INT12_HUMAN
ID INT12_HUMAN Reviewed; 462 AA.
AC Q96CB8; B2RC48; Q3B6Z3; Q9HD71;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Integrator complex subunit 12;
DE Short=Int12;
DE AltName: Full=PHD finger protein 22;
GN Name=INTS12; Synonyms=PHF22; ORFNames=SBBI22;
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 [MRNA].
RA Wan T., Li N., Zhang W., Cao X.;
RT "Hypothetical nuclear factor SBBI22 mRNA.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE INTEGRATOR
RP COMPLEX.
RX PubMed=16239144; DOI=10.1016/j.cell.2005.08.019;
RA Baillat D., Hakimi M.-A., Naeaer A.M., Shilatifard A., Cooch N.,
RA Shiekhattar R.;
RT "Integrator, a multiprotein mediator of small nuclear RNA processing,
RT associates with the C-terminal repeat of RNA polymerase II.";
RL Cell 123:265-276(2005).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-128, 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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP IDENTIFICATION BY 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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-128, AND IDENTIFICATION BY
RP 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 FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23904267; DOI=10.1091/mbc.e13-05-0254;
RA Jodoin J.N., Sitaram P., Albrecht T.R., May S.B., Shboul M., Lee E.,
RA Reversade B., Wagner E.J., Lee L.A.;
RT "Nuclear-localized Asunder regulates cytoplasmic dynein localization via
RT its role in the integrator complex.";
RL Mol. Biol. Cell 24:2954-2965(2013).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-128, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-68, 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 [15]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-68 AND LYS-254, 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: Component of the Integrator complex, a complex involved in
CC the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-
CC box-dependent processing. The Integrator complex is associated with the
CC C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A)
CC and is recruited to the U1 and U2 snRNAs genes (PubMed:16239144).
CC Mediates recruitment of cytoplasmic dynein to the nuclear envelope,
CC probably as component of the INT complex (PubMed:23904267).
CC {ECO:0000269|PubMed:16239144, ECO:0000269|PubMed:23904267}.
CC -!- SUBUNIT: Belongs to the multiprotein complex Integrator, at least
CC composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8,
CC INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12.
CC {ECO:0000269|PubMed:16239144}.
CC -!- INTERACTION:
CC Q96CB8; Q14CZ0: C16orf72; NbExp=5; IntAct=EBI-1049156, EBI-10234807;
CC Q96CB8; Q8IZU1: FAM9A; NbExp=3; IntAct=EBI-1049156, EBI-8468186;
CC Q96CB8; Q9UHL9: GTF2IRD1; NbExp=3; IntAct=EBI-1049156, EBI-372530;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23904267}.
CC -!- SIMILARITY: Belongs to the Integrator subunit 12 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF99604.1; Type=Frameshift; 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; AF242524; AAF99604.1; ALT_FRAME; mRNA.
DR EMBL; AK314939; BAG37445.1; -; mRNA.
DR EMBL; CH471057; EAX06189.1; -; Genomic_DNA.
DR EMBL; BC014442; AAH14442.1; -; mRNA.
DR EMBL; BK005729; DAA05729.1; -; mRNA.
DR CCDS; CCDS3671.1; -.
DR RefSeq; NP_001135943.1; NM_001142471.1.
DR RefSeq; NP_065128.2; NM_020395.3.
DR RefSeq; XP_005263205.1; XM_005263148.4.
DR RefSeq; XP_011530445.1; XM_011532143.2.
DR RefSeq; XP_011530447.1; XM_011532145.2.
DR AlphaFoldDB; Q96CB8; -.
DR SMR; Q96CB8; -.
DR BioGRID; 121381; 95.
DR ComplexPortal; CPX-6441; Integrator complex.
DR CORUM; Q96CB8; -.
DR DIP; DIP-48479N; -.
DR IntAct; Q96CB8; 41.
DR MINT; Q96CB8; -.
DR STRING; 9606.ENSP00000415433; -.
DR GlyGen; Q96CB8; 7 sites, 2 O-linked glycans (7 sites).
DR iPTMnet; Q96CB8; -.
DR PhosphoSitePlus; Q96CB8; -.
DR BioMuta; INTS12; -.
DR DMDM; 73621394; -.
DR EPD; Q96CB8; -.
DR jPOST; Q96CB8; -.
DR MassIVE; Q96CB8; -.
DR MaxQB; Q96CB8; -.
DR PaxDb; Q96CB8; -.
DR PeptideAtlas; Q96CB8; -.
DR PRIDE; Q96CB8; -.
DR ProteomicsDB; 76174; -.
DR Antibodypedia; 26162; 79 antibodies from 22 providers.
DR DNASU; 57117; -.
DR Ensembl; ENST00000340139.10; ENSP00000340737.5; ENSG00000138785.16.
DR Ensembl; ENST00000394735.5; ENSP00000378221.1; ENSG00000138785.16.
DR Ensembl; ENST00000451321.6; ENSP00000415433.2; ENSG00000138785.16.
DR GeneID; 57117; -.
DR KEGG; hsa:57117; -.
DR MANE-Select; ENST00000340139.10; ENSP00000340737.5; NM_020395.4; NP_065128.2.
DR UCSC; uc003hxw.4; human.
DR CTD; 57117; -.
DR DisGeNET; 57117; -.
DR GeneCards; INTS12; -.
DR HGNC; HGNC:25067; INTS12.
DR HPA; ENSG00000138785; Low tissue specificity.
DR MIM; 611355; gene.
DR neXtProt; NX_Q96CB8; -.
DR OpenTargets; ENSG00000138785; -.
DR PharmGKB; PA142671177; -.
DR VEuPathDB; HostDB:ENSG00000138785; -.
DR eggNOG; KOG4323; Eukaryota.
DR GeneTree; ENSGT00390000005218; -.
DR HOGENOM; CLU_033336_0_0_1; -.
DR InParanoid; Q96CB8; -.
DR OMA; AKQDKRN; -.
DR OrthoDB; 1631937at2759; -.
DR PhylomeDB; Q96CB8; -.
DR TreeFam; TF106418; -.
DR PathwayCommons; Q96CB8; -.
DR Reactome; R-HSA-6807505; RNA polymerase II transcribes snRNA genes.
DR SignaLink; Q96CB8; -.
DR SIGNOR; Q96CB8; -.
DR BioGRID-ORCS; 57117; 341 hits in 1096 CRISPR screens.
DR GeneWiki; INTS12; -.
DR GenomeRNAi; 57117; -.
DR Pharos; Q96CB8; Tbio.
DR PRO; PR:Q96CB8; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q96CB8; protein.
DR Bgee; ENSG00000138785; Expressed in oocyte and 201 other tissues.
DR ExpressionAtlas; Q96CB8; baseline and differential.
DR Genevisible; Q96CB8; HS.
DR GO; GO:0032039; C:integrator complex; IDA:HGNC-UCL.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0034243; P:regulation of transcription elongation from RNA polymerase II promoter; IC:ComplexPortal.
DR GO; GO:0034472; P:snRNA 3'-end processing; IBA:GO_Central.
DR GO; GO:0016180; P:snRNA processing; IDA:HGNC-UCL.
DR CDD; cd15501; PHD_Int12; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR039053; Int12.
DR InterPro; IPR039054; Int12_PHD.
DR InterPro; IPR019786; Zinc_finger_PHD-type_CS.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR001965; Znf_PHD.
DR InterPro; IPR019787; Znf_PHD-finger.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR13415:SF4; PTHR13415:SF4; 1.
DR Pfam; PF00628; PHD; 1.
DR SMART; SM00249; PHD; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS01359; ZF_PHD_1; 1.
DR PROSITE; PS50016; ZF_PHD_2; 1.
PE 1: Evidence at protein level;
KW Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..462
FT /note="Integrator complex subunit 12"
FT /id="PRO_0000059312"
FT ZN_FING 159..215
FT /note="PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT REGION 42..132
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 301..462
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 55..87
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 88..123
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 301..356
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 371..445
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT CROSSLNK 68
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 254
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 323
FT /note="T -> A (in dbSNP:rs34567094)"
FT /id="VAR_049629"
SQ SEQUENCE 462 AA; 48808 MW; 7AEF952044A3E951 CRC64;
MAATVNLELD PIFLKALGFL HSKSKDSAEK LKALLDESLA RGIDSSYRPS QKDVEPPKIS
STKNISIKQE PKISSSLPSG NNNGKVLTTE KVKKEAEKRP ADKMKSDITE GVDIPKKPRL
EKPETQSSPI TVQSSKDLPM ADLSSFEETS ADDFAMEMGL ACVVCRQMMV ASGNQLVECQ
ECHNLYHRDC HKPQVTDKEA NDPRLVWYCA RCTRQMKRMA QKTQKPPQKP APAVVSVTPA
VKDPLVKKPE TKLKQETTFL AFKRTEVKTS TVISGNSSSA SVSSSVTSGL TGWAAFAAKT
SSAGPSTAKL SSTTQNNTGK PATSSANQKP VGLTGLATSS KGGIGSKIGS NNSTTPTVPL
KPPPPLTLGK TGLSRSVSCD NVSKVGLPSP SSLVPGSSSQ LSGNGNSGTS GPSGSTTSKT
TSESSSSPSA SLKGPTSQES QLNAMKRLQM VKKKAAQKKL KK