K1586_HUMAN
ID K1586_HUMAN Reviewed; 787 AA.
AC Q9HCI6; A8K4M3; Q8IW25;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=E3 SUMO-protein ligase KIAA1586 {ECO:0000305};
DE EC=2.3.2.- {ECO:0000269|PubMed:26524493};
DE AltName: Full=E3 SUMO-protein transferase KIAA1586 {ECO:0000305};
GN Name=KIAA1586;
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=Brain;
RX PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:273-281(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-744 (ISOFORM 1).
RC TISSUE=Teratocarcinoma;
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 [5]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-85, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, DOMAIN, AND SUBUNIT.
RX PubMed=26524493; DOI=10.1038/nsmb.3114;
RA Eisenhardt N., Chaugule V.K., Koidl S., Droescher M., Dogan E., Rettich J.,
RA Sutinen P., Imanishi S.Y., Hofmann K., Palvimo J.J., Pichler A.;
RT "A new vertebrate SUMO enzyme family reveals insights into SUMO-chain
RT assembly.";
RL Nat. Struct. Mol. Biol. 22:959-967(2015).
RN [7]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-119 AND LYS-125, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
CC -!- FUNCTION: E3 SUMO-protein ligase; facilitates UBE2I/UBC9-mediated SUMO2
CC modification of target proteins (PubMed:26524493).
CC -!- PATHWAY: Protein modification; protein sumoylation.
CC {ECO:0000269|PubMed:26524493}.
CC -!- SUBUNIT: Interacts with UBE2I/UBC9 and SUMO2.
CC {ECO:0000305|PubMed:26524493}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9HCI6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9HCI6-2; Sequence=VSP_031740;
CC -!- DOMAIN: Binds UBE2I/UBC9 and two SUMO2 molecules via its N-terminus.
CC The most N-terminal region interacts with the SUMO2 chain that is
CC covalently bound to the UBE2I/UBC9 active site, while the second region
CC interacts with another SUMO2 that is non-covalently associated with the
CC same UBE2I/UBC9 chain. {ECO:0000250|UniProtKB:Q9Y4E5,
CC ECO:0000305|PubMed:26524493}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB13412.1; 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; AB046806; BAB13412.1; ALT_INIT; mRNA.
DR EMBL; AL450489; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC041125; AAH41125.1; -; mRNA.
DR EMBL; AK290988; BAF83677.1; -; mRNA.
DR CCDS; CCDS34480.1; -. [Q9HCI6-1]
DR RefSeq; NP_001273203.1; NM_001286274.1.
DR RefSeq; NP_001273204.1; NM_001286275.1.
DR RefSeq; NP_001273205.1; NM_001286276.1.
DR RefSeq; NP_065982.1; NM_020931.3. [Q9HCI6-1]
DR AlphaFoldDB; Q9HCI6; -.
DR SMR; Q9HCI6; -.
DR BioGRID; 121717; 16.
DR IntAct; Q9HCI6; 3.
DR STRING; 9606.ENSP00000359768; -.
DR iPTMnet; Q9HCI6; -.
DR PhosphoSitePlus; Q9HCI6; -.
DR BioMuta; KIAA1586; -.
DR DMDM; 172045931; -.
DR EPD; Q9HCI6; -.
DR MassIVE; Q9HCI6; -.
DR MaxQB; Q9HCI6; -.
DR PaxDb; Q9HCI6; -.
DR PeptideAtlas; Q9HCI6; -.
DR PRIDE; Q9HCI6; -.
DR ProteomicsDB; 81731; -. [Q9HCI6-1]
DR ProteomicsDB; 81732; -. [Q9HCI6-2]
DR Antibodypedia; 49175; 69 antibodies from 15 providers.
DR DNASU; 57691; -.
DR Ensembl; ENST00000370733.5; ENSP00000359768.4; ENSG00000168116.14. [Q9HCI6-1]
DR GeneID; 57691; -.
DR KEGG; hsa:57691; -.
DR MANE-Select; ENST00000370733.5; ENSP00000359768.4; NM_020931.4; NP_065982.1.
DR UCSC; uc003pdj.5; human. [Q9HCI6-1]
DR CTD; 57691; -.
DR GeneCards; KIAA1586; -.
DR HGNC; HGNC:21360; KIAA1586.
DR HPA; ENSG00000168116; Low tissue specificity.
DR neXtProt; NX_Q9HCI6; -.
DR OpenTargets; ENSG00000168116; -.
DR PharmGKB; PA134963244; -.
DR VEuPathDB; HostDB:ENSG00000168116; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000162903; -.
DR InParanoid; Q9HCI6; -.
DR OMA; PVLYMHF; -.
DR OrthoDB; 238769at2759; -.
DR PhylomeDB; Q9HCI6; -.
DR TreeFam; TF343259; -.
DR PathwayCommons; Q9HCI6; -.
DR SignaLink; Q9HCI6; -.
DR UniPathway; UPA00886; -.
DR BioGRID-ORCS; 57691; 10 hits in 1077 CRISPR screens.
DR GenomeRNAi; 57691; -.
DR Pharos; Q9HCI6; Tdark.
DR PRO; PR:Q9HCI6; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9HCI6; protein.
DR Bgee; ENSG00000168116; Expressed in calcaneal tendon and 134 other tissues.
DR ExpressionAtlas; Q9HCI6; baseline and differential.
DR Genevisible; Q9HCI6; HS.
DR GO; GO:0061665; F:SUMO ligase activity; IDA:UniProtKB.
DR GO; GO:0016925; P:protein sumoylation; IDA:UniProtKB.
DR InterPro; IPR012337; RNaseH-like_sf.
DR SUPFAM; SSF53098; SSF53098; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Isopeptide bond; Reference proteome; Transferase;
KW Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..787
FT /note="E3 SUMO-protein ligase KIAA1586"
FT /id="PRO_0000320680"
FT REGION 1..223
FT /note="Sufficient for E3 SUMO-protein ligase activity"
FT /evidence="ECO:0000305"
FT REGION 1..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 30..37
FT /note="Interaction with SUMO2 1"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E5"
FT REGION 42..50
FT /note="Interaction with SUMO2 2"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E5"
FT MOTIF 38..41
FT /note="PSRP"
FT /evidence="ECO:0000305"
FT CROSSLNK 85
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447"
FT CROSSLNK 119
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 125
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..62
FT /note="MGDPGSEIIESVPPAGPEASESTTDENEDDIQFVSEGPSRPVLEYIDLVCGD
FT DENPSAYYSD -> MNFTYICKIIFQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10997877"
FT /id="VSP_031740"
FT VARIANT 75
FT /note="F -> L (in dbSNP:rs36113897)"
FT /id="VAR_039276"
FT VARIANT 81
FT /note="V -> M (in dbSNP:rs6926980)"
FT /id="VAR_039277"
SQ SEQUENCE 787 AA; 89673 MW; ECBFB636C2F7959E CRC64;
MGDPGSEIIE SVPPAGPEAS ESTTDENEDD IQFVSEGPSR PVLEYIDLVC GDDENPSAYY
SDILFPKMPK RQGDFLHFLN VKKVKTDTEN NEVSKNHCRL SKAKEPHFEY IEQPIIEEKP
SLSSKKEIDN LVLPDCWNEK QAFMFTEQYK WLEIKEGKLG CKDCSAVRHL GSKAEKHVHV
SKEWIAYLVT PNGSNKTTRQ ASLRKKIREH DVSKAHGKIQ DLLKESTNDS ICNLVHKQNN
KNIDATVKVF NTVYSLVKHN RPLSDIEGAR ELQEKNGEVN CLNTRYSATR IAEHIAKEMK
MKIFKNIIEE NAKICIIIDE ASTVSKKTTL VIYLQCTIQS APAPVMLFVA LKELVSTIAE
CIVNTLLTTL NDCGFTNEYL KANLIAFCSD GANTILGRKS GVATKLLENF PEIIIWNCLN
HRLQLSLDDS ISEIKQINHL KIFIDKIYSI YHQPNKNQTK LLGTVAKELE TEIIKIGRVM
GPRWAACSLQ AATAVWHAYP ILYMHFSHSY SGLAKRLANI NFLQDLALMI DILEEFSVLS
TALQSRSTNI KKAQKLIKRT IRALENLKIG TGKYESQIED LIKSDKFKDI PFNKNNKFNA
LPRSILLDNI IQHMNLRLLS DRNHEDIFNY FDLLEPSTWP YEEITSPWIA GEKTLFHLCK
ILKYEVDLND FREFVNNNIK SNNVSIPTTI YKAKKIVSTI AINSAEAERG FNLMNIICTR
VRNSLTIDHV SDLMTINLLG KELADWDATP FVKSWSNCNH RLATDTRVRQ KSTKVFHENQ
LAIWNLK
