SETD5_HUMAN
ID SETD5_HUMAN Reviewed; 1442 AA.
AC Q9C0A6; Q6AI17; Q8WUB6; Q9H3X4; Q9H6V7; Q9H7S3; Q9NVI9;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Histone-lysine N-methyltransferase SETD5 {ECO:0000305};
DE EC=2.1.1.359 {ECO:0000250|UniProtKB:Q5XJV7};
DE EC=2.1.1.367 {ECO:0000250|UniProtKB:Q5XJV7};
DE AltName: Full=SET domain-containing protein 5 {ECO:0000305};
GN Name=SETD5 {ECO:0000312|HGNC:HGNC:25566};
GN Synonyms=KIAA1757 {ECO:0000303|PubMed:11214970};
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=11214970; DOI=10.1093/dnares/7.6.347;
RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:347-355(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 527-1442.
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 445-1442.
RC TISSUE=Colon;
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 456-1442.
RC TISSUE=Hepatoma, Placenta, and 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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-829, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=22939622; DOI=10.1016/j.cell.2012.06.048;
RA Pinheiro I., Margueron R., Shukeir N., Eisold M., Fritzsch C.,
RA Richter F.M., Mittler G., Genoud C., Goyama S., Kurokawa M., Son J.,
RA Reinberg D., Lachner M., Jenuwein T.;
RT "Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian
RT heterochromatin integrity.";
RL Cell 150:948-960(2012).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72 AND SER-1198, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
RP INVOLVEMENT IN MRD23, AND VARIANTS MRD23 399-LYS--SER-1442 DEL;
RP 445-ARG--SER-1442 DEL; 622-TYR--SER-1442 DEL AND 1001-ARG--SER-1442 DEL.
RX PubMed=24680889; DOI=10.1016/j.ajhg.2014.03.006;
RG UK10K Consortium;
RA Grozeva D., Carss K., Spasic-Boskovic O., Parker M.J., Archer H.,
RA Firth H.V., Park S.M., Canham N., Holder S.E., Wilson M., Hackett A.,
RA Field M., Floyd J.A., Hurles M., Raymond F.L.;
RT "De novo loss-of-function mutations in SETD5, encoding a methyltransferase
RT in a 3p25 microdeletion syndrome critical region, cause intellectual
RT disability.";
RL Am. J. Hum. Genet. 94:618-624(2014).
RN [13]
RP VARIANTS MRD23 GLY-175 AND 768-ARG--SER-1442 DEL.
RX PubMed=25138099; DOI=10.1038/ejhg.2014.165;
RA Kuechler A., Zink A.M., Wieland T., Luedecke H.J., Cremer K., Salviati L.,
RA Magini P., Najafi K., Zweier C., Czeschik J.C., Aretz S., Endele S.,
RA Tamburrino F., Pinato C., Clementi M., Gundlach J., Maylahn C.,
RA Mazzanti L., Wohlleber E., Schwarzmayr T., Kariminejad R., Schlessinger A.,
RA Wieczorek D., Strom T.M., Novarino G., Engels H.;
RT "Loss-of-function variants of SETD5 cause intellectual disability and the
RT core phenotype of microdeletion 3p25.3 syndrome.";
RL Eur. J. Hum. Genet. 23:753-760(2015).
RN [14]
RP VARIANTS MRD23 973-SER--SER-1442 DEL AND CYS-1071.
RX PubMed=27375234; DOI=10.1002/ajmg.a.37832;
RA Szczaluba K., Brzezinska M., Kot J., Rydzanicz M., Walczak A.,
RA Stawinski P., Werner B., Ploski R.;
RT "SETD5 loss-of-function mutation as a likely cause of a familial syndromic
RT intellectual disability with variable phenotypic expression.";
RL Am. J. Med. Genet. A 170:2322-2327(2016).
RN [15]
RP INVOLVEMENT IN MRD23.
RX PubMed=28905509; DOI=10.1002/ajmg.a.38461;
RG DDD Study;
RA Green C., Willoughby J., Balasubramanian M.;
RT "De novo SETD5 loss-of-function variant as a cause for intellectual
RT disability in a 10-year old boy with an aberrant blind ending bronchus.";
RL Am. J. Med. Genet. A 173:3165-3171(2017).
RN [16]
RP INVOLVEMENT IN MRD23.
RX PubMed=28549204; DOI=10.4238/gmr16029615;
RA Stur E., Soares L.A., Louro I.D.;
RT "SETD5 gene variant associated with mild intellectual disability - a case
RT report.";
RL Genet. Mol. Res. 16:0-0(2017).
RN [17]
RP VARIANTS MRD23 656-LEU--SER-1442 DEL; 768-ARG--SER-1442 DEL;
RP 973-SER--SER-1442 DEL AND 985-TYR--SER-1442 DEL.
RX PubMed=28881385; DOI=10.1111/cge.13132;
RA Powis Z., Farwell Hagman K.D., Mroske C., McWalter K., Cohen J.S.,
RA Colombo R., Serretti A., Fatemi A., David K.L., Reynolds J., Immken L.,
RA Nagakura H., Cunniff C.M., Payne K., Barbaro-Dieber T., Gripp K.W.,
RA Baker L., Stamper T., Aleck K.A., Jordan E.S., Hersh J.H., Burton J.,
RA Wentzensen I.M., Guillen Sacoto M.J., Willaert R., Cho M.T., Petrik I.,
RA Huether R., Tang S.;
RT "Expansion and further delineation of the SETD5 phenotype leading to global
RT developmental delay, variable dysmorphic features, and reduced
RT penetrance.";
RL Clin. Genet. 93:752-761(2018).
CC -!- FUNCTION: Chromatin regulator required for brain development: acts as a
CC regulator of RNA elongation rate, thereby regulating neural stem cell
CC (NSC) proliferation and synaptic transmission. May act by mediating
CC trimethylation of 'Lys-36' of histone H3 (H3K36me3), which is essential
CC to allow on-time RNA elongation dynamics. Also monomethylates 'Lys-9'
CC of histone H3 (H3K9me1) in vitro. The relevance of histone
CC methyltransferase activity is however subject to discussion.
CC {ECO:0000250|UniProtKB:Q5XJV7}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = H(+) +
CC N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:60280, Rhea:RHEA-COMP:15542, Rhea:RHEA-COMP:15546,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.367;
CC Evidence={ECO:0000250|UniProtKB:Q5XJV7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+)
CC + N(6),N(6),N(6)-trimethyl-L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60324, Rhea:RHEA-COMP:9785, Rhea:RHEA-
CC COMP:15536, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.359;
CC Evidence={ECO:0000250|UniProtKB:Q5XJV7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60325;
CC Evidence={ECO:0000250|UniProtKB:Q5XJV7};
CC -!- SUBUNIT: Interacts with components of the PAF1 complex (PAF1C) such as
CC LEO1, CTR9 and CDC73. Interacts with NCOR1. Interacts with HDAC3.
CC {ECO:0000250|UniProtKB:Q5XJV7}.
CC -!- INTERACTION:
CC Q9C0A6-2; Q8NHQ1: CEP70; NbExp=3; IntAct=EBI-10303449, EBI-739624;
CC Q9C0A6-2; Q6A162: KRT40; NbExp=3; IntAct=EBI-10303449, EBI-10171697;
CC Q9C0A6-2; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-10303449, EBI-742948;
CC Q9C0A6-3; Q13137: CALCOCO2; NbExp=3; IntAct=EBI-12233047, EBI-739580;
CC Q9C0A6-3; Q58EX7: PLEKHG4; NbExp=3; IntAct=EBI-12233047, EBI-949255;
CC Q9C0A6-3; O60504: SORBS3; NbExp=3; IntAct=EBI-12233047, EBI-741237;
CC Q9C0A6-3; Q05BL1: TP53BP2; NbExp=3; IntAct=EBI-12233047, EBI-11952721;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q5XJV7}.
CC Chromosome {ECO:0000250|UniProtKB:Q5XJV7}. Note=Localizes to active
CC transcribed genes. {ECO:0000250|UniProtKB:Q5XJV7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9C0A6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9C0A6-2; Sequence=VSP_024094;
CC Name=3;
CC IsoId=Q9C0A6-3; Sequence=VSP_024094, VSP_024095;
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 23
CC (MRD23) [MIM:615761]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period. MRD23
CC patients manifest moderate to severe intellectual disability with
CC additional variable features of brachycephaly, a low hairline,
CC depressed nasal bridge, prominent high nasal root, tubular nose,
CC upslanting palpebral fissures, long and smooth philtrum, micrognathia,
CC thin upper lip, and crowded teeth. Behavioral problems, including
CC obsessive-compulsive disorder, hand flapping with ritualized behavior,
CC and autism, are prominent features. {ECO:0000269|PubMed:24680889,
CC ECO:0000269|PubMed:25138099, ECO:0000269|PubMed:27375234,
CC ECO:0000269|PubMed:28549204, ECO:0000269|PubMed:28881385,
CC ECO:0000269|PubMed:28905509}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH20956.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA91762.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB14903.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB15144.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB21848.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB051544; BAB21848.1; ALT_INIT; mRNA.
DR EMBL; AL442073; CAC09439.2; -; mRNA.
DR EMBL; CR627408; CAH10497.1; -; mRNA.
DR EMBL; AC018506; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020956; AAH20956.1; ALT_INIT; mRNA.
DR EMBL; AK001569; BAA91762.1; ALT_INIT; mRNA.
DR EMBL; AK024384; BAB14903.1; ALT_INIT; mRNA.
DR EMBL; AK025478; BAB15144.1; ALT_INIT; mRNA.
DR CCDS; CCDS46741.1; -. [Q9C0A6-1]
DR CCDS; CCDS74892.1; -. [Q9C0A6-3]
DR RefSeq; NP_001073986.1; NM_001080517.2. [Q9C0A6-1]
DR RefSeq; NP_001278972.1; NM_001292043.1. [Q9C0A6-3]
DR RefSeq; XP_016862270.1; XM_017006781.1.
DR AlphaFoldDB; Q9C0A6; -.
DR BioGRID; 120505; 32.
DR IntAct; Q9C0A6; 19.
DR STRING; 9606.ENSP00000385852; -.
DR iPTMnet; Q9C0A6; -.
DR PhosphoSitePlus; Q9C0A6; -.
DR BioMuta; SETD5; -.
DR DMDM; 143584285; -.
DR EPD; Q9C0A6; -.
DR jPOST; Q9C0A6; -.
DR MassIVE; Q9C0A6; -.
DR MaxQB; Q9C0A6; -.
DR PaxDb; Q9C0A6; -.
DR PeptideAtlas; Q9C0A6; -.
DR PRIDE; Q9C0A6; -.
DR ProteomicsDB; 79978; -. [Q9C0A6-1]
DR ProteomicsDB; 79979; -. [Q9C0A6-2]
DR ProteomicsDB; 79980; -. [Q9C0A6-3]
DR Antibodypedia; 60053; 89 antibodies from 17 providers.
DR DNASU; 55209; -.
DR Ensembl; ENST00000402198.7; ENSP00000385852.2; ENSG00000168137.20. [Q9C0A6-1]
DR Ensembl; ENST00000406341.5; ENSP00000383939.1; ENSG00000168137.20. [Q9C0A6-1]
DR GeneID; 55209; -.
DR KEGG; hsa:55209; -.
DR MANE-Select; ENST00000402198.7; ENSP00000385852.2; NM_001080517.3; NP_001073986.1.
DR UCSC; uc003brt.3; human. [Q9C0A6-1]
DR CTD; 55209; -.
DR DisGeNET; 55209; -.
DR GeneCards; SETD5; -.
DR HGNC; HGNC:25566; SETD5.
DR HPA; ENSG00000168137; Low tissue specificity.
DR MalaCards; SETD5; -.
DR MIM; 615743; gene.
DR MIM; 615761; phenotype.
DR neXtProt; NX_Q9C0A6; -.
DR OpenTargets; ENSG00000168137; -.
DR Orphanet; 404440; Intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency.
DR PharmGKB; PA143485613; -.
DR VEuPathDB; HostDB:ENSG00000168137; -.
DR eggNOG; KOG1844; Eukaryota.
DR GeneTree; ENSGT00940000157446; -.
DR InParanoid; Q9C0A6; -.
DR OrthoDB; 86638at2759; -.
DR PhylomeDB; Q9C0A6; -.
DR TreeFam; TF106417; -.
DR PathwayCommons; Q9C0A6; -.
DR SignaLink; Q9C0A6; -.
DR SIGNOR; Q9C0A6; -.
DR BioGRID-ORCS; 55209; 96 hits in 1094 CRISPR screens.
DR ChiTaRS; SETD5; human.
DR GenomeRNAi; 55209; -.
DR Pharos; Q9C0A6; Tbio.
DR PRO; PR:Q9C0A6; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9C0A6; protein.
DR Bgee; ENSG00000168137; Expressed in adrenal tissue and 195 other tissues.
DR ExpressionAtlas; Q9C0A6; baseline and differential.
DR Genevisible; Q9C0A6; HS.
DR GO; GO:0016593; C:Cdc73/Paf1 complex; IEA:Ensembl.
DR GO; GO:0000791; C:euchromatin; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0070210; C:Rpd3L-Expanded complex; IBA:GO_Central.
DR GO; GO:0034967; C:Set3 complex; IBA:GO_Central.
DR GO; GO:0046975; F:histone methyltransferase activity (H3-K36 specific); ISS:UniProtKB.
DR GO; GO:0046974; F:histone methyltransferase activity (H3-K9 specific); ISS:UniProtKB.
DR GO; GO:0035064; F:methylated histone binding; IBA:GO_Central.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0050890; P:cognition; ISS:UniProtKB.
DR GO; GO:0097198; P:histone H3-K36 trimethylation; ISS:UniProtKB.
DR GO; GO:1902275; P:regulation of chromatin organization; ISS:UniProtKB.
DR GO; GO:0032784; P:regulation of DNA-templated transcription, elongation; ISS:UniProtKB.
DR GO; GO:0035065; P:regulation of histone acetylation; ISS:UniProtKB.
DR GO; GO:0051963; P:regulation of synapse assembly; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR CDD; cd19181; SET_SETD5; 1.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR InterPro; IPR044433; SETD5_SET.
DR Pfam; PF00856; SET; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS50280; SET; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autism; Autism spectrum disorder;
KW Chromatin regulator; Chromosome; Disease variant; Intellectual disability;
KW Methyltransferase; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Transferase.
FT CHAIN 1..1442
FT /note="Histone-lysine N-methyltransferase SETD5"
FT /id="PRO_0000281905"
FT DOMAIN 269..390
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT REGION 156..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 418..682
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 792..820
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 849..882
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 934..965
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1036..1230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1242..1389
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1407..1442
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 165..180
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 438..454
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 458..472
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 498..538
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 539..556
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 564..593
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 620..682
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1066..1081
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1085..1168
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 72
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 829
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 852
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5XJV7"
FT MOD_RES 855
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5XJV7"
FT MOD_RES 1198
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..111
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:11214970,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_024094"
FT VAR_SEQ 188
FT /note="I -> IKAFREGSRKSLRM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_024095"
FT VARIANT 77
FT /note="R -> H (in dbSNP:rs41387348)"
FT /id="VAR_051336"
FT VARIANT 119
FT /note="R -> I (in dbSNP:rs11720526)"
FT /id="VAR_051337"
FT VARIANT 175
FT /note="S -> G (in MRD23)"
FT /evidence="ECO:0000269|PubMed:25138099"
FT /id="VAR_078954"
FT VARIANT 399..1442
FT /note="Missing (in MRD23; dbSNP:rs587777325)"
FT /evidence="ECO:0000269|PubMed:24680889"
FT /id="VAR_078955"
FT VARIANT 445..1442
FT /note="Missing (in MRD23)"
FT /evidence="ECO:0000269|PubMed:24680889"
FT /id="VAR_078956"
FT VARIANT 622..1442
FT /note="Missing (in MRD23)"
FT /evidence="ECO:0000269|PubMed:24680889"
FT /id="VAR_078957"
FT VARIANT 656..1442
FT /note="Missing (in MRD23)"
FT /evidence="ECO:0000269|PubMed:28881385"
FT /id="VAR_083220"
FT VARIANT 768..1442
FT /note="Missing (in MRD23; dbSNP:rs864321657)"
FT /evidence="ECO:0000269|PubMed:25138099,
FT ECO:0000269|PubMed:28881385"
FT /id="VAR_078958"
FT VARIANT 973..1442
FT /note="Missing (in MRD23)"
FT /evidence="ECO:0000269|PubMed:27375234,
FT ECO:0000269|PubMed:28881385"
FT /id="VAR_078959"
FT VARIANT 985..1442
FT /note="Missing (in MRD23)"
FT /evidence="ECO:0000269|PubMed:28881385"
FT /id="VAR_083221"
FT VARIANT 1001..1442
FT /note="Missing (in MRD23; dbSNP:rs587777327)"
FT /evidence="ECO:0000269|PubMed:24680889"
FT /id="VAR_078960"
FT VARIANT 1071
FT /note="Y -> C (in MRD23; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:27375234"
FT /id="VAR_078961"
FT VARIANT 1137
FT /note="M -> V (in dbSNP:rs13327456)"
FT /id="VAR_051338"
FT VARIANT 1308
FT /note="T -> I (in dbSNP:rs11542009)"
FT /id="VAR_061705"
FT CONFLICT 369
FT /note="I -> N (in Ref. 2; CAH10497)"
FT /evidence="ECO:0000305"
FT CONFLICT 869
FT /note="A -> V (in Ref. 2; CAH10497)"
FT /evidence="ECO:0000305"
FT CONFLICT 985
FT /note="Y -> H (in Ref. 2; CAH10497)"
FT /evidence="ECO:0000305"
FT CONFLICT 1123
FT /note="P -> S (in Ref. 5; BAB14903)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1442 AA; 157515 MW; E3CDBA72E2ED0DB4 CRC64;
MSIAIPLGVT TSDTSYSDMA AGSDPESVEA SPAVNEKSVY STHNYGTTQR HGCRGLPYAT
IIPRSDLNGL PSPVEERCGD SPNSEGETVP TWCPCGLSQD GFLLNCDKCR GMSRGKVIRL
HRRKQDNISG GDSSATESWD EELSPSTVLY TATQHTPTSI TLTVRRTKPK KRKKSPEKGR
AAPKTKKIKN SPSEAQNLDE NTTEGWENRI RLWTDQYEEA FTNQYSADVQ NALEQHLHSS
KEFVGKPTIL DTINKTELAC NNTVIGSQMQ LQLGRVTRVQ KHRKILRAAR DLALDTLIIE
YRGKVMLRQQ FEVNGHFFKK PYPFVLFYSK FNGVEMCVDA RTFGNDARFI RRSCTPNAEV
RHMIADGMIH LCIYAVSAIT KDAEVTIAFD YEYSNCNYKV DCACHKGNRN CPIQKRNPNA
TELPLLPPPP SLPTIGAETR RRKARRKELE MEQQNEASEE NNDQQSQEVP EKVTVSSDHE
EVDNPEEKPE EEKEEVIDDQ ENLAHSRRTR EDRKVEAIMH AFENLEKRKK RRDQPLEQSN
SDVEITTTTS ETPVGEETKT EAPESEVSNS VSNVTIPSTP QSVGVNTRRS SQAGDIAAEK
LVPKPPPAKP SRPRPKSRIS RYRTSSAQRL KRQKQANAQQ AELSQAALEE GGSNSLVTPT
EAGSLDSSGE NRPLTGSDPT VVSITGSHVN RAASKYPKTK KYLVTEWLND KAEKQECPVE
CPLRITTDPT VLATTLNMLP GLIHSPLICT TPKHYIRFGS PFIPERRRRP LLPDGTFSSC
KKRWIKQALE EGMTQTSSVP QETRTQHLYQ SNENSSSSSI CKDNADLLSP LKKWKSRYLM
EQNVTKLLRP LSPVTPPPPN SGSKSPQLAT PGSSHPGEEE CRNGYSLMFS PVTSLTTASR
CNTPLQFELC HRKDLDLAKV GYLDSNTNSC ADRPSLLNSG HSDLAPHPSL GPTSETGFPS
RSGDGHQTLV RNSDQAFRTE FNLMYAYSPL NAMPRADGLY RGSPLVGDRK PLHLDGGYCS
PAEGFSSRYE HGLMKDLSRG SLSPGGERAC EGVPSAPQNP PQRKKVSLLE YRKRKQEAKE
NSAGGGGDSA QSKSKSAGAG QGSSNSVSDT GAHGVQGSSA RTPSSPHKKF SPSHSSMSHL
EAVSPSDSRG TSSSHCRPQE NISSRWMVPT SVERLREGGS IPKVLRSSVR VAQKGEPSPT
WESNITEKDS DPADGEGPET LSSALSKGAT VYSPSRYSYQ LLQCDSPRTE SQSLLQQSSS
PFRGHPTQSP GYSYRTTALR PGNPPSHGSS ESSLSSTSYS SPAHPVSTDS LAPFTGTPGY
FSSQPHSGNS TGSNLPRRSC PSSAASPTLQ GPSDSPTSDS VSQSSTGTLS STSFPQNSRS
SLPSDLRTIS LPSAGQSAVY QASRVSAVSN SQHYPHRGSG GVHQYRLQPL QGSGVKTQTG
LS
