NECP1_MOUSE
ID NECP1_MOUSE Reviewed; 275 AA.
AC Q9CR95; Q3TH13; Q78JW3; Q8C4P1;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 138.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RC TISSUE=Cerebellum, Embryonic head, Embryonic heart, and Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary gland;
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 [3]
RP IDENTIFICATION, INTERACTION WITH AP1G1 AND AP2A1, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=14555962; DOI=10.1038/sj.embor.embor7400004;
RA Ritter B., Philie J., Girard M., Tung E.C., Blondeau F., McPherson P.S.;
RT "Identification of a family of endocytic proteins that define a new alpha-
RT adaptin ear-binding motif.";
RL EMBO Rep. 4:1089-1095(2003).
RN [4]
RP MUTAGENESIS OF TRP-272; VAL-273; GLN-274 AND PHE-275, AND INTERACTION WITH
RP AP2A1; AP2A2 AND AP1G1.
RX PubMed=15359277; DOI=10.1038/sj.emboj.7600378;
RA Ritter B., Denisov A.Y., Philie J., Deprez C., Tung E.C., Gehring K.,
RA McPherson P.S.;
RT "Two WXXF-based motifs in NECAPs define the specificity of accessory
RT protein binding to AP-1 and AP-2.";
RL EMBO J. 23:3701-3710(2004).
RN [5]
RP INTERACTION WITH GGA1; GGA2; GGA3 AND AP1G1.
RX PubMed=14665628; DOI=10.1074/jbc.m311873200;
RA Mattera R., Ritter B., Sidhu S.S., McPherson P.S., Bonifacino J.S.;
RT "Definition of the consensus motif recognized by gamma-adaptin ear
RT domains.";
RL J. Biol. Chem. 279:8018-8028(2004).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP DEVELOPMENTAL STAGE.
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 [8]
RP STRUCTURE BY NMR OF 1-133.
RA Denisov A.Y., Ritter B., McPherson P.S., Gehring K.;
RT "Solution structure of NECAP1 protein.";
RL Submitted (JUL-2005) to the PDB data bank.
CC -!- FUNCTION: Involved in endocytosis. {ECO:0000250,
CC ECO:0000269|PubMed:14555962}.
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. {ECO:0000269|PubMed:14555962,
CC ECO:0000269|PubMed:14665628, ECO:0000269|PubMed:15359277}.
CC -!- INTERACTION:
CC Q9CR95; P98078: Dab2; NbExp=2; IntAct=EBI-7592476, EBI-1391846;
CC Q9CR95; Q8K285: Fcho1; NbExp=2; IntAct=EBI-7592476, EBI-16078916;
CC Q9CR95; O08838: Amph; Xeno; NbExp=8; IntAct=EBI-7592476, EBI-80080;
CC Q9CR95; P49418: AMPH; Xeno; NbExp=6; IntAct=EBI-7592476, EBI-7121510;
CC Q9CR95; P63010: AP2B1; Xeno; NbExp=2; IntAct=EBI-7592476, EBI-432924;
CC Q9CR95; O08839: Bin1; Xeno; NbExp=9; IntAct=EBI-7592476, EBI-80095;
CC Q9CR95; O00291: HIP1; Xeno; NbExp=3; IntAct=EBI-7592476, EBI-473886;
CC Q9CR95; O60641: SNAP91; Xeno; NbExp=2; IntAct=EBI-7592476, EBI-1105187;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, clathrin-coated vesicle
CC membrane {ECO:0000269|PubMed:14555962}. Cell membrane
CC {ECO:0000269|PubMed:14555962}. Note=Colocalizes with AP-2 at the plasma
CC membrane.
CC -!- TISSUE SPECIFICITY: Expressed primarily in brain (at protein level).
CC {ECO:0000269|PubMed:14555962}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the brain and spinal cord at 14.5 dpc
CC (at protein level). {ECO:0000269|PubMed:24399846}.
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.
CC -!- SIMILARITY: Belongs to the NECAP family. {ECO:0000305}.
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DR EMBL; AK004805; BAB23577.2; -; mRNA.
DR EMBL; AK005263; BAB23915.2; -; mRNA.
DR EMBL; AK081598; BAC38266.1; -; mRNA.
DR EMBL; AK168500; BAE40385.1; -; mRNA.
DR EMBL; BC011466; AAH11466.2; -; mRNA.
DR EMBL; BK000656; DAA01433.1; -; mRNA.
DR CCDS; CCDS20505.1; -.
DR RefSeq; NP_080543.2; NM_026267.2.
DR PDB; 1TQZ; NMR; -; A=1-133.
DR PDBsum; 1TQZ; -.
DR AlphaFoldDB; Q9CR95; -.
DR SMR; Q9CR95; -.
DR BioGRID; 212303; 10.
DR DIP; DIP-44062N; -.
DR IntAct; Q9CR95; 15.
DR MINT; Q9CR95; -.
DR STRING; 10090.ENSMUSP00000032477; -.
DR iPTMnet; Q9CR95; -.
DR PhosphoSitePlus; Q9CR95; -.
DR MaxQB; Q9CR95; -.
DR PaxDb; Q9CR95; -.
DR PRIDE; Q9CR95; -.
DR ProteomicsDB; 286171; -.
DR Antibodypedia; 23021; 67 antibodies from 20 providers.
DR DNASU; 67602; -.
DR Ensembl; ENSMUST00000032477; ENSMUSP00000032477; ENSMUSG00000030327.
DR GeneID; 67602; -.
DR KEGG; mmu:67602; -.
DR UCSC; uc009dpt.1; mouse.
DR CTD; 25977; -.
DR MGI; MGI:1914852; Necap1.
DR VEuPathDB; HostDB:ENSMUSG00000030327; -.
DR eggNOG; KOG2500; Eukaryota.
DR GeneTree; ENSGT00390000009359; -.
DR HOGENOM; CLU_069884_1_1_1; -.
DR InParanoid; Q9CR95; -.
DR OMA; DSSRYFM; -.
DR OrthoDB; 1605812at2759; -.
DR PhylomeDB; Q9CR95; -.
DR TreeFam; TF314482; -.
DR Reactome; R-MMU-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR BioGRID-ORCS; 67602; 4 hits in 75 CRISPR screens.
DR EvolutionaryTrace; Q9CR95; -.
DR PRO; PR:Q9CR95; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9CR95; protein.
DR Bgee; ENSMUSG00000030327; Expressed in medulla oblongata and 251 other tissues.
DR ExpressionAtlas; Q9CR95; baseline and differential.
DR Genevisible; Q9CR95; MM.
DR GO; GO:0030125; C:clathrin vesicle coat; IDA:UniProtKB.
DR GO; GO:0005905; C:clathrin-coated pit; IDA:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IMP: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 3D-structure; Cell membrane; Cytoplasmic vesicle; Endocytosis; Membrane;
KW Phosphoprotein; Protein transport; Reference proteome; Repeat; Transport.
FT CHAIN 1..275
FT /note="Adaptin ear-binding coat-associated protein 1"
FT /id="PRO_0000213068"
FT REGION 168..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 COMPBIAS 200..214
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 239..275
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 211
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8NC96"
FT MUTAGEN 270
FT /note="S->D: Loss of binding to AP-2 and can bind to AP-1;
FT when associated with G-273."
FT MUTAGEN 272
FT /note="W->A,F,Y: Loss of binding to AP-2."
FT /evidence="ECO:0000269|PubMed:15359277"
FT MUTAGEN 273
FT /note="V->A,D,E,I: No effect on binding to AP-2."
FT /evidence="ECO:0000269|PubMed:15359277"
FT MUTAGEN 273
FT /note="V->G: Loss of binding to AP-2 and can bind to AP-1;
FT when associated with D-270."
FT /evidence="ECO:0000269|PubMed:15359277"
FT MUTAGEN 273
FT /note="V->L,N,P,S: Loss of binding to AP-2."
FT /evidence="ECO:0000269|PubMed:15359277"
FT MUTAGEN 274
FT /note="Q->A,M,N,S,T: No effect on binding to AP-2."
FT /evidence="ECO:0000269|PubMed:15359277"
FT MUTAGEN 275
FT /note="F->A,F,Y: Loss of binding to AP-2."
FT /evidence="ECO:0000269|PubMed:15359277"
FT MUTAGEN 275
FT /note="F->W: No effect on binding to AP-2."
FT /evidence="ECO:0000269|PubMed:15359277"
FT STRAND 15..21
FT /evidence="ECO:0007829|PDB:1TQZ"
FT STRAND 27..30
FT /evidence="ECO:0007829|PDB:1TQZ"
FT HELIX 33..36
FT /evidence="ECO:0007829|PDB:1TQZ"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:1TQZ"
FT STRAND 43..50
FT /evidence="ECO:0007829|PDB:1TQZ"
FT STRAND 53..61
FT /evidence="ECO:0007829|PDB:1TQZ"
FT STRAND 70..74
FT /evidence="ECO:0007829|PDB:1TQZ"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:1TQZ"
FT STRAND 92..98
FT /evidence="ECO:0007829|PDB:1TQZ"
FT TURN 99..101
FT /evidence="ECO:0007829|PDB:1TQZ"
FT STRAND 102..109
FT /evidence="ECO:0007829|PDB:1TQZ"
FT HELIX 113..127
FT /evidence="ECO:0007829|PDB:1TQZ"
SQ SEQUENCE 275 AA; 29639 MW; B238B083746FF915 CRC64;
MAAELEYESV LCVKPDVSVY RIPPRASNRG YRASDWKLDQ PDWTGRLRIT SKGKIAYIKL
EDKVSGELFA QAPVEQYPGI AVETVTDSSR YFVIRIQDGT GRSAFIGIGF TDRGDAFDFN
VSLQDHFKWV KQETEISKES QEMDNRPKLD LGFKEGQTIK LSIGNITAKK GGASKPRASG
TGGLSLLPPP PGGKVTIPPP SSSVAISNHV TPPPIPKSNH GGNDSDILLD LDSPAPVSTS
APAPVSTSND LWGDFSTASS SVPNQAPQPS NWVQF
