering RNAs, Pedersen et al. (2012)
identified PHAFIN2 among a group of proteins that interfered with EGF
(131530) degradation in HeLa cells. Knockdown of PHAFIN2 inhibited
endosome fusion, resulting in reduced size of vesicles that were
positive for early endosome markers. Knockdown of PHAFIN2 also delayed,
but did not block, fluid-phase transport. Conversely, overexpression of
PHAFIN2 resulted in enlarged early endosomes that were positive for
internalized EGF and transferrin (TF; 190000). Epitope-tagged PHAFIN2
localized close to the plasma membrane in spots negative for EEA1,
suggesting that PHAFIN2 is recruited to early endocytic vesicles prior
to EEA1. Pedersen et al. (2012) concluded that PHAFIN2 has a role in
fusion of early endosomes.
MAPPING
Hartz (2013) mapped the PLEKHF2 gene to chromosome 8q22.1 based on an
alignment of the PLEKHF2 sequence (GenBank GENBANK AK023249) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Hartz, P. A.: Personal Communication. Baltimore, Md. 4/29/2013.
2. Li, C.; Liu, Q.; Li, N.; Chen, W.; Wang, L.; Wang, Y.; Yu, Y.;
Cao, X.: EAPF/phafin-2, a novel endoplasmic reticulum-associated
protein, facilitates TNF-alpha-triggered cellular apoptosis through
endoplasmic reticulum-mitochondrial apoptotic pathway. J. Molec.
Med. 86: 471-484, 2008.
3. Lin, W.-J.; Yang, C.-Y.; Lin, Y.-C.; Tsai, M.-C.; Yang, C.-W.;
Tung, C.-Y.; Ho, P.-Y.; Kao, F.-J.; Lin, C.-H.: Phafin2 modulates
the structure and function of endosomes by a Rab5-dependent mechanism. Biochem.
Biophys. Res. Commun. 391: 1043-1048, 2010.
4. Pedersen, N. M.; Raiborg, C.; Brech, A.; Skarpen, E.; Roxrud, I.;
Platta, H. W.; Liestol, K.; Stenmark, H.: The PtdIns3P-binding protein
Phafin 2 mediates epidermal growth factor receptor degradation by
promoting endosome fusion. Traffic 13: 1547-1563, 2012.
*FIELD* CD
Patricia A. Hartz: 4/29/2013
*FIELD* ED
joanna: 05/07/2013
mgross: 4/29/2013