ZFY21_HUMAN
ID ZFY21_HUMAN Reviewed; 234 AA.
AC Q9BQ24; A8K3A4; Q86T05; Q96LT1;
DT 24-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Zinc finger FYVE domain-containing protein 21;
DE Short=ZF21;
GN Name=ZFYVE21;
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] (ISOFORM 1).
RA Zheng H., Xie Y., Mao Y.;
RT "Cloning of a FYVE containing protein.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Cerebellum;
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 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow, and Skin;
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 [6]
RP FUNCTION, INTERACTION WITH PTK2/FAK1, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP OF 64-HIS-HIS-65.
RX PubMed=20439989; DOI=10.1074/jbc.m110.106443;
RA Nagano M., Hoshino D., Sakamoto T., Kawasaki N., Koshikawa N., Seiki M.;
RT "ZF21 protein regulates cell adhesion and motility.";
RL J. Biol. Chem. 285:21013-21022(2010).
RN [7]
RP STRUCTURE BY NMR OF 107-234, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND
RP PH-LIKE DOMAIN.
RX PubMed=21768110; DOI=10.1074/jbc.m110.199430;
RA Nagano M., Hoshino D., Koshiba S., Shuo T., Koshikawa N., Tomizawa T.,
RA Hayashi F., Tochio N., Harada T., Akizawa T., Watanabe S., Handa N.,
RA Shirouzu M., Kigawa T., Yokoyama S., Seiki M.;
RT "ZF21 protein, a regulator of the disassembly of focal adhesions and cancer
RT metastasis, contains a novel noncanonical pleckstrin homology domain.";
RL J. Biol. Chem. 286:31598-31609(2011).
CC -!- FUNCTION: Plays a role in cell adhesion, and thereby in cell motility
CC which requires repeated formation and disassembly of focal adhesions.
CC Regulates microtubule-induced PTK2/FAK1 dephosphorylation, an event
CC important for focal adhesion disassembly, as well as integrin beta-
CC 1/ITGB1 cell surface expression. {ECO:0000269|PubMed:20439989,
CC ECO:0000269|PubMed:21768110}.
CC -!- SUBUNIT: Interacts with PTK2/FAK1. {ECO:0000269|PubMed:20439989,
CC ECO:0000269|PubMed:21768110}.
CC -!- INTERACTION:
CC Q9BQ24; Q6RW13: AGTRAP; NbExp=3; IntAct=EBI-2849569, EBI-741181;
CC Q9BQ24; Q15041: ARL6IP1; NbExp=6; IntAct=EBI-2849569, EBI-714543;
CC Q9BQ24; Q8IZR5-2: CMTM4; NbExp=3; IntAct=EBI-2849569, EBI-17278014;
CC Q9BQ24; Q5SUL5: HLA-A; NbExp=3; IntAct=EBI-2849569, EBI-8561769;
CC Q9BQ24; Q92993: KAT5; NbExp=3; IntAct=EBI-2849569, EBI-399080;
CC Q9BQ24; Q15323: KRT31; NbExp=3; IntAct=EBI-2849569, EBI-948001;
CC Q9BQ24; O76015: KRT38; NbExp=3; IntAct=EBI-2849569, EBI-1047263;
CC Q9BQ24; Q6A162: KRT40; NbExp=3; IntAct=EBI-2849569, EBI-10171697;
CC Q9BQ24; P60370: KRTAP10-5; NbExp=3; IntAct=EBI-2849569, EBI-10172150;
CC Q9BQ24; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-2849569, EBI-10171774;
CC Q9BQ24; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-2849569, EBI-3958099;
CC Q9BQ24; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-2849569, EBI-11742507;
CC Q9BQ24; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-2849569, EBI-10172526;
CC Q9BQ24; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-2849569, EBI-742948;
CC Q9BQ24; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-2849569, EBI-945833;
CC Q9BQ24; Q5VU43: PDE4DIP; NbExp=3; IntAct=EBI-2849569, EBI-1105124;
CC Q9BQ24; P17252: PRKCA; NbExp=3; IntAct=EBI-2849569, EBI-1383528;
CC Q9BQ24; Q9UI14: RABAC1; NbExp=6; IntAct=EBI-2849569, EBI-712367;
CC Q9BQ24; Q96HR9: REEP6; NbExp=3; IntAct=EBI-2849569, EBI-750345;
CC Q9BQ24; Q96HR9-2: REEP6; NbExp=3; IntAct=EBI-2849569, EBI-14065960;
CC Q9BQ24; Q9NQC3: RTN4; NbExp=3; IntAct=EBI-2849569, EBI-715945;
CC Q9BQ24; Q9NQC3-2: RTN4; NbExp=3; IntAct=EBI-2849569, EBI-10296096;
CC Q9BQ24; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-2849569, EBI-9090795;
CC Q9BQ24; Q8IUQ4: SIAH1; NbExp=3; IntAct=EBI-2849569, EBI-747107;
CC Q9BQ24; Q71RC9: SMIM5; NbExp=3; IntAct=EBI-2849569, EBI-12334905;
CC Q9BQ24; Q13077: TRAF1; NbExp=3; IntAct=EBI-2849569, EBI-359224;
CC Q9BQ24; P14373: TRIM27; NbExp=3; IntAct=EBI-2849569, EBI-719493;
CC Q9BQ24; O95070: YIF1A; NbExp=3; IntAct=EBI-2849569, EBI-2799703;
CC Q9BQ24; P61981: YWHAG; NbExp=3; IntAct=EBI-2849569, EBI-359832;
CC -!- SUBCELLULAR LOCATION: Cell junction, focal adhesion. Cytoplasmic
CC vesicle. Endosome. Note=Within cytoplasmic vesicles, partially
CC colocalizes with EEA1, an endosomal marker.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BQ24-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BQ24-2; Sequence=VSP_013794;
CC -!- DOMAIN: The FYVE-type zinc finger mediates interaction with PTK2/FAK1,
CC and also interaction with PI(3)P and association with endosomes.
CC -!- DOMAIN: The C-terminal region exhibits a structure similar to canonical
CC PH domains, but lacks a positively charged interface to bind
CC phosphatidylinositol phosphate.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD62589.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY395756; AAR14313.1; -; mRNA.
DR EMBL; BX248261; CAD62589.1; ALT_INIT; mRNA.
DR EMBL; AK057816; BAB71589.1; -; mRNA.
DR EMBL; AK290519; BAF83208.1; -; mRNA.
DR EMBL; CH471061; EAW81844.1; -; Genomic_DNA.
DR EMBL; BC001130; AAH01130.1; -; mRNA.
DR EMBL; BC005999; AAH05999.1; -; mRNA.
DR CCDS; CCDS55948.1; -. [Q9BQ24-2]
DR CCDS; CCDS9985.1; -. [Q9BQ24-1]
DR RefSeq; NP_001185882.1; NM_001198953.1. [Q9BQ24-2]
DR RefSeq; NP_076976.1; NM_024071.3. [Q9BQ24-1]
DR PDB; 2RRF; NMR; -; A=107-234.
DR PDBsum; 2RRF; -.
DR AlphaFoldDB; Q9BQ24; -.
DR BMRB; Q9BQ24; -.
DR SMR; Q9BQ24; -.
DR BioGRID; 122502; 81.
DR IntAct; Q9BQ24; 34.
DR STRING; 9606.ENSP00000216602; -.
DR iPTMnet; Q9BQ24; -.
DR PhosphoSitePlus; Q9BQ24; -.
DR BioMuta; ZFYVE21; -.
DR DMDM; 66774028; -.
DR EPD; Q9BQ24; -.
DR jPOST; Q9BQ24; -.
DR MassIVE; Q9BQ24; -.
DR MaxQB; Q9BQ24; -.
DR PeptideAtlas; Q9BQ24; -.
DR PRIDE; Q9BQ24; -.
DR ProteomicsDB; 78615; -. [Q9BQ24-1]
DR ProteomicsDB; 78616; -. [Q9BQ24-2]
DR Antibodypedia; 28114; 108 antibodies from 23 providers.
DR DNASU; 79038; -.
DR Ensembl; ENST00000216602.10; ENSP00000216602.6; ENSG00000100711.14. [Q9BQ24-2]
DR Ensembl; ENST00000311141.7; ENSP00000310543.2; ENSG00000100711.14. [Q9BQ24-1]
DR GeneID; 79038; -.
DR KEGG; hsa:79038; -.
DR MANE-Select; ENST00000311141.7; ENSP00000310543.2; NM_024071.4; NP_076976.1.
DR UCSC; uc001yoc.4; human. [Q9BQ24-1]
DR CTD; 79038; -.
DR DisGeNET; 79038; -.
DR GeneCards; ZFYVE21; -.
DR HGNC; HGNC:20760; ZFYVE21.
DR HPA; ENSG00000100711; Low tissue specificity.
DR MIM; 613504; gene.
DR neXtProt; NX_Q9BQ24; -.
DR OpenTargets; ENSG00000100711; -.
DR PharmGKB; PA134879875; -.
DR VEuPathDB; HostDB:ENSG00000100711; -.
DR eggNOG; ENOG502QRR6; Eukaryota.
DR GeneTree; ENSGT00940000159639; -.
DR HOGENOM; CLU_103398_0_0_1; -.
DR InParanoid; Q9BQ24; -.
DR OMA; KRPAAAW; -.
DR OrthoDB; 1256682at2759; -.
DR PhylomeDB; Q9BQ24; -.
DR TreeFam; TF329481; -.
DR PathwayCommons; Q9BQ24; -.
DR SignaLink; Q9BQ24; -.
DR BioGRID-ORCS; 79038; 12 hits in 1083 CRISPR screens.
DR ChiTaRS; ZFYVE21; human.
DR EvolutionaryTrace; Q9BQ24; -.
DR GenomeRNAi; 79038; -.
DR Pharos; Q9BQ24; Tbio.
DR PRO; PR:Q9BQ24; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9BQ24; protein.
DR Bgee; ENSG00000100711; Expressed in secondary oocyte and 190 other tissues.
DR ExpressionAtlas; Q9BQ24; baseline and differential.
DR Genevisible; Q9BQ24; HS.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR Gene3D; 2.30.29.160; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR032031; ZFYVE21_C.
DR InterPro; IPR038632; ZFYVE21_C_sf.
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; PF16696; ZFYVE21_C; 1.
DR SMART; SM00064; FYVE; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS50178; ZF_FYVE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Cytoplasmic vesicle;
KW Endosome; Metal-binding; Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..234
FT /note="Zinc finger FYVE domain-containing protein 21"
FT /id="PRO_0000098720"
FT ZN_FING 44..104
FT /note="FYVE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT REGION 107..234
FT /note="PH-like"
FT BINDING 50
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 53
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 66
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 69
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 74
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 77
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 96
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 99
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT VAR_SEQ 175
FT /note="G -> GEKDIHAYTSLRGSQPASE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_013794"
FT MUTAGEN 64..65
FT /note="HH->NN: Diffuse cytoplasmic localization."
FT /evidence="ECO:0000269|PubMed:20439989"
FT HELIX 108..119
FT /evidence="ECO:0007829|PDB:2RRF"
FT STRAND 121..125
FT /evidence="ECO:0007829|PDB:2RRF"
FT STRAND 134..140
FT /evidence="ECO:0007829|PDB:2RRF"
FT STRAND 144..158
FT /evidence="ECO:0007829|PDB:2RRF"
FT TURN 159..161
FT /evidence="ECO:0007829|PDB:2RRF"
FT STRAND 174..178
FT /evidence="ECO:0007829|PDB:2RRF"
FT STRAND 185..188
FT /evidence="ECO:0007829|PDB:2RRF"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:2RRF"
FT STRAND 197..202
FT /evidence="ECO:0007829|PDB:2RRF"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:2RRF"
FT HELIX 211..230
FT /evidence="ECO:0007829|PDB:2RRF"
SQ SEQUENCE 234 AA; 26506 MW; AF8C695D2417FE98 CRC64;
MSSEVSARRD AKKLVRSPSG LRMVPEHRAF GSPFGLEEPQ WVPDKECRRC MQCDAKFDFL
TRKHHCRRCG KCFCDRCCSQ KVPLRRMCFV DPVRQCAECA LVSLKEAEFY DKQLKVLLSG
ATFLVTFGNS EKPETMTCRL SNNQRYLFLD GDSHYEIEIV HISTVQILTE GFPPGGGNAR
ATGMFLQYTV PGTEGVTQLK LTVVEDVTVG RRQAVAWLVA MHKAAKLLYE SRDQ
