DAB2P_MOUSE
ID DAB2P_MOUSE Reviewed; 1189 AA.
AC Q3UHC7; A2AUW9; A2AUX2; A5X2X2; B7ZD28; Q3TPD5; Q3UH44; Q6JTV1; Q6Y636;
AC Q80T97;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Disabled homolog 2-interacting protein;
DE Short=DAB2-interacting protein;
DE AltName: Full=ASK-interacting protein 1;
DE AltName: Full=DOC-2/DAB-2 interactive protein;
GN Name=Dab2ip; Synonyms=Kiaa1743;
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 [LARGE SCALE MRNA] (ISOFORM 2), ALTERNATIVE SPLICING,
RP AND TISSUE SPECIFICITY.
RC STRAIN=129S6/SvEvTac; TISSUE=Spleen;
RX PubMed=16629596; DOI=10.1089/dna.2006.25.232;
RA Chen H., Karam J.A., Schultz R., Zhang Z., Duncan C., Hsieh J.-T.;
RT "Cloning of mouse Dab2ip gene, a novel member of the RasGTPase-activating
RT protein family and characterization of its regulatory region in prostate.";
RL DNA Cell Biol. 25:232-245(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, SUBCELLULAR LOCATION,
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=23326475; DOI=10.1371/journal.pone.0053635;
RA Qiao S., Kim S.H., Heck D., Goldowitz D., LeDoux M.S., Homayouni R.;
RT "Dab2IP GTPase activating protein regulates dendrite development and
RT synapse number in cerebellum.";
RL PLoS ONE 8:E53635-E53635(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Brain, and Heart;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 328-1189 (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 586-1189 (ISOFORM 4), INTERACTION
RP WITH DAB2, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J;
RX PubMed=12877983; DOI=10.1016/s0169-328x(03)00176-1;
RA Homayouni R., Magdaleno S., Keshvara L., Rice D.S., Curran T.;
RT "Interaction of Disabled-1 and the GTPase activating protein Dab2IP in
RT mouse brain.";
RL Brain Res. Mol. Brain Res. 115:121-129(2003).
RN [8]
RP FUNCTION, AND INTERACTION WITH ERN1 AND TRAF2.
RX PubMed=18281285; DOI=10.1074/jbc.m710557200;
RA Luo D., He Y., Zhang H., Yu L., Chen H., Xu Z., Tang S., Urano F., Min W.;
RT "AIP1 is critical in transducing IRE1-mediated endoplasmic reticulum stress
RT response.";
RL J. Biol. Chem. 283:11905-11912(2008).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=19033661; DOI=10.1172/jci36168;
RA Zhang H., He Y., Dai S., Xu Z., Luo Y., Wan T., Luo D., Jones D., Tang S.,
RA Chen H., Sessa W.C., Min W.;
RT "AIP1 functions as an endogenous inhibitor of VEGFR2-mediated signaling and
RT inflammatory angiogenesis in mice.";
RL J. Clin. Invest. 118:3904-3916(2008).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19903888; DOI=10.1073/pnas.0908458106;
RA Xie D., Gore C., Zhou J., Pong R.C., Zhang H., Yu L., Vessella R.L.,
RA Min W., Hsieh J.T.;
RT "DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell survival and
RT apoptosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:19878-19883(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-747, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, and
RC Testis;
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 [12]
RP FUNCTION.
RX PubMed=19948740; DOI=10.1074/jbc.m109.069385;
RA Wan T., Liu T., Zhang H., Tang S., Min W.;
RT "AIP1 functions as Arf6-GAP to negatively regulate TLR4 signaling.";
RL J. Biol. Chem. 285:3750-3757(2010).
RN [13]
RP FUNCTION IN PROSTATE CANCER.
RX PubMed=20154697; DOI=10.1038/nm.2100;
RA Min J., Zaslavsky A., Fedele G., McLaughlin S.K., Reczek E.E., De Raedt T.,
RA Guney I., Strochlic D.E., Macconaill L.E., Beroukhim R., Bronson R.T.,
RA Ryeom S., Hahn W.C., Loda M., Cichowski K.;
RT "An oncogene-tumor suppressor cascade drives metastatic prostate cancer by
RT coordinately activating Ras and nuclear factor-kappaB.";
RL Nat. Med. 16:286-294(2010).
RN [14]
RP FUNCTION IN PROSTATE CANCER.
RX PubMed=20080667; DOI=10.1073/pnas.0908133107;
RA Xie D., Gore C., Liu J., Pong R.C., Mason R., Hao G., Long M., Kabbani W.,
RA Yu L., Zhang H., Chen H., Sun X., Boothman D.A., Min W., Hsieh J.T.;
RT "Role of DAB2IP in modulating epithelial-to-mesenchymal transition and
RT prostate cancer metastasis.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:2485-2490(2010).
RN [15]
RP FUNCTION.
RX PubMed=21700930; DOI=10.1161/circresaha.111.248245;
RA Yu L., Qin L., Zhang H., He Y., Chen H., Pober J.S., Tellides G., Min W.;
RT "AIP1 prevents graft arteriosclerosis by inhibiting interferon-gamma-
RT dependent smooth muscle cell proliferation and intimal expansion.";
RL Circ. Res. 109:418-427(2011).
RN [16]
RP FUNCTION IN MEDULLOBLASTOMA DEVELOPMENT, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=22696229; DOI=10.1158/1078-0432.ccr-12-0399;
RA Smits M., van Rijn S., Hulleman E., Biesmans D., van Vuurden D.G., Kool M.,
RA Haberler C., Aronica E., Vandertop W.P., Noske D.P., Wurdinger T.;
RT "EZH2-regulated DAB2IP is a medulloblastoma tumor suppressor and a positive
RT marker for survival.";
RL Clin. Cancer Res. 18:4048-4058(2012).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=23056358; DOI=10.1371/journal.pone.0046592;
RA Lee G.H., Kim S.H., Homayouni R., D'Arcangelo G.;
RT "Dab2ip regulates neuronal migration and neurite outgrowth in the
RT developing neocortex.";
RL PLoS ONE 7:E46592-E46592(2012).
CC -!- FUNCTION: Functions as a scaffold protein implicated in the regulation
CC of a large spectrum of both general and specialized signaling pathways.
CC Involved in several processes such as innate immune response,
CC inflammation and cell growth inhibition, apoptosis, cell survival,
CC angiogenesis, cell migration and maturation. Also plays a role in cell
CC cycle checkpoint control; reduces G1 phase cyclin levels resulting in
CC G0/G1 cell cycle arrest. Mediates signal transduction by receptor-
CC mediated inflammatory signals, such as the tumor necrosis factor (TNF),
CC interferon (IFN) or lipopolysaccharide (LPS). Modulates the balance
CC between phosphatidylinositol 3-kinase (PI3K)-AKT-mediated cell survival
CC and apoptosis stimulated kinase (MAP3K5)-JNK signaling pathways;
CC sequesters both AKT1 and MAP3K5 and counterbalances the activity of
CC each kinase by modulating their phosphorylation status in response to
CC pro-inflammatory stimuli. Acts as a regulator of the endoplasmic
CC reticulum (ER) unfolded protein response (UPR) pathway; specifically
CC involved in transduction of the ER stress-response to the JNK cascade
CC through ERN1. Mediates TNF-alpha-induced apoptosis activation by
CC facilitating dissociation of inhibitor 14-3-3 from MAP3K5; recruits the
CC PP2A phosphatase complex which dephosphorylates MAP3K5 on 'Ser-966',
CC leading to the dissociation of 13-3-3 proteins and activation of the
CC MAP3K5-JNK signaling pathway in endothelial cells. Mediates also
CC TNF/TRAF2-induced MAP3K5-JNK activation, while it inhibits CHUK-NF-
CC kappa-B signaling. Acts a negative regulator in the IFN-gamma-mediated
CC JAK-STAT signaling cascade by inhibiting smooth muscle cell (VSMCs)
CC proliferation and intimal expansion, and thus, prevents graft
CC arteriosclerosis (GA). Acts as a GTPase-activating protein (GAP) for
CC the ADP ribosylation factor 6 (ARF6) and Ras. Promotes hydrolysis of
CC the ARF6-bound GTP and thus, negatively regulates phosphatidylinositol
CC 4,5-bisphosphate (PIP2)-dependent TLR4-TIRAP-MyD88 and NF-kappa-B
CC signaling pathways in endothelial cells in response to
CC lipopolysaccharides (LPS). Binds specifically to phosphatidylinositol
CC 4-phosphate (PtdIns4P) and phosphatidylinositol 3-phosphate (PtdIns3P).
CC In response to vascular endothelial growth factor (VEGFA), acts as a
CC negative regulator of the VEGFR2-PI3K-mediated angiogenic signaling
CC pathway by inhibiting endothelial cell migration and tube formation. In
CC the developing brain, promotes both the transition from the multipolar
CC to the bipolar stage and the radial migration of cortical neurons from
CC the ventricular zone toward the superficial layer of the neocortex in a
CC glial-dependent locomotion process. Probable downstream effector of the
CC Reelin signaling pathway; promotes Purkinje cell (PC) dendrites
CC development and formation of cerebellar synapses. Functions also as a
CC tumor suppressor protein in prostate cancer progression; prevents cell
CC proliferation and epithelial-to-mesenchymal transition (EMT) through
CC activation of the glycogen synthase kinase-3 beta (GSK3B)-induced beta-
CC catenin and inhibition of PI3K-AKT and Ras-MAPK survival downstream
CC signaling cascades, respectively. {ECO:0000269|PubMed:18281285,
CC ECO:0000269|PubMed:19033661, ECO:0000269|PubMed:19903888,
CC ECO:0000269|PubMed:19948740, ECO:0000269|PubMed:20080667,
CC ECO:0000269|PubMed:20154697, ECO:0000269|PubMed:21700930,
CC ECO:0000269|PubMed:22696229, ECO:0000269|PubMed:23056358,
CC ECO:0000269|PubMed:23326475}.
CC -!- SUBUNIT: On plasma membrane, exists in an inactive form complexed with
CC TNFR1; in response to TNF-alpha, dissociates from TNFR1 complex,
CC translocates to cytoplasm and forms part of an intracellular signaling
CC complex comprising TRADD, RIPK1, TRAF2 and MAP3K5. Interacts with DAB1.
CC Part of a cytoplasmic complex made of HIPK1, DAB2IP and MAP3K5 in
CC response to TNF-alpha; this complex formation promotes MAP3K5-JNK
CC activation and subsequent apoptosis. Interacts (via N-terminal domain)
CC with JAK2; the interaction occurs in a IFNG/IFN-gamma-dependent manner
CC and inhibits JAK2 autophosphorylation activity. Interacts (via C2
CC domain) with GSK3B; the interaction stimulates GSK3B kinase activation.
CC Interacts (via C2 domain) with PPP2CA. Interacts (via proline-rich
CC motif) with a regulatory p85 subunit (via SH3 domain) of the PI3K
CC complex; the interaction inhibits the PI3K-AKT complex activity in a
CC TNF-alpha-dependent manner in prostate cancer (PCa) cells. Interacts
CC with AKT1; the interaction is increased in a TNF-alpha-induced manner.
CC Interacts (via C2 domain and active form preferentially) with
CC KDR/VEGFR2 (tyrosine-phosphorylated active form preferentially); the
CC interaction occurs at the late phase of VEGFA response and inhibits
CC KDR/VEGFR2 activity. Interacts (via N-terminus C2 domain) with MAP3K5
CC ('Ser-966' dephosphorylated form preferentially); the interaction
CC occurs in a TNF-alpha-induced manner. Interacts (via Ras-GAP domain)
CC with the catalytic subunit of protein phosphatase PP2A; the interaction
CC occurs in resting endothelial cells, is further enhanced by TNF-alpha
CC stimulation and is required to bridge PP2A to MAP3K5. Interacts (via C-
CC terminus PER domain) with TRAF2 (via zinc fingers); the interaction
CC occurs in a TNF-alpha-dependent manner. Interacts with 14-3-3 proteins;
CC the interaction occurs in a TNF-alpha-dependent manner. Interacts (via
CC Ras-GAP domain) with RIPK1 (via kinase domain); the interaction occurs
CC in a TNF-alpha-dependent manner (By similarity). Interacts (via PH
CC domain) with ERN1. Interacts with TRAF2. Interacts (via NPXY motif)
CC with DAB2 (via PID domain). {ECO:0000250, ECO:0000269|PubMed:12877983,
CC ECO:0000269|PubMed:18281285}.
CC -!- INTERACTION:
CC Q3UHC7; P97318: Dab1; NbExp=3; IntAct=EBI-6306507, EBI-81680;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane {ECO:0000305};
CC Peripheral membrane protein {ECO:0000305}. Cell projection, dendrite.
CC Note=Colocalizes with TIRAP at the plasma membrane. Colocalizes with
CC ARF6 at the plasma membrane and endocytic vesicles. Translocates from
CC the plasma membrane to the cytoplasm in response to TNF-alpha.
CC Phosphatidylinositol 4-phosphate (PtdIns4P) binding is essential for
CC plasma membrane localization (By similarity). Localized in soma and
CC dendrites of Purkinje cells as well as in scattered cell bodies in the
CC molecular layer of the cerebellum. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q3UHC7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UHC7-2; Sequence=VSP_020956;
CC Name=3;
CC IsoId=Q3UHC7-3; Sequence=VSP_020957;
CC Name=4; Synonyms=Dab2IP-L;
CC IsoId=Q3UHC7-4; Sequence=VSP_046519, VSP_046520;
CC -!- TISSUE SPECIFICITY: Expressed in vascular endothelium of muscle and
CC aorta, in smooth muscle cells of aorta and epithelial cells of lung.
CC Expressed throughout the brain, including olfactory bulb, hypothalamus,
CC cerebellum and cerebral cortex. Expressed in the soma and processes of
CC neurons in a variety of brain structures, including the developing
CC cerebral cortex, CA1 pyramidal neurons and Purkinje cells. Poorly
CC expressed in medulloblastoma cells compared to cerebellar precursor
CC proliferating progenitor cells (at protein level). Highly expressed in
CC the brain, salivary gland, and testis; moderate expression in kidney
CC and heart. Low expression in the lung, seminal vesicle, ventral
CC prostate, epididymis, liver, and bladder. Very low expression in the
CC coagulation gland and skeleton muscles. Lowest expression seen in
CC spleen. {ECO:0000269|PubMed:12877983, ECO:0000269|PubMed:16629596,
CC ECO:0000269|PubMed:19033661, ECO:0000269|PubMed:22696229,
CC ECO:0000269|PubMed:23326475}.
CC -!- DEVELOPMENTAL STAGE: Expressed in cortical plate neurons at 16 dpc.
CC Expressed in the neocortex, including the cortical plate (CP) at 16.5
CC dpc, onward (at protein level). Expressed in brain at 13.5 dpc, onward.
CC Expressed during embryogenesis in the vasculature.
CC {ECO:0000269|PubMed:12877983, ECO:0000269|PubMed:19033661,
CC ECO:0000269|PubMed:23056358}.
CC -!- INDUCTION: Down-regulated in prostate cancer and medulloblastoma.
CC {ECO:0000269|PubMed:22696229}.
CC -!- DOMAIN: Exists in a closed inactive form by an intramolecular
CC interaction between the N- and the C-terminal domains. The proline-rich
CC motif is critical both for PI3K-AKT activity inhibition and MAP3K5
CC activation. The PH and C2 domains are necessary for the binding to
CC phosphatidylinositol phosphate. The Ras-GAP domain is necessary for its
CC tumor-suppressive function (By similarity). The C2 and GAP domains
CC constitutively bind to MAP3K5 and facilitate the release of 14-3-3
CC proteins from MAP3K5. The PH and Ras-GAP domains, but not the NPXY
CC motif, are crucial for its cell membrane localization and neuronal
CC migration function. The PH domain is necessary but not sufficient to
CC activate the JNK signaling pathway through ERN1. {ECO:0000250}.
CC -!- PTM: In response to TNF-alpha-induction, phosphorylated at Ser-728;
CC phosphorylation leads to a conformational change, and thus, increases
CC its association with 14-3-3 proteins, MAP3K5, RIPK1 and TRAF2 in
CC endothelial cells; also stimulates regulatory p85 subunit sequestring
CC and PI3K-p85 complex activity inhibition. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile but show a number of
CC cerebellar abnormalities such as a delay in the Purkinje cell (PC)
CC dendrites development and a disruption of late-born cortical neurons
CC migration. Develope a prostate hyperplasia in epithelial compartment at
CC 6 months of age. Show normal vasculature development but enhanced
CC inflammatory angiogenesis. {ECO:0000269|PubMed:19033661,
CC ECO:0000269|PubMed:19903888, ECO:0000269|PubMed:23056358,
CC ECO:0000269|PubMed:23326475}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ77379.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAQ77380.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAQ77381.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY305656; AAQ77379.1; ALT_INIT; mRNA.
DR EMBL; AY305657; AAQ77380.1; ALT_INIT; mRNA.
DR EMBL; AY305658; AAQ77381.1; ALT_INIT; mRNA.
DR EMBL; DQ473307; ABF13290.1; -; mRNA.
DR EMBL; AK147464; BAE27930.1; -; mRNA.
DR EMBL; AK147593; BAE28013.1; -; mRNA.
DR EMBL; AK164475; BAE37801.1; -; mRNA.
DR EMBL; AL929241; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC118530; AAI18531.1; -; mRNA.
DR EMBL; AK122548; BAC65830.1; -; mRNA.
DR EMBL; AY178784; AAP31233.1; -; mRNA.
DR CCDS; CCDS50577.1; -. [Q3UHC7-4]
DR CCDS; CCDS50578.1; -. [Q3UHC7-1]
DR CCDS; CCDS71045.1; -. [Q3UHC7-2]
DR RefSeq; NP_001001602.2; NM_001001602.2.
DR RefSeq; NP_001107596.1; NM_001114124.2. [Q3UHC7-1]
DR RefSeq; NP_001107597.1; NM_001114125.1. [Q3UHC7-4]
DR RefSeq; NP_001277568.1; NM_001290639.1. [Q3UHC7-2]
DR RefSeq; NP_001277569.1; NM_001290640.1.
DR RefSeq; NP_001277570.1; NM_001290641.1. [Q3UHC7-2]
DR RefSeq; XP_006498370.2; XM_006498307.2. [Q3UHC7-2]
DR AlphaFoldDB; Q3UHC7; -.
DR SMR; Q3UHC7; -.
DR BioGRID; 213562; 28.
DR CORUM; Q3UHC7; -.
DR IntAct; Q3UHC7; 5.
DR MINT; Q3UHC7; -.
DR STRING; 10090.ENSMUSP00000088532; -.
DR iPTMnet; Q3UHC7; -.
DR PhosphoSitePlus; Q3UHC7; -.
DR EPD; Q3UHC7; -.
DR jPOST; Q3UHC7; -.
DR MaxQB; Q3UHC7; -.
DR PaxDb; Q3UHC7; -.
DR PeptideAtlas; Q3UHC7; -.
DR PRIDE; Q3UHC7; -.
DR ProteomicsDB; 279149; -. [Q3UHC7-1]
DR ProteomicsDB; 279150; -. [Q3UHC7-2]
DR ProteomicsDB; 279151; -. [Q3UHC7-3]
DR ProteomicsDB; 279152; -. [Q3UHC7-4]
DR Antibodypedia; 48362; 112 antibodies from 21 providers.
DR DNASU; 69601; -.
DR Ensembl; ENSMUST00000091010; ENSMUSP00000088532; ENSMUSG00000026883. [Q3UHC7-1]
DR Ensembl; ENSMUST00000112983; ENSMUSP00000108607; ENSMUSG00000026883. [Q3UHC7-2]
DR Ensembl; ENSMUST00000112986; ENSMUSP00000108610; ENSMUSG00000026883. [Q3UHC7-4]
DR Ensembl; ENSMUST00000112992; ENSMUSP00000108616; ENSMUSG00000026883. [Q3UHC7-3]
DR GeneID; 69601; -.
DR KEGG; mmu:69601; -.
DR UCSC; uc008jkr.2; mouse. [Q3UHC7-1]
DR UCSC; uc008jkv.2; mouse. [Q3UHC7-3]
DR UCSC; uc008jkx.2; mouse. [Q3UHC7-4]
DR CTD; 153090; -.
DR MGI; MGI:1916851; Dab2ip.
DR VEuPathDB; HostDB:ENSMUSG00000026883; -.
DR eggNOG; KOG3508; Eukaryota.
DR GeneTree; ENSGT00940000155853; -.
DR HOGENOM; CLU_001727_1_0_1; -.
DR InParanoid; Q3UHC7; -.
DR PhylomeDB; Q3UHC7; -.
DR TreeFam; TF105303; -.
DR Reactome; R-MMU-5658442; Regulation of RAS by GAPs.
DR BioGRID-ORCS; 69601; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Dab2ip; mouse.
DR PRO; PR:Q3UHC7; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q3UHC7; protein.
DR Bgee; ENSMUSG00000026883; Expressed in cortical plate and 261 other tissues.
DR ExpressionAtlas; Q3UHC7; baseline and differential.
DR Genevisible; Q3UHC7; MM.
DR GO; GO:1990597; C:AIP1-IRE1 complex; IPI:ParkinsonsUK-UCL.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0044300; C:cerebellar mossy fiber; IDA:UniProtKB.
DR GO; GO:0044301; C:climbing fiber; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0030139; C:endocytic vesicle; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB.
DR GO; GO:0032809; C:neuronal cell body membrane; IDA:UniProtKB.
DR GO; GO:1990032; C:parallel fiber; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0071889; F:14-3-3 protein binding; ISO:MGI.
DR GO; GO:0005123; F:death receptor binding; ISO:MGI.
DR GO; GO:0005096; F:GTPase activator activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; ISO:MGI.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; ISO:MGI.
DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; ISS:UniProtKB.
DR GO; GO:0036312; F:phosphatidylinositol 3-kinase regulatory subunit binding; ISS:UniProtKB.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; ISS:UniProtKB.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:MGI.
DR GO; GO:0051721; F:protein phosphatase 2A binding; ISO:MGI.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISS:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; ISS:UniProtKB.
DR GO; GO:0035591; F:signaling adaptor activity; ISO:MGI.
DR GO; GO:0043184; F:vascular endothelial growth factor receptor 2 binding; ISO:MGI.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0021814; P:cell motility involved in cerebral cortex radial glia guided migration; IMP:UniProtKB.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISO:MGI.
DR GO; GO:0071347; P:cellular response to interleukin-1; IDA:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IMP:BHF-UCL.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; ISO:MGI.
DR GO; GO:0007252; P:I-kappaB phosphorylation; IMP:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IMP:BHF-UCL.
DR GO; GO:0021819; P:layer formation in cerebral cortex; IMP:UniProtKB.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:BHF-UCL.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0010596; P:negative regulation of endothelial cell migration; IMP:UniProtKB.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; ISO:MGI.
DR GO; GO:0010633; P:negative regulation of epithelial cell migration; ISS:UniProtKB.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IMP:BHF-UCL.
DR GO; GO:0070317; P:negative regulation of G0 to G1 transition; ISS:UniProtKB.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IMP:UniProtKB.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0043553; P:negative regulation of phosphatidylinositol 3-kinase activity; ISS:UniProtKB.
DR GO; GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; ISS:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IMP:BHF-UCL.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; ISO:MGI.
DR GO; GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0030948; P:negative regulation of vascular endothelial growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:1900747; P:negative regulation of vascular endothelial growth factor signaling pathway; IDA:UniProtKB.
DR GO; GO:0048812; P:neuron projection morphogenesis; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:BHF-UCL.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:1900006; P:positive regulation of dendrite development; IMP:UniProtKB.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISS:UniProtKB.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IMP:BHF-UCL.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:2001224; P:positive regulation of neuron migration; IMP:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:UniProtKB.
DR GO; GO:1901800; P:positive regulation of proteasomal protein catabolic process; ISS:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IMP:UniProtKB.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IMP:BHF-UCL.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:MGI.
DR GO; GO:0090129; P:positive regulation of synapse maturation; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0030163; P:protein catabolic process; ISS:UniProtKB.
DR GO; GO:0038026; P:reelin-mediated signaling pathway; IEA:InterPro.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; IMP:UniProtKB.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:1900744; P:regulation of p38MAPK cascade; IMP:UniProtKB.
DR GO; GO:0043254; P:regulation of protein-containing complex assembly; IMP:UniProtKB.
DR GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
DR GO; GO:0035148; P:tube formation; IMP:UniProtKB.
DR GO; GO:0036324; P:vascular endothelial growth factor receptor-2 signaling pathway; IMP:UniProtKB.
DR Gene3D; 1.10.506.10; -; 2.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR030403; DAB2IP.
DR InterPro; IPR021887; DAB2P_C.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR039360; Ras_GTPase.
DR InterPro; IPR023152; RasGAP_CS.
DR InterPro; IPR001936; RasGAP_dom.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR PANTHER; PTHR10194; PTHR10194; 1.
DR PANTHER; PTHR10194:SF26; PTHR10194:SF26; 1.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF12004; DUF3498; 1.
DR Pfam; PF00616; RasGAP; 2.
DR SMART; SM00239; C2; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00323; RasGAP; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00509; RAS_GTPASE_ACTIV_1; 1.
DR PROSITE; PS50018; RAS_GTPASE_ACTIV_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Angiogenesis; Apoptosis; Cell cycle; Cell membrane;
KW Cell projection; Coiled coil; Cytoplasm; Developmental protein;
KW Growth regulation; GTPase activation; Immunity; Inflammatory response;
KW Innate immunity; Membrane; Phosphoprotein; Reference proteome;
KW Stress response; Tumor suppressor; Unfolded protein response.
FT CHAIN 1..1189
FT /note="Disabled homolog 2-interacting protein"
FT /id="PRO_0000252408"
FT DOMAIN 101..202
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 193..311
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 371..563
FT /note="Ras-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00167"
FT REGION 1..75
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 646..943
FT /note="Necessary for interaction with AKT1"
FT /evidence="ECO:0000250"
FT REGION 653..679
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 715..738
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 804..823
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 843..865
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 895..998
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1015..1034
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1163..1189
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1025..1159
FT /evidence="ECO:0000255"
FT COMPBIAS 50..75
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 849..865
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 897..915
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 916..935
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 937..956
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 964..978
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1019..1034
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 728
FT /note="Phosphoserine; by MAP3K5 and RIPK1"
FT /evidence="ECO:0000250|UniProtKB:Q5VWQ8"
FT MOD_RES 747
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 978
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5VWQ8"
FT MOD_RES 995
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5VWQ8"
FT VAR_SEQ 1..124
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072, ECO:0000303|PubMed:16629596"
FT /id="VSP_020956"
FT VAR_SEQ 1..42
FT /note="MSAGGNARKSTGRPSYYYRLLRRPRLQRQRSRSRSRTRPARE -> MEPDSL
FT LDPGDSYE (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:12877983,
FT ECO:0000303|PubMed:23326475"
FT /id="VSP_046519"
FT VAR_SEQ 990..1040
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12693553"
FT /id="VSP_020957"
FT VAR_SEQ 1157..1189
FT /note="ERYSMQARNGVSPTNPTKLQITENGEFRNSSNC -> ESMH (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:12877983,
FT ECO:0000303|PubMed:23326475"
FT /id="VSP_046520"
FT CONFLICT 282
FT /note="K -> E (in Ref. 2; ABF13290)"
FT /evidence="ECO:0000305"
FT CONFLICT 517
FT /note="I -> V (in Ref. 2; ABF13290)"
FT /evidence="ECO:0000305"
FT CONFLICT 880
FT /note="E -> G (in Ref. 2; ABF13290)"
FT /evidence="ECO:0000305"
FT CONFLICT 1058
FT /note="E -> K (in Ref. 2; ABF13290)"
FT /evidence="ECO:0000305"
FT CONFLICT 1108
FT /note="S -> P (in Ref. 2; ABF13290)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1189 AA; 131726 MW; E3AF3FDA71FF96C3 CRC64;
MSAGGNARKS TGRPSYYYRL LRRPRLQRQR SRSRSRTRPA RESPQERPGS RRSLPGSMSE
KNPSMEPSAS TPFRVTGFLS RRLKGSIKRT KSQPKLDRNH SFRHILPGFR SAAAAAADNE
RSHLMPRLKE SRSHESLLSP SSAVEALDLS MEEEVIIKPV HSSILGQDYC FEVTTSSGSK
CFSCRSAAER DKWMENLRRA VHPNKDNSRR VEHILKLWVI EAKDLPAKKK YLCELCLDDV
LYARTTSKLK TDNVFWGEHF EFHNLPPLRT VTVHLYRETD KKKKKERNSY LGLVSLPAAS
VAGRQFVEKW YPVVTPNPKG GKGPGPMIRI KARYQTVSIL PMEMYKEFAE HITNHYLGLC
AALEPILSAK TKEEMASALV HILQSTGKVK DFLTDLMMSE VDRCGDNEHL IFRENTLATK
AIEEYLKLVG QKYLQDALGE FIKALYESDE NCEVDPSKCS SADLPEHQGN LKMCCELAFC
KIINSYCVFP RELKEVFASW RQECSSRGRP DISERLISAS LFLRFLCPAI MSPSLFNLLQ
EYPDDRTART LTLIAKVTQN LANFAKFGSK EEYMSFMNQF LEHEWTNMQR FLLEISNPET
LSNTAGFEGY IDLGRELSSL HSLLWEAVSQ LDQSVVSKLG PLPRILRDVH TALSTPGSGQ
LPGTNDLAST PGSGSSSVSA GLQKMVIEND LSGLIDFTRL PSPTPENKDL FFVTRSSGVQ
PSPARSSSYS EANEPDLQMA NGSKSLSMVD LQDARTLDGE AGSPVGPDAL PADGQVPATQ
LLAGWPARAA PVSLAGLATV RRAVPTPTTP GTSEGAPGRP QLLAPLSFQN PVYQMAAGLP
LSPRGLGDSG SEGHSSLSSH SNSEELAAAA KLGSFSTAAE ELARRPGELA RRQMSLTEKG
GQPTVPRQNS AGPQRRIDQP PPPPPPPPPA PRGRTPPTLL STLQYPRPSS GTLASASPDW
AGPGTRLRQQ SSSSKGDSPE LKPRAMHKQG PSPVSPNALD RTAAWLLTMN AQLLEDEGLG
PDPPHRDRLR SKEELSQAEK DLAVLQDKLR ISTKKLEEYE TLFKCQEETT QKLVLEYQAR
LEEGEERLRR QQEDKDIQMK GIISRLMSVE EELKKDHAEM QAAVDSKQKI IDAQEKRIAS
LDAANARLMS ALTQLKERYS MQARNGVSPT NPTKLQITEN GEFRNSSNC
