BICD2_HUMAN
ID BICD2_HUMAN Reviewed; 824 AA.
AC Q8TD16; O75181; Q5TBQ2; Q5TBQ3; Q96LH2; Q9BT84; Q9H561;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Protein bicaudal D homolog 2;
DE Short=Bic-D 2;
GN Name=BICD2; Synonyms=KIAA0699;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH NEK9,
RP PHOSPHORYLATION BY NEK9, AND SUBCELLULAR LOCATION.
RX PubMed=11864968; DOI=10.1074/jbc.m108662200;
RA Holland P.M., Milne A., Garka K., Johnson R.S., Willis C., Sims J.E.,
RA Rauch C.T., Bird T.A., Virca G.D.;
RT "Purification, cloning, and characterization of Nek8, a novel NIMA-related
RT kinase, and its candidate substrate Bicd2.";
RL J. Biol. Chem. 277:16229-16240(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 239-824 (ISOFORM 1).
RC TISSUE=Pancreas, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-582, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-582, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-190; SER-224; SER-343;
RP SER-395 AND SER-582, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-190; THR-821 AND SER-823, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [11]
RP INTERACTION WITH RANBP2, AND SUBCELLULAR LOCATION.
RX PubMed=20386726; DOI=10.1371/journal.pbio.1000350;
RA Splinter D., Tanenbaum M.E., Lindqvist A., Jaarsma D., Flotho A., Yu K.L.,
RA Grigoriev I., Engelsma D., Haasdijk E.D., Keijzer N., Demmers J.,
RA Fornerod M., Melchior F., Hoogenraad C.C., Medema R.H., Akhmanova A.;
RT "Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes
RT and regulate centrosome and nuclear positioning during mitotic entry.";
RL PLoS Biol. 8:E1000350-E1000350(2010).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-582, AND IDENTIFICATION BY
RP 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 [13]
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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-582, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-224; SER-318; THR-319;
RP SER-568; SER-574; SER-582 AND THR-602, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-582, 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 [18]
RP INTERACTION WITH KIF1C.
RX PubMed=24482476; DOI=10.1126/science.1247363;
RA Novarino G., Fenstermaker A.G., Zaki M.S., Hofree M., Silhavy J.L.,
RA Heiberg A.D., Abdellateef M., Rosti B., Scott E., Mansour L., Masri A.,
RA Kayserili H., Al-Aama J.Y., Abdel-Salam G.M., Karminejad A., Kara M.,
RA Kara B., Bozorgmehri B., Ben-Omran T., Mojahedi F., Mahmoud I.G.,
RA Bouslam N., Bouhouche A., Benomar A., Hanein S., Raymond L., Forlani S.,
RA Mascaro M., Selim L., Shehata N., Al-Allawi N., Bindu P.S., Azam M.,
RA Gunel M., Caglayan A., Bilguvar K., Tolun A., Issa M.Y., Schroth J.,
RA Spencer E.G., Rosti R.O., Akizu N., Vaux K.K., Johansen A., Koh A.A.,
RA Megahed H., Durr A., Brice A., Stevanin G., Gabriel S.B., Ideker T.,
RA Gleeson J.G.;
RT "Exome sequencing links corticospinal motor neuron disease to common
RT neurodegenerative disorders.";
RL Science 343:506-511(2014).
RN [19]
RP FUNCTION.
RX PubMed=25962623; DOI=10.1016/j.bbamcr.2015.05.005;
RA Matsuto M., Kano F., Murata M.;
RT "Reconstitution of the targeting of Rab6A to the Golgi apparatus in semi-
RT intact HeLa cells: A role of BICD2 in stabilizing Rab6A on Golgi membranes
RT and a concerted role of Rab6A/BICD2 interactions in Golgi-to-ER retrograde
RT transport.";
RL Biochim. Biophys. Acta 1853:2592-2609(2015).
RN [20]
RP INTERACTION WITH DYNC1H1.
RX PubMed=25512093; DOI=10.1002/humu.22744;
RA Peeters K., Bervoets S., Chamova T., Litvinenko I., De Vriendt E.,
RA Bichev S., Kancheva D., Mitev V., Kennerson M., Timmerman V., De Jonghe P.,
RA Tournev I., MacMillan J., Jordanova A.;
RT "Novel mutations in the DYNC1H1 tail domain refine the genetic and clinical
RT spectrum of dyneinopathies.";
RL Hum. Mutat. 36:287-291(2015).
RN [21]
RP VARIANTS SMALED2A LEU-107 AND GLY-774, CHARACTERIZATION OF VARIANTS
RP SMALED2A LEU-107 AND GLY-774, INTERACTION WITH DNAI1 AND RAB6A, AND
RP SUBCELLULAR LOCATION.
RX PubMed=23664119; DOI=10.1016/j.ajhg.2013.04.013;
RA Peeters K., Litvinenko I., Asselbergh B., Almeida-Souza L., Chamova T.,
RA Geuens T., Ydens E., Zimon M., Irobi J., De Vriendt E., De Winter V.,
RA Ooms T., Timmerman V., Tournev I., Jordanova A.;
RT "Molecular defects in the motor adaptor BICD2 cause proximal spinal
RT muscular atrophy with autosomal-dominant inheritance.";
RL Am. J. Hum. Genet. 92:955-964(2013).
RN [22]
RP VARIANTS SMALED2A LEU-107; PHE-189; PRO-501 AND THR-508, CHARACTERIZATION
RP OF VARIANTS SMALED2A LEU-107 AND PRO-501, INTERACTION WITH DNAI1, AND
RP SUBCELLULAR LOCATION.
RX PubMed=23664120; DOI=10.1016/j.ajhg.2013.04.018;
RG UK10K;
RA Oates E.C., Rossor A.M., Hafezparast M., Gonzalez M., Speziani F.,
RA Macarthur D.G., Lek M., Cottenie E., Scoto M., Foley A.R., Hurles M.,
RA Houlden H., Greensmith L., Auer-Grumbach M., Pieber T.R., Strom T.M.,
RA Schule R., Herrmann D.N., Sowden J.E., Acsadi G., Menezes M.P.,
RA Clarke N.F., Zuechner S., Muntoni F., North K.N., Reilly M.M.;
RT "Mutations in BICD2 cause dominant congenital spinal muscular atrophy and
RT hereditary spastic paraplegia.";
RL Am. J. Hum. Genet. 92:965-973(2013).
RN [23]
RP VARIANTS SMALED2A LEU-107; THR-188 AND MET-703, CHARACTERIZATION OF
RP VARIANTS SMALED2A LEU-107; THR-188 AND MET-703, VARIANT ARG-90, AND
RP SUBCELLULAR LOCATION.
RX PubMed=23664116; DOI=10.1016/j.ajhg.2013.04.011;
RA Neveling K., Martinez-Carrera L.A., Hoelker I., Heister A., Verrips A.,
RA Hosseini-Barkooie S.M., Gilissen C., Vermeer S., Pennings M., Meijer R.,
RA Te Riele M., Frijns C.J., Suchowersky O., Maclaren L.,
RA Rudnik-Schoeneborn S., Sinke R.J., Zerres K., Lowry R.B., Lemmink H.H.,
RA Garbes L., Veltman J.A., Schelhaas H.J., Scheffer H., Wirth B.;
RT "Mutations in BICD2, which encodes a golgin and important motor adaptor,
RT cause congenital autosomal-dominant spinal muscular atrophy.";
RL Am. J. Hum. Genet. 92:946-954(2013).
RN [24]
RP VARIANT SMALED2B CYS-694, AND INVOLVEMENT IN SMALED2B.
RX PubMed=27751653; DOI=10.1016/j.nmd.2016.09.009;
RA Ravenscroft G., Di Donato N., Hahn G., Davis M.R., Craven P.D., Poke G.,
RA Neas K.R., Neuhann T.M., Dobyns W.B., Laing N.G.;
RT "Recurrent de novo BICD2 mutation associated with arthrogryposis multiplex
RT congenita and bilateral perisylvian polymicrogyria.";
RL Neuromuscul. Disord. 26:744-748(2016).
RN [25]
RP VARIANTS SMALED2B ARG-194; TRP-542 AND CYS-694, VARIANT SMALED2A MET-703,
RP AND INVOLVEMENT IN SMALED2B.
RX PubMed=28635954; DOI=10.1038/ejhg.2017.98;
RA Storbeck M., Horsberg Eriksen B., Unger A., Hoelker I., Aukrust I.,
RA Martinez-Carrera L.A., Linke W.A., Ferbert A., Heller R., Vorgerd M.,
RA Houge G., Wirth B.;
RT "Phenotypic extremes of BICD2-opathies: from lethal, congenital muscular
RT atrophy with arthrogryposis to asymptomatic with subclinical features.";
RL Eur. J. Hum. Genet. 25:1040-1048(2017).
RN [26]
RP VARIANT SMALED2B ASN-546 DEL.
RX PubMed=30054298; DOI=10.1101/mcs.a003160;
RA Koboldt D.C., Kastury R.D., Waldrop M.A., Kelly B.J., Mosher T.M.,
RA McLaughlin H., Corsmeier D., Slaughter J.L., Flanigan K.M., McBride K.L.,
RA Mehta L., Wilson R.K., White P.;
RT "In-frame de novo mutation in BICD2 in two patients with muscular atrophy
RT and arthrogryposis.";
RL Cold Spring Harb. Mol. Case Stud. 4:0-0(2018).
CC -!- FUNCTION: Acts as an adapter protein linking the dynein motor complex
CC to various cargos and converts dynein from a non-processive to a highly
CC processive motor in the presence of dynactin. Facilitates and
CC stabilizes the interaction between dynein and dynactin and activates
CC dynein processivity (the ability to move along a microtubule for a long
CC distance without falling off the track) (By similarity). Facilitates
CC the binding of RAB6A to the Golgi by stabilizing its GTP-bound form.
CC Regulates coat complex coatomer protein I (COPI)-independent Golgi-
CC endoplasmic reticulum transport via its interaction with RAB6A and
CC recruitment of the dynein-dynactin motor complex (PubMed:25962623).
CC Contributes to nuclear and centrosomal positioning prior to mitotic
CC entry through regulation of both dynein and kinesin-1. During G2 phase
CC of the cell cycle, associates with RANBP2 at the nuclear pores and
CC recruits dynein and dynactin to the nuclear envelope to ensure proper
CC positioning of the nucleus relative to centrosomes prior to the onset
CC of mitosis (By similarity). {ECO:0000250|UniProtKB:Q921C5,
CC ECO:0000269|PubMed:25962623}.
CC -!- SUBUNIT: Interacts with CPNE4 (via VWFA domain) (By similarity).
CC Interacts with RAB6A (PubMed:23664119). Interacts with NEK9
CC (PubMed:11864968). Interacts with DNAI1 (PubMed:23664119,
CC PubMed:23664120). Interacts with DYNC1H1 (PubMed:25512093). Interacts
CC with RANBP2 (PubMed:20386726). Forms a complex with dynein and
CC dynactin. Binds preferentially to tyrosinated microtubules than to
CC detyrosinated microtubules. Interacts with DYNLL1, DYNC1I2; DCTN1,
CC DCTN2 and KIF5A (By similarity). Interacts with KIF1C
CC (PubMed:24482476). {ECO:0000250|UniProtKB:Q921C5,
CC ECO:0000269|PubMed:11864968, ECO:0000269|PubMed:20386726,
CC ECO:0000269|PubMed:23664119, ECO:0000269|PubMed:23664120,
CC ECO:0000269|PubMed:24482476, ECO:0000269|PubMed:25512093}.
CC -!- INTERACTION:
CC Q8TD16; O14576: DYNC1I1; NbExp=2; IntAct=EBI-2372628, EBI-366267;
CC Q8TD16; P20340: RAB6A; NbExp=3; IntAct=EBI-2372628, EBI-1052826;
CC Q8TD16; P49792: RANBP2; NbExp=2; IntAct=EBI-2372628, EBI-973138;
CC Q8TD16-2; Q92619: ARHGAP45; NbExp=3; IntAct=EBI-11975051, EBI-2825900;
CC Q8TD16-2; O75828: CBR3; NbExp=3; IntAct=EBI-11975051, EBI-714504;
CC Q8TD16-2; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-11975051, EBI-10175300;
CC Q8TD16-2; O43602-2: DCX; NbExp=3; IntAct=EBI-11975051, EBI-14148644;
CC Q8TD16-2; Q9BQ89: FAM110A; NbExp=3; IntAct=EBI-11975051, EBI-1752811;
CC Q8TD16-2; Q3B820: FAM161A; NbExp=3; IntAct=EBI-11975051, EBI-719941;
CC Q8TD16-2; Q96MY7: FAM161B; NbExp=3; IntAct=EBI-11975051, EBI-7225287;
CC Q8TD16-2; Q9Y247: FAM50B; NbExp=3; IntAct=EBI-11975051, EBI-742802;
CC Q8TD16-2; P56524-2: HDAC4; NbExp=3; IntAct=EBI-11975051, EBI-11953488;
CC Q8TD16-2; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-11975051, EBI-739832;
CC Q8TD16-2; P55081: MFAP1; NbExp=3; IntAct=EBI-11975051, EBI-1048159;
CC Q8TD16-2; Q8IVT4: MGC50722; NbExp=3; IntAct=EBI-11975051, EBI-14086479;
CC Q8TD16-2; P00540: MOS; NbExp=3; IntAct=EBI-11975051, EBI-1757866;
CC Q8TD16-2; Q6P1K2: PMF1; NbExp=4; IntAct=EBI-11975051, EBI-713832;
CC Q8TD16-2; Q8WUT1: POLDIP3; NbExp=3; IntAct=EBI-11975051, EBI-10276663;
CC Q8TD16-2; Q6NYC8: PPP1R18; NbExp=3; IntAct=EBI-11975051, EBI-2557469;
CC Q8TD16-2; Q99633: PRPF18; NbExp=3; IntAct=EBI-11975051, EBI-2798416;
CC Q8TD16-2; Q8WWY3: PRPF31; NbExp=3; IntAct=EBI-11975051, EBI-1567797;
CC Q8TD16-2; Q9NRW1: RAB6B; NbExp=3; IntAct=EBI-11975051, EBI-1760079;
CC Q8TD16-2; Q96IZ5: RBM41; NbExp=3; IntAct=EBI-11975051, EBI-740773;
CC Q8TD16-2; Q13573: SNW1; NbExp=3; IntAct=EBI-11975051, EBI-632715;
CC Q8TD16-2; Q969Z0: TBRG4; NbExp=3; IntAct=EBI-11975051, EBI-702328;
CC Q8TD16-2; Q15560: TCEA2; NbExp=3; IntAct=EBI-11975051, EBI-710310;
CC Q8TD16-2; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-11975051, EBI-11955057;
CC Q8TD16-2; Q3SY00: TSGA10IP; NbExp=3; IntAct=EBI-11975051, EBI-10241197;
CC Q8TD16-2; O75604: USP2; NbExp=3; IntAct=EBI-11975051, EBI-743272;
CC Q8TD16-2; Q5TAP6: UTP14C; NbExp=3; IntAct=EBI-11975051, EBI-11737646;
CC Q8TD16-2; P07947: YES1; NbExp=3; IntAct=EBI-11975051, EBI-515331;
CC Q8TD16-2; Q53FD0-2: ZC2HC1C; NbExp=3; IntAct=EBI-11975051, EBI-14104088;
CC Q8TD16-2; Q96NC0: ZMAT2; NbExp=3; IntAct=EBI-11975051, EBI-2682299;
CC Q8TD16-2; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-11975051, EBI-740727;
CC Q8TD16-2; Q9P2J8: ZNF624; NbExp=3; IntAct=EBI-11975051, EBI-9116427;
CC Q8TD16-2; Q5T619: ZNF648; NbExp=3; IntAct=EBI-11975051, EBI-11985915;
CC Q8TD16-2; Q96BR6: ZNF669; NbExp=3; IntAct=EBI-11975051, EBI-12006574;
CC Q8TD16-2; Q9BS34: ZNF670; NbExp=3; IntAct=EBI-11975051, EBI-745276;
CC Q8TD16-2; O43309: ZSCAN12; NbExp=3; IntAct=EBI-11975051, EBI-1210440;
CC Q8TD16-2; Q3MJ62: ZSCAN23; NbExp=3; IntAct=EBI-11975051, EBI-5667532;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus {ECO:0000269|PubMed:23664116,
CC ECO:0000269|PubMed:23664119}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:11864968}. Cytoplasm {ECO:0000269|PubMed:23664116,
CC ECO:0000269|PubMed:23664120}. Nucleus envelope
CC {ECO:0000269|PubMed:20386726}. Nucleus, nuclear pore complex
CC {ECO:0000269|PubMed:20386726}. Note=In interphase cells mainly
CC localizes to the Golgi complex and colocalizes with dynactin at
CC microtubule plus ends (By similarity). Localizes to the nuclear
CC envelope and cytoplasmic stacks of nuclear pore complex known as
CC annulate lamellae in a RANBP2-dependent manner during G2 phase of the
CC cell cycle (PubMed:20386726). {ECO:0000250|UniProtKB:Q921C5,
CC ECO:0000269|PubMed:11864968, ECO:0000269|PubMed:20386726}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TD16-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TD16-2; Sequence=VSP_007969;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DOMAIN: The fourth coiled coil region is involved in Golgi targeting
CC and in the interaction with DCTN2. {ECO:0000250|UniProtKB:Q921C5}.
CC -!- PTM: Phosphorylated by NEK9 in vitro. {ECO:0000269|PubMed:11864968}.
CC -!- DISEASE: Spinal muscular atrophy, lower extremity-predominant 2A,
CC childhood onset, autosomal dominant (SMALED2A) [MIM:615290]: An
CC autosomal dominant form of spinal muscular atrophy characterized by
CC early-childhood onset of muscle weakness and atrophy predominantly
CC affecting the proximal and distal muscles of the lower extremity,
CC although some patients may show upper extremity involvement. The
CC disorder results in delayed walking, waddling gait, difficulty walking,
CC and loss of distal reflexes. Some patients may have foot deformities or
CC hyperlordosis, and some show mild upper motor signs, such as
CC spasticity. Sensation, bulbar function, and cognitive function are
CC preserved. The disorder shows very slow progression throughout life.
CC {ECO:0000269|PubMed:23664116, ECO:0000269|PubMed:23664119,
CC ECO:0000269|PubMed:23664120, ECO:0000269|PubMed:28635954}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Spinal muscular atrophy, lower extremity-predominant, 2B,
CC prenatal onset, autosomal dominant (SMALED2B) [MIM:618291]: An
CC autosomal dominant neuromuscular disorder characterized by decreased
CC fetal movements, fractures in utero, severe congenital joint
CC contractures, arthrogryposis multiplex congenita, severe hypotonia,
CC muscle atrophy, and respiratory insufficiency and failure due to muscle
CC weakness. Some patients may have dysmorphic facial features and/or
CC abnormalities on brain imaging. Death in early childhood may occur.
CC {ECO:0000269|PubMed:27751653, ECO:0000269|PubMed:28635954,
CC ECO:0000269|PubMed:30054298}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Due to intron retention. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the BicD family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA31674.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AY052562; AAL12246.1; -; mRNA.
DR EMBL; AB014599; BAA31674.1; ALT_INIT; mRNA.
DR EMBL; AL137074; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL136981; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004296; AAH04296.1; -; mRNA.
DR EMBL; BC073970; AAH73970.1; -; mRNA.
DR CCDS; CCDS35064.1; -. [Q8TD16-2]
DR CCDS; CCDS6700.1; -. [Q8TD16-1]
DR RefSeq; NP_001003800.1; NM_001003800.1. [Q8TD16-2]
DR RefSeq; NP_056065.1; NM_015250.3. [Q8TD16-1]
DR PDB; 6OFP; X-ray; 2.01 A; A/B=715-804.
DR PDB; 6PSE; X-ray; 2.40 A; A/B=1-98.
DR PDBsum; 6OFP; -.
DR PDBsum; 6PSE; -.
DR AlphaFoldDB; Q8TD16; -.
DR SMR; Q8TD16; -.
DR BioGRID; 116891; 394.
DR CORUM; Q8TD16; -.
DR DIP; DIP-53426N; -.
DR IntAct; Q8TD16; 83.
DR STRING; 9606.ENSP00000349351; -.
DR iPTMnet; Q8TD16; -.
DR PhosphoSitePlus; Q8TD16; -.
DR BioMuta; BICD2; -.
DR DMDM; 34098604; -.
DR EPD; Q8TD16; -.
DR jPOST; Q8TD16; -.
DR MassIVE; Q8TD16; -.
DR MaxQB; Q8TD16; -.
DR PaxDb; Q8TD16; -.
DR PeptideAtlas; Q8TD16; -.
DR PRIDE; Q8TD16; -.
DR ProteomicsDB; 74215; -. [Q8TD16-1]
DR ProteomicsDB; 74216; -. [Q8TD16-2]
DR Antibodypedia; 13783; 208 antibodies from 27 providers.
DR DNASU; 23299; -.
DR Ensembl; ENST00000356884.11; ENSP00000349351.6; ENSG00000185963.14. [Q8TD16-2]
DR Ensembl; ENST00000375512.3; ENSP00000364662.3; ENSG00000185963.14. [Q8TD16-1]
DR GeneID; 23299; -.
DR KEGG; hsa:23299; -.
DR MANE-Select; ENST00000356884.11; ENSP00000349351.6; NM_001003800.2; NP_001003800.1. [Q8TD16-2]
DR UCSC; uc004aso.2; human. [Q8TD16-1]
DR CTD; 23299; -.
DR DisGeNET; 23299; -.
DR GeneCards; BICD2; -.
DR HGNC; HGNC:17208; BICD2.
DR HPA; ENSG00000185963; Tissue enhanced (skin).
DR MalaCards; BICD2; -.
DR MIM; 609797; gene.
DR MIM; 615290; phenotype.
DR MIM; 618291; phenotype.
DR neXtProt; NX_Q8TD16; -.
DR OpenTargets; ENSG00000185963; -.
DR Orphanet; 363454; BICD2-related autosomal dominant childhood-onset proximal spinal muscular atrophy.
DR PharmGKB; PA134969018; -.
DR VEuPathDB; HostDB:ENSG00000185963; -.
DR eggNOG; KOG0999; Eukaryota.
DR GeneTree; ENSGT00940000154471; -.
DR HOGENOM; CLU_014107_1_0_1; -.
DR InParanoid; Q8TD16; -.
DR OMA; AYTNHRK; -.
DR PhylomeDB; Q8TD16; -.
DR TreeFam; TF323833; -.
DR PathwayCommons; Q8TD16; -.
DR Reactome; R-HSA-6811436; COPI-independent Golgi-to-ER retrograde traffic.
DR SignaLink; Q8TD16; -.
DR SIGNOR; Q8TD16; -.
DR BioGRID-ORCS; 23299; 21 hits in 1080 CRISPR screens.
DR ChiTaRS; BICD2; human.
DR GeneWiki; BICD2; -.
DR GenomeRNAi; 23299; -.
DR Pharos; Q8TD16; Tbio.
DR PRO; PR:Q8TD16; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q8TD16; protein.
DR Bgee; ENSG00000185963; Expressed in gingival epithelium and 206 other tissues.
DR Genevisible; Q8TD16; HS.
DR GO; GO:0005642; C:annulate lamellae; IDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; IMP:ARUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IMP:ARUK-UCL.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0005643; C:nuclear pore; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0008093; F:cytoskeletal anchor activity; IEA:InterPro.
DR GO; GO:0034452; F:dynactin binding; ISS:UniProtKB.
DR GO; GO:0070840; F:dynein complex binding; ISS:UniProtKB.
DR GO; GO:0051959; F:dynein light intermediate chain binding; IBA:GO_Central.
DR GO; GO:0031267; F:small GTPase binding; ISS:BHF-UCL.
DR GO; GO:0051642; P:centrosome localization; IMP:UniProtKB.
DR GO; GO:0072393; P:microtubule anchoring at microtubule organizing center; ISS:BHF-UCL.
DR GO; GO:0007018; P:microtubule-based movement; IBA:GO_Central.
DR GO; GO:0072385; P:minus-end-directed organelle transport along microtubule; ISS:BHF-UCL.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0034067; P:protein localization to Golgi apparatus; IMP:UniProtKB.
DR GO; GO:0033365; P:protein localization to organelle; IBA:GO_Central.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IGI:ARUK-UCL.
DR GO; GO:0006890; P:retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum; IMP:UniProtKB.
DR InterPro; IPR018477; BICD.
DR PANTHER; PTHR31233; PTHR31233; 1.
DR Pfam; PF09730; BicD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Coiled coil; Cytoplasm;
KW Cytoskeleton; Disease variant; Golgi apparatus; mRNA transport;
KW Neurodegeneration; Nuclear pore complex; Nucleus; Phosphoprotein;
KW Protein transport; Reference proteome; Translocation; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..824
FT /note="Protein bicaudal D homolog 2"
FT /id="PRO_0000205359"
FT REGION 25..398
FT /note="Interacts with DYNLL1, DYNC1H1, DYNC1I2, DCTN1 and
FT DCTN2"
FT /evidence="ECO:0000250|UniProtKB:Q921C5"
FT REGION 311..330
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 334..599
FT /note="Interaction with KIF5A"
FT /evidence="ECO:0000250|UniProtKB:Q921C5"
FT REGION 398..425
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 559..622
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 590..824
FT /note="Interaction with RANBP2"
FT /evidence="ECO:0000250|UniProtKB:Q921C5"
FT REGION 666..814
FT /note="Interacts with RAB6A"
FT /evidence="ECO:0000250|UniProtKB:Q921C5"
FT REGION 804..824
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 20..269
FT /evidence="ECO:0000255"
FT COILED 338..537
FT /evidence="ECO:0000255"
FT COILED 666..808
FT /evidence="ECO:0000255"
FT COMPBIAS 404..425
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 190
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 319
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 395
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 568
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 574
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 582
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15144186,
FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 602
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 821
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 823
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 824
FT /note="L -> VSHTCACASDRAEGTGLANQVFCSEKHSIYCD (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:9734811"
FT /id="VSP_007969"
FT VARIANT 90
FT /note="K -> R (in dbSNP:rs61754130)"
FT /evidence="ECO:0000269|PubMed:23664116"
FT /id="VAR_070111"
FT VARIANT 107
FT /note="S -> L (in SMALED2A; causes Golgi fragmentation;
FT affects interaction with RAB6A and DNAI1 and the
FT subcellular location of the protein; dbSNP:rs398123028)"
FT /evidence="ECO:0000269|PubMed:23664116,
FT ECO:0000269|PubMed:23664119, ECO:0000269|PubMed:23664120"
FT /id="VAR_070112"
FT VARIANT 188
FT /note="N -> T (in SMALED2A; causes Golgi fragmentation;
FT dbSNP:rs398123029)"
FT /evidence="ECO:0000269|PubMed:23664116"
FT /id="VAR_070113"
FT VARIANT 189
FT /note="I -> F (in SMALED2A; dbSNP:rs1587671674)"
FT /evidence="ECO:0000269|PubMed:23664120"
FT /id="VAR_070114"
FT VARIANT 194
FT /note="Q -> R (in SMALED2B; dbSNP:rs1564061982)"
FT /evidence="ECO:0000269|PubMed:28635954"
FT /id="VAR_081854"
FT VARIANT 501
FT /note="R -> P (in SMALED2A; the mutation causes increased
FT interaction with dynein; the mutant protein accumulates
FT abnormally in the perinuclear region where it forms ring-
FT like structures that colocalize with RAB6A;
FT dbSNP:rs398123032)"
FT /evidence="ECO:0000269|PubMed:23664120"
FT /id="VAR_070115"
FT VARIANT 508
FT /note="K -> T (in SMALED2A; dbSNP:rs398123031)"
FT /evidence="ECO:0000269|PubMed:23664120"
FT /id="VAR_070116"
FT VARIANT 542
FT /note="C -> W (in SMALED2B)"
FT /evidence="ECO:0000269|PubMed:28635954"
FT /id="VAR_081855"
FT VARIANT 546
FT /note="Missing (in SMALED2B; dbSNP:rs1064795760)"
FT /evidence="ECO:0000269|PubMed:30054298"
FT /id="VAR_081856"
FT VARIANT 694
FT /note="R -> C (in SMALED2B; dbSNP:rs797045412)"
FT /evidence="ECO:0000269|PubMed:27751653,
FT ECO:0000269|PubMed:28635954"
FT /id="VAR_081857"
FT VARIANT 703
FT /note="T -> M (in SMALED2A; causes Golgi fragmentation;
FT dbSNP:rs371707778)"
FT /evidence="ECO:0000269|PubMed:23664116,
FT ECO:0000269|PubMed:28635954"
FT /id="VAR_070117"
FT VARIANT 774
FT /note="E -> G (in SMALED2A; affects interaction with RAB6A
FT and DNAI1 and the subcellular location of the protein;
FT dbSNP:rs398123030)"
FT /evidence="ECO:0000269|PubMed:23664119"
FT /id="VAR_070118"
FT HELIX 6..16
FT /evidence="ECO:0007829|PDB:6PSE"
FT HELIX 19..78
FT /evidence="ECO:0007829|PDB:6PSE"
FT HELIX 715..740
FT /evidence="ECO:0007829|PDB:6OFP"
FT HELIX 743..799
FT /evidence="ECO:0007829|PDB:6OFP"
SQ SEQUENCE 824 AA; 93533 MW; 9C49138FF416378D CRC64;
MSAPSEEEEY ARLVMEAQPE WLRAEVKRLS HELAETTREK IQAAEYGLAV LEEKHQLKLQ
FEELEVDYEA IRSEMEQLKE AFGQAHTNHK KVAADGESRE ESLIQESASK EQYYVRKVLE
LQTELKQLRN VLTNTQSENE RLASVAQELK EINQNVEIQR GRLRDDIKEY KFREARLLQD
YSELEEENIS LQKQVSVLRQ NQVEFEGLKH EIKRLEEETE YLNSQLEDAI RLKEISERQL
EEALETLKTE REQKNSLRKE LSHYMSINDS FYTSHLHVSL DGLKFSDDAA EPNNDAEALV
NGFEHGGLAK LPLDNKTSTP KKEGLAPPSP SLVSDLLSEL NISEIQKLKQ QLMQMEREKA
GLLATLQDTQ KQLEHTRGSL SEQQEKVTRL TENLSALRRL QASKERQTAL DNEKDRDSHE
DGDYYEVDIN GPEILACKYH VAVAEAGELR EQLKALRSTH EAREAQHAEE KGRYEAEGQA
LTEKVSLLEK ASRQDRELLA RLEKELKKVS DVAGETQGSL SVAQDELVTF SEELANLYHH
VCMCNNETPN RVMLDYYREG QGGAGRTSPG GRTSPEARGR RSPILLPKGL LAPEAGRADG
GTGDSSPSPG SSLPSPLSDP RREPMNIYNL IAIIRDQIKH LQAAVDRTTE LSRQRIASQE
LGPAVDKDKE ALMEEILKLK SLLSTKREQI TTLRTVLKAN KQTAEVALAN LKSKYENEKA
MVTETMMKLR NELKALKEDA ATFSSLRAMF ATRCDEYITQ LDEMQRQLAA AEDEKKTLNS
LLRMAIQQKL ALTQRLELLE LDHEQTRRGR AKAAPKTKPA TPSL
