ASB2_HUMAN
ID ASB2_HUMAN Reviewed; 635 AA.
AC Q96Q27; B2RDP9; B4E166; Q9NSU5; Q9Y567;
DT 10-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Ankyrin repeat and SOCS box protein 2;
DE Short=ASB-2;
GN Name=ASB2;
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 2), AND INDUCTION.
RX PubMed=11566180; DOI=10.1016/s0014-5793(01)02829-0;
RA Kohroki J., Fujita S., Itoh N., Yamada Y., Imai H., Yumoto N.,
RA Nakanishi T., Tanaka K.;
RT "ATRA-regulated Asb-2 gene induced in differentiation of HL-60 leukemia
RT cells.";
RL FEBS Lett. 505:223-228(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INDUCTION.
RX PubMed=11682484; DOI=10.1074/jbc.m108476200;
RA Guibal F.C., Moog-Lutz C., Smolewski P., Di Gioia Y., Darzynkiewicz Z.,
RA Lutz P.G., Cayre Y.E.;
RT "ASB-2 inhibits growth and promotes commitment in myeloid leukemia cells.";
RL J. Biol. Chem. 277:218-224(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Kohroki J., Kuroda S., Takiguchi E., Kawakami T., Nakamura T.,
RA Nishiyama T., Masuho Y.;
RT "Ubiquitin-interacting motif on ankyrin repeat and SOCS box-containing
RT protein (ASB) 2a and its application to purify polyubiquitinated proteins
RT and associated proteins without denaturation.";
RL Submitted (FEB-2009) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney, and Stomach;
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=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Blood;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 79-635.
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 90-635.
RX PubMed=11111040; DOI=10.1016/s0378-1119(00)00402-9;
RA Kile B.T., Viney E.M., Willson T.A., Brodnicki T.C., Cancilla M.R.,
RA Herlihy A.S., Croker B.A., Baca M., Nicola N.A., Hilton D.J.,
RA Alexander W.S.;
RT "Cloning and characterization of the genes encoding the ankyrin repeat and
RT SOCS box-containing proteins Asb-1, Asb-2, Asb-3 and Asb-4.";
RL Gene 258:31-41(2000).
RN [10]
RP FUNCTION, SUBUNIT, INTERACTION WITH CUL5 AND RNF7, AND MUTAGENESIS OF
RP 599-LEU-CYS-600 AND 619-LEU--PRO-622.
RX PubMed=16325183; DOI=10.1016/j.febslet.2005.11.016;
RA Kohroki J., Nishiyama T., Nakamura T., Masuho Y.;
RT "ASB proteins interact with cullin5 and Rbx2 to form E3 ubiquitin ligase
RT complexes.";
RL FEBS Lett. 579:6796-6802(2005).
RN [11]
RP FUNCTION, SUBUNIT, INTERACTION WITH ELOC, AND MUTAGENESIS OF LEU-596 AND
RP CYS-600.
RX PubMed=15590664; DOI=10.1074/jbc.m413040200;
RA Heuze M.L., Guibal F.C., Banks C.A., Conaway J.W., Conaway R.C.,
RA Cayre Y.E., Benecke A., Lutz P.G.;
RT "ASB2 is an elongin BC-interacting protein that can assemble with cullin 5
RT and Rbx1 to reconstitute an E3 ubiquitin ligase complex.";
RL J. Biol. Chem. 280:5468-5474(2005).
RN [12]
RP FUNCTION (ISOFORM 1), SUBUNIT, ALTERNATIVE SPLICING, AND TISSUE
RP SPECIFICITY.
RX PubMed=19300455; DOI=10.1038/cdd.2009.27;
RA Bello N.F., Lamsoul I., Heuze M.L., Metais A., Moreaux G., Calderwood D.A.,
RA Duprez D., Moog-Lutz C., Lutz P.G.;
RT "The E3 ubiquitin ligase specificity subunit ASB2beta is a novel regulator
RT of muscle differentiation that targets filamin B to proteasomal
RT degradation.";
RL Cell Death Differ. 16:921-932(2009).
RN [13]
RP FUNCTION, INTERACTION WITH CUL5; ELOB; ELOC; JAK2 AND SKP2, INDUCTION, AND
RP DOMAIN SOCS BOX.
RX PubMed=21119685; DOI=10.1038/cr.2010.165;
RA Nie L., Zhao Y., Wu W., Yang Y.Z., Wang H.C., Sun X.H.;
RT "Notch-induced Asb2 expression promotes protein ubiquitination by forming
RT non-canonical E3 ligase complexes.";
RL Cell Res. 21:754-769(2011).
RN [14]
RP FUNCTION, AND ALTERNATIVE SPLICING.
RX PubMed=21737450; DOI=10.1074/jbc.m111.220921;
RA Lamsoul I., Burande C.F., Razinia Z., Houles T.C., Menoret D.,
RA Baldassarre M., Erard M., Moog-Lutz C., Calderwood D.A., Lutz P.G.;
RT "Functional and structural insights into ASB2alpha, a novel regulator of
RT integrin-dependent adhesion of hematopoietic cells.";
RL J. Biol. Chem. 286:30571-30581(2011).
RN [15]
RP UBIQUITINATION (ISOFORM 1), UIM DOMAIN (ISOFORM 1), AND MUTAGENESIS OF
RP 27-GLU--GLU-29 AND SER-38 (ISOFORM 1).
RX PubMed=22382022; DOI=10.1016/j.bbrc.2012.02.070;
RA Nishiyama T., Kuroda S., Takiguchi E., Nakamura T., Hashimoto K.,
RA Tsuzuranuki K., Kawakami T., Masuho Y., Kohroki J.;
RT "The ASB2beta Ubiquitin-interacting motif is involved in its
RT monoubiquitination.";
RL Biochem. Biophys. Res. Commun. 420:487-491(2012).
RN [16]
RP FUNCTION (ISOFORM 2).
RX PubMed=22916308; DOI=10.1371/journal.pone.0043798;
RA Lamsoul I., Erard M., van der Ven P.F., Lutz P.G.;
RT "Filamins but not Janus kinases are substrates of the ASB2alpha cullin-ring
RT E3 ubiquitin ligase in hematopoietic cells.";
RL PLoS ONE 7:e43798-e43798(2012).
RN [17]
RP FUNCTION (ISOFORM 2), SUBUNIT, SUBCELLULAR LOCATION, PHOSPHORYLATION AT
RP SER-371, AND MUTAGENESIS OF SER-371.
RX PubMed=24044920; DOI=10.1016/j.cellsig.2013.09.011;
RA Zakaria R., Lamsoul I., Uttenweiler-Joseph S., Erard M., Monsarrat B.,
RA Burlet-Schiltz O., Moog-Lutz C., Lutz P.G.;
RT "Phosphorylation of serine 323 of ASB2alpha is pivotal for the targeting of
RT filamin A to degradation.";
RL Cell. Signal. 25:2823-2830(2013).
RN [18]
RP FUNCTION (ISOFORM 2).
RX PubMed=24052262; DOI=10.1074/jbc.m113.496604;
RA Razinia Z., Baldassarre M., Cantelli G., Calderwood D.A.;
RT "ASB2alpha, an E3 ubiquitin ligase specificity subunit, regulates cell
RT spreading and triggers proteasomal degradation of filamins by targeting the
RT filamin calponin homology 1 domain.";
RL J. Biol. Chem. 288:32093-32105(2013).
RN [19]
RP INDUCTION.
RX PubMed=29955039; DOI=10.1038/s41419-018-0769-5;
RA Cappella M., Perfetti A., Cardinali B., Garcia-Manteiga J.M., Carrara M.,
RA Provenzano C., Fuschi P., Cardani R., Renna L.V., Meola G., Falcone G.,
RA Martelli F.;
RT "High-throughput analysis of the RNA-induced silencing complex in myotonic
RT dystrophy type 1 patients identifies the dysregulation of miR-29c and its
RT target ASB2.";
RL Cell Death Dis. 9:729-729(2018).
RN [20]
RP FUNCTION.
RX PubMed=32179481; DOI=10.1016/j.isci.2020.100959;
RA Yamak A., Hu D., Mittal N., Buikema J.W., Ditta S., Lutz P.G.,
RA Moog-Lutz C., Ellinor P.T., Domian I.J.;
RT "Loss of Asb2 Impairs Cardiomyocyte Differentiation and Leads to Congenital
RT Double Outlet Right Ventricle.";
RL IScience 23:100959-100959(2020).
CC -!- FUNCTION: Substrate-recognition component of a SCF-like ECS (Elongin-
CC Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which
CC mediates the ubiquitination and subsequent proteasomal degradation of
CC target proteins (PubMed:16325183, PubMed:15590664). Mediates Notch-
CC induced ubiquitination and degradation of substrates including TCF3/E2A
CC and JAK2 (PubMed:21119685). Required during embryonic heart development
CC for complete heart looping (By similarity). Required for cardiomyocyte
CC differentiation (PubMed:32179481). {ECO:0000250|UniProtKB:Q8K0L0,
CC ECO:0000269|PubMed:15590664, ECO:0000269|PubMed:16325183,
CC ECO:0000269|PubMed:21119685, ECO:0000269|PubMed:32179481}.
CC -!- FUNCTION: [Isoform 1]: Involved in myogenic differentiation and targets
CC filamin FLNB for proteasomal degradation but not filamin FLNA
CC (PubMed:19300455). Also targets DES for proteasomal degradation (By
CC similarity). Acts as a negative regulator of skeletal muscle mass (By
CC similarity). {ECO:0000250|UniProtKB:Q8K0L0,
CC ECO:0000269|PubMed:19300455}.
CC -!- FUNCTION: [Isoform 2]: Targets filamins FLNA and FLNB for proteasomal
CC degradation (PubMed:21737450, PubMed:22916308, PubMed:24044920,
CC PubMed:24052262). This leads to enhanced adhesion of hematopoietic
CC cells to fibronectin (PubMed:21737450). Required for FLNA degradation
CC in immature cardiomyocytes which is necessary for actin cytoskeleton
CC remodeling, leading to proper organization of myofibrils and function
CC of mature cardiomyocytes (By similarity). Required for degradation of
CC FLNA and FLNB in immature dendritic cells (DC) which enhances immature
CC DC migration by promoting DC podosome formation and DC-mediated
CC degradation of the extracellular matrix (By similarity). Does not
CC promote proteasomal degradation of tyrosine-protein kinases JAK1 or
CC JAK2 in hematopoietic cells (PubMed:22916308).
CC {ECO:0000250|UniProtKB:Q8K0L0, ECO:0000269|PubMed:21737450,
CC ECO:0000269|PubMed:22916308, ECO:0000269|PubMed:24044920,
CC ECO:0000269|PubMed:24052262}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of a probable ECS E3 ubiquitin-protein ligase
CC complex which contains CUL5, either RBX1 or RNF7/RBX2, Elongin BC
CC complex (ELOB and ELOC) and ASB2 (PubMed:15590664, PubMed:16325183,
CC PubMed:19300455, PubMed:24044920, PubMed:21119685). Interacts with SKP2
CC (PubMed:21119685). Through its interaction with SKP2, likely to bridge
CC the formation of dimeric E3-ubiquitin-protein ligase complexes composed
CC of an ECS complex and an SCF(SKP2) complex (PubMed:21119685). Interacts
CC with JAK2; the interaction targets JAK2 for Notch-mediated proteasomal
CC degradation (PubMed:21119685). Interacts with TCF3/E2A; the interaction
CC is mediated by SKP2 and targets TCF3 for Notch-mediated proteasomal
CC degradation (PubMed:21119685). {ECO:0000269|PubMed:15590664,
CC ECO:0000269|PubMed:16325183, ECO:0000269|PubMed:19300455,
CC ECO:0000269|PubMed:21119685, ECO:0000269|PubMed:24044920}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with DES.
CC {ECO:0000250|UniProtKB:Q8K0L0}.
CC -!- INTERACTION:
CC Q96Q27-2; Q93034: CUL5; NbExp=3; IntAct=EBI-28950233, EBI-1057139;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, stress fiber
CC {ECO:0000269|PubMed:24044920}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm, myofibril, sarcomere, Z
CC line {ECO:0000250|UniProtKB:Q8K0L0}. Note=Localizes to the Z line in
CC cardiomyocytes. {ECO:0000250|UniProtKB:Q8K0L0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=ASB2beta, muscle-type {ECO:0000303|PubMed:21737450};
CC IsoId=Q96Q27-2; Sequence=Displayed;
CC Name=2; Synonyms=ASB2alpha, hematopoietic-type
CC {ECO:0000303|PubMed:21737450};
CC IsoId=Q96Q27-1; Sequence=VSP_061164;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in muscle cells.
CC {ECO:0000269|PubMed:19300455}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in hematopoietic cells.
CC {ECO:0000269|PubMed:19300455}.
CC -!- INDUCTION: Induced by all-trans retinoic acid (ATRA) (PubMed:11566180,
CC PubMed:11682484). Induced by Notch signaling (PubMed:21119685).
CC Repressed by microRNA miR-29c (PubMed:29955039).
CC {ECO:0000269|PubMed:11566180, ECO:0000269|PubMed:11682484,
CC ECO:0000269|PubMed:21119685, ECO:0000269|PubMed:29955039}.
CC -!- DOMAIN: The SOCS box domain mediates the interaction with the Elongin
CC BC complex, an adapter module in different E3 ubiquitin-protein ligase
CC complexes. {ECO:0000269|PubMed:21119685}.
CC -!- DOMAIN: [Isoform 2]: Both the N-terminus and ANK repeats 1 to 10 are
CC necessary for interaction with filamins. {ECO:0000269|PubMed:21737450}.
CC -!- DOMAIN: [Isoform 1]: The UIM domain is required for monoubiquitination.
CC {ECO:0000269|PubMed:22382022}.
CC -!- PTM: [Isoform 1]: Monoubiquitinated. {ECO:0000269|PubMed:22382022}.
CC -!- PTM: [Isoform 2]: Not monoubiquitinated. {ECO:0000269|PubMed:22382022}.
CC -!- PTM: [Isoform 2]: Phosphorylation at Ser-371 is required for
CC association with FLNA and subsequent FLNA degradation.
CC {ECO:0000269|PubMed:24044920}.
CC -!- SIMILARITY: Belongs to the ankyrin SOCS box (ASB) family.
CC {ECO:0000305}.
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DR EMBL; AB056723; BAB64532.1; -; mRNA.
DR EMBL; AJ251238; CAC17765.1; -; mRNA.
DR EMBL; AB488462; BAI77868.1; -; mRNA.
DR EMBL; AK303686; BAG64678.1; -; mRNA.
DR EMBL; AK315628; BAG37996.1; -; mRNA.
DR EMBL; AL079302; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL132642; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471061; EAW81540.1; -; Genomic_DNA.
DR EMBL; CH471061; EAW81542.1; -; Genomic_DNA.
DR EMBL; BC032354; AAH32354.1; -; mRNA.
DR EMBL; AL137735; CAB70899.1; -; mRNA.
DR EMBL; AF159164; AAD45345.1; -; mRNA.
DR CCDS; CCDS55940.1; -. [Q96Q27-2]
DR CCDS; CCDS9915.1; -. [Q96Q27-1]
DR PIR; T46507; T46507.
DR RefSeq; NP_001189358.1; NM_001202429.1. [Q96Q27-2]
DR RefSeq; NP_057234.2; NM_016150.4. [Q96Q27-1]
DR RefSeq; XP_005267815.1; XM_005267758.3. [Q96Q27-2]
DR AlphaFoldDB; Q96Q27; -.
DR SMR; Q96Q27; -.
DR BioGRID; 119674; 46.
DR CORUM; Q96Q27; -.
DR IntAct; Q96Q27; 9.
DR MINT; Q96Q27; -.
DR STRING; 9606.ENSP00000451575; -.
DR iPTMnet; Q96Q27; -.
DR PhosphoSitePlus; Q96Q27; -.
DR BioMuta; ASB2; -.
DR DMDM; 20531999; -.
DR MassIVE; Q96Q27; -.
DR PaxDb; Q96Q27; -.
DR PeptideAtlas; Q96Q27; -.
DR PRIDE; Q96Q27; -.
DR ProteomicsDB; 77816; -. [Q96Q27-1]
DR ProteomicsDB; 77817; -. [Q96Q27-2]
DR Antibodypedia; 16; 192 antibodies from 25 providers.
DR DNASU; 51676; -.
DR Ensembl; ENST00000315988.8; ENSP00000320675.4; ENSG00000100628.12. [Q96Q27-1]
DR Ensembl; ENST00000555019.6; ENSP00000451575.1; ENSG00000100628.12. [Q96Q27-2]
DR Ensembl; ENST00000612647.3; ENSP00000480388.1; ENSG00000278693.3. [Q96Q27-2]
DR Ensembl; ENST00000629617.2; ENSP00000487399.1; ENSG00000278693.3. [Q96Q27-1]
DR GeneID; 51676; -.
DR KEGG; hsa:51676; -.
DR MANE-Select; ENST00000555019.6; ENSP00000451575.1; NM_001202429.2; NP_001189358.1.
DR UCSC; uc001ycc.3; human. [Q96Q27-2]
DR CTD; 51676; -.
DR DisGeNET; 51676; -.
DR GeneCards; ASB2; -.
DR HGNC; HGNC:16012; ASB2.
DR HPA; ENSG00000100628; Group enriched (skeletal muscle, tongue).
DR MIM; 605759; gene.
DR neXtProt; NX_Q96Q27; -.
DR OpenTargets; ENSG00000100628; -.
DR PharmGKB; PA25030; -.
DR VEuPathDB; HostDB:ENSG00000100628; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000155490; -.
DR InParanoid; Q96Q27; -.
DR OMA; WTCIKEK; -.
DR PhylomeDB; Q96Q27; -.
DR TreeFam; TF315127; -.
DR PathwayCommons; Q96Q27; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q96Q27; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 51676; 8 hits in 1101 CRISPR screens.
DR ChiTaRS; ASB2; human.
DR GeneWiki; ASB2; -.
DR GenomeRNAi; 51676; -.
DR Pharos; Q96Q27; Tbio.
DR PRO; PR:Q96Q27; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q96Q27; protein.
DR Bgee; ENSG00000100628; Expressed in skeletal muscle tissue and 103 other tissues.
DR ExpressionAtlas; Q96Q27; baseline and differential.
DR Genevisible; Q96Q27; HS.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0030018; C:Z disc; ISS:UniProtKB.
DR GO; GO:0097602; F:cullin family protein binding; IPI:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0055013; P:cardiac muscle cell development; ISS:UniProtKB.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; IMP:UniProtKB.
DR GO; GO:0036336; P:dendritic cell migration; ISS:UniProtKB.
DR GO; GO:0001947; P:heart looping; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0071800; P:podosome assembly; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0014732; P:skeletal muscle atrophy; ISS:UniProtKB.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR CDD; cd03721; SOCS_ASB2; 1.
DR Gene3D; 1.25.40.20; -; 3.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR037330; ASB2_SOCS.
DR InterPro; IPR001496; SOCS_box.
DR InterPro; IPR036036; SOCS_box-like_dom_sf.
DR Pfam; PF12796; Ank_2; 3.
DR Pfam; PF07525; SOCS_box; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 11.
DR SMART; SM00253; SOCS; 1.
DR SMART; SM00969; SOCS_box; 1.
DR SUPFAM; SSF158235; SSF158235; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 8.
DR PROSITE; PS50088; ANK_REPEAT; 9.
DR PROSITE; PS50225; SOCS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Cytoplasm; Cytoskeleton; Phosphoprotein;
KW Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..635
FT /note="Ankyrin repeat and SOCS box protein 2"
FT /id="PRO_0000066925"
FT DOMAIN 26..45
FT /note="UIM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT REPEAT 104..133
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 137..167
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 171..200
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 204..233
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT REPEAT 237..266
FT /note="ANK 5"
FT /evidence="ECO:0000255"
FT REPEAT 270..299
FT /note="ANK 6"
FT /evidence="ECO:0000255"
FT REPEAT 303..332
FT /note="ANK 7"
FT /evidence="ECO:0000255"
FT REPEAT 336..365
FT /note="ANK 8"
FT /evidence="ECO:0000255"
FT REPEAT 368..397
FT /note="ANK 9"
FT /evidence="ECO:0000255"
FT REPEAT 410..439
FT /note="ANK 10"
FT /evidence="ECO:0000255"
FT REPEAT 440..469
FT /note="ANK 11"
FT /evidence="ECO:0000255"
FT REPEAT 476..504
FT /note="ANK 12"
FT /evidence="ECO:0000255"
FT DOMAIN 586..635
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT MOD_RES 371
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000269|PubMed:24044920"
FT VAR_SEQ 1..68
FT /note="MATQISTRGSQCTIGQEEYSLYSSLSEDELVQMAIEQSLADKTRGPTTAEAT
FT ASACTNRQPAHFYPWT -> MTRFSYAEYFSLFHSCSAPS (in isoform 2)"
FT /id="VSP_061164"
FT VARIANT 208
FT /note="P -> S (in dbSNP:rs2295213)"
FT /id="VAR_022089"
FT MUTAGEN 27..29
FT /note="EDE->AAA: Abolishes monoubiquitination."
FT /evidence="ECO:0000269|PubMed:22382022"
FT MUTAGEN 38
FT /note="S->A: Abolishes monoubiquitination."
FT /evidence="ECO:0000269|PubMed:22382022"
FT MUTAGEN 371
FT /note="S->A: Abolishes phosphorylation. Abolishes
FT degradation of FLNA. No effect on assembly into ubiquitin-
FT protein ligase complex."
FT /evidence="ECO:0000269|PubMed:24044920"
FT MUTAGEN 371
FT /note="S->D: Phosphomimetic mutant. No effect on isoform 2
FT FLNA degradation. No effect on assembly into ubiquitin-
FT protein ligase complex."
FT /evidence="ECO:0000269|PubMed:24044920"
FT MUTAGEN 596
FT /note="L->P: No interaction with Elongin BC complex."
FT /evidence="ECO:0000269|PubMed:15590664"
FT MUTAGEN 599..600
FT /note="LC->PF: No interaction with CUL5 or RNF7."
FT /evidence="ECO:0000269|PubMed:16325183"
FT MUTAGEN 600
FT /note="C->P: No interaction with Elongin BC complex."
FT /evidence="ECO:0000269|PubMed:15590664"
FT MUTAGEN 619..622
FT /note="LPLP->AAAA: No interaction with CUL5 or RNF7."
FT /evidence="ECO:0000269|PubMed:16325183"
FT CONFLICT 224
FT /note="Missing (in Ref. 9; AAD45345)"
FT /evidence="ECO:0000305"
FT CONFLICT 460
FT /note="Missing (in Ref. 9; AAD45345)"
FT /evidence="ECO:0000305"
FT REGION Q96Q27-1:8..16
FT /note="Required for FLNA degradation"
FT /evidence="ECO:0000269|PubMed:21737450"
SQ SEQUENCE 635 AA; 70212 MW; B91E4EB394531076 CRC64;
MATQISTRGS QCTIGQEEYS LYSSLSEDEL VQMAIEQSLA DKTRGPTTAE ATASACTNRQ
PAHFYPWTRS TAPPESSPAR APMGLFQGVM QKYSSSLFKT SQLAPADPLI KAIKDGDEEA
LKTMIKEGKN LAEPNKEGWL PLHEAAYYGQ VGCLKVLQRA YPGTIDQRTL QEETAVYLAT
CRGHLDCLLS LLQAGAEPDI SNKSRETPLY KACERKNAEA VKILVQHNAD TNHRCNRGWT
ALHESVSRND LEVMQILVSG GAKVESKNAY GITPLFVAAQ SGQLEALRFL AKYGADINTQ
ASDNASALYE ACKNEHEEVV EFLLSQGADA NKTNKDGLLP LHIASKKGNY RIVQMLLPVT
SRTRIRRSGV SPLHLAAERN HDEVLEALLS ARFDVNTPLA PERARLYEDR RSSALYFAVV
NNNVYATELL LQHGADPNRD VISPLLVAIR HGCLRTMQLL LDHGANIDAY IATHPTAFPA
TIMFAMKCLS LLKFLMDLGC DGEPCFSCLY GNGPHPPAPQ PSSRFNDAPA ADKEPSVVQF
CEFVSAPEVS RWAGPIIDVL LDYVGNVQLC SRLKEHIDSF EDWAVIKEKA EPPRPLAHLC
RLRVRKAIGK YRIKLLDTLP LPGRLIRYLK YENTQ
