NECP1_HUMAN
ID NECP1_HUMAN Reviewed; 275 AA.
AC Q8NC96; Q2NL73; Q5XG95; Q6NWY6; Q8N153; Q8NCB0; Q9BU52; Q9Y407;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Adaptin ear-binding coat-associated protein 1;
DE AltName: Full=NECAP endocytosis-associated protein 1;
DE Short=NECAP-1;
GN Name=NECAP1;
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=Teratocarcinoma;
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 MRNA] (ISOFORM 2).
RC TISSUE=Kidney;
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 MRNA] (ISOFORM 1).
RC TISSUE=Brain, Lung, Lymph, and Muscle;
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 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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-211, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [6]
RP INVOLVEMENT IN DEE21.
RX PubMed=24399846; DOI=10.1136/jmedgenet-2013-102030;
RA Alazami A.M., Hijazi H., Kentab A.Y., Alkuraya F.S.;
RT "NECAP1 loss of function leads to a severe infantile epileptic
RT encephalopathy.";
RL J. Med. Genet. 51:224-228(2014).
RN [7]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-180, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
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 -!- INTERACTION:
CC Q8NC96; Q10567-3: AP1B1; NbExp=3; IntAct=EBI-2609792, EBI-11978055;
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=2;
CC Name=1;
CC IsoId=Q8NC96-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NC96-2; Sequence=VSP_013232, VSP_013233;
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. The WXXF motif 1,
CC which is preceded by an acidic residue and has a glycine in second
CC position mediates specific interaction with AP-1. The WXXF motif 2,
CC which is followed by the C-terminal carboxyl group negative charge,
CC allows specific interaction with AP-2 (By similarity). {ECO:0000250}.
CC -!- DISEASE: Developmental and epileptic encephalopathy 21 (DEE21)
CC [MIM:615833]: A severe disease characterized by intractable seizures,
CC profound global developmental delay, and persistent severe axial
CC hypotonia as well as appendicular hypertonia.
CC {ECO:0000269|PubMed:24399846}. Note=The disease is caused by variants
CC affecting the gene represented in this 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 -!- SIMILARITY: Belongs to the NECAP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH02888.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK074858; BAC11250.1; -; mRNA.
DR EMBL; AK074880; BAC11264.1; -; mRNA.
DR EMBL; AK074923; BAC11296.1; -; mRNA.
DR EMBL; AK075013; BAC11352.1; -; mRNA.
DR EMBL; AL050272; CAB43373.2; -; mRNA.
DR EMBL; BC002888; AAH02888.1; ALT_INIT; mRNA.
DR EMBL; BC067367; AAH67367.1; -; mRNA.
DR EMBL; BC084551; AAH84551.1; -; mRNA.
DR EMBL; BC110876; AAI10877.1; -; mRNA.
DR CCDS; CCDS8589.1; -. [Q8NC96-1]
DR PIR; T08719; T08719.
DR RefSeq; NP_056324.2; NM_015509.3. [Q8NC96-1]
DR PDB; 6RH5; NMR; -; A=1-133.
DR PDB; 6RH6; NMR; -; A=1-133.
DR PDBsum; 6RH5; -.
DR PDBsum; 6RH6; -.
DR AlphaFoldDB; Q8NC96; -.
DR SMR; Q8NC96; -.
DR BioGRID; 117461; 23.
DR IntAct; Q8NC96; 11.
DR STRING; 9606.ENSP00000341737; -.
DR GlyGen; Q8NC96; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8NC96; -.
DR PhosphoSitePlus; Q8NC96; -.
DR BioMuta; NECAP1; -.
DR DMDM; 62287155; -.
DR EPD; Q8NC96; -.
DR jPOST; Q8NC96; -.
DR MassIVE; Q8NC96; -.
DR MaxQB; Q8NC96; -.
DR PaxDb; Q8NC96; -.
DR PeptideAtlas; Q8NC96; -.
DR PRIDE; Q8NC96; -.
DR ProteomicsDB; 72863; -. [Q8NC96-1]
DR ProteomicsDB; 72864; -. [Q8NC96-2]
DR Antibodypedia; 23021; 67 antibodies from 20 providers.
DR DNASU; 25977; -.
DR Ensembl; ENST00000339754.11; ENSP00000341737.5; ENSG00000089818.18. [Q8NC96-1]
DR Ensembl; ENST00000450991.6; ENSP00000401963.2; ENSG00000089818.18. [Q8NC96-2]
DR Ensembl; ENST00000639955.1; ENSP00000491067.1; ENSG00000089818.18. [Q8NC96-1]
DR GeneID; 25977; -.
DR KEGG; hsa:25977; -.
DR MANE-Select; ENST00000339754.11; ENSP00000341737.5; NM_015509.4; NP_056324.2.
DR UCSC; uc001qtx.3; human. [Q8NC96-1]
DR CTD; 25977; -.
DR DisGeNET; 25977; -.
DR GeneCards; NECAP1; -.
DR HGNC; HGNC:24539; NECAP1.
DR HPA; ENSG00000089818; Low tissue specificity.
DR MalaCards; NECAP1; -.
DR MIM; 611623; gene.
DR MIM; 615833; phenotype.
DR neXtProt; NX_Q8NC96; -.
DR OpenTargets; ENSG00000089818; -.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR PharmGKB; PA142671267; -.
DR VEuPathDB; HostDB:ENSG00000089818; -.
DR eggNOG; KOG2500; Eukaryota.
DR GeneTree; ENSGT00390000009359; -.
DR HOGENOM; CLU_069884_1_1_1; -.
DR InParanoid; Q8NC96; -.
DR OrthoDB; 1605812at2759; -.
DR PhylomeDB; Q8NC96; -.
DR TreeFam; TF314482; -.
DR PathwayCommons; Q8NC96; -.
DR Reactome; R-HSA-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR SignaLink; Q8NC96; -.
DR SIGNOR; Q8NC96; -.
DR BioGRID-ORCS; 25977; 8 hits in 1073 CRISPR screens.
DR ChiTaRS; NECAP1; human.
DR GenomeRNAi; 25977; -.
DR Pharos; Q8NC96; Tbio.
DR PRO; PR:Q8NC96; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q8NC96; protein.
DR Bgee; ENSG00000089818; Expressed in cortical plate and 193 other tissues.
DR ExpressionAtlas; Q8NC96; baseline and differential.
DR Genevisible; Q8NC96; HS.
DR GO; GO:0030125; C:clathrin vesicle coat; IBA:GO_Central.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
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 3D-structure; Alternative splicing; Cell membrane; Cytoplasmic vesicle;
KW Endocytosis; Epilepsy; Membrane; Methylation; Phosphoprotein;
KW Protein transport; Reference proteome; Repeat; Transport.
FT CHAIN 1..275
FT /note="Adaptin ear-binding coat-associated protein 1"
FT /id="PRO_0000213067"
FT REGION 170..191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 254..275
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 252..255
FT /note="WXXF motif 1"
FT MOTIF 272..275
FT /note="WXXF motif 2"
FT MOD_RES 180
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 211
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 102
FT /note="R -> G (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_013232"
FT VAR_SEQ 103..275
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_013233"
FT VARIANT 224
FT /note="D -> N (in dbSNP:rs2231752)"
FT /id="VAR_034153"
FT CONFLICT 77
FT /note="Y -> F (in Ref. 2; CAB43373)"
FT /evidence="ECO:0000305"
FT CONFLICT 232
FT /note="D -> G (in Ref. 1; BAC11250)"
FT /evidence="ECO:0000305"
FT CONFLICT 239
FT /note="T -> A (in Ref. 1; BAC11264)"
FT /evidence="ECO:0000305"
FT STRAND 2..4
FT /evidence="ECO:0007829|PDB:6RH6"
FT STRAND 9..21
FT /evidence="ECO:0007829|PDB:6RH5"
FT TURN 27..29
FT /evidence="ECO:0007829|PDB:6RH5"
FT HELIX 33..35
FT /evidence="ECO:0007829|PDB:6RH6"
FT TURN 36..39
FT /evidence="ECO:0007829|PDB:6RH6"
FT STRAND 42..52
FT /evidence="ECO:0007829|PDB:6RH5"
FT STRAND 55..61
FT /evidence="ECO:0007829|PDB:6RH5"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:6RH5"
FT STRAND 68..79
FT /evidence="ECO:0007829|PDB:6RH5"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:6RH5"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:6RH6"
FT STRAND 91..97
FT /evidence="ECO:0007829|PDB:6RH5"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:6RH5"
FT STRAND 103..109
FT /evidence="ECO:0007829|PDB:6RH5"
FT HELIX 113..127
FT /evidence="ECO:0007829|PDB:6RH5"
FT TURN 128..132
FT /evidence="ECO:0007829|PDB:6RH5"
SQ SEQUENCE 275 AA; 29737 MW; 22FC4CCEC7E3B713 CRC64;
MATELEYESV LCVKPDVSVY RIPPRASNRG YRASDWKLDQ PDWTGRLRIT SKGKTAYIKL
EDKVSGELFA QAPVEQYPGI AVETVTDSSR YFVIRIQDGT GRSAFIGIGF TDRGDAFDFN
VSLQDHFKWV KQESEISKES QEMDARPKLD LGFKEGQTIK LCIGNITNKK GGASKPRTAR
GGGLSLLPPP PGGKVTIPPP SSSVAISNHV TPPPIPKSNH GGSDADILLD LDSPAPVTTP
APTPVSVSND LWGDFSTASS SVPNQAPQPS NWVQF
