NECP2_HUMAN
ID NECP2_HUMAN Reviewed; 263 AA.
AC Q9NVZ3; B4DY19; E9PGQ8; Q5VSU4; Q5VSU5; Q9H7L1; Q9H8L1;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Adaptin ear-binding coat-associated protein 2;
DE AltName: Full=NECAP endocytosis-associated protein 2;
DE Short=NECAP-2;
GN Name=NECAP2;
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).
RC TISSUE=Spleen;
RX PubMed=11214971; DOI=10.1093/dnares/7.6.357;
RA Hattori A., Okumura K., Nagase T., Kikuno R., Hirosawa M., Ohara O.;
RT "Characterization of long cDNA clones from human adult spleen.";
RL DNA Res. 7:357-366(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4).
RC TISSUE=Placenta, Spleen, and Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon, and Eye;
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 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 [6]
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, AND IDENTIFICATION BY
RP 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 [8]
RP IDENTIFICATION BY 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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Involved in endocytosis. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with AP1G1 and AP2A1 components of the adapter
CC protein complexes AP-1 and AP-2. Interacts with the GAE domain proteins
CC GGA1, GGA2 and GGA3 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, clathrin-coated vesicle
CC membrane {ECO:0000250}. Cell membrane {ECO:0000250}. Note=Colocalizes
CC with AP-2 at the plasma membrane. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9NVZ3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NVZ3-2; Sequence=VSP_013236;
CC Name=3;
CC IsoId=Q9NVZ3-3; Sequence=VSP_013234, VSP_013235;
CC Name=4;
CC IsoId=Q9NVZ3-4; Sequence=VSP_041726;
CC -!- DOMAIN: The WXXF motifs mediate binding of accessory proteins to the
CC ear-domain of AP-1, GGAs and AP-2 through hydrophobic interactions.
CC Selective binding to the GAE domains of AP-1 or to the alpha-ear domain
CC of AP-2 is tuned by the acidic context surrounding the motif and the
CC properties of the second residue of the motif itself (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the NECAP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15758.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK024468; BAB15758.1; ALT_INIT; mRNA.
DR EMBL; AK302227; BAG63581.1; -; mRNA.
DR EMBL; AK001282; BAA91598.1; -; mRNA.
DR EMBL; AK023545; BAB14605.1; -; mRNA.
DR EMBL; AL137802; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL669962; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017014; AAH17014.1; -; mRNA.
DR EMBL; BC018914; AAH18914.1; -; mRNA.
DR CCDS; CCDS173.1; -. [Q9NVZ3-1]
DR CCDS; CCDS44066.1; -. [Q9NVZ3-2]
DR CCDS; CCDS44067.1; -. [Q9NVZ3-4]
DR RefSeq; NP_001138749.1; NM_001145277.1. [Q9NVZ3-2]
DR RefSeq; NP_001138750.1; NM_001145278.1. [Q9NVZ3-4]
DR RefSeq; NP_060560.1; NM_018090.4. [Q9NVZ3-1]
DR AlphaFoldDB; Q9NVZ3; -.
DR SMR; Q9NVZ3; -.
DR BioGRID; 120832; 43.
DR IntAct; Q9NVZ3; 23.
DR STRING; 9606.ENSP00000391942; -.
DR GlyGen; Q9NVZ3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NVZ3; -.
DR MetOSite; Q9NVZ3; -.
DR PhosphoSitePlus; Q9NVZ3; -.
DR BioMuta; NECAP2; -.
DR DMDM; 62287168; -.
DR EPD; Q9NVZ3; -.
DR jPOST; Q9NVZ3; -.
DR MassIVE; Q9NVZ3; -.
DR MaxQB; Q9NVZ3; -.
DR PaxDb; Q9NVZ3; -.
DR PeptideAtlas; Q9NVZ3; -.
DR PRIDE; Q9NVZ3; -.
DR ProteomicsDB; 82880; -. [Q9NVZ3-1]
DR ProteomicsDB; 82881; -. [Q9NVZ3-2]
DR ProteomicsDB; 82882; -. [Q9NVZ3-3]
DR ProteomicsDB; 82883; -. [Q9NVZ3-4]
DR Antibodypedia; 29202; 64 antibodies from 22 providers.
DR DNASU; 55707; -.
DR Ensembl; ENST00000337132.10; ENSP00000338746.5; ENSG00000157191.20. [Q9NVZ3-1]
DR Ensembl; ENST00000443980.6; ENSP00000391942.2; ENSG00000157191.20. [Q9NVZ3-2]
DR Ensembl; ENST00000457722.6; ENSP00000407091.2; ENSG00000157191.20. [Q9NVZ3-4]
DR Ensembl; ENST00000492095.5; ENSP00000427620.1; ENSG00000157191.20. [Q9NVZ3-1]
DR GeneID; 55707; -.
DR KEGG; hsa:55707; -.
DR MANE-Select; ENST00000337132.10; ENSP00000338746.5; NM_018090.5; NP_060560.1.
DR UCSC; uc001ayo.4; human. [Q9NVZ3-1]
DR CTD; 55707; -.
DR DisGeNET; 55707; -.
DR GeneCards; NECAP2; -.
DR HGNC; HGNC:25528; NECAP2.
DR HPA; ENSG00000157191; Low tissue specificity.
DR MIM; 611624; gene.
DR neXtProt; NX_Q9NVZ3; -.
DR OpenTargets; ENSG00000157191; -.
DR PharmGKB; PA142671268; -.
DR VEuPathDB; HostDB:ENSG00000157191; -.
DR eggNOG; KOG2500; Eukaryota.
DR GeneTree; ENSGT00390000009359; -.
DR HOGENOM; CLU_069884_1_0_1; -.
DR InParanoid; Q9NVZ3; -.
DR OMA; NEGHRAQ; -.
DR OrthoDB; 1605812at2759; -.
DR PhylomeDB; Q9NVZ3; -.
DR TreeFam; TF314482; -.
DR PathwayCommons; Q9NVZ3; -.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR SignaLink; Q9NVZ3; -.
DR BioGRID-ORCS; 55707; 6 hits in 1074 CRISPR screens.
DR ChiTaRS; NECAP2; human.
DR GeneWiki; NECAP2; -.
DR GenomeRNAi; 55707; -.
DR Pharos; Q9NVZ3; Tdark.
DR PRO; PR:Q9NVZ3; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9NVZ3; protein.
DR Bgee; ENSG00000157191; Expressed in oocyte and 177 other tissues.
DR ExpressionAtlas; Q9NVZ3; baseline and differential.
DR Genevisible; Q9NVZ3; HS.
DR GO; GO:0030125; C:clathrin vesicle coat; ISS:UniProtKB.
DR GO; GO:0005905; C:clathrin-coated pit; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR CDD; cd13228; PHear_NECAP; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR012466; NECAP_PHear.
DR InterPro; IPR011993; PH-like_dom_sf.
DR Pfam; PF07933; DUF1681; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasmic vesicle; Endocytosis;
KW Membrane; Phosphoprotein; Protein transport; Reference proteome; Repeat;
KW Transport.
FT CHAIN 1..263
FT /note="Adaptin ear-binding coat-associated protein 2"
FT /id="PRO_0000213071"
FT REGION 166..194
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 219..263
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 240..243
FT /note="WXXF motif 1"
FT MOTIF 260..263
FT /note="WXXF motif 2"
FT COMPBIAS 240..263
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 181
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 6..31
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041726"
FT VAR_SEQ 164..172
FT /note="NMKKKEGAA -> VSSTLAWLW (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11214971"
FT /id="VSP_013234"
FT VAR_SEQ 173..263
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11214971"
FT /id="VSP_013235"
FT VAR_SEQ 223..263
FT /note="GGAPVPWPQPNPATADIWGDFTKSTGSTSSQTQPGTGWVQF -> DQLPARP
FT SQAQAGSSSDLSTVFPHVTSGKALPHLGQRKEDEALLSWPVFGA (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_013236"
FT VARIANT 149
FT /note="D -> A (in dbSNP:rs35056694)"
FT /id="VAR_034154"
FT CONFLICT 192
FT /note="P -> S (in Ref. 2; BAG63581)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 263 AA; 28339 MW; 6F4DE1B8335852D4 CRC64;
MEESGYESVL CVKPDVHVYR IPPRATNRGY RAAEWQLDQP SWSGRLRITA KGQMAYIKLE
DRTSGELFAQ APVDQFPGTA VESVTDSSRY FVIRIEDGNG RRAFIGIGFG DRGDAFDFNV
ALQDHFKWVK QQCEFAKQAQ NPDQGPKLDL GFKEGQTIKL NIANMKKKEG AAGNPRVRPA
STGGLSLLPP PPGGKTSTLI PPPGEQLAVG GSLVQPAVAP SSGGAPVPWP QPNPATADIW
GDFTKSTGST SSQTQPGTGW VQF