HAX1_MOUSE
ID HAX1_MOUSE Reviewed; 280 AA.
AC O35387; Q542F8;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=HCLS1-associated protein X-1;
DE AltName: Full=HS1-associating protein X-1;
DE Short=HAX-1;
DE AltName: Full=HS1-binding protein 1;
DE Short=HSP1BP-1;
GN Name=Hax1; Synonyms=Hs1bp1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Watanabe T., Takeshita H.;
RT "Mouse HAX-1 short form (HAX-1s).";
RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Kidney, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [4]
RP INTERACTION WITH PKD2 AND CTTN, AND SUBCELLULAR LOCATION.
RX PubMed=10760273; DOI=10.1073/pnas.97.8.4017;
RA Gallagher A.R., Cedzich A., Gretz N., Somlo S., Witzgall R.;
RT "The polycystic kidney disease protein PKD2 interacts with Hax-1, a protein
RT associated with the actin cytoskeleton.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:4017-4022(2000).
RN [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16814492; DOI=10.1016/j.gene.2006.04.027;
RA Hippe A., Bylaite M., Chen M., von Mikecz A., Wolf R., Ruzicka T., Walz M.;
RT "Expression and tissue distribution of mouse Hax1.";
RL Gene 379:116-126(2006).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=18288109; DOI=10.1038/nature06604;
RA Chao J.R., Parganas E., Boyd K., Hong C.Y., Opferman J.T., Ihle J.N.;
RT "Hax1-mediated processing of HtrA2 by Parl allows survival of lymphocytes
RT and neurons.";
RL Nature 452:98-102(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP INTERACTION WITH KCNC3.
RX PubMed=26997484; DOI=10.1016/j.cell.2016.02.009;
RA Zhang Y., Zhang X.F., Fleming M.R., Amiri A., El-Hassar L., Surguchev A.A.,
RA Hyland C., Jenkins D.P., Desai R., Brown M.R., Gazula V.R., Waters M.F.,
RA Large C.H., Horvath T.L., Navaratnam D., Vaccarino F.M., Forscher P.,
RA Kaczmarek L.K.;
RT "Kv3.3 channels bind Hax-1 and Arp2/3 to assemble a stable local actin
RT network that regulates channel gating.";
RL Cell 165:434-448(2016).
CC -!- FUNCTION: Recruits the Arp2/3 complex to the cell cortex and regulates
CC reorganization of the cortical actin cytoskeleton via its interaction
CC with KCNC3 and the Arp2/3 complex. Slows down the rate of inactivation
CC of KCNC3 channels. Promotes GNA13-mediated cell migration. Involved in
CC the clathrin-mediated endocytosis pathway. May be involved in
CC internalization of ABC transporters such as ABCB11. May inhibit CASP9
CC and CASP3. Promotes cell survival. May regulate intracellular calcium
CC pools. {ECO:0000250|UniProtKB:O00165}.
CC -!- SUBUNIT: Interacts with ABCB1, ABCB4 and ABCB11 (By similarity).
CC Directly associates with HCLS1/HS1, through binding to its N-terminal
CC region (By similarity). Interacts with CTTN (PubMed:10760273).
CC Interacts with PKD2(PubMed:10760273). Interacts with GNA13. Interacts
CC with CASP9. Interacts with ITGB6. Interacts with PLN and ATP2A2; these
CC interactions are inhibited by calcium. Interacts with GRB7. Interacts
CC (via C-terminus) with XIAP/BIRC4 (via BIR 2 domain and BIR 3 domain)
CC and this interaction blocks ubiquitination of XIAP/BIRC4. Interacts
CC with TPC2. Interacts with KCNC3 (PubMed:26997484). Interacts with XPO1
CC (By similarity). Interacts with RNF217 (By similarity).
CC {ECO:0000250|UniProtKB:O00165, ECO:0000250|UniProtKB:Q7TSE9,
CC ECO:0000269|PubMed:10760273}.
CC -!- INTERACTION:
CC O35387; Q8BWG8: Arrb1; NbExp=6; IntAct=EBI-642449, EBI-641778;
CC O35387; Q9JIY5: Htra2; NbExp=3; IntAct=EBI-642449, EBI-2365838;
CC O35387; Q5XJY4: Parl; NbExp=2; IntAct=EBI-642449, EBI-5395457;
CC O35387; P42227: Stat3; NbExp=11; IntAct=EBI-642449, EBI-602878;
CC O35387; Q13563: PKD2; Xeno; NbExp=3; IntAct=EBI-642449, EBI-7813714;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16814492}.
CC Endoplasmic reticulum {ECO:0000269|PubMed:10760273}. Nucleus membrane
CC {ECO:0000305|PubMed:16814492}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:10760273, ECO:0000269|PubMed:16814492}. Cytoplasm,
CC cell cortex {ECO:0000250|UniProtKB:O00165}. Cell membrane
CC {ECO:0000250|UniProtKB:O00165}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:O00165}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:O00165}. Sarcoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q7TSE9}. Cytoplasm, P-body
CC {ECO:0000250|UniProtKB:O00165}. Cytoplasm
CC {ECO:0000250|UniProtKB:O00165}. Nucleus {ECO:0000250|UniProtKB:O00165}.
CC Note=Predominantly cytoplasmic. Also detected in the nucleus when
CC nuclear export is inhibited (in vitro). {ECO:0000250|UniProtKB:O00165}.
CC -!- TISSUE SPECIFICITY: Ubiquitous, with highest levels in kidney and liver
CC (at protein level). {ECO:0000269|PubMed:16814492}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking Hax1 fail to survive longer than 14
CC weeks, due to a loss of motor coordination and activity, leading to
CC failure to eat and drink. They display extensive apoptosis of neurons
CC in the striatum and cerebellum, and a loss of lymphocytes in spleen,
CC bone marrow and thymus. {ECO:0000269|PubMed:18288109}.
CC -!- SIMILARITY: Belongs to the HAX1 family. {ECO:0000305}.
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DR EMBL; AF023482; AAB81081.1; -; mRNA.
DR EMBL; AK002256; BAB21969.1; -; mRNA.
DR EMBL; AK010633; BAB27077.1; -; mRNA.
DR EMBL; AK088746; BAC40544.1; -; mRNA.
DR EMBL; BC006688; AAH06688.1; -; mRNA.
DR EMBL; BC098225; AAH98225.1; -; mRNA.
DR CCDS; CCDS17519.1; -.
DR RefSeq; NP_035956.1; NM_011826.4.
DR AlphaFoldDB; O35387; -.
DR SMR; O35387; -.
DR BioGRID; 204783; 17.
DR CORUM; O35387; -.
DR DIP; DIP-49445N; -.
DR IntAct; O35387; 22.
DR MINT; O35387; -.
DR STRING; 10090.ENSMUSP00000078661; -.
DR iPTMnet; O35387; -.
DR PhosphoSitePlus; O35387; -.
DR EPD; O35387; -.
DR jPOST; O35387; -.
DR MaxQB; O35387; -.
DR PaxDb; O35387; -.
DR PRIDE; O35387; -.
DR ProteomicsDB; 269814; -.
DR Antibodypedia; 34150; 507 antibodies from 38 providers.
DR DNASU; 23897; -.
DR Ensembl; ENSMUST00000079724; ENSMUSP00000078661; ENSMUSG00000027944.
DR GeneID; 23897; -.
DR KEGG; mmu:23897; -.
DR UCSC; uc008qaj.2; mouse.
DR CTD; 10456; -.
DR MGI; MGI:1346319; Hax1.
DR VEuPathDB; HostDB:ENSMUSG00000027944; -.
DR eggNOG; ENOG502S0AE; Eukaryota.
DR GeneTree; ENSGT00390000018324; -.
DR InParanoid; O35387; -.
DR OMA; SKFNDIW; -.
DR OrthoDB; 1567048at2759; -.
DR PhylomeDB; O35387; -.
DR TreeFam; TF328619; -.
DR BioGRID-ORCS; 23897; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Hax1; mouse.
DR PRO; PR:O35387; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; O35387; protein.
DR Bgee; ENSMUSG00000027944; Expressed in morula and 66 other tissues.
DR ExpressionAtlas; O35387; baseline and differential.
DR Genevisible; O35387; MM.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:BHF-UCL.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0030136; C:clathrin-coated vesicle; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0030027; C:lamellipodium; IDA:BHF-UCL.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISO:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000932; C:P-body; IEA:UniProtKB-SubCell.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:CACAO.
DR GO; GO:0005667; C:transcription regulator complex; ISO:MGI.
DR GO; GO:0019966; F:interleukin-1 binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:MGI.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:MGI.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; ISO:MGI.
DR GO; GO:0030854; P:positive regulation of granulocyte differentiation; ISO:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0030833; P:regulation of actin filament polymerization; ISO:MGI.
DR InterPro; IPR017248; HAX-1.
DR PANTHER; PTHR14938; PTHR14938; 1.
DR PIRSF; PIRSF037634; HS1-associating_X-1; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell membrane; Cytoplasm; Cytoplasmic vesicle;
KW Endoplasmic reticulum; Membrane; Mitochondrion; Nucleus; Phosphoprotein;
KW Reference proteome; Sarcoplasmic reticulum.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O00165"
FT CHAIN 2..280
FT /note="HCLS1-associated protein X-1"
FT /id="PRO_0000083907"
FT REGION 2..45
FT /note="Required for localization in mitochondria"
FT /evidence="ECO:0000250"
FT REGION 12..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 100..263
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 115..280
FT /note="Involved in HCLS1 binding"
FT /evidence="ECO:0000250"
FT REGION 176..207
FT /note="Involved in CASP9 binding"
FT /evidence="ECO:0000250"
FT REGION 177..248
FT /note="Involved in GNA13 binding"
FT /evidence="ECO:0000250"
FT REGION 184..280
FT /note="Required for localization in sarcoplasmic reticulum"
FT /evidence="ECO:0000250"
FT REGION 185..280
FT /note="Involved in PKD2 binding"
FT REGION 204..246
FT /note="Involved in ATP2A2 binding"
FT /evidence="ECO:0000250"
FT REGION 204..226
FT /note="Involved in PLN binding"
FT /evidence="ECO:0000250"
FT REGION 271..280
FT /note="Required for ITGB6 binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 28..44
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 114..128
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 174..191
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 195..218
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 220..258
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 128..129
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:O00165"
FT MOD_RES 190
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00165"
FT MOD_RES 193
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00165"
SQ SEQUENCE 280 AA; 31654 MW; 3123979BA10B45D1 CRC64;
MSVFDLFRGF FGFPGPRSHR DPFFGGMTRD DDDDDDDDDE AEEDRGAWGR ESYAFDGSQP
PEEFGFSFSP RGGMRFHGNF GFDDLVRDFN SIFSEMGAWT LPSHSPELPG PESETPGERL
REGQTLRDSM LKYPDSHQPR IFEGVLESHA KPESPKPAPD WGSQGPFHRL DDTWPVSPHS
RAKEDKDLDS QVSQEGLGPL LQPQPKSYFK SISVTKITKP DGTVEERRTV VDSEGRRETT
VTHQEAHDSS RSDPDSQRSS ALDDPFSILD LLLGRWFRSR
