ITFG2_HUMAN
ID ITFG2_HUMAN Reviewed; 447 AA.
AC Q969R8; A8K4Z5; D3DUQ2; Q6PKU5; Q96SX6;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=KICSTOR complex protein ITFG2 {ECO:0000305};
DE AltName: Full=Integrin-alpha FG-GAP repeat-containing protein 2 {ECO:0000312|HGNC:HGNC:30879};
GN Name=ITFG2 {ECO:0000312|HGNC:HGNC:30879};
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] (ISOFORM 2).
RA Zhou G., Zhong G., Ke R., Li H., Shen C., Lin L., Yang S.;
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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].
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 [4]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Ovary;
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 [6]
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-104 AND SER-220, 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 [8]
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:0000269|PubMed:28199306}.
CC Note=Localization to lysosomes is amino acid-independent.
CC {ECO:0000269|PubMed:28199306}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q969R8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q969R8-2; Sequence=VSP_055985, VSP_055986;
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DR EMBL; AY599883; AAT09136.1; -; mRNA.
DR EMBL; AK027483; BAB55145.1; -; mRNA.
DR EMBL; AK291110; BAF83799.1; -; mRNA.
DR EMBL; AC005841; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471116; EAW88886.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88887.1; -; Genomic_DNA.
DR EMBL; BC006552; AAH06552.1; -; mRNA.
DR EMBL; BC013399; AAH13399.1; -; mRNA.
DR CCDS; CCDS8513.1; -. [Q969R8-1]
DR RefSeq; NP_060933.3; NM_018463.3. [Q969R8-1]
DR AlphaFoldDB; Q969R8; -.
DR BioGRID; 120948; 26.
DR ComplexPortal; CPX-6229; KICSTOR complex.
DR CORUM; Q969R8; -.
DR IntAct; Q969R8; 14.
DR STRING; 9606.ENSP00000228799; -.
DR iPTMnet; Q969R8; -.
DR PhosphoSitePlus; Q969R8; -.
DR BioMuta; ITFG2; -.
DR DMDM; 74731058; -.
DR EPD; Q969R8; -.
DR jPOST; Q969R8; -.
DR MassIVE; Q969R8; -.
DR MaxQB; Q969R8; -.
DR PaxDb; Q969R8; -.
DR PeptideAtlas; Q969R8; -.
DR PRIDE; Q969R8; -.
DR ProteomicsDB; 67246; -.
DR ProteomicsDB; 75823; -. [Q969R8-1]
DR Antibodypedia; 22171; 276 antibodies from 22 providers.
DR DNASU; 55846; -.
DR Ensembl; ENST00000228799.7; ENSP00000228799.2; ENSG00000111203.13. [Q969R8-1]
DR Ensembl; ENST00000540929.5; ENSP00000443329.1; ENSG00000111203.13. [Q969R8-2]
DR Ensembl; ENST00000644517.1; ENSP00000496068.1; ENSG00000111203.13. [Q969R8-2]
DR GeneID; 55846; -.
DR KEGG; hsa:55846; -.
DR MANE-Select; ENST00000228799.7; ENSP00000228799.2; NM_018463.4; NP_060933.3.
DR UCSC; uc001qlb.3; human. [Q969R8-1]
DR CTD; 55846; -.
DR GeneCards; ITFG2; -.
DR HGNC; HGNC:30879; ITFG2.
DR HPA; ENSG00000111203; Low tissue specificity.
DR MIM; 617421; gene.
DR neXtProt; NX_Q969R8; -.
DR OpenTargets; ENSG00000111203; -.
DR PharmGKB; PA143485507; -.
DR VEuPathDB; HostDB:ENSG00000111203; -.
DR eggNOG; ENOG502QUBC; Eukaryota.
DR GeneTree; ENSGT00390000005378; -.
DR HOGENOM; CLU_021730_0_0_1; -.
DR InParanoid; Q969R8; -.
DR OMA; GGQNSPC; -.
DR PhylomeDB; Q969R8; -.
DR TreeFam; TF329010; -.
DR PathwayCommons; Q969R8; -.
DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1.
DR SignaLink; Q969R8; -.
DR BioGRID-ORCS; 55846; 16 hits in 1081 CRISPR screens.
DR ChiTaRS; ITFG2; human.
DR GenomeRNAi; 55846; -.
DR Pharos; Q969R8; Tbio.
DR PRO; PR:Q969R8; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q969R8; protein.
DR Bgee; ENSG00000111203; Expressed in right lobe of thyroid gland and 166 other tissues.
DR ExpressionAtlas; Q969R8; baseline and differential.
DR Genevisible; Q969R8; HS.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0140007; C:KICSTOR complex; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
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:0002314; P:germinal center B cell differentiation; IEA:Ensembl.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:UniProtKB.
DR GO; GO:0032006; P:regulation of TOR signaling; IBA:GO_Central.
DR Gene3D; 2.130.10.130; -; 1.
DR InterPro; IPR028994; Integrin_alpha_N.
DR InterPro; IPR031793; KICSTOR_ITFG2.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR16317; PTHR16317; 1.
DR Pfam; PF15907; Itfg2; 1.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF69318; SSF69318; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Lysosome; Membrane; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..447
FT /note="KICSTOR complex protein ITFG2"
FT /id="PRO_0000289292"
FT REPEAT 19..48
FT /note="FG-GAP 1; atypical"
FT REPEAT 126..155
FT /note="FG-GAP 2; atypical"
FT MOD_RES 104
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 136..147
FT /note="DGDGCRELVVGY -> GGHAYLCRQPGE (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_055985"
FT VAR_SEQ 148..447
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_055986"
FT CONFLICT 68
FT /note="V -> A (in Ref. 2; BAB55145)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 447 AA; 49313 MW; 8CB025338EE04A17 CRC64;
MRSVSYVQRV ALEFSGSLFP HAICLGDVDN DTLNELVVGD TSGKVSVYKN DDSRPWLTCS
CQGMLTCVGV GDVCNKGKNL LVAVSAEGWF HLFDLTPAKV LDASGHHETL IGEEQRPVFK
QHIPANTKVM LISDIDGDGC RELVVGYTDR VVRAFRWEEL GEGPEHLTGQ LVSLKKWMLE
GQVDSLSVTL GPLGLPELMV SQPGCAYAIL LCTWKKDTGS PPASEGPTDG SRETPAARDV
VLHQTSGRIH NKNVSTHLIG NIKQGHGTES SGSGLFALCT LDGTLKLMEE MEEADKLLWS
VQVDHQLFAL EKLDVTGNGH EEVVACAWDG QTYIIDHNRT VVRFQVDENI RAFCAGLYAC
KEGRNSPCLV YVTFNQKIYV YWEVQLERME STNLVKLLET KPEYHSLLQE LGVDPDDLPV
TRALLHQTLY HPDQPPQCAP SSLQDPT
