R144A_HUMAN
ID R144A_HUMAN Reviewed; 292 AA.
AC P50876; D6W4Y6; Q585H5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=E3 ubiquitin-protein ligase RNF144A;
DE EC=2.3.2.31 {ECO:0000250|UniProtKB:O60260};
DE AltName: Full=RING finger protein 144A;
DE AltName: Full=UbcM4-interacting protein 4;
DE AltName: Full=Ubiquitin-conjugating enzyme 7-interacting protein 4;
GN Name=RNF144A; Synonyms=KIAA0161, RNF144, UBCE7IP4;
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], AND VARIANT ALA-4.
RC TISSUE=Bone marrow;
RX PubMed=8724849; DOI=10.1093/dnares/3.1.17;
RA Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. V. The
RT coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 3:17-24(1996).
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], AND VARIANT ALA-4.
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], AND VARIANT ALA-4.
RC TISSUE=Ovary;
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 INTERACTION WITH UBE2L3.
RX PubMed=10431818; DOI=10.1016/s0014-5793(99)00823-6;
RA Martinez-Noel G., Niedenthal R., Tamura T., Harbers K.;
RT "A family of structurally related RING finger proteins interacts
RT specifically with the ubiquitin-conjugating enzyme UbcM4.";
RL FEBS Lett. 454:257-261(1999).
RN [6]
RP FUNCTION, AUTOUBIQUITINATION, AND SUBCELLULAR LOCATION.
RX PubMed=24979766; DOI=10.1073/pnas.1323107111;
RA Ho S.R., Mahanic C.S., Lee Y.J., Lin W.C.;
RT "RNF144A, an E3 ubiquitin ligase for DNA-PKcs, promotes apoptosis during
RT DNA damage.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E2646-E2655(2014).
RN [7]
RP STRUCTURE BY NMR OF 20-100.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the RING finger domain of the human UbcM4-
RT interacting protein 4.";
RL Submitted (NOV-2004) to the PDB data bank.
CC -!- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from E2
CC ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a
CC thioester and then directly transfers the ubiquitin to targeted
CC substrates. Mediates the ubiquitination and degradation of the DNA
CC damage kinase PRKDC. {ECO:0000250, ECO:0000269|PubMed:24979766}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + [acceptor protein]-N(6)-ubiquitinyl-L-lysine.;
CC EC=2.3.2.31; Evidence={ECO:0000250|UniProtKB:O60260};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with UBE2L3. {ECO:0000269|PubMed:10431818}.
CC -!- INTERACTION:
CC P50876; Q6ZPD8: DGAT2L6; NbExp=3; IntAct=EBI-2340657, EBI-12831978;
CC P50876; Q6N075: MFSD5; NbExp=3; IntAct=EBI-2340657, EBI-3920969;
CC P50876; Q6TCH4: PAQR6; NbExp=3; IntAct=EBI-2340657, EBI-17265310;
CC P50876; Q96AA3: RFT1; NbExp=3; IntAct=EBI-2340657, EBI-6269616;
CC P50876; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-2340657, EBI-8652744;
CC P50876; O43765: SGTA; NbExp=3; IntAct=EBI-2340657, EBI-347996;
CC P50876; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-2340657, EBI-744081;
CC P50876; P30825: SLC7A1; NbExp=3; IntAct=EBI-2340657, EBI-4289564;
CC P50876; P68036: UBE2L3; NbExp=4; IntAct=EBI-2340657, EBI-711173;
CC P50876; O95070: YIF1A; NbExp=3; IntAct=EBI-2340657, EBI-2799703;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24979766};
CC Single-pass membrane protein {ECO:0000305}. Cytoplasmic vesicle
CC membrane {ECO:0000269|PubMed:24979766}.
CC -!- DOMAIN: Members of the RBR family are atypical E3 ligases. They
CC interact with the E2 conjugating enzyme UBE2L3 and function like HECT-
CC type E3 enzymes: they bind E2s via the first RING domain, but require
CC an obligate trans-thiolation step during the ubiquitin transfer,
CC requiring a conserved cysteine residue in the second RING domain.
CC {ECO:0000250|UniProtKB:O60260}.
CC -!- PTM: Autoubiquitinated. {ECO:0000269|PubMed:24979766}.
CC -!- SIMILARITY: Belongs to the RBR family. RNF144 subfamily. {ECO:0000305}.
CC -!- CAUTION: Lacks the His residue in the RING-type domain 2 that is one of
CC the conserved features of the family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA11478.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; D79983; BAA11478.2; ALT_INIT; mRNA.
DR EMBL; AC068481; AAX82010.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX01030.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX01031.1; -; Genomic_DNA.
DR EMBL; BC050373; AAH50373.1; -; mRNA.
DR CCDS; CCDS1657.1; -.
DR RefSeq; NP_055561.2; NM_014746.4.
DR RefSeq; XP_005246257.1; XM_005246200.3.
DR RefSeq; XP_005246259.1; XM_005246202.4.
DR RefSeq; XP_016860885.1; XM_017005396.1.
DR RefSeq; XP_016860886.1; XM_017005397.1.
DR PDB; 1WIM; NMR; -; A=20-100.
DR PDB; 6L99; NMR; -; A=13-87.
DR PDBsum; 1WIM; -.
DR PDBsum; 6L99; -.
DR AlphaFoldDB; P50876; -.
DR BMRB; P50876; -.
DR SMR; P50876; -.
DR BioGRID; 115125; 91.
DR IntAct; P50876; 17.
DR MINT; P50876; -.
DR STRING; 9606.ENSP00000321330; -.
DR iPTMnet; P50876; -.
DR PhosphoSitePlus; P50876; -.
DR BioMuta; RNF144A; -.
DR DMDM; 160358924; -.
DR MassIVE; P50876; -.
DR PaxDb; P50876; -.
DR PeptideAtlas; P50876; -.
DR PRIDE; P50876; -.
DR ProteomicsDB; 56267; -.
DR Antibodypedia; 26428; 183 antibodies from 29 providers.
DR DNASU; 9781; -.
DR Ensembl; ENST00000320892.11; ENSP00000321330.6; ENSG00000151692.15.
DR GeneID; 9781; -.
DR KEGG; hsa:9781; -.
DR MANE-Select; ENST00000320892.11; ENSP00000321330.6; NM_014746.6; NP_055561.2.
DR UCSC; uc002qys.4; human.
DR CTD; 9781; -.
DR DisGeNET; 9781; -.
DR GeneCards; RNF144A; -.
DR HGNC; HGNC:20457; RNF144A.
DR HPA; ENSG00000151692; Tissue enhanced (brain).
DR MIM; 619454; gene.
DR neXtProt; NX_P50876; -.
DR OpenTargets; ENSG00000151692; -.
DR PharmGKB; PA162401542; -.
DR VEuPathDB; HostDB:ENSG00000151692; -.
DR eggNOG; KOG1815; Eukaryota.
DR GeneTree; ENSGT00940000157701; -.
DR HOGENOM; CLU_053598_1_0_1; -.
DR InParanoid; P50876; -.
DR OMA; ESGPQNP; -.
DR OrthoDB; 1188714at2759; -.
DR PhylomeDB; P50876; -.
DR TreeFam; TF324777; -.
DR BRENDA; 2.3.2.31; 2681.
DR PathwayCommons; P50876; -.
DR Reactome; R-HSA-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR SignaLink; P50876; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 9781; 13 hits in 1123 CRISPR screens.
DR ChiTaRS; RNF144A; human.
DR EvolutionaryTrace; P50876; -.
DR GenomeRNAi; 9781; -.
DR Pharos; P50876; Tbio.
DR PRO; PR:P50876; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P50876; protein.
DR Bgee; ENSG00000151692; Expressed in cerebellar hemisphere and 179 other tissues.
DR ExpressionAtlas; P50876; baseline and differential.
DR Genevisible; P50876; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IBA:GO_Central.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; EXP:Reactome.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; TAS:Reactome.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR031127; E3_UB_ligase_RBR.
DR InterPro; IPR002867; IBR_dom.
DR InterPro; IPR044066; TRIAD_supradom.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR11685; PTHR11685; 1.
DR Pfam; PF01485; IBR; 2.
DR SMART; SM00647; IBR; 2.
DR PROSITE; PS51873; TRIAD; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasmic vesicle; Membrane; Metal-binding;
KW Reference proteome; Repeat; Transferase; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..292
FT /note="E3 ubiquitin-protein ligase RNF144A"
FT /id="PRO_0000056298"
FT TRANSMEM 250..270
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ZN_FING 20..70
FT /note="RING-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 91..156
FT /note="IBR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 185..214
FT /note="RING-type 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT REGION 16..236
FT /note="TRIAD supradomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ACT_SITE 198
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 20
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 23
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 43
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 46
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 111
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 116
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 135
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 138
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 143
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 146
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 151
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 156
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 185
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 188
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 203
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 206
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 211
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 214
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 226
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 232
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT VARIANT 4
FT /note="T -> A (in dbSNP:rs364891)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:8724849, ECO:0000269|Ref.3"
FT /id="VAR_035375"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:1WIM"
FT HELIX 29..31
FT /evidence="ECO:0007829|PDB:1WIM"
FT STRAND 32..35
FT /evidence="ECO:0007829|PDB:1WIM"
FT TURN 36..39
FT /evidence="ECO:0007829|PDB:1WIM"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:1WIM"
FT HELIX 44..57
FT /evidence="ECO:0007829|PDB:1WIM"
FT HELIX 78..84
FT /evidence="ECO:0007829|PDB:1WIM"
FT HELIX 87..99
FT /evidence="ECO:0007829|PDB:1WIM"
SQ SEQUENCE 292 AA; 32890 MW; E5BE7BC9560DCF93 CRC64;
MTTTRYRPTW DLALDPLVSC KLCLGEYPVE QMTTIAQCQC IFCTLCLKQY VELLIKEGLE
TAISCPDAAC PKQGHLQENE IECMVAAEIM QRYKKLQFER EVLFDPCRTW CPASTCQAVC
QLQDVGLQTP QPVQCKACRM EFCSTCKASW HPGQGCPETM PITFLPGETS AAFKMEEDDA
PIKRCPKCKV YIERDEGCAQ MMCKNCKHAF CWYCLESLDD DFLLIHYDKG PCRNKLGHSR
ASVIWHRTQV VGIFAGFGLL LLVASPFLLL ATPFVLCCKC KCSKGDDDPL PT
