KPTN_HUMAN
ID KPTN_HUMAN Reviewed; 436 AA.
AC Q9Y664; B3KN86; B4DQ76; Q96GT1;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=KICSTOR complex protein kaptin {ECO:0000305|PubMed:10099934};
DE AltName: Full=Actin-associated protein 2E4 {ECO:0000303|PubMed:10099934};
GN Name=KPTN {ECO:0000312|HGNC:HGNC:6404};
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 1).
RX PubMed=1372044; DOI=10.1523/jneurosci.12-03-00750.1992;
RA Bearer E.L.;
RT "An actin-associated protein present in the microtubule organizing center
RT and the growth cones of PC-12 cells.";
RL J. Neurosci. 12:750-761(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=10099934; DOI=10.1016/s0171-9335(99)80013-2;
RA Bearer E.L., Abraham M.T.;
RT "2E4 (kaptin): a novel actin-associated protein from human blood platelets
RT found in lamellipodia and the tips of the stereocilia of the inner ear.";
RL Eur. J. Cell Biol. 78:117-126(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
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] (ISOFORM 1).
RC TISSUE=Muscle;
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 ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
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).
RN [9]
RP VARIANT MRT41 241-MET--GLN-246 INS, CHARACTERIZATION OF VARIANT MRT41
RP 241-MET--GLN-246 INS, AND SUBCELLULAR LOCATION.
RX PubMed=24239382; DOI=10.1016/j.ajhg.2013.10.001;
RA Baple E.L., Maroofian R., Chioza B.A., Izadi M., Cross H.E., Al-Turki S.,
RA Barwick K., Skrzypiec A., Pawlak R., Wagner K., Coblentz R., Zainy T.,
RA Patton M.A., Mansour S., Rich P., Qualmann B., Hurles M.E., Kessels M.M.,
RA Crosby A.H.;
RT "Mutations in KPTN cause macrocephaly, neurodevelopmental delay, and
RT seizures.";
RL Am. J. Hum. Genet. 94:87-94(2014).
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 mediates the direct interaction with the
CC GATOR1 complex (PubMed:28199306). May associate with F-actin filaments
CC (PubMed:10099934). {ECO:0000269|PubMed:10099934,
CC ECO:0000269|PubMed:28199306}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:28199306}.
CC Cell projection, lamellipodium {ECO:0000269|PubMed:10099934,
CC ECO:0000269|PubMed:24239382}. Cell projection, stereocilium
CC {ECO:0000250|UniProtKB:A0A1D5PJB7}. Note=Localization to lysosomes is
CC amino acid-independent (PubMed:28199306). Colocalizes with F-actin
CC (PubMed:24239382). {ECO:0000269|PubMed:24239382,
CC ECO:0000269|PubMed:28199306}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y664-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y664-2; Sequence=VSP_053990;
CC -!- DISEASE: Intellectual developmental disorder, autosomal recessive 41
CC (MRT41) [MIM:615637]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period. MRT41
CC most consistent features are global developmental delay, macrocephaly
CC with frontal bossing, high levels of anxiety, and some features
CC suggestive of a pervasive developmental disorder. Less common features
CC include fifth finger clinodactyly, recurrent pneumonia, and
CC hepatosplenomegaly. {ECO:0000269|PubMed:24239382}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD39358.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF105369; AAD39358.1; ALT_FRAME; mRNA.
DR EMBL; AF243529; AAF98790.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AK023996; BAG51248.1; -; mRNA.
DR EMBL; AK298672; BAG60838.1; -; mRNA.
DR EMBL; AC073548; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471126; EAW57487.1; -; Genomic_DNA.
DR EMBL; BC009249; AAH09249.1; -; mRNA.
DR CCDS; CCDS42583.1; -. [Q9Y664-1]
DR RefSeq; NP_001278225.1; NM_001291296.1.
DR RefSeq; NP_008990.2; NM_007059.3. [Q9Y664-1]
DR AlphaFoldDB; Q9Y664; -.
DR BioGRID; 116306; 56.
DR ComplexPortal; CPX-6229; KICSTOR complex.
DR CORUM; Q9Y664; -.
DR IntAct; Q9Y664; 29.
DR STRING; 9606.ENSP00000337850; -.
DR iPTMnet; Q9Y664; -.
DR PhosphoSitePlus; Q9Y664; -.
DR BioMuta; KPTN; -.
DR DMDM; 108936022; -.
DR EPD; Q9Y664; -.
DR jPOST; Q9Y664; -.
DR MassIVE; Q9Y664; -.
DR MaxQB; Q9Y664; -.
DR PaxDb; Q9Y664; -.
DR PeptideAtlas; Q9Y664; -.
DR PRIDE; Q9Y664; -.
DR ProteomicsDB; 4853; -.
DR ProteomicsDB; 86607; -. [Q9Y664-1]
DR Antibodypedia; 31573; 183 antibodies from 25 providers.
DR DNASU; 11133; -.
DR Ensembl; ENST00000338134.8; ENSP00000337850.2; ENSG00000118162.14. [Q9Y664-1]
DR GeneID; 11133; -.
DR KEGG; hsa:11133; -.
DR MANE-Select; ENST00000338134.8; ENSP00000337850.2; NM_007059.4; NP_008990.2.
DR UCSC; uc002pgy.4; human. [Q9Y664-1]
DR CTD; 11133; -.
DR DisGeNET; 11133; -.
DR GeneCards; KPTN; -.
DR HGNC; HGNC:6404; KPTN.
DR HPA; ENSG00000118162; Low tissue specificity.
DR MalaCards; KPTN; -.
DR MIM; 615620; gene.
DR MIM; 615637; phenotype.
DR neXtProt; NX_Q9Y664; -.
DR OpenTargets; ENSG00000118162; -.
DR Orphanet; 397612; Macrocephaly-developmental delay syndrome.
DR PharmGKB; PA30194; -.
DR VEuPathDB; HostDB:ENSG00000118162; -.
DR eggNOG; ENOG502QTF2; Eukaryota.
DR GeneTree; ENSGT00390000002548; -.
DR HOGENOM; CLU_037754_0_0_1; -.
DR InParanoid; Q9Y664; -.
DR OMA; VHLYKEN; -.
DR OrthoDB; 692881at2759; -.
DR PhylomeDB; Q9Y664; -.
DR TreeFam; TF328973; -.
DR PathwayCommons; Q9Y664; -.
DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1.
DR SignaLink; Q9Y664; -.
DR BioGRID-ORCS; 11133; 19 hits in 1078 CRISPR screens.
DR ChiTaRS; KPTN; human.
DR GeneWiki; Kaptin_(actin_binding_protein); -.
DR GenomeRNAi; 11133; -.
DR Pharos; Q9Y664; Tbio.
DR PRO; PR:Q9Y664; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9Y664; protein.
DR Bgee; ENSG00000118162; Expressed in right hemisphere of cerebellum and 145 other tissues.
DR ExpressionAtlas; Q9Y664; baseline and differential.
DR Genevisible; Q9Y664; HS.
DR GO; GO:0140007; C:KICSTOR complex; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0098871; C:postsynaptic actin cytoskeleton; IDA:UniProtKB.
DR GO; GO:0032420; C:stereocilium; ISS:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; IDA:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IEA:InterPro.
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 InterPro; IPR028994; Integrin_alpha_N.
DR InterPro; IPR029982; Kptn.
DR PANTHER; PTHR15435; PTHR15435; 1.
DR SUPFAM; SSF69318; SSF69318; 1.
PE 1: Evidence at protein level;
KW Acetylation; Actin-binding; Alternative splicing; Cell projection;
KW Disease variant; Intellectual disability; Lysosome; Membrane;
KW Reference proteome.
FT CHAIN 1..436
FT /note="KICSTOR complex protein kaptin"
FT /id="PRO_0000239234"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT VAR_SEQ 1..240
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_053990"
FT VARIANT 241
FT /note="M -> MWSVLQ (in MRT41; loss of localization to F-
FT actin-rich regions; cytoplasmic accumulation at irregular
FT perinuclear sites)"
FT /evidence="ECO:0000269|PubMed:24239382"
FT /id="VAR_070974"
FT CONFLICT 26
FT /note="S -> N (in Ref. 1; AAD39358/AAF98790)"
FT /evidence="ECO:0000305"
FT CONFLICT 121
FT /note="P -> T (in Ref. 1; AAD39358/AAF98790)"
FT /evidence="ECO:0000305"
FT CONFLICT 124
FT /note="E -> V (in Ref. 1; AAD39358/AAF98790)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="D -> V (in Ref. 1; AAD39358/AAF98790)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 436 AA; 48080 MW; 128C0D87C0850E8E CRC64;
MMGEAAVAAG PCPLREDSFT RFSSQSNVYG LAGGAGGRGE LLAATLKGKV LGFRYQDLRQ
KIRPVAKELQ FNYIPVDAEI VSIDTFNKSP PKRGLVVGIT FIKDSGDKGS PFLNIYCDYE
PGSEYNLDSI AQSCLNLELQ FTPFQLCHAE VQVGDQLETV FLLSGNDPAI HLYKENEGLH
QFEEQPVENL FPELTNLTSS VLWLDVHNFP GTSRRLSALG CQSGYVRVAH VDQRSREVLQ
MWSVLQDGPI SRVIVFSLSA AKETKDRPLQ DEYSVLVASM LEPAVVYRDL LNRGLEDQLL
LPGSDQFDSV LCSLVTDVDL DGRPEVLVAT YGQELLCYKY RGPESGLPEA QHGFHLLWQR
SFSSPLLAMA HVDLTGDGLQ ELAVVSLKGV HILQHSLIQA SELVLTRLRH QVEQRRRRLQ
GLEDGAGAGP AENAAS
