ANKL2_HUMAN
ID ANKL2_HUMAN Reviewed; 938 AA.
AC Q86XL3; A8KAG3; B3KN97; B3KSF8; O75176; Q6P6A5; Q8TAZ9; Q96DH4;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 4.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Ankyrin repeat and LEM domain-containing protein 2;
DE AltName: Full=LEM domain-containing protein 4;
GN Name=ANKLE2; Synonyms=KIAA0692, LEM4;
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 [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 409-938 (ISOFORM 1).
RC TISSUE=Testis, and Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 208-938 (ISOFORM 2), AND VARIANTS TYR-122 AND
RP HIS-720.
RC TISSUE=Brain, 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 156-938 (ISOFORM 1), AND VARIANT
RP HIS-720.
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259; SER-268; SER-488;
RP SER-496; SER-512; SER-662; SER-896 AND SER-914, AND IDENTIFICATION BY MASS
RP 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 [7]
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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-496 AND SER-662, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-662, 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 [11]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND INTERACTION WITH BANF1 AND
RP PROTEIN PHOSPHATASE 2A.
RX PubMed=22770216; DOI=10.1016/j.cell.2012.04.043;
RA Asencio C., Davidson I.F., Santarella-Mellwig R., Ly-Hartig T.B., Mall M.,
RA Wallenfang M.R., Mattaj I.W., Gorjanacz M.;
RT "Coordination of kinase and phosphatase activities by Lem4 enables nuclear
RT envelope reassembly during mitosis.";
RL Cell 150:122-135(2012).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268; SER-496; SER-512;
RP SER-528; SER-662 AND SER-804, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [13]
RP INVOLVEMENT IN MCPH16, VARIANTS MCPH16 VAL-573 AND 782-GLN--LEU-938 DEL,
RP AND FUNCTION.
RX PubMed=25259927; DOI=10.1016/j.cell.2014.09.002;
RA Yamamoto S., Jaiswal M., Charng W.L., Gambin T., Karaca E., Mirzaa G.,
RA Wiszniewski W., Sandoval H., Haelterman N.A., Xiong B., Zhang K., Bayat V.,
RA David G., Li T., Chen K., Gala U., Harel T., Pehlivan D., Penney S.,
RA Vissers L.E., de Ligt J., Jhangiani S.N., Xie Y., Tsang S.H., Parman Y.,
RA Sivaci M., Battaloglu E., Muzny D., Wan Y.W., Liu Z., Lin-Moore A.T.,
RA Clark R.D., Curry C.J., Link N., Schulze K.L., Boerwinkle E., Dobyns W.B.,
RA Allikmets R., Gibbs R.A., Chen R., Lupski J.R., Wangler M.F., Bellen H.J.;
RT "A drosophila genetic resource of mutants to study mechanisms underlying
RT human genetic diseases.";
RL Cell 159:200-214(2014).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-528, 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 [15]
RP INTERACTION WITH ZIKA VIRUS MR-766 NS4A AND ZIKA VIRUS FRENCH POLYNESIA
RP 10087PF 2013 NS4A.
RX PubMed=30550790; DOI=10.1016/j.cell.2018.11.028;
RA Shah P.S., Link N., Jang G.M., Sharp P.P., Zhu T., Swaney D.L.,
RA Johnson J.R., Von Dollen J., Ramage H.R., Satkamp L., Newton B.,
RA Huettenhain R., Petit M.J., Baum T., Everitt A., Laufman O., Tassetto M.,
RA Shales M., Stevenson E., Iglesias G.N., Shokat L., Tripathi S.,
RA Balasubramaniam V., Webb L.G., Aguirre S., Willsey A.J., Garcia-Sastre A.,
RA Pollard K.S., Cherry S., Gamarnik A.V., Marazzi I., Taunton J.,
RA Fernandez-Sesma A., Bellen H.J., Andino R., Krogan N.J.;
RT "Comparative Flavivirus-Host Protein Interaction Mapping Reveals Mechanisms
RT of Dengue and Zika Virus Pathogenesis.";
RL Cell 175:1931-1945(2018).
RN [16]
RP FUNCTION, VARIANTS MCPH16 VAL-8; GLY-27; PRO-109; TRP-201; GLY-229;
RP 236-ARG--LEU-938 DEL; CYS-536; VAL-573 AND 782-GLN--LEU-938 DEL, AND
RP CHARACTERIZATION OF VARIANT MCPH16 GLY-229.
RX PubMed=31735666; DOI=10.1016/j.devcel.2019.10.009;
RA Link N., Chung H., Jolly A., Withers M., Tepe B., Arenkiel B.R., Shah P.S.,
RA Krogan N.J., Aydin H., Geckinli B.B., Tos T., Isikay S., Tuysuz B.,
RA Mochida G.H., Thomas A.X., Clark R.D., Mirzaa G.M., Lupski J.R.,
RA Bellen H.J.;
RT "Mutations in ANKLE2, a ZIKA Virus Target, Disrupt an Asymmetric Cell
RT Division Pathway in Drosophila Neuroblasts to Cause Microcephaly.";
RL Dev. Cell 51:713-729.e6(2019).
RN [17]
RP VARIANTS MCPH16 PRO-109 AND VAL-585.
RX PubMed=30214071; DOI=10.1038/s41436-018-0140-3;
RA Shaheen R., Maddirevula S., Ewida N., Alsahli S., Abdel-Salam G.M.H.,
RA Zaki M.S., Tala S.A., Alhashem A., Softah A., Al-Owain M., Alazami A.M.,
RA Abadel B., Patel N., Al-Sheddi T., Alomar R., Alobeid E., Ibrahim N.,
RA Hashem M., Abdulwahab F., Hamad M., Tabarki B., Alwadei A.H., Alhazzani F.,
RA Bashiri F.A., Kentab A., Sahintuerk S., Sherr E., Fregeau B., Sogati S.,
RA Alshahwan S.A.M., Alkhalifi S., Alhumaidi Z., Temtamy S., Aglan M.,
RA Otaify G., Girisha K.M., Tulbah M., Seidahmed M.Z., Salih M.A.,
RA Abouelhoda M., Momin A.A., Saffar M.A., Partlow J.N., Arold S.T.,
RA Faqeih E., Walsh C., Alkuraya F.S.;
RT "Genomic and phenotypic delineation of congenital microcephaly.";
RL Genet. Med. 21:545-552(2019).
CC -!- FUNCTION: Involved in mitotic nuclear envelope reassembly by promoting
CC dephosphorylation of BAF/BANF1 during mitotic exit (PubMed:22770216).
CC Coordinates the control of BAF/BANF1 dephosphorylation by inhibiting
CC VRK1 kinase and promoting dephosphorylation of BAF/BANF1 by protein
CC phosphatase 2A (PP2A), thereby facilitating nuclear envelope assembly
CC (PubMed:22770216). May regulate nuclear localization of VRK1 in non-
CC dividing cells (PubMed:31735666). It is unclear whether it acts as a
CC real PP2A regulatory subunit or whether it is involved in recruitment
CC of the PP2A complex (PubMed:22770216). Involved in brain development
CC (PubMed:25259927). {ECO:0000269|PubMed:22770216,
CC ECO:0000269|PubMed:25259927, ECO:0000269|PubMed:31735666}.
CC -!- SUBUNIT: Interacts with BAF/BANF1. Interacts with protein phosphatase
CC 2A (PP2A) components PPP2C (PPP2CA or PPP2CB) and PPP2R1A.
CC {ECO:0000269|PubMed:22770216}.
CC -!- SUBUNIT: (Microbial infection) May interact with non-structural protein
CC 4A/NS4A from Zika virus strains Mr-766 or French Polynesia
CC 10087PF/2013; the interaction may inhibit ANKLE2 function and
CC contribute to defects in brain development, such as microcephaly.
CC {ECO:0000269|PubMed:30550790}.
CC -!- INTERACTION:
CC Q86XL3; Q19848: vrk-1; Xeno; NbExp=2; IntAct=EBI-1773621, EBI-2414048;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:22770216}; Single-pass type III membrane protein
CC {ECO:0000269|PubMed:22770216}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q86XL3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86XL3-2; Sequence=VSP_023574, VSP_023575;
CC Name=3;
CC IsoId=Q86XL3-3; Sequence=VSP_044173;
CC -!- DISEASE: Microcephaly 16, primary, autosomal recessive (MCPH16)
CC [MIM:616681]: A form of microcephaly, a disease defined as a head
CC circumference more than 3 standard deviations below the age, sex and
CC ethnically matched mean. Brain weight is markedly reduced and the
CC cerebral cortex is disproportionately small.
CC {ECO:0000269|PubMed:25259927, ECO:0000269|PubMed:30214071,
CC ECO:0000269|PubMed:31735666}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ANKLE2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAG51259.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK024061; BAG51259.1; ALT_INIT; mRNA.
DR EMBL; AK093451; BAG52720.1; -; mRNA.
DR EMBL; AK293028; BAF85717.1; -; mRNA.
DR EMBL; AC135586; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC136467; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001530; AAH01530.2; -; mRNA.
DR EMBL; BC025347; AAH25347.1; -; mRNA.
DR EMBL; BC043157; AAH43157.2; -; mRNA.
DR EMBL; BC062373; AAH62373.1; -; mRNA.
DR EMBL; BC082962; AAH82962.1; -; mRNA.
DR EMBL; AB014592; BAA31667.1; -; mRNA.
DR CCDS; CCDS41869.1; -. [Q86XL3-1]
DR PIR; T00354; T00354.
DR RefSeq; NP_055929.1; NM_015114.2. [Q86XL3-1]
DR RefSeq; XP_011533089.1; XM_011534787.2. [Q86XL3-2]
DR RefSeq; XP_011533090.1; XM_011534788.1. [Q86XL3-2]
DR AlphaFoldDB; Q86XL3; -.
DR SMR; Q86XL3; -.
DR BioGRID; 116758; 201.
DR IntAct; Q86XL3; 43.
DR MINT; Q86XL3; -.
DR STRING; 9606.ENSP00000350686; -.
DR iPTMnet; Q86XL3; -.
DR MetOSite; Q86XL3; -.
DR PhosphoSitePlus; Q86XL3; -.
DR BioMuta; ANKLE2; -.
DR DMDM; 269849748; -.
DR EPD; Q86XL3; -.
DR jPOST; Q86XL3; -.
DR MassIVE; Q86XL3; -.
DR MaxQB; Q86XL3; -.
DR PaxDb; Q86XL3; -.
DR PeptideAtlas; Q86XL3; -.
DR PRIDE; Q86XL3; -.
DR ProteomicsDB; 1900; -.
DR ProteomicsDB; 70296; -. [Q86XL3-1]
DR ProteomicsDB; 70297; -. [Q86XL3-2]
DR Antibodypedia; 1225; 106 antibodies from 23 providers.
DR DNASU; 23141; -.
DR Ensembl; ENST00000357997.10; ENSP00000350686.5; ENSG00000176915.15. [Q86XL3-1]
DR Ensembl; ENST00000542282.5; ENSP00000437807.1; ENSG00000176915.15. [Q86XL3-3]
DR Ensembl; ENST00000542657.5; ENSP00000438551.1; ENSG00000176915.15. [Q86XL3-3]
DR GeneID; 23141; -.
DR KEGG; hsa:23141; -.
DR MANE-Select; ENST00000357997.10; ENSP00000350686.5; NM_015114.3; NP_055929.1.
DR UCSC; uc001ukx.3; human. [Q86XL3-1]
DR CTD; 23141; -.
DR DisGeNET; 23141; -.
DR GeneCards; ANKLE2; -.
DR HGNC; HGNC:29101; ANKLE2.
DR HPA; ENSG00000176915; Low tissue specificity.
DR MalaCards; ANKLE2; -.
DR MIM; 616062; gene.
DR MIM; 616681; phenotype.
DR neXtProt; NX_Q86XL3; -.
DR OpenTargets; ENSG00000176915; -.
DR Orphanet; 2512; Autosomal recessive primary microcephaly.
DR PharmGKB; PA162376532; -.
DR VEuPathDB; HostDB:ENSG00000176915; -.
DR eggNOG; ENOG502QQ4Z; Eukaryota.
DR GeneTree; ENSGT00390000016767; -.
DR HOGENOM; CLU_017564_0_0_1; -.
DR InParanoid; Q86XL3; -.
DR OMA; EYLEDRC; -.
DR OrthoDB; 567264at2759; -.
DR PhylomeDB; Q86XL3; -.
DR TreeFam; TF317729; -.
DR PathwayCommons; Q86XL3; -.
DR Reactome; R-HSA-2995383; Initiation of Nuclear Envelope (NE) Reformation.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013408; RHOG GTPase cycle.
DR SignaLink; Q86XL3; -.
DR SIGNOR; Q86XL3; -.
DR BioGRID-ORCS; 23141; 775 hits in 1089 CRISPR screens.
DR ChiTaRS; ANKLE2; human.
DR GenomeRNAi; 23141; -.
DR Pharos; Q86XL3; Tbio.
DR PRO; PR:Q86XL3; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q86XL3; protein.
DR Bgee; ENSG00000176915; Expressed in stromal cell of endometrium and 200 other tissues.
DR ExpressionAtlas; Q86XL3; baseline and differential.
DR Genevisible; Q86XL3; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IDA:UniProtKB.
DR GO; GO:0019888; F:protein phosphatase regulator activity; TAS:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007417; P:central nervous system development; IDA:UniProtKB.
DR GO; GO:0007084; P:mitotic nuclear membrane reassembly; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0042326; P:negative regulation of phosphorylation; IDA:UniProtKB.
DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; IDA:UniProtKB.
DR GO; GO:0050790; P:regulation of catalytic activity; TAS:UniProtKB.
DR CDD; cd12944; LEM_ANKL2; 1.
DR Gene3D; 1.10.720.40; -; 1.
DR Gene3D; 1.25.40.20; -; 1.
DR Gene3D; 3.40.970.10; -; 1.
DR InterPro; IPR035007; ANKLE2.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR011015; LEM/LEM-like_dom_sf.
DR InterPro; IPR035006; LEM_ANKL2.
DR InterPro; IPR003887; LEM_dom.
DR InterPro; IPR011320; RNase_H1_N.
DR InterPro; IPR037056; RNase_H1_N_sf.
DR PANTHER; PTHR12349:SF4; PTHR12349:SF4; 1.
DR Pfam; PF01693; Cauli_VI; 1.
DR Pfam; PF03020; LEM; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF63451; SSF63451; 1.
DR PROSITE; PS50954; LEM; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Cell cycle; Cell division;
KW Disease variant; Endoplasmic reticulum; Membrane; Mitosis; Phosphoprotein;
KW Primary microcephaly; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..938
FT /note="Ankyrin repeat and LEM domain-containing protein 2"
FT /id="PRO_0000280242"
FT TOPO_DOM 1..12
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 13..32
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 33..938
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 69..113
FT /note="LEM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00313"
FT REPEAT 411..440
FT /note="ANK"
FT REGION 609..636
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 870..924
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 889..903
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 259
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 268
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 488
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 496
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 512
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 528
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 804
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 896
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 914
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 1..645
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044173"
FT VAR_SEQ 631..648
FT /note="GSNSISVRAFLDEDDMSL -> VEMRFHRIDQAGLELLTS (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023574"
FT VAR_SEQ 649..938
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023575"
FT VARIANT 8
FT /note="A -> V (in MCPH16; unknown pathological
FT significance; dbSNP:rs986142623)"
FT /evidence="ECO:0000269|PubMed:31735666"
FT /id="VAR_083604"
FT VARIANT 27
FT /note="A -> G (in MCPH16; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:31735666"
FT /id="VAR_083605"
FT VARIANT 109
FT /note="A -> P (in MCPH16)"
FT /evidence="ECO:0000269|PubMed:30214071,
FT ECO:0000269|PubMed:31735666"
FT /id="VAR_083606"
FT VARIANT 122
FT /note="H -> Y (in dbSNP:rs1132375)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_031097"
FT VARIANT 148
FT /note="Q -> E (in dbSNP:rs7968520)"
FT /id="VAR_031098"
FT VARIANT 201
FT /note="G -> W (in MCPH16; dbSNP:rs1185537869)"
FT /evidence="ECO:0000269|PubMed:31735666"
FT /id="VAR_083607"
FT VARIANT 229
FT /note="V -> G (in MCPH16; unknown pathological
FT significance; severe loss of VRK1 nuclear localization in
FT non-dividing cells)"
FT /evidence="ECO:0000269|PubMed:31735666"
FT /id="VAR_083608"
FT VARIANT 236..938
FT /note="Missing (in MCPH16; unknown pathological
FT significance; dbSNP:rs753596204)"
FT /evidence="ECO:0000269|PubMed:31735666"
FT /id="VAR_083609"
FT VARIANT 536
FT /note="R -> C (in MCPH16; unknown pathological
FT significance; dbSNP:rs761627940)"
FT /evidence="ECO:0000269|PubMed:31735666"
FT /id="VAR_083610"
FT VARIANT 573
FT /note="L -> V (in MCPH16; unknown pathological
FT significance; dbSNP:rs863225465)"
FT /evidence="ECO:0000269|PubMed:25259927,
FT ECO:0000269|PubMed:31735666"
FT /id="VAR_076205"
FT VARIANT 585
FT /note="G -> V (in MCPH16; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30214071"
FT /id="VAR_083611"
FT VARIANT 720
FT /note="R -> H (in dbSNP:rs10781634)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9734811"
FT /id="VAR_031099"
FT VARIANT 782..938
FT /note="Missing (in MCPH16; dbSNP:rs201785518)"
FT /evidence="ECO:0000269|PubMed:25259927,
FT ECO:0000269|PubMed:31735666"
FT /id="VAR_083612"
FT CONFLICT 266
FT /note="P -> Q (in Ref. 3; AAH43157)"
FT /evidence="ECO:0000305"
FT CONFLICT 481
FT /note="L -> V (in Ref. 3; AAH43157)"
FT /evidence="ECO:0000305"
FT CONFLICT 647
FT /note="S -> N (in Ref. 3; AAH43157)"
FT /evidence="ECO:0000305"
FT CONFLICT 662
FT /note="S -> I (in Ref. 1; BAG52720)"
FT /evidence="ECO:0000305"
FT CONFLICT 680
FT /note="E -> K (in Ref. 1; BAG52720)"
FT /evidence="ECO:0000305"
FT CONFLICT 863
FT /note="L -> P (in Ref. 1; BAG51259)"
FT /evidence="ECO:0000305"
FT CONFLICT 891
FT /note="G -> A (in Ref. 1; BAG52720)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 938 AA; 104114 MW; ED2F25F05E8106F2 CRC64;
MLWPRLAAAE WAALAWELLG ASVLLIAVRW LVRRLGPRPG GLGRSGTPVP PPSAAAAPAS
GEMTMDALLA RLKLLNPDDL REEIVKAGLK CGPITSTTRF IFEKKLAQAL LEQGGRLSSF
YHHEAGVTAL SQDPQRILKP AEGNPTDQAG FSEDRDFGYS VGLNPPEEEA VTSKTCSVPP
SDTDTYRAGA TASKEPPLYY GVCPVYEDVP ARNERIYVYE NKKEALQAVK MIKGSRFKAF
STREDAEKFA RGICDYFPSP SKTSLPLSPV KTAPLFSNDR LKDGLCLSES ETVNKERANS
YKNPRTQDLT AKLRKAVEKG EEDTFSDLIW SNPRYLIGSG DNPTIVQEGC RYNVMHVAAK
ENQASICQLT LDVLENPDFM RLMYPDDDEA MLQKRIRYVV DLYLNTPDKM GYDTPLHFAC
KFGNADVVNV LSSHHLIVKN SRNKYDKTPE DVICERSKNK SVELKERIRE YLKGHYYVPL
LRAEETSSPV IGELWSPDQT AEASHVSRYG GSPRDPVLTL RAFAGPLSPA KAEDFRKLWK
TPPREKAGFL HHVKKSDPER GFERVGRELA HELGYPWVEY WEFLGCFVDL SSQEGLQRLE
EYLTQQEIGK KAQQETGERE ASCRDKATTS GSNSISVRAF LDEDDMSLEE IKNRQNAARN
NSPPTVGAFG HTRCSAFPLE QEADLIEAAE PGGPHSSRNG LCHPLNHSRT LAGKRPKAPR
GEEAHLPPVS DLTVEFDKLN LQNIGRSVSK TPDESTKTKD QILTSRINAV ERDLLEPSPA
DQLGNGHRRT ESEMSARIAK MSLSPSSPRH EDQLEVTREP ARRLFLFGEE PSKLDQDVLA
ALECADVDPH QFPAVHRWKS AVLCYSPSDR QSWPSPAVKG RFKSQLPDLS GPHSYSPGRN
SVAGSNPAKP GLGSPGRYSP VHGSQLRRMA RLAELAAL
