RNFT1_HUMAN
ID RNFT1_HUMAN Reviewed; 435 AA.
AC Q5M7Z0; Q8N7D0; Q96IZ9; Q9Y686;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2006, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=E3 ubiquitin-protein ligase RNFT1 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:27485036};
DE AltName: Full=Protein PTD016;
DE AltName: Full=RING finger and transmembrane domain-containing protein 1;
GN Name=RNFT1; ORFNames=PTD016;
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] (ISOFORM 2).
RC TISSUE=Pituitary tumor;
RA Zhang Q., Guan Z., Dai M., Song H., Mao Y., Zhang Q., Mao M., Fu G.,
RA Luo M., Chen J., Hu R.;
RT "Human PTD016 mRNA.";
RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
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] (ISOFORMS 1 AND 3).
RC TISSUE=Brain, and Testis;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 177-435 (ISOFORM 1).
RC TISSUE=Testis;
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 [6]
RP TISSUE SPECIFICITY.
RX PubMed=17074343; DOI=10.1016/j.fertnstert.2006.04.039;
RA Lin Y.H., Lin Y.M., Teng Y.N., Hsieh T.Y., Lin Y.S., Kuo P.L.;
RT "Identification of ten novel genes involved in human spermatogenesis by
RT microarray analysis of testicular tissue.";
RL Fertil. Steril. 86:1650-1658(2006).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP INDUCTION, AND MUTAGENESIS OF CYS-375 AND CYS-378.
RX PubMed=27485036; DOI=10.1038/srep30955;
RA Kaneko M., Iwase I., Yamasaki Y., Takai T., Wu Y., Kanemoto S.,
RA Matsuhisa K., Asada R., Okuma Y., Watanabe T., Imaizumi K., Nomura Y.;
RT "Genome-wide identification and gene expression profiling of ubiquitin
RT ligases for endoplasmic reticulum protein degradation.";
RL Sci. Rep. 6:30955-30955(2016).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that acts in the endoplasmic
CC reticulum (ER)-associated degradation (ERAD) pathway, which targets
CC misfolded proteins that accumulate in the endoplasmic reticulum (ER)
CC for ubiquitination and subsequent proteasome-mediated degradation.
CC Protects cells from ER stress-induced apoptosis.
CC {ECO:0000269|PubMed:27485036}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:27485036};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:27485036}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:27485036}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q5M7Z0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5M7Z0-2; Sequence=VSP_031698, VSP_031699;
CC Name=3;
CC IsoId=Q5M7Z0-3; Sequence=VSP_031700, VSP_031701;
CC -!- TISSUE SPECIFICITY: Expressed at highest levels in testis, lower levels
CC in heart, liver, lung, and kidney (PubMed:17074343). Not detected in
CC brain, ovary, and uterus (PubMed:17074343). Down-regulated in testis
CC from patients with maturation arrest (MA) or Sertoli cell-only syndrome
CC (SCOS) (PubMed:17074343). Ubiquitously expressed with high expression
CC in testis (PubMed:27485036). {ECO:0000269|PubMed:17074343,
CC ECO:0000269|PubMed:27485036}.
CC -!- INDUCTION: Up-regulated by endoplasmic reticulum (ER) stress triggered
CC by thapsigargin or tunicamycin. {ECO:0000269|PubMed:27485036}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD43009.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAC05364.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- SEQUENCE CAUTION: [Isoform 2]:
CC Sequence=AAD43009.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF100745; AAD43009.1; ALT_FRAME; mRNA.
DR EMBL; AC004686; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC005702; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CH471109; EAW94381.1; -; Genomic_DNA.
DR EMBL; BC006971; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC088365; AAH88365.2; -; mRNA.
DR EMBL; AK098649; BAC05364.1; ALT_INIT; mRNA.
DR CCDS; CCDS11622.2; -. [Q5M7Z0-1]
DR RefSeq; NP_057209.3; NM_016125.3. [Q5M7Z0-1]
DR AlphaFoldDB; Q5M7Z0; -.
DR BioGRID; 119323; 35.
DR IntAct; Q5M7Z0; 5.
DR MINT; Q5M7Z0; -.
DR STRING; 9606.ENSP00000304670; -.
DR iPTMnet; Q5M7Z0; -.
DR PhosphoSitePlus; Q5M7Z0; -.
DR BioMuta; RNFT1; -.
DR DMDM; 121947809; -.
DR EPD; Q5M7Z0; -.
DR jPOST; Q5M7Z0; -.
DR MassIVE; Q5M7Z0; -.
DR MaxQB; Q5M7Z0; -.
DR PaxDb; Q5M7Z0; -.
DR PeptideAtlas; Q5M7Z0; -.
DR PRIDE; Q5M7Z0; -.
DR ProteomicsDB; 63564; -. [Q5M7Z0-1]
DR ProteomicsDB; 63565; -. [Q5M7Z0-2]
DR ProteomicsDB; 63566; -. [Q5M7Z0-3]
DR Antibodypedia; 2746; 87 antibodies from 15 providers.
DR DNASU; 51136; -.
DR Ensembl; ENST00000305783.13; ENSP00000304670.8; ENSG00000189050.16. [Q5M7Z0-1]
DR Ensembl; ENST00000482446.5; ENSP00000436144.1; ENSG00000189050.16. [Q5M7Z0-3]
DR GeneID; 51136; -.
DR KEGG; hsa:51136; -.
DR MANE-Select; ENST00000305783.13; ENSP00000304670.8; NM_016125.4; NP_057209.3.
DR UCSC; uc002iya.4; human. [Q5M7Z0-1]
DR CTD; 51136; -.
DR GeneCards; RNFT1; -.
DR HGNC; HGNC:30206; RNFT1.
DR HPA; ENSG00000189050; Tissue enhanced (testis).
DR MIM; 615172; gene.
DR neXtProt; NX_Q5M7Z0; -.
DR OpenTargets; ENSG00000189050; -.
DR PharmGKB; PA162401921; -.
DR VEuPathDB; HostDB:ENSG00000189050; -.
DR eggNOG; KOG0802; Eukaryota.
DR eggNOG; KOG4638; Eukaryota.
DR GeneTree; ENSGT00940000156740; -.
DR HOGENOM; CLU_039460_2_1_1; -.
DR InParanoid; Q5M7Z0; -.
DR OMA; GCIHSRL; -.
DR OrthoDB; 1321151at2759; -.
DR PhylomeDB; Q5M7Z0; -.
DR TreeFam; TF331930; -.
DR PathwayCommons; Q5M7Z0; -.
DR SignaLink; Q5M7Z0; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 51136; 9 hits in 1109 CRISPR screens.
DR ChiTaRS; RNFT1; human.
DR GenomeRNAi; 51136; -.
DR Pharos; Q5M7Z0; Tdark.
DR PRO; PR:Q5M7Z0; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q5M7Z0; protein.
DR Bgee; ENSG00000189050; Expressed in adult organism and 172 other tissues.
DR ExpressionAtlas; Q5M7Z0; baseline and differential.
DR Genevisible; Q5M7Z0; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:1904294; P:positive regulation of ERAD pathway; IMP:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR044235; RNFT1/2.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR15860; PTHR15860; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Membrane; Metal-binding;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..435
FT /note="E3 ubiquitin-protein ligase RNFT1"
FT /id="PRO_0000320635"
FT TRANSMEM 158..178
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 203..223
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 256..276
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 298..318
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 323..343
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ZN_FING 375..413
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 368..419
FT /note="Required for ubiquitin ligase activity and for
FT protection against ER stress-induced cell death"
FT /evidence="ECO:0000269|PubMed:27485036"
FT COMPBIAS 17..31
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 40..62
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 198..245
FT /note="ERSSKIQCAWLLVFLAGSSVLLYYTFHSQSLYYSLIFLNPTLDHLSFW ->
FT LNFFKSYFGPFELLGSILDCWNYRLHSEILFHGLKMPYFIGAFFHHAF (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_031700"
FT VAR_SEQ 198..203
FT /note="ERSSKI -> VSITSN (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_031698"
FT VAR_SEQ 204..435
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_031699"
FT VAR_SEQ 246..435
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_031701"
FT MUTAGEN 375
FT /note="C->S: Decreased ubiquitin ligase activity; when
FT associated with S-378."
FT /evidence="ECO:0000269|PubMed:27485036"
FT MUTAGEN 378
FT /note="C->S: Decreased ubiquitin ligase activity; when
FT associated with S-375."
FT /evidence="ECO:0000269|PubMed:27485036"
FT CONFLICT Q5M7Z0-2:199
FT /note="S -> K (in Ref. 1; AAD43009)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 435 AA; 49710 MW; 60773323485B08A8 CRC64;
MPLFLLSLPT PPSASGHERR QRPEAKTSGS EKKYLRAMQA NRSQLHSPPG TGSSEDASTP
QCVHTRLTGE GSCPHSGDVH IQINSIPKEC AENASSRNIR SGVHSCAHGC VHSRLRGHSH
SEARLTDDTA AESGDHGSSS FSEFRYLFKW LQKSLPYILI LSVKLVMQHI TGISLGIGLL
TTFMYANKSI VNQVFLRERS SKIQCAWLLV FLAGSSVLLY YTFHSQSLYY SLIFLNPTLD
HLSFWEVFWI VGITDFILKF FFMGLKCLIL LVPSFIMPFK SKGYWYMLLE ELCQYYRTFV
PIPVWFRYLI SYGEFGNVTR WSLGILLALL YLILKLLEFF GHLRTFRQVL RIFFTQPSYG
VAASKRQCSD VDDICSICQA EFQKPILLIC QHIFCEECMT LWFNREKTCP LCRTVISDHI
NKWKDGATSS HLQIY
