IMPCT_HUMAN
ID IMPCT_HUMAN Reviewed; 320 AA.
AC Q9P2X3; A8MXG0; Q49AM0; Q9H2X4;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Protein IMPACT;
DE AltName: Full=Imprinted and ancient gene protein homolog;
GN Name=IMPACT;
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 [GENOMIC DNA / MRNA] (ISOFORM 1), LACK OF IMPRINTING,
RP TISSUE SPECIFICITY, AND VARIANT VAL-151.
RX PubMed=11116084; DOI=10.1101/gr.139200;
RA Okamura K., Hagiwara-Takeuchi Y., Li T., Vu T.H., Hirai M., Hattori M.,
RA Sakaki Y., Hoffman A.R., Ito T.;
RT "Comparative genome analysis of the mouse imprinted gene impact and its
RT nonimprinted human homolog IMPACT: toward the structural basis for species-
RT specific imprinting.";
RL Genome Res. 10:1878-1889(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=11244491; DOI=10.1038/sj.mp.4000799;
RA Kosaki K., Suzuki T., Kosaki R., Yoshihashi H., Itoh M., Goto Y.,
RA Matsuo N.;
RT "Human homolog of the mouse imprinted gene Impact resides at the
RT pericentric region of chromosome 18 within the critical region for bipolar
RT affective disorder.";
RL Mol. Psychiatry 6:87-91(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-151.
RC TISSUE=Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-151.
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP VAL-151.
RC TISSUE=Brain, and Lung;
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP IDENTIFICATION BY 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 [9]
RP VARIANT VAL-74.
RX PubMed=27607563; DOI=10.1111/cge.12850;
RA Mahmud A.A., Nahid N.A., Nassif C., Sayeed M.S., Ahmed M.U., Parveen M.,
RA Khalil M.I., Islam M.M., Nahar Z., Rypens F., Hamdan F.F., Rouleau G.A.,
RA Hasnat A., Michaud J.L.;
RT "Loss of the proprioception and touch sensation channel PIEZO2 in siblings
RT with a progressive form of contractures.";
RL Clin. Genet. 91:470-475(2017).
CC -!- FUNCTION: Translational regulator that ensures constant high levels of
CC translation upon a variety of stress conditions, such as amino acid
CC starvation, UV-C irradiation, proteasome inhibitor treatment and
CC glucose deprivation. Plays a role as a negative regulator of the
CC EIF2AK4/GCN2 kinase activity; impairs GCN1-mediated EIF2AK4/GCN2
CC activation, and hence EIF2AK4/GCN2-mediated eIF-2-alpha phosphorylation
CC and subsequent down-regulation of protein synthesis. May be required to
CC regulate translation in specific neuronal cells under amino acid
CC starvation conditions by preventing GCN2 activation and therefore ATF4
CC synthesis. Through its inhibitory action on EIF2AK4/GCN2, plays a role
CC in differentiation of neuronal cells by stimulating neurite outgrowth.
CC {ECO:0000250|UniProtKB:O55091}.
CC -!- SUBUNIT: Interacts with GCN1; prevents the interaction of GCN1 with
CC EIF2AK4/GCN2 and inhibits EIF2AK4/GCN2 kinase activity. Interaction
CC with RPL39; this interaction occurs in a GCN1-independent manner.
CC Associates with ribosomes; this interaction occurs in a GCN1-
CC independent manner. Associates with actin; this interaction occurs in a
CC GCN1-independent manner. {ECO:0000250|UniProtKB:O55091}.
CC -!- INTERACTION:
CC Q9P2X3; P20618: PSMB1; NbExp=3; IntAct=EBI-2857352, EBI-372273;
CC Q9P2X3; P36955: SERPINF1; NbExp=3; IntAct=EBI-2857352, EBI-2932733;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O55091}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9P2X3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9P2X3-2; Sequence=VSP_033136;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at high level in brain.
CC {ECO:0000269|PubMed:11116084, ECO:0000269|PubMed:11244491}.
CC -!- MISCELLANEOUS: In contrast to the mouse or rabbit ortholog, the IMPACT
CC locus is not imprinted in human.
CC -!- SIMILARITY: Belongs to the IMPACT family. {ECO:0000305}.
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DR EMBL; AF232229; AAG23917.1; -; Genomic_DNA.
DR EMBL; AB026264; BAA95160.1; -; mRNA.
DR EMBL; AF208694; AAG35736.1; -; mRNA.
DR EMBL; AK292533; BAF85222.1; -; mRNA.
DR EMBL; AC007922; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC020937; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471088; EAX01186.1; -; Genomic_DNA.
DR EMBL; BC034016; AAH34016.1; -; mRNA.
DR EMBL; BC036074; AAH36074.1; -; mRNA.
DR CCDS; CCDS11886.1; -. [Q9P2X3-1]
DR RefSeq; NP_060909.1; NM_018439.3. [Q9P2X3-1]
DR AlphaFoldDB; Q9P2X3; -.
DR SMR; Q9P2X3; -.
DR BioGRID; 120642; 50.
DR IntAct; Q9P2X3; 33.
DR STRING; 9606.ENSP00000284202; -.
DR iPTMnet; Q9P2X3; -.
DR PhosphoSitePlus; Q9P2X3; -.
DR BioMuta; IMPACT; -.
DR DMDM; 296434540; -.
DR EPD; Q9P2X3; -.
DR jPOST; Q9P2X3; -.
DR MassIVE; Q9P2X3; -.
DR MaxQB; Q9P2X3; -.
DR PaxDb; Q9P2X3; -.
DR PeptideAtlas; Q9P2X3; -.
DR PRIDE; Q9P2X3; -.
DR ProteomicsDB; 83909; -. [Q9P2X3-1]
DR ProteomicsDB; 83910; -. [Q9P2X3-2]
DR Antibodypedia; 22092; 122 antibodies from 19 providers.
DR DNASU; 55364; -.
DR Ensembl; ENST00000284202.9; ENSP00000284202.4; ENSG00000154059.11. [Q9P2X3-1]
DR GeneID; 55364; -.
DR KEGG; hsa:55364; -.
DR MANE-Select; ENST00000284202.9; ENSP00000284202.4; NM_018439.4; NP_060909.2.
DR UCSC; uc002kvh.5; human. [Q9P2X3-1]
DR CTD; 55364; -.
DR DisGeNET; 55364; -.
DR GeneCards; IMPACT; -.
DR HGNC; HGNC:20387; IMPACT.
DR HPA; ENSG00000154059; Low tissue specificity.
DR MIM; 615319; gene.
DR neXtProt; NX_Q9P2X3; -.
DR OpenTargets; ENSG00000154059; -.
DR PharmGKB; PA143485502; -.
DR VEuPathDB; HostDB:ENSG00000154059; -.
DR eggNOG; KOG3299; Eukaryota.
DR GeneTree; ENSGT00390000017571; -.
DR HOGENOM; CLU_045276_1_0_1; -.
DR InParanoid; Q9P2X3; -.
DR OrthoDB; 1400092at2759; -.
DR PhylomeDB; Q9P2X3; -.
DR TreeFam; TF314823; -.
DR PathwayCommons; Q9P2X3; -.
DR Reactome; R-HSA-9633012; Response of EIF2AK4 (GCN2) to amino acid deficiency.
DR SignaLink; Q9P2X3; -.
DR BioGRID-ORCS; 55364; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; IMPACT; human.
DR GenomeRNAi; 55364; -.
DR Pharos; Q9P2X3; Tbio.
DR PRO; PR:Q9P2X3; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q9P2X3; protein.
DR Bgee; ENSG00000154059; Expressed in calcaneal tendon and 194 other tissues.
DR ExpressionAtlas; Q9P2X3; baseline and differential.
DR Genevisible; Q9P2X3; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005844; C:polysome; ISS:UniProtKB.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0043022; F:ribosome binding; IEA:Ensembl.
DR GO; GO:0071468; P:cellular response to acidic pH; ISS:UniProtKB.
DR GO; GO:0034198; P:cellular response to amino acid starvation; ISS:UniProtKB.
DR GO; GO:0072755; P:cellular response to benomyl; ISS:UniProtKB.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISS:UniProtKB.
DR GO; GO:1990253; P:cellular response to leucine starvation; ISS:UniProtKB.
DR GO; GO:0071494; P:cellular response to UV-C; ISS:UniProtKB.
DR GO; GO:0140469; P:GCN2-mediated signaling; ISS:UniProtKB.
DR GO; GO:0060548; P:negative regulation of cell death; ISS:UniProtKB.
DR GO; GO:0031953; P:negative regulation of protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0097201; P:negative regulation of transcription from RNA polymerase II promoter in response to stress; ISS:UniProtKB.
DR GO; GO:1990138; P:neuron projection extension; ISS:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:0071264; P:positive regulation of translational initiation in response to starvation; ISS:UniProtKB.
DR GO; GO:0006446; P:regulation of translational initiation; IBA:GO_Central.
DR Gene3D; 3.10.110.10; -; 1.
DR Gene3D; 3.30.230.30; -; 1.
DR InterPro; IPR023582; Impact.
DR InterPro; IPR001498; Impact_N.
DR InterPro; IPR036956; Impact_N_sf.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR InterPro; IPR006575; RWD-domain.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR InterPro; IPR020569; UPF0029_Impact_CS.
DR PANTHER; PTHR16301; PTHR16301; 1.
DR Pfam; PF05773; RWD; 1.
DR Pfam; PF01205; UPF0029; 1.
DR SMART; SM00591; RWD; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF54495; SSF54495; 1.
DR PROSITE; PS50908; RWD; 1.
DR PROSITE; PS00910; UPF0029; 1.
PE 1: Evidence at protein level;
KW Actin-binding; Alternative splicing; Cytoplasm; Differentiation;
KW Neurogenesis; Phosphoprotein; Reference proteome; Repressor;
KW Stress response; Translation regulation.
FT CHAIN 1..320
FT /note="Protein IMPACT"
FT /id="PRO_0000330850"
FT DOMAIN 14..116
FT /note="RWD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00179"
FT REGION 296..320
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 297
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5GFD9"
FT VAR_SEQ 1..118
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033136"
FT VARIANT 74
FT /note="A -> V (in dbSNP:rs544203385)"
FT /evidence="ECO:0000269|PubMed:27607563"
FT /id="VAR_077844"
FT VARIANT 125
FT /note="D -> E (in dbSNP:rs582234)"
FT /id="VAR_042723"
FT VARIANT 151
FT /note="L -> V (in dbSNP:rs677688)"
FT /evidence="ECO:0000269|PubMed:11116084,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:16177791"
FT /id="VAR_042724"
SQ SEQUENCE 320 AA; 36476 MW; 75AAB91E00594212 CRC64;
MAEGDAGSDQ RQNEEIEAMA AIYGEEWCVI DDCAKIFCIR ISDDIDDPKW TLCLQVMLPN
EYPGTAPPIY QLNAPWLKGQ ERADLSNSLE EIYIQNIGES ILYLWVEKIR DVLIQKSQMT
EPGPDVKKKT EEEDVECEDD LILACQPESS LKALDFDISE TRTEVEVEEL PPIDHGIPIT
DRRSTFQAHL APVVCPKQVK MVLSKLYENK KIASATHNIY AYRIYCEDKQ TFLQDCEDDG
ETAAGGRLLH LMEILNVKNV MVVVSRWYGG ILLGPDRFKH INNCARNILV EKNYTNSPEE
SSKALGKNKK VRKDKKRNEH
