HAX1_HUMAN
ID HAX1_HUMAN Reviewed; 279 AA.
AC O00165; A8W4W9; A8W4X0; B4DUJ7; Q5VYD5; Q5VYD7; Q96AU4; Q9BS80;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2002, sequence version 2.
DT 03-AUG-2022, entry version 198.
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 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, SUBCELLULAR LOCATION,
RP INTERACTION WITH HCLS1, AND TISSUE SPECIFICITY.
RC TISSUE=Cervix adenocarcinoma;
RX PubMed=9058808;
RA Suzuki Y., Demoliere C., Kitamura D., Takeshita H., Deuschle U.,
RA Watanabe T.;
RT "HAX-1, a novel intracellular protein, localized on mitochondria, directly
RT associates with HS1, a substrate of Src family tyrosine kinases.";
RL J. Immunol. 158:2736-2744(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5 AND 6).
RX PubMed=18472110; DOI=10.1016/j.jmb.2008.04.020;
RA Lees D.M., Hart I.R., Marshall J.F.;
RT "Existence of multiple isoforms of HS1-associated protein X-1 in murine and
RT human tissues.";
RL J. Mol. Biol. 379:645-655(2008).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Lung;
RA Trebinska A., Grzybowska E.A.;
RL Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4).
RC TISSUE=Amygdala, Heart, and Skeletal muscle;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLY-151.
RC TISSUE=Brain, Lung, and Skin;
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 [8]
RP PROTEIN SEQUENCE OF 2-17 AND 140-150, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Hepatoma;
RA Bienvenut W.V., Boldt K., von Kriegsheim A.F., Kolch W.;
RL Submitted (JUL-2007) to UniProtKB.
RN [9]
RP INTERACTION WITH PKD2.
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 [10]
RP INTERACTION WITH GNA13, AND FUNCTION.
RX PubMed=15339924; DOI=10.1074/jbc.m408836200;
RA Radhika V., Onesime D., Ha J.H., Dhanasekaran N.;
RT "Galpha13 stimulates cell migration through cortactin-interacting protein
RT Hax-1.";
RL J. Biol. Chem. 279:49406-49413(2004).
RN [11]
RP INTERACTION WITH CASP9, AND FUNCTION.
RX PubMed=16857965; DOI=10.1161/01.res.0000237387.05259.a5;
RA Han Y., Chen Y.S., Liu Z., Bodyak N., Rigor D., Bisping E., Pu W.T.,
RA Kang P.M.;
RT "Overexpression of HAX-1 protects cardiac myocytes from apoptosis through
RT caspase-9 inhibition.";
RL Circ. Res. 99:415-423(2006).
RN [12]
RP INTERACTION WITH ITGB6, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17545607; DOI=10.1158/0008-5472.can-07-0318;
RA Ramsay A.G., Keppler M.D., Jazayeri M., Thomas G.J., Parsons M.,
RA Violette S., Weinreb P., Hart I.R., Marshall J.F.;
RT "HS1-associated protein X-1 regulates carcinoma cell migration and invasion
RT via clathrin-mediated endocytosis of integrin alphavbeta6.";
RL Cancer Res. 67:5275-5284(2007).
RN [13]
RP INTERACTION WITH PLN.
RX PubMed=17241641; DOI=10.1016/j.jmb.2006.10.057;
RA Vafiadaki E., Sanoudou D., Arvanitis D.A., Catino D.H., Kranias E.G.,
RA Kontrogianni-Konstantopoulos A.;
RT "Phospholamban interacts with HAX-1, a mitochondrial protein with anti-
RT apoptotic function.";
RL J. Mol. Biol. 367:65-79(2007).
RN [14]
RP INVOLVEMENT IN SCN3.
RX PubMed=17187068; DOI=10.1038/ng1940;
RA Klein C., Grudzien M., Appaswamy G., Germeshausen M., Sandrock I.,
RA Schaeffer A.A., Rathinam C., Boztug K., Schwinzer B., Rezaei N., Bohn G.,
RA Melin M., Carlsson G., Fadeel B., Dahl N., Palmblad J., Henter J.-I.,
RA Zeidler C., Grimbacher B., Welte K.;
RT "HAX1 deficiency causes autosomal recessive severe congenital neutropenia
RT (Kostmann disease).";
RL Nat. Genet. 39:86-92(2007).
RN [15]
RP INVOLVEMENT IN SCN3, AND ISOFORM DEPENDENT GENOTYPE-PHENOTYPE ASSOCIATIONS.
RX PubMed=18337561; DOI=10.1182/blood-2007-11-120667;
RA Germeshausen M., Grudzien M., Zeidler C., Abdollahpour H., Yetgin S.,
RA Rezaei N., Ballmaier M., Grimbacher B., Welte K., Klein C.;
RT "Novel HAX1 mutations in patients with severe congenital neutropenia reveal
RT isoform-dependent genotype-phenotype associations.";
RL Blood 111:4954-4957(2008).
RN [16]
RP CLEAVAGE SITE, AND FUNCTION.
RX PubMed=18319618;
RA Lee A.Y., Lee Y., Park Y.K., Bae K.-H., Cho S., Lee do H., Park B.C.,
RA Kang S., Park S.G.;
RT "HS 1-associated protein X-1 is cleaved by caspase-3 during apoptosis.";
RL Mol. Cells 25:86-90(2008).
RN [17]
RP INTERACTION WITH ATP2A2 AND PLN, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18971376; DOI=10.1091/mbc.e08-06-0587;
RA Vafiadaki E., Arvanitis D.A., Pagakis S.N., Papalouka V., Sanoudou D.,
RA Kontrogianni-Konstantopoulos A., Kranias E.G.;
RT "The anti-apoptotic protein HAX-1 interacts with SERCA2 and regulates its
RT protein levels to promote cell survival.";
RL Mol. Biol. Cell 20:306-318(2009).
RN [18]
RP INTERACTION WITH XIAP/BIRC4.
RX PubMed=20171186; DOI=10.1016/j.bbrc.2010.02.084;
RA Kang Y.J., Jang M., Park Y.K., Kang S., Bae K.H., Cho S., Lee C.K.,
RA Park B.C., Chi S.W., Park S.G.;
RT "Molecular interaction between HAX-1 and XIAP inhibits apoptosis.";
RL Biochem. Biophys. Res. Commun. 393:794-799(2010).
RN [19]
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 [20]
RP INTERACTION WITH GRB7.
RX PubMed=20665473; DOI=10.1002/jmr.1062;
RA Siamakpour-Reihani S., Peterson T.A., Bradford A.M., Argiros H.J.,
RA Haas L.L., Lor S.N., Haulsee Z.M., Spuches A.M., Johnson D.L.,
RA Rohrschneider L.R., Shuster C.B., Lyons B.A.;
RT "Grb7 binds to Hax-1 and undergoes an intramolecular domain association
RT that offers a model for Grb7 regulation.";
RL J. Mol. Recognit. 24:314-321(2011).
RN [21]
RP ALTERNATIVE SPLICING, SUBCELLULAR LOCATION (ISOFORMS 1; 3; 4 AND 5), AND
RP INTERACTION WITH XPO1.
RX PubMed=23164465; DOI=10.1111/febs.12066;
RA Grzybowska E.A., Zayat V., Konopinski R., Trebinska A., Szwarc M.,
RA Sarnowska E., Macech E., Korczynski J., Knapp A., Siedlecki J.A.;
RT "HAX-1 is a nucleocytoplasmic shuttling protein with a possible role in
RT mRNA processing.";
RL FEBS J. 280:256-272(2013).
RN [22]
RP INTERACTION WITH TPC2.
RX PubMed=24188827; DOI=10.1016/j.febslet.2013.10.031;
RA Lam A.K., Galione A., Lai F.A., Zissimopoulos S.;
RT "Hax-1 identified as a two-pore channel (TPC)-binding protein.";
RL FEBS Lett. 587:3782-3786(2013).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-189 AND SER-192, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [25]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH RNF217.
RX PubMed=25298122; DOI=10.1038/srep06565;
RA Fontanari Krause L.M., Japp A.S., Krause A., Mooster J., Chopra M.,
RA Mueschen M., Bohlander S.K.;
RT "Identification and characterization of OSTL (RNF217) encoding a RING-IBR-
RT RING protein adjacent to a translocation breakpoint involving ETV6 in
RT childhood ALL.";
RL Sci. Rep. 4:6565-6565(2014).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [27]
RP FUNCTION, INTERACTION WITH KCNC3, AND SUBCELLULAR LOCATION.
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).
RN [28]
RP VARIANT SCN3 LEU-141.
RX PubMed=19796188; DOI=10.1111/j.1399-0004.2009.01244.x;
RA Faiyaz-Ul-Haque M., Al-Jefri A., Abalkhail H.A., Toulimat M.,
RA Al-Muallimi M.A., Pulicat M.S., Gaafar A., Alaiya A.A., Al-Dayel F.,
RA Peltekova I., Zaidi S.H.;
RT "A novel missense mutation in the HAX1 gene in severe congenital
RT neutropenia patients (Kostmann disease).";
RL Clin. Genet. 76:569-572(2009).
RN [29]
RP VARIANTS SCN3 ARG-130 AND ILE-172.
RX PubMed=20220065; DOI=10.3324/haematol.2009.017665;
RA Germeshausen M., Zeidler C., Stuhrmann M., Lanciotti M., Ballmaier M.,
RA Welte K.;
RT "Digenic mutations in severe congenital neutropenia.";
RL Haematologica 95:1207-1210(2010).
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 (PubMed:26997484). Slows down the
CC rate of inactivation of KCNC3 channels (PubMed:26997484). Promotes
CC GNA13-mediated cell migration. Involved in the clathrin-mediated
CC endocytosis pathway. May be involved in internalization of ABC
CC transporters such as ABCB11. May inhibit CASP9 and CASP3. Promotes cell
CC survival. May regulate intracellular calcium pools.
CC {ECO:0000269|PubMed:15339924, ECO:0000269|PubMed:16857965,
CC ECO:0000269|PubMed:17545607, ECO:0000269|PubMed:18319618,
CC ECO:0000269|PubMed:18971376, ECO:0000269|PubMed:26997484,
CC ECO:0000269|PubMed:9058808}.
CC -!- SUBUNIT: Interacts with ABCB1, ABCB4 and ABCB11 (By similarity).
CC Directly associates with HCLS1/HS1, through binding to its N-terminal
CC region (PubMed:9058808). Interacts with CTTN (By similarity). Interacts
CC with PKD2 (PubMed:10760273). Interacts with GNA13 (PubMed:15339924).
CC Interacts with CASP9 (PubMed:16857965). Interacts with ITGB6
CC (PubMed:17545607). Interacts with PLN and ATP2A2; these interactions
CC are inhibited by calcium (PubMed:17241641, PubMed:18971376). Interacts
CC with GRB7 (PubMed:20665473). Interacts (via C-terminus) with XIAP/BIRC4
CC (via BIR 2 domain and BIR 3 domain) and this interaction blocks
CC ubiquitination of XIAP/BIRC4 (PubMed:20171186). Interacts with TPC2
CC (PubMed:24188827). Interacts with KCNC3 (PubMed:26997484). Interacts
CC with XPO1 (PubMed:23164465). Interacts with RNF217 (PubMed:25298122).
CC {ECO:0000250|UniProtKB:Q7TSE9, ECO:0000269|PubMed:10760273,
CC ECO:0000269|PubMed:15339924, ECO:0000269|PubMed:16857965,
CC ECO:0000269|PubMed:17241641, ECO:0000269|PubMed:17545607,
CC ECO:0000269|PubMed:18971376, ECO:0000269|PubMed:20171186,
CC ECO:0000269|PubMed:20665473, ECO:0000269|PubMed:23164465,
CC ECO:0000269|PubMed:24188827, ECO:0000269|PubMed:25298122,
CC ECO:0000269|PubMed:26997484, ECO:0000269|PubMed:9058808}.
CC -!- INTERACTION:
CC O00165; P03372: ESR1; NbExp=2; IntAct=EBI-357001, EBI-78473;
CC O00165; Q14451: GRB7; NbExp=2; IntAct=EBI-357001, EBI-970191;
CC O00165; P42858: HTT; NbExp=14; IntAct=EBI-357001, EBI-466029;
CC O00165; P01583: IL1A; NbExp=3; IntAct=EBI-357001, EBI-1749782;
CC O00165; Q92993: KAT5; NbExp=3; IntAct=EBI-357001, EBI-399080;
CC O00165; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-357001, EBI-11742507;
CC O00165; Q9BRX2: PELO; NbExp=7; IntAct=EBI-357001, EBI-1043580;
CC O00165; Q9H4B6: SAV1; NbExp=7; IntAct=EBI-357001, EBI-1017775;
CC O00165; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-357001, EBI-9090795;
CC O00165; Q9ULQ1: TPCN1; NbExp=2; IntAct=EBI-357001, EBI-5239895;
CC O00165; Q8NHX9: TPCN2; NbExp=4; IntAct=EBI-357001, EBI-5239949;
CC O00165; P61981: YWHAG; NbExp=3; IntAct=EBI-357001, EBI-359832;
CC O00165; Q68871; Xeno; NbExp=3; IntAct=EBI-357001, EBI-12522528;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:18971376,
CC ECO:0000269|PubMed:9058808}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:18971376, ECO:0000269|PubMed:9058808}. Nucleus
CC membrane {ECO:0000269|PubMed:9058808}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:O35387}. Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:26997484}. Cell membrane
CC {ECO:0000269|PubMed:26997484}; Peripheral membrane protein
CC {ECO:0000269|PubMed:26997484}; Cytoplasmic side
CC {ECO:0000269|PubMed:26997484}. Sarcoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q7TSE9}. Cytoplasm, P-body
CC {ECO:0000269|PubMed:23164465}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm
CC {ECO:0000269|PubMed:23164465, ECO:0000269|PubMed:25298122}. Nucleus
CC {ECO:0000269|PubMed:23164465}. Note=Predominantly cytoplasmic. Also
CC detected in the nucleus when nuclear export is inhibited, and in
CC response to cellular stress caused by arsenite (in vitro).
CC {ECO:0000269|PubMed:23164465}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm
CC {ECO:0000269|PubMed:23164465}. Nucleus {ECO:0000269|PubMed:23164465}.
CC Note=Predominantly cytoplasmic. Also detected in the nucleus when
CC nuclear export is inhibited (in vitro). {ECO:0000269|PubMed:23164465}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm
CC {ECO:0000269|PubMed:23164465}. Nucleus {ECO:0000269|PubMed:23164465}.
CC Note=Shuttles between nucleus and cytoplasm.
CC {ECO:0000269|PubMed:23164465}.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Cytoplasm
CC {ECO:0000269|PubMed:23164465}. Note=Predominantly cytoplasmic.
CC {ECO:0000269|PubMed:23164465}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=O00165-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00165-2; Sequence=VSP_038537;
CC Name=3;
CC IsoId=O00165-3; Sequence=VSP_038536;
CC Name=4;
CC IsoId=O00165-4; Sequence=VSP_038538, VSP_038539;
CC Name=5;
CC IsoId=O00165-5; Sequence=VSP_038543;
CC Name=6;
CC IsoId=O00165-6; Sequence=VSP_038544, VSP_038545;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Up-regulated in oral cancers.
CC {ECO:0000269|PubMed:17545607, ECO:0000269|PubMed:9058808}.
CC -!- PTM: Proteolytically cleaved by caspase-3 during apoptosis.
CC {ECO:0000269|PubMed:18319618}.
CC -!- DISEASE: Neutropenia, severe congenital 3, autosomal recessive (SCN3)
CC [MIM:610738]: A disorder of hematopoiesis characterized by maturation
CC arrest of granulopoiesis at the level of promyelocytes with peripheral
CC blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of
CC severe bacterial infections. Some patients affected by severe
CC congenital neutropenia type 3 have neurological manifestations such as
CC psychomotor retardation and seizures. {ECO:0000269|PubMed:17187068,
CC ECO:0000269|PubMed:18337561, ECO:0000269|PubMed:19796188,
CC ECO:0000269|PubMed:20220065}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. The clinical phenotype
CC due to HAX1 deficiency appears to depend on the localization of the
CC mutations and their influence on the transcript variants. Mutations
CC affecting exclusively isoform 1 are associated with isolated congenital
CC neutropenia, whereas mutations affecting both isoform 1 and isoform 5
CC are associated with additional neurologic symptoms (PubMed:18337561).
CC {ECO:0000269|PubMed:18337561}.
CC -!- SIMILARITY: Belongs to the HAX1 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=HAX1base; Note=HAX1 mutation db;
CC URL="http://structure.bmc.lu.se/idbase/HAX1base/";
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DR EMBL; U68566; AAB51196.1; -; mRNA.
DR EMBL; EU190982; ABW73998.1; -; mRNA.
DR EMBL; EU190983; ABW73999.1; -; mRNA.
DR EMBL; AK290626; BAF83315.1; -; mRNA.
DR EMBL; AK294298; BAG57580.1; -; mRNA.
DR EMBL; AK300676; BAG62359.1; -; mRNA.
DR EMBL; AL354980; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53212.1; -; Genomic_DNA.
DR EMBL; BC005240; AAH05240.1; -; mRNA.
DR EMBL; BC014314; AAH14314.1; -; mRNA.
DR EMBL; BC015209; AAH15209.1; -; mRNA.
DR EMBL; BC016730; AAH16730.1; -; mRNA.
DR CCDS; CCDS1064.1; -. [O00165-1]
DR CCDS; CCDS44230.1; -. [O00165-5]
DR RefSeq; NP_001018238.1; NM_001018837.1. [O00165-5]
DR RefSeq; NP_006109.2; NM_006118.3. [O00165-1]
DR AlphaFoldDB; O00165; -.
DR BioGRID; 115719; 397.
DR CORUM; O00165; -.
DR DIP; DIP-36771N; -.
DR IntAct; O00165; 211.
DR MINT; O00165; -.
DR STRING; 9606.ENSP00000329002; -.
DR ChEMBL; CHEMBL4295644; -.
DR GlyGen; O00165; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O00165; -.
DR PhosphoSitePlus; O00165; -.
DR BioMuta; HAX1; -.
DR EPD; O00165; -.
DR jPOST; O00165; -.
DR MassIVE; O00165; -.
DR MaxQB; O00165; -.
DR PaxDb; O00165; -.
DR PeptideAtlas; O00165; -.
DR PRIDE; O00165; -.
DR ProteomicsDB; 47750; -. [O00165-1]
DR ProteomicsDB; 47751; -. [O00165-2]
DR ProteomicsDB; 47752; -. [O00165-3]
DR ProteomicsDB; 47753; -. [O00165-4]
DR ProteomicsDB; 47754; -. [O00165-5]
DR ProteomicsDB; 47755; -. [O00165-6]
DR TopDownProteomics; O00165-2; -. [O00165-2]
DR Antibodypedia; 34150; 507 antibodies from 38 providers.
DR DNASU; 10456; -.
DR Ensembl; ENST00000328703.12; ENSP00000329002.7; ENSG00000143575.15. [O00165-1]
DR Ensembl; ENST00000447768.6; ENSP00000403848.2; ENSG00000143575.15. [O00165-6]
DR Ensembl; ENST00000457918.6; ENSP00000411448.2; ENSG00000143575.15. [O00165-5]
DR Ensembl; ENST00000483970.6; ENSP00000435088.1; ENSG00000143575.15. [O00165-2]
DR GeneID; 10456; -.
DR KEGG; hsa:10456; -.
DR MANE-Select; ENST00000328703.12; ENSP00000329002.7; NM_006118.4; NP_006109.2.
DR UCSC; uc001fes.5; human. [O00165-1]
DR CTD; 10456; -.
DR DisGeNET; 10456; -.
DR GeneCards; HAX1; -.
DR HGNC; HGNC:16915; HAX1.
DR HPA; ENSG00000143575; Low tissue specificity.
DR MalaCards; HAX1; -.
DR MIM; 605998; gene.
DR MIM; 610738; phenotype.
DR neXtProt; NX_O00165; -.
DR OpenTargets; ENSG00000143575; -.
DR Orphanet; 99749; Kostmann syndrome.
DR PharmGKB; PA142671700; -.
DR VEuPathDB; HostDB:ENSG00000143575; -.
DR eggNOG; ENOG502S0AE; Eukaryota.
DR GeneTree; ENSGT00390000018324; -.
DR HOGENOM; CLU_086695_0_0_1; -.
DR InParanoid; O00165; -.
DR OMA; SKFNDIW; -.
DR PhylomeDB; O00165; -.
DR TreeFam; TF328619; -.
DR PathwayCommons; O00165; -.
DR SignaLink; O00165; -.
DR SIGNOR; O00165; -.
DR BioGRID-ORCS; 10456; 94 hits in 1083 CRISPR screens.
DR ChiTaRS; HAX1; human.
DR GeneWiki; HAX1; -.
DR GenomeRNAi; 10456; -.
DR Pharos; O00165; Tbio.
DR PRO; PR:O00165; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O00165; protein.
DR Bgee; ENSG00000143575; Expressed in apex of heart and 213 other tissues.
DR ExpressionAtlas; O00165; baseline and differential.
DR Genevisible; O00165; HS.
DR GO; GO:0015629; C:actin cytoskeleton; ISS:BHF-UCL.
DR GO; GO:0016324; C:apical plasma membrane; IBA:GO_Central.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0030136; C:clathrin-coated vesicle; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:BHF-UCL.
DR GO; GO:0030027; C:lamellipodium; ISS:BHF-UCL.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; TAS:ProtInc.
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; IBA:GO_Central.
DR GO; GO:0005667; C:transcription regulator complex; IDA:BHF-UCL.
DR GO; GO:0019966; F:interleukin-1 binding; IDA:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IDA:UniProtKB.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IMP:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; IMP:BHF-UCL.
DR GO; GO:0030854; P:positive regulation of granulocyte differentiation; IMP:BHF-UCL.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:BHF-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:BHF-UCL.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IMP:BHF-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0030833; P:regulation of actin filament polymerization; IMP:BHF-UCL.
DR GO; GO:0042981; P:regulation of apoptotic process; TAS:ParkinsonsUK-UCL.
DR GO; GO:1903146; P:regulation of autophagy of mitochondrion; TAS:ParkinsonsUK-UCL.
DR GO; GO:1903214; P:regulation of protein targeting to mitochondrion; TAS:ParkinsonsUK-UCL.
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; Alternative splicing; Cell membrane; Cytoplasm;
KW Cytoplasmic vesicle; Direct protein sequencing; Disease variant;
KW Endoplasmic reticulum; Membrane; Mitochondrion; Nucleus; Phosphoprotein;
KW Reference proteome; Sarcoplasmic reticulum.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:25944712"
FT CHAIN 2..279
FT /note="HCLS1-associated protein X-1"
FT /id="PRO_0000083906"
FT REGION 2..41
FT /note="Required for localization in mitochondria"
FT /evidence="ECO:0000250"
FT REGION 16..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 99..262
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 114..279
FT /note="Involved in HCLS1 binding"
FT REGION 175..206
FT /note="Involved in CASP9 binding"
FT REGION 176..247
FT /note="Involved in GNA13 binding"
FT REGION 183..279
FT /note="Required for localization in sarcoplasmic reticulum"
FT /evidence="ECO:0000250"
FT REGION 184..279
FT /note="Involved in PKD2 binding"
FT REGION 203..245
FT /note="Involved in ATP2A2 binding"
FT REGION 203..225
FT /note="Involved in PLN binding"
FT REGION 270..279
FT /note="Required for ITGB6 binding"
FT COMPBIAS 113..127
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 164..189
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 190..213
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 219..251
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 127..128
FT /note="Cleavage; by caspase-3"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:25944712"
FT MOD_RES 189
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 192
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..26
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:18472110, ECO:0000303|Ref.3"
FT /id="VSP_038536"
FT VAR_SEQ 18..65
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:18472110"
FT /id="VSP_038543"
FT VAR_SEQ 85..264
FT /note="VRDFNSIFSDMGAWTLPSHPPELPGPESETPGERLREGQTLRDSMLKYPDSH
FT QPRIFGGVLESDARSESPQPAPDWGSQRPFHRFDDVWPMDPHPRTREDNDLDSQVSQEG
FT LGPVLQPQPKSYFKSISVTKITKPDGIVEERRTVVDSEGRTETTVTRHEADSSPRGDPE
FT SPRPPALDDA -> NFQVLSQRHLVRDYGRDRHFGTQCLSIQIVTSPGSLGGSWRVMQE
FT VNPPNQHQTGAPRGHFIGLMMYGLWTPILEPERTMILIPRFPRRVLARFYSPSPNPISR
FT ASL (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:18472110"
FT /id="VSP_038544"
FT VAR_SEQ 105
FT /note="P -> PANTCHLSA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:18472110"
FT /id="VSP_038537"
FT VAR_SEQ 106..124
FT /note="ELPGPESETPGERLREGQT -> GVWLSLRGNLWFLVGWWVK (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:18472110, ECO:0000303|Ref.3"
FT /id="VSP_038538"
FT VAR_SEQ 125..279
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:18472110, ECO:0000303|Ref.3"
FT /id="VSP_038539"
FT VAR_SEQ 265..279
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:18472110"
FT /id="VSP_038545"
FT VARIANT 49
FT /note="P -> S (in dbSNP:rs11556344)"
FT /id="VAR_062258"
FT VARIANT 130
FT /note="L -> R (in SCN3; dbSNP:rs179363871)"
FT /evidence="ECO:0000269|PubMed:20220065"
FT /id="VAR_064514"
FT VARIANT 141
FT /note="F -> L (in SCN3; mild form; dbSNP:rs179363870)"
FT /evidence="ECO:0000269|PubMed:19796188"
FT /id="VAR_062259"
FT VARIANT 151
FT /note="S -> G (in dbSNP:rs17851425)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_062260"
FT VARIANT 172
FT /note="V -> I (in SCN3; likely benign variant;
FT dbSNP:rs141970914)"
FT /evidence="ECO:0000269|PubMed:20220065"
FT /id="VAR_064515"
FT VARIANT 278
FT /note="S -> P (in dbSNP:rs1804715)"
FT /id="VAR_062261"
FT CONFLICT 25
FT /note="G -> V (in Ref. 3; BAG62359)"
FT /evidence="ECO:0000305"
FT CONFLICT 45
FT /note="G -> R (in Ref. 1; AAB51196)"
FT /evidence="ECO:0000305"
FT CONFLICT 201
FT /note="Q -> T (in Ref. 1; AAB51196)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 279 AA; 31621 MW; 87EEF0C46857704B CRC64;
MSLFDLFRGF FGFPGPRSHR DPFFGGMTRD EDDDEEEEEE GGSWGRGNPR FHSPQHPPEE
FGFGFSFSPG GGIRFHDNFG FDDLVRDFNS IFSDMGAWTL PSHPPELPGP ESETPGERLR
EGQTLRDSML KYPDSHQPRI FGGVLESDAR SESPQPAPDW GSQRPFHRFD DVWPMDPHPR
TREDNDLDSQ VSQEGLGPVL QPQPKSYFKS ISVTKITKPD GIVEERRTVV DSEGRTETTV
TRHEADSSPR GDPESPRPPA LDDAFSILDL FLGRWFRSR
