RMD5A_HUMAN
ID RMD5A_HUMAN Reviewed; 391 AA.
AC Q9H871; D6W5M6; Q6NTF0; Q9H6W5; Q9H9H2;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=E3 ubiquitin-protein transferase RMND5A;
DE EC=2.3.2.27 {ECO:0000269|PubMed:29911972};
DE AltName: Full=P44CTLH {ECO:0000303|PubMed:17467196};
DE AltName: Full=Protein RMD5 homolog A;
GN Name=RMND5A;
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 1).
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=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
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 2).
RC TISSUE=Eye, Muscle, 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 IDENTIFICATION IN THE CTLH COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY,
RP AND SUBCELLULAR LOCATION.
RX PubMed=17467196; DOI=10.1016/j.gene.2007.02.032;
RA Kobayashi N., Yang J., Ueda A., Suzuki T., Tomaru K., Takeno M., Okuda K.,
RA Ishigatsubo Y.;
RT "RanBPM, Muskelin, p48EMLP, p44CTLH, and the armadillo-repeat proteins
RT ARMC8alpha and ARMC8beta are components of the CTLH complex.";
RL Gene 396:236-247(2007).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP 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).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=24143168; DOI=10.1371/journal.pone.0075217;
RA Francis O., Han F., Adams J.C.;
RT "Molecular phylogeny of a RING E3 ubiquitin ligase, conserved in eukaryotic
RT cells and dominated by homologous components, the muskelin/RanBPM/CTLH
RT complex.";
RL PLoS ONE 8:E75217-E75217(2013).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=25793641; DOI=10.1371/journal.pone.0120342;
RA Pfirrmann T., Villavicencio-Lorini P., Subudhi A.K., Menssen R., Wolf D.H.,
RA Hollemann T.;
RT "RMND5 from Xenopus laevis is an E3 ubiquitin-ligase and functions in early
RT embryonic forebrain development.";
RL PLoS ONE 10:E0120342-E0120342(2015).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION IN THE CTLH COMPLEX, SUBUNIT,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=29911972; DOI=10.7554/elife.35528;
RA Lampert F., Stafa D., Goga A., Soste M.V., Gilberto S., Olieric N.,
RA Picotti P., Stoffel M., Peter M.;
RT "The multi-subunit GID/CTLH E3 ligase promotes proliferation and targets
RT the transcription factor Hbp1 for degradation.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Core component of the CTLH E3 ubiquitin-protein ligase
CC complex that selectively accepts ubiquitin from UBE2H and mediates
CC ubiquitination and subsequent proteasomal degradation of the
CC transcription factor HBP1. MAEA and RMND5A are both required for
CC catalytic activity of the CTLH E3 ubiquitin-protein ligase complex
CC (PubMed:29911972). Catalytic activity of the complex is required for
CC normal cell proliferation (PubMed:29911972). The CTLH E3 ubiquitin-
CC protein ligase complex is not required for the degradation of enzymes
CC involved in gluconeogenesis, such as FBP1 (PubMed:29911972).
CC {ECO:0000269|PubMed:29911972}.
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:29911972};
CC -!- SUBUNIT: Identified in the CTLH complex that contains GID4, RANBP9
CC and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog
CC RMND5B), GID8, ARMC8, WDR26 and YPEL5 (PubMed:17467196,
CC PubMed:29911972). Within this complex, MAEA, RMND5A (or alternatively
CC its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10 form the
CC catalytic core, while GID4, MKLN1, ARMC8 and YPEL5 have ancillary roles
CC (PubMed:29911972). {ECO:0000269|PubMed:17467196,
CC ECO:0000269|PubMed:29911972}.
CC -!- INTERACTION:
CC Q9H871; P54253: ATXN1; NbExp=6; IntAct=EBI-2797992, EBI-930964;
CC Q9H871; Q9NWU2: GID8; NbExp=8; IntAct=EBI-2797992, EBI-1051077;
CC Q9H871; P50222: MEOX2; NbExp=3; IntAct=EBI-2797992, EBI-748397;
CC Q9H871; P49821: NDUFV1; NbExp=3; IntAct=EBI-2797992, EBI-748312;
CC Q9H871; Q13148: TARDBP; NbExp=3; IntAct=EBI-2797992, EBI-372899;
CC Q9H871; O76024: WFS1; NbExp=3; IntAct=EBI-2797992, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:17467196, ECO:0000269|PubMed:24143168,
CC ECO:0000269|PubMed:25793641}. Cytoplasm {ECO:0000269|PubMed:17467196,
CC ECO:0000269|PubMed:24143168, ECO:0000269|PubMed:25793641}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H871-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H871-2; Sequence=VSP_022454, VSP_022455;
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DR EMBL; AK022815; BAB14257.1; -; mRNA.
DR EMBL; AK023972; BAB14746.1; -; mRNA.
DR EMBL; AK025448; BAB15135.1; -; mRNA.
DR EMBL; AC064848; AAX88863.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99442.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99443.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99445.1; -; Genomic_DNA.
DR EMBL; BC012165; AAH12165.1; -; mRNA.
DR EMBL; BC047668; AAH47668.1; -; mRNA.
DR EMBL; BC069048; AAH69048.1; -; mRNA.
DR CCDS; CCDS1991.1; -. [Q9H871-1]
DR RefSeq; NP_073617.1; NM_022780.3. [Q9H871-1]
DR AlphaFoldDB; Q9H871; -.
DR SMR; Q9H871; -.
DR BioGRID; 122303; 196.
DR CORUM; Q9H871; -.
DR IntAct; Q9H871; 50.
DR MINT; Q9H871; -.
DR STRING; 9606.ENSP00000283632; -.
DR GlyGen; Q9H871; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9H871; -.
DR PhosphoSitePlus; Q9H871; -.
DR BioMuta; RMND5A; -.
DR DMDM; 74733774; -.
DR EPD; Q9H871; -.
DR jPOST; Q9H871; -.
DR MassIVE; Q9H871; -.
DR MaxQB; Q9H871; -.
DR PaxDb; Q9H871; -.
DR PeptideAtlas; Q9H871; -.
DR PRIDE; Q9H871; -.
DR ProteomicsDB; 81195; -. [Q9H871-1]
DR ProteomicsDB; 81196; -. [Q9H871-2]
DR Antibodypedia; 32147; 211 antibodies from 21 providers.
DR DNASU; 64795; -.
DR Ensembl; ENST00000283632.5; ENSP00000283632.4; ENSG00000153561.13. [Q9H871-1]
DR GeneID; 64795; -.
DR KEGG; hsa:64795; -.
DR MANE-Select; ENST00000283632.5; ENSP00000283632.4; NM_022780.4; NP_073617.1.
DR UCSC; uc002srr.3; human. [Q9H871-1]
DR CTD; 64795; -.
DR DisGeNET; 64795; -.
DR GeneCards; RMND5A; -.
DR HGNC; HGNC:25850; RMND5A.
DR HPA; ENSG00000153561; Low tissue specificity.
DR MIM; 618964; gene.
DR neXtProt; NX_Q9H871; -.
DR OpenTargets; ENSG00000153561; -.
DR PharmGKB; PA144596388; -.
DR VEuPathDB; HostDB:ENSG00000153561; -.
DR eggNOG; KOG2817; Eukaryota.
DR GeneTree; ENSGT00940000153203; -.
DR HOGENOM; CLU_020227_3_1_1; -.
DR InParanoid; Q9H871; -.
DR OMA; QEWLAMK; -.
DR OrthoDB; 987270at2759; -.
DR PhylomeDB; Q9H871; -.
DR TreeFam; TF315176; -.
DR PathwayCommons; Q9H871; -.
DR SignaLink; Q9H871; -.
DR BioGRID-ORCS; 64795; 69 hits in 1068 CRISPR screens.
DR ChiTaRS; RMND5A; human.
DR GenomeRNAi; 64795; -.
DR Pharos; Q9H871; Tbio.
DR PRO; PR:Q9H871; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9H871; protein.
DR Bgee; ENSG00000153561; Expressed in secondary oocyte and 208 other tissues.
DR Genevisible; Q9H871; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0034657; C:GID complex; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:InterPro.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR CDD; cd16794; dRING_RMD5A; 1.
DR InterPro; IPR013144; CRA_dom.
DR InterPro; IPR024964; CTLH/CRA.
DR InterPro; IPR006595; CTLH_C.
DR InterPro; IPR045098; Fyv10_fam.
DR InterPro; IPR006594; LisH.
DR InterPro; IPR037680; RMD5A_dRING.
DR InterPro; IPR044063; ZF_RING_GID.
DR InterPro; IPR027370; Znf-RING_LisH.
DR PANTHER; PTHR12170; PTHR12170; 1.
DR Pfam; PF10607; CLTH; 1.
DR Pfam; PF13445; zf-RING_UBOX; 1.
DR SMART; SM00757; CRA; 1.
DR SMART; SM00668; CTLH; 1.
DR SMART; SM00667; LisH; 1.
DR PROSITE; PS50897; CTLH; 1.
DR PROSITE; PS50896; LISH; 1.
DR PROSITE; PS51867; ZF_RING_GID; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; Metal-binding; Nucleus;
KW Reference proteome; Transferase; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..391
FT /note="E3 ubiquitin-protein transferase RMND5A"
FT /id="PRO_0000272648"
FT DOMAIN 114..146
FT /note="LisH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00126"
FT DOMAIN 153..210
FT /note="CTLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00058"
FT ZN_FING 336..377
FT /note="RING-Gid-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01215"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT VAR_SEQ 96..98
FT /note="NFD -> DSL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022454"
FT VAR_SEQ 99..391
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022455"
FT CONFLICT 181
FT /note="E -> G (in Ref. 1; BAB14257)"
FT /evidence="ECO:0000305"
FT CONFLICT 187
FT /note="N -> D (in Ref. 1; BAB14257)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 391 AA; 43993 MW; A6043EBEED61FBB7 CRC64;
MDQCVTVERE LEKVLHKFSG YGQLCERGLE ELIDYTGGLK HEILQSHGQD AELSGTLSLV
LTQCCKRIKD TVQKLASDHK DIHSSVSRVG KAIDKNFDSD ISSVGIDGCW QADSQRLLNE
VMVEHFFRQG MLDVAEELCQ ESGLSVDPSQ KEPFVELNRI LEALKVRVLR PALEWAVSNR
EMLIAQNSSL EFKLHRLYFI SLLMGGTTNQ REALQYAKNF QPFALNHQKD IQVLMGSLVY
LRQGIENSPY VHLLDANQWA DICDIFTRDA CALLGLSVES PLSVSFSAGC VALPALINIK
AVIEQRQCTG VWNQKDELPI EVDLGKKCWY HSIFACPILR QQTTDNNPPM KLVCGHIISR
DALNKMFNGS KLKCPYCPME QSPGDAKQIF F
