ATCAY_HUMAN
ID ATCAY_HUMAN Reviewed; 371 AA.
AC Q86WG3; Q8NAQ2; Q8TAQ3; Q96HC6; Q96JF5;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Caytaxin;
DE AltName: Full=Ataxia cayman type protein;
DE AltName: Full=BNIP-2-homology;
DE Short=BNIP-H {ECO:0000303|PubMed:16899818};
GN Name=ATCAY; Synonyms=KIAA1872;
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), FUNCTION, INTERACTION WITH GLS, AND
RP SUBCELLULAR LOCATION.
RX PubMed=16899818; DOI=10.1242/jcs.03061;
RA Buschdorf J.P., Li Chew L., Zhang B., Cao Q., Liang F.Y., Liou Y.C.,
RA Zhou Y.T., Low B.C.;
RT "Brain-specific BNIP-2-homology protein Caytaxin relocalises glutaminase to
RT neurite terminals and reduces glutamate levels.";
RL J. Cell Sci. 119:3337-3350(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 214-371 (ISOFORM 2).
RC TISSUE=Brain;
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 DISEASE, AND VARIANT ATCAY ARG-301.
RX PubMed=14556008; DOI=10.1038/ng1255;
RA Bomar J.M., Benke P.J., Slattery E.L., Puttagunta R., Taylor L.P.,
RA Seong E., Nystuen A., Chen W., Albin R.L., Patel P.D., Kittles R.A.,
RA Sheffield V.C., Burmeister M.;
RT "Mutations in a novel gene encoding a CRAL-TRIO domain cause human Cayman
RT ataxia and ataxia/dystonia in the jittery mouse.";
RL Nat. Genet. 35:264-269(2003).
RN [6]
RP UBIQUITINATION BY STUB1.
RX PubMed=16275660; DOI=10.1074/mcp.m500198-mcp200;
RA Grelle G., Kostka S., Otto A., Kersten B., Genser K.F., Muller E.C.,
RA Walter S., Boddrich A., Stelzl U., Hanig C., Volkmer-Engert R.,
RA Landgraf C., Alberti S., Hohfeld J., Strodicke M., Wanker E.E.;
RT "Identification of VCP/p97, carboxyl terminus of Hsp70-interacting protein
RT (CHIP), and amphiphysin II interaction partners using membrane-based human
RT proteome arrays.";
RL Mol. Cell. Proteomics 5:234-244(2006).
RN [7]
RP INTERACTION WITH PIN1.
RX PubMed=18628984; DOI=10.1371/journal.pone.0002686;
RA Buschdorf J.P., Chew L.L., Soh U.J., Liou Y.C., Low B.C.;
RT "Nerve growth factor stimulates interaction of Cayman ataxia protein BNIP-
RT H/Caytaxin with peptidyl-prolyl isomerase Pin1 in differentiating
RT neurons.";
RL PLoS ONE 3:E2686-E2686(2008).
RN [8]
RP MUTAGENESIS OF ASP-105, PROTEOLYTIC CLEAVAGE AT ASP-105 BY CASP3,
RP PROTEOLYTIC CLEAVAGE BY CASP7, AND INTERACTION WITH MAP2K2.
RX PubMed=21369758; DOI=10.1007/s11064-011-0430-5;
RA Itoh M., Li S., Ohta K., Yamada A., Hayakawa-Yano Y., Ueda M., Hida Y.,
RA Suzuki Y., Ohta E., Mizuno A., Banno Y., Nakagawa T.;
RT "Cayman ataxia-related protein is a presynapse-specific caspase-3
RT substrate.";
RL Neurochem. Res. 36:1304-1313(2011).
CC -!- FUNCTION: Functions in the development of neural tissues, particularly
CC the postnatal maturation of the cerebellar cortex. May play a role in
CC neurotransmission through regulation of glutaminase/GLS, an enzyme
CC responsible for the production in neurons of the glutamate
CC neurotransmitter. Alternatively, may regulate the localization of
CC mitochondria within axons and dendrites. {ECO:0000269|PubMed:16899818}.
CC -!- SUBUNIT: Interacts with KLC1; may link mitochondria to KLC1 and
CC regulate mitochondria localization into neuron projections (By
CC similarity). Interacts with GLS; the interaction is direct and may
CC control GLS localization, negatively regulating its activity. Interacts
CC with PIN1 (via WW domain); upon NGF stimulation. The interaction with
CC PIN1 and GLS is competitive. May interact with MAP2K2. {ECO:0000250,
CC ECO:0000269|PubMed:16899818, ECO:0000269|PubMed:18628984,
CC ECO:0000269|PubMed:21369758}.
CC -!- INTERACTION:
CC Q86WG3; Q07866-2: KLC1; NbExp=3; IntAct=EBI-1783328, EBI-11979975;
CC Q86WG3; Q9UNE7: STUB1; NbExp=4; IntAct=EBI-1783328, EBI-357085;
CC -!- SUBCELLULAR LOCATION: Cell projection, axon
CC {ECO:0000250|UniProtKB:Q1M168}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q1M168}. Presynapse
CC {ECO:0000269|PubMed:16899818}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q1M168}. Cell projection, growth cone
CC {ECO:0000250|UniProtKB:Q1M168}. Cytoplasm
CC {ECO:0000269|PubMed:16899818}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q86WG3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86WG3-3; Sequence=VSP_008748;
CC -!- DOMAIN: The CRAL-TRIO domain is known to bind small hydrophobic
CC molecules. {ECO:0000250}.
CC -!- PTM: Cleaved by CASP3 and CASP7. The potential C-terminal product
CC released by CASP3 cleavage may inhibit the ERK signaling pathway
CC through MAP2K2. {ECO:0000269|PubMed:21369758}.
CC -!- PTM: May be ubiquitinated by STUB1. {ECO:0000269|PubMed:16275660}.
CC -!- DISEASE: Cerebellar ataxia, cayman type (ATCAY) [MIM:601238]: Found in
CC a population isolate on Grand Cayman Island and causes a marked
CC psychomotor retardation and prominent nonprogressive cerebellar
CC dysfunction including nystagmus, intention tremor, dysarthria, and
CC wide-based ataxic gait. Hypotonia is present from early childhood.
CC {ECO:0000269|PubMed:14556008}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB47501.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC03859.1; Type=Miscellaneous discrepancy; Note=Unlikely isoform. Aberrant splice sites.; Evidence={ECO:0000305};
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DR EMBL; AY220297; AAO63019.1; -; mRNA.
DR EMBL; AB058775; BAB47501.1; ALT_INIT; mRNA.
DR EMBL; AK092309; BAC03859.1; ALT_SEQ; mRNA.
DR EMBL; BC008736; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC026217; AAH26217.1; -; mRNA.
DR CCDS; CCDS45923.1; -. [Q86WG3-1]
DR RefSeq; NP_149053.1; NM_033064.4. [Q86WG3-1]
DR AlphaFoldDB; Q86WG3; -.
DR BioGRID; 124463; 10.
DR ELM; Q86WG3; -.
DR IntAct; Q86WG3; 4.
DR STRING; 9606.ENSP00000390941; -.
DR iPTMnet; Q86WG3; -.
DR PhosphoSitePlus; Q86WG3; -.
DR BioMuta; ATCAY; -.
DR DMDM; 38257451; -.
DR EPD; Q86WG3; -.
DR jPOST; Q86WG3; -.
DR MassIVE; Q86WG3; -.
DR MaxQB; Q86WG3; -.
DR PaxDb; Q86WG3; -.
DR PeptideAtlas; Q86WG3; -.
DR PRIDE; Q86WG3; -.
DR ProteomicsDB; 70155; -. [Q86WG3-1]
DR ProteomicsDB; 70157; -. [Q86WG3-3]
DR Antibodypedia; 23397; 68 antibodies from 19 providers.
DR DNASU; 85300; -.
DR Ensembl; ENST00000450849.7; ENSP00000390941.1; ENSG00000167654.18. [Q86WG3-1]
DR Ensembl; ENST00000600960.1; ENSP00000470842.1; ENSG00000167654.18. [Q86WG3-3]
DR GeneID; 85300; -.
DR KEGG; hsa:85300; -.
DR MANE-Select; ENST00000450849.7; ENSP00000390941.1; NM_033064.5; NP_149053.1.
DR UCSC; uc002lyy.5; human. [Q86WG3-1]
DR CTD; 85300; -.
DR DisGeNET; 85300; -.
DR GeneCards; ATCAY; -.
DR HGNC; HGNC:779; ATCAY.
DR HPA; ENSG00000167654; Group enriched (brain, pituitary gland, retina).
DR MalaCards; ATCAY; -.
DR MIM; 601238; phenotype.
DR MIM; 608179; gene.
DR neXtProt; NX_Q86WG3; -.
DR OpenTargets; ENSG00000167654; -.
DR Orphanet; 94122; Cerebellar ataxia, Cayman type.
DR PharmGKB; PA25080; -.
DR VEuPathDB; HostDB:ENSG00000167654; -.
DR eggNOG; KOG3308; Eukaryota.
DR GeneTree; ENSGT00940000158364; -.
DR HOGENOM; CLU_039135_0_0_1; -.
DR InParanoid; Q86WG3; -.
DR OMA; AKNMPGN; -.
DR PhylomeDB; Q86WG3; -.
DR TreeFam; TF324164; -.
DR PathwayCommons; Q86WG3; -.
DR SignaLink; Q86WG3; -.
DR BioGRID-ORCS; 85300; 10 hits in 1064 CRISPR screens.
DR ChiTaRS; ATCAY; human.
DR GenomeRNAi; 85300; -.
DR Pharos; Q86WG3; Tbio.
DR PRO; PR:Q86WG3; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q86WG3; protein.
DR Bgee; ENSG00000167654; Expressed in middle temporal gyrus and 127 other tissues.
DR ExpressionAtlas; Q86WG3; baseline and differential.
DR Genevisible; Q86WG3; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell.
DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR GO; GO:0098793; C:presynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; ISS:UniProtKB.
DR GO; GO:0019894; F:kinesin binding; IPI:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IBA:GO_Central.
DR GO; GO:0048311; P:mitochondrion distribution; ISS:UniProtKB.
DR GO; GO:2000212; P:negative regulation of glutamate metabolic process; IDA:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; IDA:UniProtKB.
DR CDD; cd00170; SEC14; 1.
DR Gene3D; 3.40.525.10; -; 1.
DR InterPro; IPR022181; Bcl2-/adenovirus-E1B.
DR InterPro; IPR001251; CRAL-TRIO_dom.
DR InterPro; IPR036865; CRAL-TRIO_dom_sf.
DR Pfam; PF12496; BNIP2; 1.
DR Pfam; PF13716; CRAL_TRIO_2; 1.
DR SMART; SM00516; SEC14; 1.
DR SUPFAM; SSF52087; SSF52087; 1.
DR PROSITE; PS50191; CRAL_TRIO; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Cytoplasm; Disease variant;
KW Mitochondrion; Neurogenesis; Reference proteome; Synapse; Transport;
KW Ubl conjugation.
FT CHAIN 1..371
FT /note="Caytaxin"
FT /id="PRO_0000210767"
FT DOMAIN 171..328
FT /note="CRAL-TRIO"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00056"
FT REGION 1..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 115..120
FT /note="Required for interaction with KLC1"
FT /evidence="ECO:0000250"
FT REGION 190..371
FT /note="Mediates interaction with GLS"
FT /evidence="ECO:0000269|PubMed:16899818"
FT REGION 331..371
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 10..29
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 331..354
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 105..106
FT /note="Cleavage; by CASP3"
FT /evidence="ECO:0000269|PubMed:21369758"
FT VAR_SEQ 370..371
FT /note="MS -> LQPLHRSS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008748"
FT VARIANT 301
FT /note="S -> R (in ATCAY)"
FT /evidence="ECO:0000269|PubMed:14556008"
FT /id="VAR_017164"
FT MUTAGEN 105
FT /note="D->E: Alters cleavage by CASP3."
FT /evidence="ECO:0000269|PubMed:21369758"
FT MUTAGEN 115..117
FT /note="ELE->AAA: Reduced interaction with KLC1."
FT MUTAGEN 118..120
FT /note="WED->AAA: Completely abolishes interaction with
FT KLC1."
FT CONFLICT 9
FT /note="R -> W (in Ref. 1; AAO63019)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 371 AA; 42120 MW; C09174CE3AD77764 CRC64;
MGTTEATLRM ENVDVKEEWQ DEDLPRPLPE ETGVELLGSP VEDTSSPPNT LNFNGAHRKR
KTLVAPEINI SLDQSEGSLL SDDFLDTPDD LDINVDDIET PDETDSLEFL GNGNELEWED
DTPVATAKNM PGDSADLFGD GTTEDGSAAN GRLWRTVIIG EQEHRIDLHM IRPYMKVVTH
GGYYGEGLNA IIVFAACFLP DSSLPDYHYI MENLFLYVIS SLELLVAEDY MIVYLNGATP
RRRMPGIGWL KKCYQMIDRR LRKNLKSLII VHPSWFIRTV LAISRPFISV KFINKIQYVH
SLEDLEQLIP MEHVQIPDCV LQYEEERLKA RRESARPQPE FVLPRSEEKP EVAPVENRSA
LVSEDQETSM S
