DEFI8_HUMAN
ID DEFI8_HUMAN Reviewed; 512 AA.
AC Q6ZN54; B3KT65; B4DK62; B4E0S9; B7Z3H6; H3BUG7; Q8N8N3; Q9NXL0;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Differentially expressed in FDCP 8 homolog;
DE Short=DEF-8;
GN Name=DEF8;
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 [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3; 4 AND 5).
RC TISSUE=Brain, Cerebellum, Colon mucosa, Hippocampus, Thalamus, and Thymus;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(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 2).
RC TISSUE=Pancreas, 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 [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 (ISOFORMS 2; 3; 5 AND 6), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Positively regulates lysosome peripheral distribution and
CC ruffled border formation in osteoclasts. Involved in bone resorption.
CC {ECO:0000250|UniProtKB:Q99J78}.
CC -!- SUBUNIT: Interacts (via C-terminus) with PLEKHM1; this interaction is
CC weak but increased in a RAB7A-dependent manner.
CC {ECO:0000250|UniProtKB:Q99J78}.
CC -!- INTERACTION:
CC Q6ZN54-2; P22607: FGFR3; NbExp=3; IntAct=EBI-12346463, EBI-348399;
CC Q6ZN54-2; Q14957: GRIN2C; NbExp=3; IntAct=EBI-12346463, EBI-8285963;
CC Q6ZN54-2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12346463, EBI-16439278;
CC Q6ZN54-2; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-12346463, EBI-740727;
CC Q6ZN54-2; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-12346463, EBI-6427977;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1;
CC IsoId=Q6ZN54-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZN54-2; Sequence=VSP_031821, VSP_031823, VSP_031824;
CC Name=3;
CC IsoId=Q6ZN54-3; Sequence=VSP_031821, VSP_031822;
CC Name=4;
CC IsoId=Q6ZN54-4; Sequence=VSP_037523;
CC Name=5;
CC IsoId=Q6ZN54-5; Sequence=VSP_031821;
CC Name=6;
CC IsoId=Q6ZN54-6; Sequence=VSP_031821, VSP_047179;
CC -!- SIMILARITY: Belongs to the DEF8 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC04802.1; Type=Miscellaneous discrepancy; Note=Unlikely isoform. Aberrant splice sites.; Evidence={ECO:0000305};
CC Sequence=BAG64541.1; Type=Miscellaneous discrepancy; Note=Unlikely isoform. Aberrant splice sites.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK000193; BAA91000.1; -; mRNA.
DR EMBL; AK095051; BAG52977.1; -; mRNA.
DR EMBL; AK096485; BAC04802.1; ALT_SEQ; mRNA.
DR EMBL; AK131370; BAD18521.1; -; mRNA.
DR EMBL; AK295880; BAH12212.1; -; mRNA.
DR EMBL; AK296410; BAG59074.1; -; mRNA.
DR EMBL; AK303510; BAG64541.1; ALT_SEQ; mRNA.
DR EMBL; AC092143; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471184; EAW66667.1; -; Genomic_DNA.
DR EMBL; BC015482; AAH15482.1; -; mRNA.
DR EMBL; BC105592; AAI05593.1; -; mRNA.
DR CCDS; CCDS10989.1; -. [Q6ZN54-1]
DR CCDS; CCDS45555.1; -. [Q6ZN54-2]
DR CCDS; CCDS58493.1; -. [Q6ZN54-5]
DR CCDS; CCDS58494.1; -. [Q6ZN54-6]
DR CCDS; CCDS58495.1; -. [Q6ZN54-3]
DR CCDS; CCDS58496.1; -. [Q6ZN54-4]
DR RefSeq; NP_001229745.1; NM_001242816.1. [Q6ZN54-3]
DR RefSeq; NP_001229746.1; NM_001242817.1. [Q6ZN54-4]
DR RefSeq; NP_001229747.1; NM_001242818.1. [Q6ZN54-5]
DR RefSeq; NP_001229748.1; NM_001242819.1. [Q6ZN54-6]
DR RefSeq; NP_001229749.1; NM_001242820.1. [Q6ZN54-5]
DR RefSeq; NP_001229750.1; NM_001242821.1. [Q6ZN54-2]
DR RefSeq; NP_001229751.1; NM_001242822.1. [Q6ZN54-2]
DR RefSeq; NP_060172.1; NM_017702.3. [Q6ZN54-2]
DR RefSeq; NP_997397.1; NM_207514.2. [Q6ZN54-1]
DR RefSeq; XP_005256375.2; XM_005256318.2. [Q6ZN54-6]
DR RefSeq; XP_016878847.1; XM_017023358.1. [Q6ZN54-5]
DR RefSeq; XP_016878849.1; XM_017023360.1. [Q6ZN54-6]
DR RefSeq; XP_016878852.1; XM_017023363.1. [Q6ZN54-1]
DR RefSeq; XP_016878856.1; XM_017023367.1. [Q6ZN54-5]
DR RefSeq; XP_016878857.1; XM_017023368.1. [Q6ZN54-5]
DR RefSeq; XP_016878858.1; XM_017023369.1. [Q6ZN54-6]
DR AlphaFoldDB; Q6ZN54; -.
DR SMR; Q6ZN54; -.
DR BioGRID; 120199; 56.
DR IntAct; Q6ZN54; 38.
DR MINT; Q6ZN54; -.
DR STRING; 9606.ENSP00000268676; -.
DR iPTMnet; Q6ZN54; -.
DR PhosphoSitePlus; Q6ZN54; -.
DR BioMuta; DEF8; -.
DR DMDM; 239938619; -.
DR EPD; Q6ZN54; -.
DR jPOST; Q6ZN54; -.
DR MassIVE; Q6ZN54; -.
DR MaxQB; Q6ZN54; -.
DR PaxDb; Q6ZN54; -.
DR PeptideAtlas; Q6ZN54; -.
DR PRIDE; Q6ZN54; -.
DR ProteomicsDB; 42925; -.
DR ProteomicsDB; 67977; -. [Q6ZN54-1]
DR ProteomicsDB; 67978; -. [Q6ZN54-2]
DR ProteomicsDB; 67979; -. [Q6ZN54-3]
DR ProteomicsDB; 67980; -. [Q6ZN54-4]
DR ProteomicsDB; 67981; -. [Q6ZN54-5]
DR Antibodypedia; 57197; 171 antibodies from 18 providers.
DR DNASU; 54849; -.
DR Ensembl; ENST00000268676.11; ENSP00000268676.7; ENSG00000140995.17. [Q6ZN54-1]
DR Ensembl; ENST00000418391.6; ENSP00000412784.2; ENSG00000140995.17. [Q6ZN54-2]
DR Ensembl; ENST00000563594.6; ENSP00000458019.1; ENSG00000140995.17. [Q6ZN54-5]
DR Ensembl; ENST00000563795.1; ENSP00000457627.1; ENSG00000140995.17. [Q6ZN54-6]
DR Ensembl; ENST00000567874.5; ENSP00000456095.1; ENSG00000140995.17. [Q6ZN54-4]
DR Ensembl; ENST00000569453.5; ENSP00000456501.1; ENSG00000140995.17. [Q6ZN54-5]
DR Ensembl; ENST00000570182.5; ENSP00000456799.1; ENSG00000140995.17. [Q6ZN54-3]
DR Ensembl; ENST00000610455.4; ENSP00000480073.1; ENSG00000140995.17. [Q6ZN54-2]
DR Ensembl; ENST00000617948.4; ENSP00000482524.1; ENSG00000140995.17. [Q6ZN54-5]
DR GeneID; 54849; -.
DR KEGG; hsa:54849; -.
DR MANE-Select; ENST00000563594.6; ENSP00000458019.1; NM_001242818.2; NP_001229747.1. [Q6ZN54-5]
DR UCSC; uc002fpl.4; human. [Q6ZN54-1]
DR CTD; 54849; -.
DR DisGeNET; 54849; -.
DR GeneCards; DEF8; -.
DR HGNC; HGNC:25969; DEF8.
DR HPA; ENSG00000140995; Low tissue specificity.
DR neXtProt; NX_Q6ZN54; -.
DR OpenTargets; ENSG00000140995; -.
DR PharmGKB; PA162383526; -.
DR VEuPathDB; HostDB:ENSG00000140995; -.
DR eggNOG; KOG1829; Eukaryota.
DR GeneTree; ENSGT00940000159182; -.
DR HOGENOM; CLU_034500_3_0_1; -.
DR InParanoid; Q6ZN54; -.
DR OMA; IEPRLCD; -.
DR OrthoDB; 177737at2759; -.
DR PhylomeDB; Q6ZN54; -.
DR TreeFam; TF317067; -.
DR PathwayCommons; Q6ZN54; -.
DR SignaLink; Q6ZN54; -.
DR BioGRID-ORCS; 54849; 32 hits in 1076 CRISPR screens.
DR ChiTaRS; DEF8; human.
DR GenomeRNAi; 54849; -.
DR Pharos; Q6ZN54; Tdark.
DR PRO; PR:Q6ZN54; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q6ZN54; protein.
DR Bgee; ENSG00000140995; Expressed in right hemisphere of cerebellum and 184 other tissues.
DR ExpressionAtlas; Q6ZN54; baseline and differential.
DR Genevisible; Q6ZN54; HS.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0032418; P:lysosome localization; ISS:UniProtKB.
DR GO; GO:0045780; P:positive regulation of bone resorption; ISS:UniProtKB.
DR GO; GO:1900029; P:positive regulation of ruffle assembly; ISS:UniProtKB.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR025258; Zf-RING_9.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF13901; zf-RING_9; 1.
DR SMART; SM00109; C1; 2.
DR SMART; SM01175; DUF4206; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; Zinc; Zinc-finger.
FT CHAIN 1..512
FT /note="Differentially expressed in FDCP 8 homolog"
FT /id="PRO_0000321913"
FT ZN_FING 199..250
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 429..489
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 77..116
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 501
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99J78"
FT VAR_SEQ 1..121
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_037523"
FT VAR_SEQ 1..61
FT /note="Missing (in isoform 2, isoform 3, isoform 5 and
FT isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_031821"
FT VAR_SEQ 136..145
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_031822"
FT VAR_SEQ 234..258
FT /note="CYYRCHSKCLNLISKPCVSSKVSHQ -> GPRPRRGVRNERDQSSCLRWAHI
FT QM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_031823"
FT VAR_SEQ 259..512
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_031824"
FT VAR_SEQ 395..411
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_047179"
FT VARIANT 90
FT /note="Q -> E (in dbSNP:rs7194844)"
FT /id="VAR_061485"
FT CONFLICT 283
FT /note="A -> V (in Ref. 1; BAD18521)"
FT /evidence="ECO:0000305"
FT CONFLICT 293
FT /note="E -> A (in Ref. 1; BAG52977)"
FT /evidence="ECO:0000305"
FT MOD_RES Q6ZN54-2:1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES Q6ZN54-3:1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES Q6ZN54-5:1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES Q6ZN54-6:1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
SQ SEQUENCE 512 AA; 58710 MW; 2909333CBD68F5C7 CRC64;
MAILSLRAPG PWQAMQVWAD RTLLTPHTGV TSQVLGVAAA VMTPLPGGHA AGRTREARWD
AMEYDEKLAR FRQAHLNPFN KQSGPRQHEQ GPGEEVPDVT PEEALPELPP GEPEFRCPER
VMDLGLSEDH FSRPVGLFLA SDVQQLRQAI EECKQVILEL PEQSEKQKDA VVRLIHLRLK
LQELKDPNED EPNIRVLLEH RFYKEKSKSV KQTCDKCNTI IWGLIQTWYT CTGCYYRCHS
KCLNLISKPC VSSKVSHQAE YELNICPETG LDSQDYRCAE CRAPISLRGV PSEARQCDYT
GQYYCSHCHW NDLAVIPARV VHNWDFEPRK VSRCSMRYLA LMVSRPVLRL REINPLLFSY
VEELVEIRKL RQDILLMKPY FITCREAMEA RLLLQLQDRQ HFVENDEMYS VQDLLDVHAG
RLGCSLTEIH TLFAKHIKLD CERCQAKGFV CELCREGDVL FPFDSHTSVC ADCSAVFHRD
CYYDNSTTCP KCARLSLRKQ SLFQEPGPDV EA
