KICS2_HUMAN
ID KICS2_HUMAN Reviewed; 445 AA.
AC Q96MD2; C9JX54; Q8IYA0;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 5.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=KICSTOR subunit 2 {ECO:0000305};
DE AltName: Full=KICSTOR complex protein C12orf66 {ECO:0000305|PubMed:28199306};
GN Name=KICS2 {ECO:0000312|HGNC:HGNC:26517}; Synonyms=C12orf66;
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 SER-443.
RC TISSUE=Spleen;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-443.
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], AND VARIANT SER-443.
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 FUNCTION, IDENTIFICATION IN THE KICSTOR COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=28199306; DOI=10.1038/nature21423;
RA Wolfson R.L., Chantranupong L., Wyant G.A., Gu X., Orozco J.M., Shen K.,
RA Condon K.J., Petri S., Kedir J., Scaria S.M., Abu-Remaileh M.,
RA Frankel W.N., Sabatini D.M.;
RT "KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to
RT regulate mTORC1.";
RL Nature 543:438-442(2017).
CC -!- FUNCTION: As part of the KICSTOR complex functions in the amino acid-
CC sensing branch of the TORC1 signaling pathway. Recruits, in an amino
CC acid-independent manner, the GATOR1 complex to the lysosomal membranes
CC and allows its interaction with GATOR2 and the RAG GTPases. Functions
CC upstream of the RAG GTPases and is required to negatively regulate
CC mTORC1 signaling in absence of amino acids. In absence of the KICSTOR
CC complex mTORC1 is constitutively localized to the lysosome and
CC activated. The KICSTOR complex is also probably involved in the
CC regulation of mTORC1 by glucose. {ECO:0000269|PubMed:28199306}.
CC -!- SUBUNIT: Part of the KICSTOR complex composed of KPTN, ITFG2, KICS2 and
CC SZT2. SZT2 probably serves as a link between the other three proteins
CC in the KICSTOR complex and may mediate the direct interaction with the
CC GATOR complex via GATOR1. The KICSTOR complex interacts directly with
CC the GATOR1 complex and most probably indirectly with the GATOR2 complex
CC in an amino acid-independent manner. {ECO:0000269|PubMed:28199306}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000305|PubMed:28199306}.
CC -!- SIMILARITY: Belongs to the KICS2 family. {ECO:0000305}.
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DR EMBL; AK057111; BAB71367.1; -; mRNA.
DR EMBL; AC012158; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW97124.1; -; Genomic_DNA.
DR EMBL; BC071634; AAH71634.1; -; mRNA.
DR CCDS; CCDS41803.1; -.
DR RefSeq; NP_689653.3; NM_152440.4.
DR AlphaFoldDB; Q96MD2; -.
DR BioGRID; 126862; 13.
DR ComplexPortal; CPX-6229; KICSTOR complex.
DR CORUM; Q96MD2; -.
DR IntAct; Q96MD2; 5.
DR STRING; 9606.ENSP00000311486; -.
DR iPTMnet; Q96MD2; -.
DR PhosphoSitePlus; Q96MD2; -.
DR BioMuta; C12orf66; -.
DR DMDM; 296439467; -.
DR EPD; Q96MD2; -.
DR jPOST; Q96MD2; -.
DR MassIVE; Q96MD2; -.
DR MaxQB; Q96MD2; -.
DR PaxDb; Q96MD2; -.
DR PeptideAtlas; Q96MD2; -.
DR PRIDE; Q96MD2; -.
DR ProteomicsDB; 77335; -.
DR Antibodypedia; 53140; 10 antibodies from 6 providers.
DR DNASU; 144577; -.
DR Ensembl; ENST00000398055.8; ENSP00000381132.4; ENSG00000174206.13.
DR GeneID; 144577; -.
DR KEGG; hsa:144577; -.
DR MANE-Select; ENST00000398055.8; ENSP00000381132.4; NM_152440.5; NP_689653.4.
DR UCSC; uc001srw.5; human.
DR CTD; 144577; -.
DR DisGeNET; 144577; -.
DR GeneCards; KICS2; -.
DR HGNC; HGNC:26517; KICS2.
DR HPA; ENSG00000174206; Low tissue specificity.
DR MIM; 617420; gene.
DR neXtProt; NX_Q96MD2; -.
DR OpenTargets; ENSG00000174206; -.
DR VEuPathDB; HostDB:ENSG00000174206; -.
DR eggNOG; ENOG502QTBE; Eukaryota.
DR GeneTree; ENSGT00390000009583; -.
DR HOGENOM; CLU_050627_0_0_1; -.
DR InParanoid; Q96MD2; -.
DR OrthoDB; 365605at2759; -.
DR PhylomeDB; Q96MD2; -.
DR TreeFam; TF329125; -.
DR PathwayCommons; Q96MD2; -.
DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1.
DR SignaLink; Q96MD2; -.
DR BioGRID-ORCS; 144577; 17 hits in 1060 CRISPR screens.
DR ChiTaRS; C12orf66; human.
DR GenomeRNAi; 144577; -.
DR Pharos; Q96MD2; Tbio.
DR PRO; PR:Q96MD2; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q96MD2; protein.
DR Bgee; ENSG00000174206; Expressed in secondary oocyte and 159 other tissues.
DR ExpressionAtlas; Q96MD2; baseline and differential.
DR Genevisible; Q96MD2; HS.
DR GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0140007; C:KICSTOR complex; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0005764; C:lysosome; IDA:HPA.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IMP:UniProtKB.
DR GO; GO:0042149; P:cellular response to glucose starvation; IMP:UniProtKB.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:UniProtKB.
DR GO; GO:0061462; P:protein localization to lysosome; IMP:UniProtKB.
DR Gene3D; 1.10.3450.30; -; 1.
DR InterPro; IPR038060; C12orf66-like_central_sf.
DR InterPro; IPR018544; KICS_2.
DR PANTHER; PTHR31581; PTHR31581; 1.
DR Pfam; PF09404; C12orf66_like; 1.
DR SUPFAM; SSF158548; SSF158548; 1.
PE 1: Evidence at protein level;
KW Lysosome; Membrane; Reference proteome.
FT CHAIN 1..445
FT /note="KICSTOR subunit 2"
FT /id="PRO_0000321902"
FT VARIANT 139
FT /note="I -> M (in dbSNP:rs2335390)"
FT /id="VAR_039371"
FT VARIANT 443
FT /note="A -> S (in dbSNP:rs699638)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3"
FT /id="VAR_039372"
SQ SEQUENCE 445 AA; 50397 MW; B61F5B31E6174FB5 CRC64;
MGESIPLAAP VPVEQAVLET FFSHLGIFSY DKAKDNVEKE REANKSAGGS WLSLLAALAH
LAAAEKVYHS LTYLGQKLGG QSFFSRKDSI RTIYTSLHNE LKKVVTGRGA LGGTAPHVEE
LLSHLSEQLC FFVQARMEIA DFYEKMYTLS TQKFINAEEL VGLLDAIMKK YSSRFHHPIL
SPLESSFQLE VDVLCHLLKA QAQVSEWKFL PSLVNLHSAH TKLQTWGQIF EKQRETKKHL
FGGQSQKAVQ PPHLFLWLMK LKNMLLAKFS FYFHEALSRQ TTASEMKTLT AKANPDFFGK
ISSFIRKYDA ANVSLIFDNR GSESFQGHGY HHPHSYREAP KGVDQYPAVV SLPSDRPVMH
WPNVIMIMTD RTSDLNSLEK VVHFYDDKVQ STYFLTRPEP HFTIVIIFES KKSERDSHFI
SFLNEVSLAL KNPKVFASLK PGAKG
