ID   HECW2_HUMAN             Reviewed;        1572 AA.
AC   Q9P2P5; B8ZZB4; Q17RT5; Q68DF8; Q9NPS9;
DT   20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT   20-FEB-2007, sequence version 2.
DT   27-MAR-2024, entry version 171.
DE   RecName: Full=E3 ubiquitin-protein ligase HECW2;
DE            EC=2.3.2.26;
DE   AltName: Full=HECT, C2 and WW domain-containing protein 2;
DE   AltName: Full=HECT-type E3 ubiquitin transferase HECW2;
DE   AltName: Full=NEDD4-like E3 ubiquitin-protein ligase 2;
GN   Name=HECW2; Synonyms=KIAA1301, NEDL2;
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 1).
RC   TISSUE=Brain;
RX   PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA   Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XVI. The
RT   complete sequences of 150 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 7:65-73(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 1352-1572 (ISOFORM 1).
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Heart, and Lung;
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   FUNCTION, INTERACTION WITH TP73, AND TISSUE SPECIFICITY.
RX   PubMed=12890487; DOI=10.1016/s0006-291x(03)01347-0;
RA   Miyazaki K., Ozaki T., Kato C., Hanamoto T., Fujita T., Irino S.,
RA   Watanabe K., Nakagawa T., Nakagawara A.;
RT   "A novel HECT-type E3 ubiquitin ligase, NEDL2, stabilizes p73 and enhances
RT   its transcriptional activity.";
RL   Biochem. Biophys. Res. Commun. 308:106-113(2003).
RN   [6]
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   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [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   [8]
RP   IDENTIFICATION BY 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   [9]
RP   FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FZR1, AND UBIQUITINATION.
RX   PubMed=24163370; DOI=10.1074/jbc.m113.472076;
RA   Lu L., Hu S., Wei R., Qiu X., Lu K., Fu Y., Li H., Xing G., Li D., Peng R.,
RA   He F., Zhang L.;
RT   "The HECT type ubiquitin ligase NEDL2 is degraded by anaphase-promoting
RT   complex/cyclosome (APC/C)-Cdh1, and its tight regulation maintains the
RT   metaphase to anaphase transition.";
RL   J. Biol. Chem. 288:35637-35650(2013).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48; SER-852 AND SER-909, AND
RP   IDENTIFICATION BY MASS 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   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1175, 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   [12]
RP   INVOLVEMENT IN NDHSAL, AND VARIANTS NDHSAL GLN-1191; VAL-1193; TRP-1330 AND
RP   GLY-1445.
RX   PubMed=27389779; DOI=10.1136/jmedgenet-2016-103943;
RA   Berko E.R., Cho M.T., Eng C., Shao Y., Sweetser D.A., Waxler J.,
RA   Robin N.H., Brewer F., Donkervoort S., Mohassel P., Boennemann C.G.,
RA   Bialer M., Moore C., Wolfe L.A., Tifft C.J., Shen Y., Retterer K.,
RA   Millan F., Chung W.K.;
RT   "De novo missense variants in HECW2 are associated with neurodevelopmental
RT   delay and hypotonia.";
RL   J. Med. Genet. 54:84-86(2017).
CC   -!- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of
CC       TP73. Acts to stabilize TP73 and enhance activation of transcription by
CC       TP73 (PubMed:12890487). Involved in the regulation of mitotic
CC       metaphase/anaphase transition (PubMed:24163370).
CC       {ECO:0000269|PubMed:12890487, ECO:0000269|PubMed:24163370}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC         [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC         cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC         EC=2.3.2.26;
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Interacts with TP73 (PubMed:12890487). Interacts with FZR1
CC       (PubMed:24163370). {ECO:0000269|PubMed:12890487,
CC       ECO:0000269|PubMed:24163370}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasm, cytoskeleton,
CC       spindle {ECO:0000269|PubMed:24163370}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9P2P5-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9P2P5-2; Sequence=VSP_059106, VSP_059107, VSP_059108;
CC   -!- TISSUE SPECIFICITY: Predominantly expressed in adult brain, lung and
CC       heart. {ECO:0000269|PubMed:12890487}.
CC   -!- PTM: Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1.
CC       {ECO:0000269|PubMed:24163370}.
CC   -!- DISEASE: Neurodevelopmental disorder with hypotonia, seizures, and
CC       absent language (NDHSAL) [MIM:617268]: A neurodevelopmental disorder
CC       characterized by severely delayed psychomotor development, absent
CC       speech, epilepsy, encephalopathy, hypotonia, dystonia/dyskinesia, and
CC       macrocephaly. Brain imaging show cerebral atrophy, enlarged ventricles,
CC       and white matter abnormalities. {ECO:0000269|PubMed:27389779}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC       premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC       decay. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA92539.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=CAH18262.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
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DR   EMBL; AB037722; BAA92539.1; ALT_INIT; mRNA.
DR   EMBL; AL390186; CAB99103.1; -; mRNA.
DR   EMBL; CR749424; CAH18262.1; ALT_SEQ; mRNA.
DR   EMBL; AC020571; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC068544; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC073905; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC074090; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC093379; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC117194; AAI17195.1; -; mRNA.
DR   EMBL; BC117198; AAI17199.1; -; mRNA.
DR   CCDS; CCDS33354.1; -. [Q9P2P5-1]
DR   PIR; T51886; T51886.
DR   RefSeq; NP_065811.1; NM_020760.2. [Q9P2P5-1]
DR   RefSeq; XP_016860052.1; XM_017004563.1.
DR   PDB; 2LFE; NMR; -; A=43-162.
DR   PDBsum; 2LFE; -.
DR   AlphaFoldDB; Q9P2P5; -.
DR   SMR; Q9P2P5; -.
DR   BioGRID; 121581; 322.
DR   IntAct; Q9P2P5; 12.
DR   MINT; Q9P2P5; -.
DR   STRING; 9606.ENSP00000260983; -.
DR   GlyGen; Q9P2P5; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9P2P5; -.
DR   PhosphoSitePlus; Q9P2P5; -.
DR   BioMuta; HECW2; -.
DR   DMDM; 126215718; -.
DR   EPD; Q9P2P5; -.
DR   jPOST; Q9P2P5; -.
DR   MassIVE; Q9P2P5; -.
DR   MaxQB; Q9P2P5; -.
DR   PaxDb; 9606-ENSP00000260983; -.
DR   PeptideAtlas; Q9P2P5; -.
DR   ProteomicsDB; 83874; -. [Q9P2P5-1]
DR   ProteomicsDB; 83875; -. [Q9P2P5-2]
DR   Pumba; Q9P2P5; -.
DR   Antibodypedia; 34059; 208 antibodies from 26 providers.
DR   DNASU; 57520; -.
DR   Ensembl; ENST00000260983.8; ENSP00000260983.2; ENSG00000138411.13. [Q9P2P5-1]
DR   Ensembl; ENST00000644256.1; ENSP00000494649.1; ENSG00000138411.13. [Q9P2P5-1]
DR   Ensembl; ENST00000644978.2; ENSP00000495418.1; ENSG00000138411.13. [Q9P2P5-1]
DR   Ensembl; ENST00000647236.1; ENSP00000494800.1; ENSG00000138411.13. [Q9P2P5-2]
DR   GeneID; 57520; -.
DR   KEGG; hsa:57520; -.
DR   MANE-Select; ENST00000644978.2; ENSP00000495418.1; NM_001348768.2; NP_001335697.1.
DR   UCSC; uc002utl.2; human. [Q9P2P5-1]
DR   AGR; HGNC:29853; -.
DR   DisGeNET; 57520; -.
DR   GeneCards; HECW2; -.
DR   HGNC; HGNC:29853; HECW2.
DR   HPA; ENSG00000138411; Low tissue specificity.
DR   MalaCards; HECW2; -.
DR   MIM; 617245; gene.
DR   MIM; 617268; phenotype.
DR   neXtProt; NX_Q9P2P5; -.
DR   OpenTargets; ENSG00000138411; -.
DR   PharmGKB; PA134925001; -.
DR   VEuPathDB; HostDB:ENSG00000138411; -.
DR   eggNOG; KOG0940; Eukaryota.
DR   GeneTree; ENSGT00940000155466; -.
DR   HOGENOM; CLU_002173_14_0_1; -.
DR   InParanoid; Q9P2P5; -.
DR   OMA; TAGQHRE; -.
DR   OrthoDB; 5480520at2759; -.
DR   PhylomeDB; Q9P2P5; -.
DR   TreeFam; TF313938; -.
DR   PathwayCommons; Q9P2P5; -.
DR   Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   SignaLink; Q9P2P5; -.
DR   SIGNOR; Q9P2P5; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 57520; 16 hits in 1191 CRISPR screens.
DR   ChiTaRS; HECW2; human.
DR   GenomeRNAi; 57520; -.
DR   Pharos; Q9P2P5; Tbio.
DR   PRO; PR:Q9P2P5; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; Q9P2P5; Protein.
DR   Bgee; ENSG00000138411; Expressed in left ventricle myocardium and 166 other cell types or tissues.
DR   ExpressionAtlas; Q9P2P5; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB.
DR   GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR   GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR   GO; GO:0048814; P:regulation of dendrite morphogenesis; IBA:GO_Central.
DR   GO; GO:0030071; P:regulation of mitotic metaphase/anaphase transition; IMP:UniProtKB.
DR   CDD; cd08691; C2_NEDL1-like; 1.
DR   CDD; cd00078; HECTc; 1.
DR   CDD; cd00201; WW; 2.
DR   Gene3D; 2.20.70.10; -; 2.
DR   Gene3D; 2.60.40.2840; -; 1.
DR   Gene3D; 2.60.40.150; C2 domain; 1.
DR   Gene3D; 3.30.2160.10; Hect, E3 ligase catalytic domain; 1.
DR   Gene3D; 3.30.2410.10; Hect, E3 ligase catalytic domain; 1.
DR   Gene3D; 3.90.1750.10; Hect, E3 ligase catalytic domains; 1.
DR   InterPro; IPR000008; C2_dom.
DR   InterPro; IPR035892; C2_domain_sf.
DR   InterPro; IPR037795; C2_HECW.
DR   InterPro; IPR000569; HECT_dom.
DR   InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR   InterPro; IPR040524; HECW1_helix.
DR   InterPro; IPR032348; HECW_N.
DR   InterPro; IPR001202; WW_dom.
DR   InterPro; IPR036020; WW_dom_sf.
DR   PANTHER; PTHR11254:SF127; E3 UBIQUITIN-PROTEIN LIGASE HECW2; 1.
DR   PANTHER; PTHR11254; HECT DOMAIN UBIQUITIN-PROTEIN LIGASE; 1.
DR   Pfam; PF00168; C2; 1.
DR   Pfam; PF00632; HECT; 1.
DR   Pfam; PF18436; HECW1_helix; 1.
DR   Pfam; PF16562; HECW_N; 1.
DR   Pfam; PF00397; WW; 1.
DR   SMART; SM00239; C2; 1.
DR   SMART; SM00119; HECTc; 1.
DR   SMART; SM00456; WW; 2.
DR   SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1.
DR   SUPFAM; SSF56204; Hect, E3 ligase catalytic domain; 1.
DR   SUPFAM; SSF51045; WW domain; 2.
DR   PROSITE; PS50004; C2; 1.
DR   PROSITE; PS50237; HECT; 1.
DR   PROSITE; PS01159; WW_DOMAIN_1; 2.
DR   PROSITE; PS50020; WW_DOMAIN_2; 2.
DR   Genevisible; Q9P2P5; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Coiled coil; Cytoplasm; Cytoskeleton;
KW   Disease variant; Phosphoprotein; Reference proteome; Repeat; Transferase;
KW   Ubl conjugation; Ubl conjugation pathway.
FT   CHAIN           1..1572
FT                   /note="E3 ubiquitin-protein ligase HECW2"
FT                   /id="PRO_0000277667"
FT   DOMAIN          167..301
FT                   /note="C2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   DOMAIN          807..840
FT                   /note="WW 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT   DOMAIN          985..1018
FT                   /note="WW 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT   DOMAIN          1237..1572
FT                   /note="HECT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT   REGION          341..452
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          489..796
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          737..1068
FT                   /note="Interaction with TP73"
FT                   /evidence="ECO:0000269|PubMed:12890487"
FT   REGION          1024..1069
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1161..1187
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          847..874
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        382..413
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        430..452
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        510..534
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        563..627
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        641..672
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        691..707
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        775..796
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1163..1181
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        1540
FT                   /note="Glycyl thioester intermediate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT   MOD_RES         48
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         852
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         909
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         1175
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   VAR_SEQ         1..131
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:17974005"
FT                   /id="VSP_059106"
FT   VAR_SEQ         191..213
FT                   /note="DLRAVGLKKGMFFNPDPYLKMSI -> ARKEEQFPHLCPPRAGETVYYHQ
FT                   (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:17974005"
FT                   /id="VSP_059107"
FT   VAR_SEQ         214..1572
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:17974005"
FT                   /id="VSP_059108"
FT   VARIANT         1191
FT                   /note="R -> Q (in NDHSAL; dbSNP:rs878854416)"
FT                   /evidence="ECO:0000269|PubMed:27389779"
FT                   /id="VAR_077905"
FT   VARIANT         1193
FT                   /note="F -> V (in NDHSAL; dbSNP:rs878854422)"
FT                   /evidence="ECO:0000269|PubMed:27389779"
FT                   /id="VAR_077906"
FT   VARIANT         1330
FT                   /note="R -> W (in NDHSAL; dbSNP:rs878854417)"
FT                   /evidence="ECO:0000269|PubMed:27389779"
FT                   /id="VAR_077907"
FT   VARIANT         1445
FT                   /note="E -> G (in NDHSAL; dbSNP:rs878854424)"
FT                   /evidence="ECO:0000269|PubMed:27389779"
FT                   /id="VAR_077908"
FT   CONFLICT        1074
FT                   /note="Q -> H (in Ref. 2; CAH18262)"
FT                   /evidence="ECO:0000305"
FT   STRAND          60..64
FT                   /evidence="ECO:0007829|PDB:2LFE"
FT   STRAND          66..69
FT                   /evidence="ECO:0007829|PDB:2LFE"
FT   STRAND          76..81
FT                   /evidence="ECO:0007829|PDB:2LFE"
FT   STRAND          91..96
FT                   /evidence="ECO:0007829|PDB:2LFE"
FT   STRAND          117..123
FT                   /evidence="ECO:0007829|PDB:2LFE"
FT   STRAND          133..144
FT                   /evidence="ECO:0007829|PDB:2LFE"
FT   TURN            145..148
FT                   /evidence="ECO:0007829|PDB:2LFE"
FT   STRAND          149..153
FT                   /evidence="ECO:0007829|PDB:2LFE"
FT   STRAND          157..160
FT                   /evidence="ECO:0007829|PDB:2LFE"
SQ   SEQUENCE   1572 AA;  175769 MW;  DCFF0146ADFAF8BE CRC64;
     MASSAREHLL FVRRRNPQMR YTLSPENLQS LAAQSSMPEN MTLQRANSDT DLVTSESRSS
     LTASMYEYTL GQAQNLIIFW DIKEEVDPSD WIGLYHIDEN SPANFWDSKN RGVTGTQKGQ
     IVWRIEPGPY FMEPEIKICF KYYHGISGAL RATTPCITVK NPAVMMGAEG MEGGASGNLH
     SRKLVSFTLS DLRAVGLKKG MFFNPDPYLK MSIQPGKKSS FPTCAHHGQE RRSTIISNTT
     NPIWHREKYS FFALLTDVLE IEIKDKFAKS RPIIKRFLGK LTIPVQRLLE RQAIGDQMLS
     YNLGRRLPAD HVSGYLQFKV EVTSSVHEDA SPEAVGTILG VNSVNGDLGS PSDDEDMPGS
     HHDSQVCSNG PVSEDSAADG TPKHSFRTSS TLEIDTEELT STSSRTSPPR GRQDSLNDYL
     DAIEHNGHSR PGTATCSERS MGASPKLRSS FPTDTRLNAM LHIDSDEEDH EFQQDLGYPS
     SLEEEGGLIM FSRASRADDG SLTSQTKLED NPVENEEAST HEAASFEDKP ENLPELAESS
     LPAGPAPEEG EGGPEPQPSA DQGSAELCGS QEVDQPTSGA DTGTSDASGG SRRAVSETES
     LDQGSEPSQV SSETEPSDPA RTESVSEAST RPEGESDLEC ADSSCNESVT TQLSSVDTRC
     SSLESARFPE TPAFSSQEEE DGACAAEPTS SGPAEGSQES VCTAGSLPVV QVPSGEDEGP
     GAESATVPDQ EELGEVWQRR GSLEGAAAAA ESPPQEEGSA GEAQGTCEGA TAQEEGATGG
     SQANGHQPLR SLPSVRQDVS RYQRVDEALP PNWEARIDSH GRIFYVDHVN RTTTWQRPTA
     PPAPQVLQRS NSIQQMEQLN RRYQSIRRTM TNERPEENTN AIDGAGEEAD FHQASADFRR
     ENILPHSTSR SRITLLLQSP PVKFLISPEF FTVLHSNPSA YRMFTNNTCL KHMITKVRRD
     THHFERYQHN RDLVGFLNMF ANKQLELPRG WEMKHDHQGK AFFVDHNSRT TTFIDPRLPL
     QSSRPTSALV HRQHLTRQRS HSAGEVGEDS RHAGPPVLPR PSSTFNTVSR PQYQDMVPVA
     YNDKIVAFLR QPNIFEILQE RQPDLTRNHS LREKIQFIRT EGTPGLVRLS SDADLVMLLS
     LFEEEIMSYV PPHALLHPSY CQSPRGSPVS SPQNSPGTQR ANARAPAPYK RDFEAKLRNF
     YRKLETKGYG QGPGKLKLII RRDHLLEDAF NQIMGYSRKD LQRNKLYVTF VGEEGLDYSG
     PSREFFFLVS RELFNPYYGL FEYSANDTYT VQISPMSAFV DNHHEWFRFS GRILGLALIH
     QYLLDAFFTR PFYKALLRIL CDLSDLEYLD EEFHQSLQWM KDNDIHDILD LTFTVNEEVF
     GQITERELKP GGANIPVTEK NKKEYIERMV KWRIERGVVQ QTESLVRGFY EVVDARLVSV
     FDARELELVI AGTAEIDLSD WRNNTEYRGG YHDNHIVIRW FWAAVERFNN EQRLRLLQFV
     TGTSSIPYEG FASLRGSNGP RRFCVEKWGK ITALPRAHTC FNRLDLPPYP SFSMLYEKLL
     TAVEETSTFG LE
//