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   22-APR-2020, entry version 167.
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};
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; 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   PDBsum; 1WIM; -.
DR   SMR; P50876; -.
DR   BioGrid; 115125; 69.
DR   IntAct; P50876; 17.
DR   MINT; P50876; -.
DR   STRING; 9606.ENSP00000321330; -.
DR   iPTMnet; P50876; -.
DR   BioMuta; RNF144A; -.
DR   DMDM; 160358924; -.
DR   PaxDb; P50876; -.
DR   PeptideAtlas; P50876; -.
DR   PRIDE; P50876; -.
DR   ProteomicsDB; 56267; -.
DR   Antibodypedia; 26428; 177 antibodies.
DR   DNASU; 9781; -.
DR   Ensembl; ENST00000320892; ENSP00000321330; ENSG00000151692.
DR   GeneID; 9781; -.
DR   KEGG; hsa:9781; -.
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   neXtProt; NX_P50876; -.
DR   OpenTargets; ENSG00000151692; -.
DR   PharmGKB; PA162401542; -.
DR   eggNOG; KOG1815; Eukaryota.
DR   eggNOG; ENOG410XP9Y; LUCA.
DR   GeneTree; ENSGT00940000157701; -.
DR   HOGENOM; CLU_053598_1_0_1; -.
DR   InParanoid; P50876; -.
DR   KO; K11975; -.
DR   OMA; PGQGCQE; -.
DR   OrthoDB; 1188714at2759; -.
DR   PhylomeDB; P50876; -.
DR   TreeFam; TF324777; -.
DR   Reactome; R-HSA-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR   UniPathway; UPA00143; -.
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 corpus callosum and 205 other tissues.
DR   ExpressionAtlas; P50876; baseline and differential.
DR   Genevisible; P50876; HS.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
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; 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   Polymorphism; 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   METAL           20
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           23
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           43
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           46
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           111
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           116
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           135
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           138
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           143
FT                   /note="Zinc 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           146
FT                   /note="Zinc 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           151
FT                   /note="Zinc 3; via tele nitrogen"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           156
FT                   /note="Zinc 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           185
FT                   /note="Zinc 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           188
FT                   /note="Zinc 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           203
FT                   /note="Zinc 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           206
FT                   /note="Zinc 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           211
FT                   /note="Zinc 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           214
FT                   /note="Zinc 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           226
FT                   /note="Zinc 5; via tele nitrogen"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT   METAL           232
FT                   /note="Zinc 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:0000244|PDB:1WIM"
FT   HELIX           29..31
FT                   /evidence="ECO:0000244|PDB:1WIM"
FT   STRAND          32..35
FT                   /evidence="ECO:0000244|PDB:1WIM"
FT   TURN            36..39
FT                   /evidence="ECO:0000244|PDB:1WIM"
FT   STRAND          40..43
FT                   /evidence="ECO:0000244|PDB:1WIM"
FT   HELIX           44..57
FT                   /evidence="ECO:0000244|PDB:1WIM"
FT   HELIX           78..84
FT                   /evidence="ECO:0000244|PDB:1WIM"
FT   HELIX           87..99
FT                   /evidence="ECO:0000244|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
//