HIP1_HUMAN
ID HIP1_HUMAN Reviewed; 1037 AA.
AC O00291; B4E3I7; E7ES17; O00328; Q2TB58; Q8TDL4; V5LU97;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 5.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Huntingtin-interacting protein 1;
DE Short=HIP-1;
DE AltName: Full=Huntingtin-interacting protein I;
DE Short=HIP-I;
GN Name=HIP1;
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 4).
RA Kim R.N., Lira M.E., Takeuchi K., Song J.Y., Hong M., Oh E., Mao M.,
RA Han J., Choi S.J., Kim J., Choi Y.L.;
RL Submitted (JUL-2013) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Uterus;
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=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 NUCLEOTIDE SEQUENCE [MRNA] OF 8-1037, INTERACTION WITH IFT57, SUBUNIT, AND
RP DOMAIN.
RX PubMed=11788820; DOI=10.1038/ncb735;
RA Gervais F.G., Singaraja R., Xanthoudakis S., Gutekunst C.-A., Leavitt B.R.,
RA Metzler M., Hackam A.S., Tam J., Vaillancourt J.P., Houtzager V.,
RA Rasper D.M., Roy S., Hayden M.R., Nicholson D.W.;
RT "Recruitment and activation of caspase-8 by the Huntingtin-interacting
RT protein Hip-1 and a novel partner Hippi.";
RL Nat. Cell Biol. 4:95-105(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 43-1037.
RA Huq A.H.M.M., Nichol K., Osborne L., Scherer S.W., Squitieri F.,
RA Hayden M.R.;
RT "Genomic organization of the human HIP1 gene and its exclusion as a
RT candidate gene in a family diagnosed with Huntington disease without CAG
RT expansion.";
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 43-1037, INTERACTION WITH HTT, AND TISSUE
RP SPECIFICITY.
RX PubMed=9140394; DOI=10.1038/ng0597-44;
RA Kalchman M.A., Koide H.B., McCutcheon K., Graham R.K., Nichol K.,
RA Nishiyama K., Kazemi-Esfarjani P., Lynn F.C., Wellington C., Metzler M.,
RA Goldberg Y.P., Kanazawa I., Geitz R.D., Hayden M.R.;
RT "HIP1, a human homologue of S. cerevisiae Sla2p, interacts with membrane-
RT associated huntingtin in the brain.";
RL Nat. Genet. 16:44-53(1997).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 245-644, FUNCTION, INTERACTION WITH HTT, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9147654; DOI=10.1093/hmg/6.3.487;
RA Wanker E.E., Rovira C., Scherzinger E., Hasenbank R., Waelter S., Tait D.,
RA Colicelli J., Lehrach H.;
RT "HIP-I: a huntingtin interacting protein isolated by the yeast two-hybrid
RT system.";
RL Hum. Mol. Genet. 6:487-495(1997).
RN [9]
RP CHROMOSOMAL TRANSLOCATION.
RX PubMed=9616134;
RA Ross T.S., Bernard O.A., Berger R., Gilliland D.G.;
RT "Fusion of Huntingtin interacting protein 1 to platelet-derived growth
RT factor beta receptor (PDGFbetaR) in chronic myelomonocytic leukemia with
RT t(5;7)(q33;q11.2).";
RL Blood 91:4419-4426(1998).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF PHE-432.
RX PubMed=11007801; DOI=10.1074/jbc.m008408200;
RA Hackam A.S., Yassa A.S., Singaraja R., Metzler M., Gutekunst C.-A., Gan L.,
RA Warby S., Wellington C.L., Vaillancourt J., Chen N., Gervais F.G.,
RA Raymond L., Nicholson D.W., Hayden M.R.;
RT "Huntingtin interacting protein 1 induces apoptosis via a novel caspase-
RT dependent death effector domain.";
RL J. Biol. Chem. 275:41299-41308(2000).
RN [11]
RP ALTERNATIVE SPLICING.
RX PubMed=11063258; DOI=10.1007/s003350010195;
RA Chopra V.S., Metzler M., Rasper D.M., Engqvist-Goldstein A.E.Y.,
RA Singaraja R., Gan L., Fichter K.M., McCutcheon K., Drubin D.,
RA Nicholson D.W., Hayden M.R.;
RT "HIP12 is a non-proapoptotic member of a gene family including HIP1, an
RT interacting protein with huntingtin.";
RL Mamm. Genome 11:1006-1015(2000).
RN [12]
RP FUNCTION, INTERACTION WITH AP2A1; AP2A2 AND CLTC, AND SUBCELLULAR LOCATION.
RX PubMed=11532990; DOI=10.1093/hmg/10.17.1807;
RA Waelter S., Scherzinger E., Hasenbank R., Nordhoff E., Lurz R., Goehler H.,
RA Gauss C., Sathasivam K., Bates G.P., Lehrach H., Wanker E.E.;
RT "The huntingtin interacting protein HIP1 is a clathrin and alpha-adaptin-
RT binding protein involved in receptor-mediated endocytosis.";
RL Hum. Mol. Genet. 10:1807-1817(2001).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=11517213; DOI=10.1074/jbc.c100401200;
RA Metzler M., Legendre-Guillemin V., Gan L., Chopra V., Kwok A.,
RA McPherson P.S., Hayden M.R.;
RT "HIP1 functions in clathrin-mediated endocytosis through binding to
RT clathrin and adaptor protein 2.";
RL J. Biol. Chem. 276:39271-39276(2001).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11577110; DOI=10.1074/jbc.m108177200;
RA Mishra S.K., Agostinelli N.R., Brett T.J., Mizukami I., Ross T.S.,
RA Traub L.M.;
RT "Clathrin- and AP-2-binding sites in HIP1 uncover a general assembly role
RT for endocytic accessory proteins.";
RL J. Biol. Chem. 276:46230-46236(2001).
RN [15]
RP FUNCTION, INTERACTION WITH CLTB AND HIP1R, AND SUBCELLULAR LOCATION.
RX PubMed=11889126; DOI=10.1074/jbc.m112310200;
RA Legendre-Guillemin V., Metzler M., Charbonneau M., Gan L., Chopra V.,
RA Philie J., Hayden M.R., McPherson P.S.;
RT "HIP1 and HIP12 display differential binding to F-actin, AP2, and clathrin.
RT Identification of a novel interaction with clathrin light chain.";
RL J. Biol. Chem. 277:19897-19904(2002).
RN [16]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12163454; DOI=10.1172/jci15529;
RA Rao D.S., Hyun T.S., Kumar P.D., Mizukami I.F., Rubin M.A., Lucas P.C.,
RA Sanda M.G., Ross T.S.;
RT "Huntingtin-interacting protein 1 is overexpressed in prostate and colon
RT cancer and is critical for cellular survival.";
RL J. Clin. Invest. 110:351-360(2002).
RN [17]
RP FUNCTION.
RX PubMed=14732715; DOI=10.1074/jbc.m312645200;
RA Hyun T.S., Rao D.S., Saint-Dic D., Michael L.E., Kumar P.D., Bradley S.V.,
RA Mizukami I.F., Oravecz-Wilson K.I., Ross T.S.;
RT "HIP1 and HIP1r stabilize receptor tyrosine kinases and bind 3-
RT phosphoinositides via epsin N-terminal homology domains.";
RL J. Biol. Chem. 279:14294-14306(2004).
RN [18]
RP INTERACTION WITH CLTB.
RX PubMed=15533940; DOI=10.1074/jbc.m408454200;
RA Chen C.-Y., Brodsky F.M.;
RT "Huntingtin-interacting protein 1 (Hip1) and Hip1-related protein (Hip1R)
RT bind the conserved sequence of clathrin light chains and thereby influence
RT clathrin assembly in vitro and actin distribution in vivo.";
RL J. Biol. Chem. 280:6109-6117(2005).
RN [19]
RP FUNCTION, INTERACTION WITH AR, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP LYS-56; LYS-58 AND ARG-1005.
RX PubMed=16027218; DOI=10.1083/jcb.200503106;
RA Mills I.G., Gaughan L., Robson C., Ross T., McCracken S., Kelly J.,
RA Neal D.E.;
RT "Huntingtin interacting protein 1 modulates the transcriptional activity of
RT nuclear hormone receptors.";
RL J. Cell Biol. 170:191-200(2005).
RN [20]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH F-ACTIN.
RX PubMed=18790740; DOI=10.1074/jbc.m802863200;
RA Wilbur J.D., Chen C.-Y., Manalo V., Hwang P.K., Fletterick R.J.,
RA Brodsky F.M.;
RT "Actin binding by Hip1 (huntingtin-interacting protein 1) and Hip1R (Hip1-
RT related protein) is regulated by clathrin light chain.";
RL J. Biol. Chem. 283:32870-32879(2008).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [22]
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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-338, AND IDENTIFICATION BY
RP 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 [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [25]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 474-579.
RX PubMed=17257618; DOI=10.1016/j.jmb.2006.12.052;
RA Ybe J.A., Mishra S., Helms S., Nix J.;
RT "Crystal structure at 2.8 A of the DLLRKN-containing coiled-coil domain of
RT huntingtin-interacting protein 1 (HIP1) reveals a surface suitable for
RT clathrin light chain binding.";
RL J. Mol. Biol. 367:8-15(2007).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 362-474.
RX PubMed=18155047; DOI=10.1016/j.jmb.2007.11.036;
RA Niu Q., Ybe J.A.;
RT "Crystal structure at 2.8 A of Huntingtin-interacting protein 1 (HIP1)
RT coiled-coil domain reveals a charged surface suitable for HIP1 protein
RT interactor (HIPPI).";
RL J. Mol. Biol. 375:1197-1205(2008).
CC -!- FUNCTION: Plays a role in clathrin-mediated endocytosis and trafficking
CC (PubMed:11532990, PubMed:11577110, PubMed:11889126). Involved in
CC regulating AMPA receptor trafficking in the central nervous system in
CC an NMDA-dependent manner (By similarity). Regulates presynaptic nerve
CC terminal activity (By similarity). Enhances androgen receptor (AR)-
CC mediated transcription (PubMed:16027218). May act as a proapoptotic
CC protein that induces cell death by acting through the intrinsic
CC apoptosis pathway (PubMed:11007801). Binds 3-phosphoinositides (via
CC ENTH domain) (PubMed:14732715). May act through the ENTH domain to
CC promote cell survival by stabilizing receptor tyrosine kinases
CC following ligand-induced endocytosis (PubMed:14732715). May play a
CC functional role in the cell filament networks (PubMed:18790740). May be
CC required for differentiation, proliferation, and/or survival of somatic
CC and germline progenitors (PubMed:11007801, PubMed:12163454).
CC {ECO:0000250|UniProtKB:Q8VD75, ECO:0000269|PubMed:11007801,
CC ECO:0000269|PubMed:11532990, ECO:0000269|PubMed:11577110,
CC ECO:0000269|PubMed:11889126, ECO:0000269|PubMed:12163454,
CC ECO:0000269|PubMed:14732715, ECO:0000269|PubMed:16027218,
CC ECO:0000269|PubMed:18790740, ECO:0000269|PubMed:9147654}.
CC -!- SUBUNIT: Homodimer. Binds actin. Binds HTT (via N-terminus). This
CC interaction is restricted to the brain. Binds to IFT57. In normal
CC conditions, it poorly interacts with IFT57, HIP1 being strongly
CC associated with HTT. However, in mutant HTT proteins with a long poly-
CC Gln region, interaction between HTT and HIP1 is inhibited, promoting
CC the interaction between HIP1 and IFT57. Interacts with CLTB (via N-
CC terminus). Interacts (via coiled coil domain) with AR. Interacts with
CC AP2A1, AP2A2, CLTC and HIP1R. Interacts with GRIA1, GRIN2A AND GRIN2B.
CC {ECO:0000269|PubMed:11532990, ECO:0000269|PubMed:11788820,
CC ECO:0000269|PubMed:11889126, ECO:0000269|PubMed:15533940,
CC ECO:0000269|PubMed:16027218, ECO:0000269|PubMed:18790740,
CC ECO:0000269|PubMed:9140394, ECO:0000269|PubMed:9147654}.
CC -!- INTERACTION:
CC O00291; Q9Y614: ACTL7B; NbExp=3; IntAct=EBI-473886, EBI-25835070;
CC O00291; Q96MA6: AK8; NbExp=3; IntAct=EBI-473886, EBI-8466265;
CC O00291; Q9Y303-2: AMDHD2; NbExp=3; IntAct=EBI-473886, EBI-12323557;
CC O00291; Q9H0Y0: ATG10; NbExp=3; IntAct=EBI-473886, EBI-1048913;
CC O00291; Q14032: BAAT; NbExp=3; IntAct=EBI-473886, EBI-8994378;
CC O00291; Q9NSI6-4: BRWD1; NbExp=3; IntAct=EBI-473886, EBI-10693038;
CC O00291; Q8WZ55: BSND; NbExp=3; IntAct=EBI-473886, EBI-7996695;
CC O00291; Q13901: C1D; NbExp=3; IntAct=EBI-473886, EBI-3844053;
CC O00291; Q3SXR2: C3orf36; NbExp=3; IntAct=EBI-473886, EBI-18036948;
CC O00291; Q5JTY5: CBWD3; NbExp=3; IntAct=EBI-473886, EBI-723434;
CC O00291; O00257-3: CBX4; NbExp=3; IntAct=EBI-473886, EBI-4392727;
CC O00291; P42773: CDKN2C; NbExp=3; IntAct=EBI-473886, EBI-711290;
CC O00291; Q96M91: CFAP53; NbExp=3; IntAct=EBI-473886, EBI-742422;
CC O00291; P09496-2: CLTA; NbExp=3; IntAct=EBI-473886, EBI-4401010;
CC O00291; P02458-1: COL2A1; NbExp=3; IntAct=EBI-473886, EBI-12375799;
CC O00291; Q9UKG9-2: CROT; NbExp=3; IntAct=EBI-473886, EBI-25835363;
CC O00291; P35222: CTNNB1; NbExp=3; IntAct=EBI-473886, EBI-491549;
CC O00291; Q9NUQ9: CYRIB; NbExp=3; IntAct=EBI-473886, EBI-1055930;
CC O00291; Q15038: DAZAP2; NbExp=4; IntAct=EBI-473886, EBI-724310;
CC O00291; Q9BPU6: DPYSL5; NbExp=3; IntAct=EBI-473886, EBI-724653;
CC O00291; Q08426: EHHADH; NbExp=3; IntAct=EBI-473886, EBI-2339219;
CC O00291; Q96KS9: FAM167A; NbExp=3; IntAct=EBI-473886, EBI-10290462;
CC O00291; Q92567-2: FAM168A; NbExp=3; IntAct=EBI-473886, EBI-11978259;
CC O00291; Q8IZU1: FAM9A; NbExp=3; IntAct=EBI-473886, EBI-8468186;
CC O00291; Q06547-3: GABPB1; NbExp=3; IntAct=EBI-473886, EBI-9088619;
CC O00291; Q9UI32: GLS2; NbExp=3; IntAct=EBI-473886, EBI-3938654;
CC O00291; Q49A26-4: GLYR1; NbExp=3; IntAct=EBI-473886, EBI-12143817;
CC O00291; Q96EW2-2: HSPBAP1; NbExp=3; IntAct=EBI-473886, EBI-25835621;
CC O00291; P42858: HTT; NbExp=7; IntAct=EBI-473886, EBI-466029;
CC O00291; Q9UK76: JPT1; NbExp=3; IntAct=EBI-473886, EBI-720411;
CC O00291; Q8N5Z5: KCTD17; NbExp=3; IntAct=EBI-473886, EBI-743960;
CC O00291; Q8N4N3-2: KLHL36; NbExp=3; IntAct=EBI-473886, EBI-10973851;
CC O00291; Q9H2C1: LHX5; NbExp=3; IntAct=EBI-473886, EBI-25835523;
CC O00291; Q99732: LITAF; NbExp=6; IntAct=EBI-473886, EBI-725647;
CC O00291; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-473886, EBI-739832;
CC O00291; Q16609: LPAL2; NbExp=3; IntAct=EBI-473886, EBI-10238012;
CC O00291; Q8IYG6: LRRC56; NbExp=3; IntAct=EBI-473886, EBI-14752528;
CC O00291; P34949-2: MPI; NbExp=3; IntAct=EBI-473886, EBI-21823432;
CC O00291; Q15742-2: NAB2; NbExp=3; IntAct=EBI-473886, EBI-25834665;
CC O00291; Q8NDH3-5: NPEPL1; NbExp=3; IntAct=EBI-473886, EBI-12329915;
CC O00291; P36639-4: NUDT1; NbExp=3; IntAct=EBI-473886, EBI-25834643;
CC O00291; Q6N063-2: OGFOD2; NbExp=3; IntAct=EBI-473886, EBI-22006224;
CC O00291; Q8NCQ7-2: PROCA1; NbExp=3; IntAct=EBI-473886, EBI-25836043;
CC O00291; Q8WUD1-2: RAB2B; NbExp=3; IntAct=EBI-473886, EBI-25835884;
CC O00291; P54727: RAD23B; NbExp=3; IntAct=EBI-473886, EBI-954531;
CC O00291; Q09028: RBBP4; NbExp=3; IntAct=EBI-473886, EBI-620823;
CC O00291; Q04864: REL; NbExp=3; IntAct=EBI-473886, EBI-307352;
CC O00291; P47804-3: RGR; NbExp=3; IntAct=EBI-473886, EBI-25834767;
CC O00291; Q15382: RHEB; NbExp=3; IntAct=EBI-473886, EBI-1055287;
CC O00291; Q8N5U6: RNF10; NbExp=3; IntAct=EBI-473886, EBI-714023;
CC O00291; Q9NS64: RPRM; NbExp=3; IntAct=EBI-473886, EBI-1052363;
CC O00291; P22307-3: SCP2; NbExp=3; IntAct=EBI-473886, EBI-25834804;
CC O00291; Q15393: SF3B3; NbExp=3; IntAct=EBI-473886, EBI-346977;
CC O00291; Q9BZQ2: SHCBP1L; NbExp=3; IntAct=EBI-473886, EBI-10818532;
CC O00291; Q86US8: SMG6; NbExp=3; IntAct=EBI-473886, EBI-3232100;
CC O00291; Q13573: SNW1; NbExp=3; IntAct=EBI-473886, EBI-632715;
CC O00291; Q8N0X7: SPART; NbExp=3; IntAct=EBI-473886, EBI-2643803;
CC O00291; Q5W111-2: SPRYD7; NbExp=3; IntAct=EBI-473886, EBI-12408727;
CC O00291; Q96BD6: SPSB1; NbExp=3; IntAct=EBI-473886, EBI-2659201;
CC O00291; O60506-4: SYNCRIP; NbExp=3; IntAct=EBI-473886, EBI-11123832;
CC O00291; Q9BSW7: SYT17; NbExp=3; IntAct=EBI-473886, EBI-745392;
CC O00291; O15273: TCAP; NbExp=3; IntAct=EBI-473886, EBI-954089;
CC O00291; Q15560: TCEA2; NbExp=3; IntAct=EBI-473886, EBI-710310;
CC O00291; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-473886, EBI-11955057;
CC O00291; Q96A09: TENT5B; NbExp=3; IntAct=EBI-473886, EBI-752030;
CC O00291; P54274-2: TERF1; NbExp=3; IntAct=EBI-473886, EBI-711018;
CC O00291; O43548: TGM5; NbExp=3; IntAct=EBI-473886, EBI-12027348;
CC O00291; Q9P2T0: THEG; NbExp=3; IntAct=EBI-473886, EBI-751020;
CC O00291; Q9NQ88: TIGAR; NbExp=3; IntAct=EBI-473886, EBI-3920747;
CC O00291; P36406: TRIM23; NbExp=3; IntAct=EBI-473886, EBI-740098;
CC O00291; Q9P1Q0-4: VPS54; NbExp=3; IntAct=EBI-473886, EBI-25835297;
CC O00291; Q8NA23-2: WDR31; NbExp=3; IntAct=EBI-473886, EBI-25835937;
CC O00291; O43829: ZBTB14; NbExp=3; IntAct=EBI-473886, EBI-10176632;
CC O00291; Q8IWT0-2: ZBTB8OS; NbExp=3; IntAct=EBI-473886, EBI-12956041;
CC O00291; Q53FD0-2: ZC2HC1C; NbExp=3; IntAct=EBI-473886, EBI-14104088;
CC O00291; Q9EPV5: Apaf1; Xeno; NbExp=2; IntAct=EBI-473886, EBI-6978501;
CC O00291; Q9CR95: Necap1; Xeno; NbExp=3; IntAct=EBI-473886, EBI-7592476;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Endomembrane system.
CC Cytoplasmic vesicle, clathrin-coated vesicle membrane. Note=Shuttles
CC between cytoplasm and nucleus. Nuclear translocation can be induced by
CC AR.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=HIP1-1;
CC IsoId=O00291-1; Sequence=Displayed;
CC Name=HIP1-2;
CC IsoId=O00291-2; Sequence=Not described;
CC Name=3;
CC IsoId=O00291-3; Sequence=VSP_044736;
CC Name=4;
CC IsoId=O00291-4; Sequence=VSP_057400;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with the highest level in
CC brain. Expression is up-regulated in prostate and colon cancer.
CC {ECO:0000269|PubMed:12163454, ECO:0000269|PubMed:9140394,
CC ECO:0000269|PubMed:9147654}.
CC -!- DOMAIN: The pseudo DED region (pDED) mediates the interaction with
CC IFT57. {ECO:0000269|PubMed:11788820}.
CC -!- DOMAIN: Binds F-actin via the talin-like I/LWEQ domain.
CC {ECO:0000269|PubMed:11788820}.
CC -!- DISEASE: Note=A chromosomal aberration involving HIP1 is found in a
CC form of chronic myelomonocytic leukemia (CMML). Translocation
CC t(5;7)(q33;q11.2) with PDGFRB (PubMed:9616134). The chimeric HIP1-
CC PDGFRB transcript results from an in-frame fusion of the two genes
CC (PubMed:9616134). The reciprocal PDGFRB-HIP1 transcript is not
CC expressed (PubMed:9616134). {ECO:0000269|PubMed:9616134}.
CC -!- MISCELLANEOUS: The affinity of the huntingtin protein-HIP1 interaction
CC is inversely correlated to the length of the polyglutamine tract added
CC to the huntingtin protein in Huntington disease.
CC -!- SIMILARITY: Belongs to the SLA2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC51257.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HIP1ID138.html";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; KF437291; AHA56631.1; -; mRNA.
DR EMBL; AK304738; BAG65499.1; -; mRNA.
DR EMBL; AC004491; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC018720; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC211429; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF495977; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC110545; AAI10546.1; -; mRNA.
DR EMBL; AF365404; AAL87037.1; -; mRNA.
DR EMBL; AH006397; AAC33564.1; -; Genomic_DNA.
DR EMBL; U79734; AAC51257.1; ALT_INIT; mRNA.
DR EMBL; Y09420; CAA70574.1; -; mRNA.
DR CCDS; CCDS34669.1; -. [O00291-1]
DR CCDS; CCDS59060.1; -. [O00291-3]
DR RefSeq; NP_001230127.1; NM_001243198.2. [O00291-3]
DR RefSeq; NP_005329.3; NM_005338.6. [O00291-1]
DR RefSeq; XP_005250361.1; XM_005250304.2.
DR RefSeq; XP_011514418.1; XM_011516116.2. [O00291-1]
DR PDB; 2NO2; X-ray; 2.80 A; A=482-586.
DR PDB; 2QA7; X-ray; 2.80 A; A/B/C/D=370-481.
DR PDB; 3I00; X-ray; 2.30 A; A/B=361-480.
DR PDBsum; 2NO2; -.
DR PDBsum; 2QA7; -.
DR PDBsum; 3I00; -.
DR AlphaFoldDB; O00291; -.
DR SMR; O00291; -.
DR BioGRID; 109339; 88.
DR DIP; DIP-17041N; -.
DR ELM; O00291; -.
DR IntAct; O00291; 107.
DR MINT; O00291; -.
DR STRING; 9606.ENSP00000336747; -.
DR MoonDB; O00291; Curated.
DR TCDB; 1.N.7.1.1; the endomembrane fusion/trafficking (emfst) family.
DR GlyGen; O00291; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O00291; -.
DR MetOSite; O00291; -.
DR PhosphoSitePlus; O00291; -.
DR SwissPalm; O00291; -.
DR BioMuta; HIP1; -.
DR EPD; O00291; -.
DR jPOST; O00291; -.
DR MassIVE; O00291; -.
DR MaxQB; O00291; -.
DR PaxDb; O00291; -.
DR PeptideAtlas; O00291; -.
DR PRIDE; O00291; -.
DR ProteomicsDB; 17894; -.
DR ProteomicsDB; 47823; -. [O00291-1]
DR Antibodypedia; 2857; 284 antibodies from 35 providers.
DR DNASU; 3092; -.
DR Ensembl; ENST00000336926.11; ENSP00000336747.6; ENSG00000127946.17. [O00291-1]
DR Ensembl; ENST00000434438.6; ENSP00000410300.2; ENSG00000127946.17. [O00291-3]
DR Ensembl; ENST00000616821.4; ENSP00000484528.1; ENSG00000127946.17. [O00291-4]
DR GeneID; 3092; -.
DR KEGG; hsa:3092; -.
DR MANE-Select; ENST00000336926.11; ENSP00000336747.6; NM_005338.7; NP_005329.3.
DR UCSC; uc003uds.4; human. [O00291-1]
DR UCSC; uc064emn.1; human.
DR CTD; 3092; -.
DR DisGeNET; 3092; -.
DR GeneCards; HIP1; -.
DR HGNC; HGNC:4913; HIP1.
DR HPA; ENSG00000127946; Tissue enhanced (brain).
DR MIM; 601767; gene.
DR neXtProt; NX_O00291; -.
DR OpenTargets; ENSG00000127946; -.
DR PharmGKB; PA29289; -.
DR VEuPathDB; HostDB:ENSG00000127946; -.
DR eggNOG; KOG0980; Eukaryota.
DR GeneTree; ENSGT00940000153594; -.
DR HOGENOM; CLU_006034_0_0_1; -.
DR InParanoid; O00291; -.
DR OMA; DPTHISC; -.
DR PhylomeDB; O00291; -.
DR TreeFam; TF316860; -.
DR PathwayCommons; O00291; -.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-HSA-9700645; ALK mutants bind TKIs.
DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants.
DR SignaLink; O00291; -.
DR SIGNOR; O00291; -.
DR BioGRID-ORCS; 3092; 20 hits in 1079 CRISPR screens.
DR ChiTaRS; HIP1; human.
DR EvolutionaryTrace; O00291; -.
DR GenomeRNAi; 3092; -.
DR Pharos; O00291; Tbio.
DR PRO; PR:O00291; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; O00291; protein.
DR Bgee; ENSG00000127946; Expressed in corpus callosum and 188 other tissues.
DR ExpressionAtlas; O00291; baseline and differential.
DR Genevisible; O00291; HS.
DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:UniProtKB.
DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005856; C:cytoskeleton; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IEA:Ensembl.
DR GO; GO:0098890; C:extrinsic component of postsynaptic membrane; IBA:GO_Central.
DR GO; GO:0098888; C:extrinsic component of presynaptic membrane; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; TAS:ParkinsonsUK-UCL.
DR GO; GO:0098794; C:postsynapse; TAS:ParkinsonsUK-UCL.
DR GO; GO:0098793; C:presynapse; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051015; F:actin filament binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0035612; F:AP-2 adaptor complex binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0035615; F:clathrin adaptor activity; IBA:GO_Central.
DR GO; GO:0030276; F:clathrin binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032051; F:clathrin light chain binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; TAS:ParkinsonsUK-UCL.
DR GO; GO:0035254; F:glutamate receptor binding; TAS:ParkinsonsUK-UCL.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:ParkinsonsUK-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0007015; P:actin filament organization; IBA:GO_Central.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:MGI.
DR GO; GO:0006915; P:apoptotic process; IDA:MGI.
DR GO; GO:0097190; P:apoptotic signaling pathway; IDA:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0048268; P:clathrin coat assembly; IDA:UniProtKB.
DR GO; GO:0072583; P:clathrin-dependent endocytosis; IEA:InterPro.
DR GO; GO:0006897; P:endocytosis; IBA:GO_Central.
DR GO; GO:0099637; P:neurotransmitter receptor transport; TAS:ParkinsonsUK-UCL.
DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:2000588; P:positive regulation of platelet-derived growth factor receptor-beta signaling pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IC:ParkinsonsUK-UCL.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; IMP:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:ParkinsonsUK-UCL.
DR GO; GO:0042981; P:regulation of apoptotic process; IDA:MGI.
DR GO; GO:0030100; P:regulation of endocytosis; NAS:ParkinsonsUK-UCL.
DR Gene3D; 1.25.40.90; -; 1.
DR InterPro; IPR011417; ANTH_dom.
DR InterPro; IPR013809; ENTH.
DR InterPro; IPR008942; ENTH_VHS.
DR InterPro; IPR030554; HIP1.
DR InterPro; IPR032422; HIP1_clath-bd.
DR InterPro; IPR035964; I/LWEQ_dom_sf.
DR InterPro; IPR002558; ILWEQ_dom.
DR InterPro; IPR030224; Sla2_fam.
DR PANTHER; PTHR10407; PTHR10407; 1.
DR PANTHER; PTHR10407:SF14; PTHR10407:SF14; 1.
DR Pfam; PF07651; ANTH; 1.
DR Pfam; PF16515; HIP1_clath_bdg; 1.
DR Pfam; PF01608; I_LWEQ; 1.
DR SMART; SM00273; ENTH; 1.
DR SMART; SM00307; ILWEQ; 1.
DR SUPFAM; SSF109885; SSF109885; 1.
DR SUPFAM; SSF48464; SSF48464; 1.
DR PROSITE; PS50942; ENTH; 1.
DR PROSITE; PS50945; I_LWEQ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Activator; Alternative splicing; Apoptosis;
KW Chromosomal rearrangement; Coiled coil; Cytoplasm; Cytoplasmic vesicle;
KW Differentiation; Endocytosis; Membrane; Neurodegeneration; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..1037
FT /note="Huntingtin-interacting protein 1"
FT /id="PRO_0000083986"
FT DOMAIN 32..160
FT /note="ENTH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00243"
FT DOMAIN 771..1012
FT /note="I/LWEQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00292"
FT REGION 410..491
FT /note="pDED"
FT REGION 867..924
FT /note="Important for actin binding"
FT /evidence="ECO:0000250"
FT REGION 1017..1037
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 368..644
FT /evidence="ECO:0000255"
FT MOD_RES 338
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..40
FT /note="MDRMASSMKQVPNPLPKVLSRRGVGAGLEAAERESFERTQ -> MMFPNPEP
FT PPE (in isoform 4)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_057400"
FT VAR_SEQ 803..853
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044736"
FT VARIANT 263
FT /note="M -> K (in dbSNP:rs17149023)"
FT /id="VAR_051032"
FT MUTAGEN 56
FT /note="K->E: Abolishes 3-phosphoinositide-binding; when
FT associated with E-58."
FT /evidence="ECO:0000269|PubMed:16027218"
FT MUTAGEN 58
FT /note="K->E: Abolishes 3-phosphoinositide-binding; when
FT associated with E-56."
FT /evidence="ECO:0000269|PubMed:16027218"
FT MUTAGEN 432
FT /note="F->G: Abolishes HIP1-induced cell death."
FT /evidence="ECO:0000269|PubMed:11007801"
FT MUTAGEN 1005
FT /note="R->E: Reduces AR-induced nuclear translocation."
FT /evidence="ECO:0000269|PubMed:16027218"
FT CONFLICT 89
FT /note="A -> P (in Ref. 5; AAC33564)"
FT /evidence="ECO:0000305"
FT CONFLICT 245..251
FT /note="KLHSCLP -> EFAAAST (in Ref. 8; CAA70574)"
FT /evidence="ECO:0000305"
FT CONFLICT 357
FT /note="S -> R (in Ref. 2; BAG65499)"
FT /evidence="ECO:0000305"
FT CONFLICT 639..644
FT /note="LNQLEE -> STRPRI (in Ref. 8; CAA70574)"
FT /evidence="ECO:0000305"
FT CONFLICT 688
FT /note="L -> F (in Ref. 5; AAL87037)"
FT /evidence="ECO:0000305"
FT HELIX 373..441
FT /evidence="ECO:0007829|PDB:3I00"
FT TURN 459..461
FT /evidence="ECO:0007829|PDB:2QA7"
FT HELIX 462..465
FT /evidence="ECO:0007829|PDB:2QA7"
FT HELIX 482..580
FT /evidence="ECO:0007829|PDB:2NO2"
SQ SEQUENCE 1037 AA; 116221 MW; F8C0369DBF0A836F CRC64;
MDRMASSMKQ VPNPLPKVLS RRGVGAGLEA AERESFERTQ TVSINKAINT QEVAVKEKHA
RTCILGTHHE KGAQTFWSVV NRLPLSSNAV LCWKFCHVFH KLLRDGHPNV LKDSLRYRNE
LSDMSRMWGH LSEGYGQLCS IYLKLLRTKM EYHTKNPRFP GNLQMSDRQL DEAGESDVNN
FFQLTVEMFD YLECELNLFQ TVFNSLDMSR SVSVTAAGQC RLAPLIQVIL DCSHLYDYTV
KLLFKLHSCL PADTLQGHRD RFMEQFTKLK DLFYRSSNLQ YFKRLIQIPQ LPENPPNFLR
ASALSEHISP VVVIPAEASS PDSEPVLEKD DLMDMDASQQ NLFDNKFDDI FGSSFSSDPF
NFNSQNGVNK DEKDHLIERL YREISGLKAQ LENMKTESQR VVLQLKGHVS ELEADLAEQQ
HLRQQAADDC EFLRAELDEL RRQREDTEKA QRSLSEIERK AQANEQRYSK LKEKYSELVQ
NHADLLRKNA EVTKQVSMAR QAQVDLEREK KELEDSLERI SDQGQRKTQE QLEVLESLKQ
ELATSQRELQ VLQGSLETSA QSEANWAAEF AELEKERDSL VSGAAHREEE LSALRKELQD
TQLKLASTEE SMCQLAKDQR KMLLVGSRKA AEQVIQDALN QLEEPPLISC AGSADHLLST
VTSISSCIEQ LEKSWSQYLA CPEDISGLLH SITLLAHLTS DAIAHGATTC LRAPPEPADS
LTEACKQYGR ETLAYLASLE EEGSLENADS TAMRNCLSKI KAIGEELLPR GLDIKQEELG
DLVDKEMAAT SAAIETATAR IEEMLSKSRA GDTGVKLEVN ERILGCCTSL MQAIQVLIVA
SKDLQREIVE SGRGTASPKE FYAKNSRWTE GLISASKAVG WGATVMVDAA DLVVQGRGKF
EELMVCSHEI AASTAQLVAA SKVKADKDSP NLAQLQQASR GVNQATAGVV ASTISGKSQI
EETDNMDFSS MTLTQIKRQE MDSQVRVLEL ENELQKERQK LGELRKKHYE LAGVAEGWEE
GTEASPPTLQ EVVTEKE
