NCKPL_HUMAN
ID NCKPL_HUMAN Reviewed; 1127 AA.
AC P55160; B4DUT5; Q52LW0;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 3.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Nck-associated protein 1-like {ECO:0000305};
DE AltName: Full=Hematopoietic protein 1 {ECO:0000303|PubMed:1932118};
DE AltName: Full=Membrane-associated protein HEM-1;
GN Name=NCKAP1L {ECO:0000312|HGNC:HGNC:4862};
GN Synonyms=HEM1 {ECO:0000312|HGNC:HGNC:4862};
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 [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=1932118; DOI=10.1016/0167-4781(91)90109-y;
RA Hromas R., Collins S., Raskind W., Deaven L., Kaushansky K.;
RT "Hem-1, a potential membrane protein, with expression restricted to blood
RT cells.";
RL Biochim. Biophys. Acta 1090:241-244(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Blood;
RX PubMed=7643388; DOI=10.1006/jmbi.1995.0414;
RA Baumgartner S., Martin D., Chiquet-Ehrismann R., Sutton J., Desai A.,
RA Huang I., Kato K., Hromas R.;
RT "The HEM proteins: a novel family of tissue-specific transmembrane proteins
RT expressed from invertebrates through mammals with an essential function in
RT oogenesis.";
RL J. Mol. Biol. 251:41-49(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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 [7]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, IDENTIFICATION IN THE
RP WAVE2 COMPLEX, AND INTERACTION WITH ARHGAP4; PIK3C3 AND PPP1R12A.
RX PubMed=16417406; DOI=10.1371/journal.pbio.0040038;
RA Weiner O.D., Rentel M.C., Ott A., Brown G.E., Jedrychowski M., Yaffe M.B.,
RA Gygi S.P., Cantley L.C., Bourne H.R., Kirschner M.W.;
RT "Hem-1 complexes are essential for Rac activation, actin polymerization,
RT and myosin regulation during neutrophil chemotaxis.";
RL PLoS Biol. 4:E38-E38(2006).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17696648; DOI=10.1371/journal.pbio.0050221;
RA Weiner O.D., Marganski W.A., Wu L.F., Altschuler S.J., Kirschner M.W.;
RT "An actin-based wave generator organizes cell motility.";
RL PLoS Biol. 5:E221-E221(2007).
RN [9]
RP REVIEW OF FUNCTION.
RX PubMed=20969869; DOI=10.1016/j.febslet.2010.10.018;
RA Park H., Chan M.M., Iritani B.M.;
RT "Hem-1: putting the 'WAVE' into actin polymerization during an immune
RT response.";
RL FEBS Lett. 584:4923-4932(2010).
RN [10]
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 [11]
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 [12]
RP INVOLVEMENT IN IMD72, VARIANTS IMD72 LEU-258; LEU-359; VAL-371 AND LEU-519,
RP CHARACTERIZATION OF VARIANTS IMD72 LEU-258; LEU-359; VAL-371 AND LEU-519,
RP FUNCTION, INTERACTION WITH MTOR; RICTOR AND WASF2, AND TISSUE SPECIFICITY.
RX PubMed=32647003; DOI=10.1126/science.aay5663;
RA Cook S.A., Comrie W.A., Poli M.C., Similuk M., Oler A.J., Faruqi A.J.,
RA Kuhns D.B., Yang S., Vargas-Hernandez A., Carisey A.F., Fournier B.,
RA Anderson D.E., Price S., Smelkinson M., Abou Chahla W., Forbes L.R.,
RA Mace E.M., Cao T.N., Coban-Akdemir Z.H., Jhangiani S.N., Muzny D.M.,
RA Gibbs R.A., Lupski J.R., Orange J.S., Cuvelier G.D.E., Al Hassani M.,
RA Al Kaabi N., Al Yafei Z., Jyonouchi S., Raje N., Caldwell J.W., Huang Y.,
RA Burkhardt J.K., Latour S., Chen B., ElGhazali G., Rao V.K., Chinn I.K.,
RA Lenardo M.J.;
RT "HEM1 deficiency disrupts mTORC2 and F-actin control in inherited
RT immunodysregulatory disease.";
RL Science 369:202-207(2020).
CC -!- FUNCTION: Essential hematopoietic-specific regulator of the actin
CC cytoskeleton (Probable). Controls lymphocyte development, activation,
CC proliferation and homeostasis, erythrocyte membrane stability, as well
CC as phagocytosis and migration by neutrophils and macrophages
CC (PubMed:16417406, PubMed:17696648). Component of the WAVE2 complex
CC which signals downstream of RAC to stimulate F-actin polymerization.
CC Required for stabilization and/or translation of the WAVE2 complex
CC proteins in hematopoietic cells (By similarity). Within the WAVE2
CC complex, enables the cortical actin network to restrain excessive
CC degranulation and granule release by T-cells (PubMed:32647003).
CC Required for efficient T-lymphocyte and neutrophil migration
CC (PubMed:32647003). Exhibits complex cycles of activation and inhibition
CC to generate waves of propagating the assembly with actin
CC (PubMed:16417406). Also involved in mechanisms WAVE-independent to
CC regulate myosin and actin polymerization during neutrophil chemotaxis
CC (PubMed:17696648). In T-cells, required for proper mechanistic target
CC of rapamycin complex 2 (mTORC2)-dependent AKT phosphorylation, cell
CC proliferation and cytokine secretion, including that of IL2 and TNF
CC (PubMed:32647003). {ECO:0000250|UniProtKB:Q8K1X4,
CC ECO:0000269|PubMed:16417406, ECO:0000269|PubMed:17696648,
CC ECO:0000269|PubMed:32647003, ECO:0000303|PubMed:20969869}.
CC -!- SUBUNIT: In hematopoietic cells, component of the WAVE2 complex
CC composed of ABI1, CYFIP1/SRA1, NCKAP1L/HEM1 and WASF2/WAVE2
CC (PubMed:16417406, PubMed:32647003). Interacts with ARHGAP4,
CC PIK3C3/VPS34 and PPP1R12A/MYPT1 (PubMed:16417406). Interacts with
CC mammalian target of rapamycin complex 2 (mTORC2) components, including
CC MTOR and RICTOR (PubMed:32647003). {ECO:0000269|PubMed:16417406,
CC ECO:0000269|PubMed:32647003}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16417406};
CC Single-pass membrane protein {ECO:0000305}; Cytoplasmic side
CC {ECO:0000305}. Cytoplasm {ECO:0000269|PubMed:16417406}. Note=Localizes
CC to the leading edge of polarized neutrophils.
CC {ECO:0000269|PubMed:16417406, ECO:0000269|PubMed:17696648}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P55160-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P55160-2; Sequence=VSP_045191;
CC -!- TISSUE SPECIFICITY: Expressed only in cells of hematopoietic origin
CC (PubMed:7643388, PubMed:1932118). Expressed in neutrophils (at protein
CC level) (PubMed:16417406). Expressed in T-cells (at protein level)
CC (PubMed:32647003). {ECO:0000269|PubMed:16417406,
CC ECO:0000269|PubMed:1932118, ECO:0000269|PubMed:32647003,
CC ECO:0000269|PubMed:7643388}.
CC -!- DISEASE: Immunodeficiency 72 with autoinflammation (IMD72)
CC [MIM:618982]: An autosomal recessive immunologic disorder characterized
CC by onset in the first year of life, recurrent bacterial and viral skin
CC infections, severe respiratory tract infections leading to pneumonia
CC and bronchiectasis, and poor specific antibody responses. Patients also
CC exhibit atopic and inflammatory disease alongside chronic
CC hepatosplenomegaly and lymphadenopathy, and autoimmune manifestations.
CC {ECO:0000269|PubMed:32647003}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the HEM-1/HEM-2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA35964.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; M58285; AAA35964.1; ALT_INIT; mRNA.
DR EMBL; AK300783; BAG62447.1; -; mRNA.
DR EMBL; AC025570; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC068789; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC079313; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW96787.1; -; Genomic_DNA.
DR EMBL; BC093769; AAH93769.1; -; mRNA.
DR EMBL; BC093771; AAH93771.1; -; mRNA.
DR CCDS; CCDS31813.1; -. [P55160-1]
DR CCDS; CCDS53799.1; -. [P55160-2]
DR PIR; S36666; S36666.
DR RefSeq; NP_001171905.1; NM_001184976.1. [P55160-2]
DR RefSeq; NP_005328.2; NM_005337.4. [P55160-1]
DR AlphaFoldDB; P55160; -.
DR SMR; P55160; -.
DR BioGRID; 109321; 16.
DR IntAct; P55160; 3.
DR MINT; P55160; -.
DR STRING; 9606.ENSP00000293373; -.
DR iPTMnet; P55160; -.
DR PhosphoSitePlus; P55160; -.
DR BioMuta; NCKAP1L; -.
DR DMDM; 218512111; -.
DR EPD; P55160; -.
DR jPOST; P55160; -.
DR MassIVE; P55160; -.
DR MaxQB; P55160; -.
DR PaxDb; P55160; -.
DR PeptideAtlas; P55160; -.
DR PRIDE; P55160; -.
DR ProteomicsDB; 5214; -.
DR ProteomicsDB; 56795; -. [P55160-1]
DR Antibodypedia; 27500; 166 antibodies from 25 providers.
DR DNASU; 3071; -.
DR Ensembl; ENST00000293373.11; ENSP00000293373.6; ENSG00000123338.13. [P55160-1]
DR Ensembl; ENST00000545638.2; ENSP00000445596.2; ENSG00000123338.13. [P55160-2]
DR GeneID; 3071; -.
DR KEGG; hsa:3071; -.
DR MANE-Select; ENST00000293373.11; ENSP00000293373.6; NM_005337.5; NP_005328.2.
DR UCSC; uc001sgc.5; human. [P55160-1]
DR CTD; 3071; -.
DR DisGeNET; 3071; -.
DR GeneCards; NCKAP1L; -.
DR HGNC; HGNC:4862; NCKAP1L.
DR HPA; ENSG00000123338; Tissue enhanced (lymphoid).
DR MalaCards; NCKAP1L; -.
DR MIM; 141180; gene.
DR MIM; 618982; phenotype.
DR neXtProt; NX_P55160; -.
DR OpenTargets; ENSG00000123338; -.
DR PharmGKB; PA29239; -.
DR VEuPathDB; HostDB:ENSG00000123338; -.
DR eggNOG; KOG1917; Eukaryota.
DR GeneTree; ENSGT00390000016619; -.
DR HOGENOM; CLU_004450_0_0_1; -.
DR InParanoid; P55160; -.
DR OMA; VYNCAHE; -.
DR OrthoDB; 138196at2759; -.
DR PhylomeDB; P55160; -.
DR TreeFam; TF313683; -.
DR PathwayCommons; P55160; -.
DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-HSA-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis.
DR SignaLink; P55160; -.
DR BioGRID-ORCS; 3071; 23 hits in 1076 CRISPR screens.
DR ChiTaRS; NCKAP1L; human.
DR GenomeRNAi; 3071; -.
DR Pharos; P55160; Tbio.
DR PRO; PR:P55160; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P55160; protein.
DR Bgee; ENSG00000123338; Expressed in monocyte and 174 other tissues.
DR ExpressionAtlas; P55160; baseline and differential.
DR Genevisible; P55160; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; NAS:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0031209; C:SCAR complex; IDA:UniProtKB.
DR GO; GO:0030667; C:secretory granule membrane; TAS:Reactome.
DR GO; GO:0005096; F:GTPase activator activity; IMP:UniProtKB.
DR GO; GO:0030295; F:protein kinase activator activity; IMP:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB.
DR GO; GO:1904841; F:TORC2 complex binding; IDA:UniProtKB.
DR GO; GO:0070358; P:actin polymerization-dependent cell motility; IMP:UniProtKB.
DR GO; GO:0001782; P:B cell homeostasis; ISS:UniProtKB.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0000902; P:cell morphogenesis; IBA:GO_Central.
DR GO; GO:0030031; P:cell projection assembly; IBA:GO_Central.
DR GO; GO:0006935; P:chemotaxis; IDA:UniProtKB.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0048821; P:erythrocyte development; IEP:UniProtKB.
DR GO; GO:0034101; P:erythrocyte homeostasis; ISS:UniProtKB.
DR GO; GO:0030011; P:maintenance of cell polarity; IMP:UniProtKB.
DR GO; GO:0002262; P:myeloid cell homeostasis; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0043318; P:negative regulation of cytotoxic T cell degranulation; IMP:UniProtKB.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; ISS:UniProtKB.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0035509; P:negative regulation of myosin-light-chain-phosphatase activity; IMP:UniProtKB.
DR GO; GO:0048812; P:neuron projection morphogenesis; IBA:GO_Central.
DR GO; GO:0030593; P:neutrophil chemotaxis; IDA:UniProtKB.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IMP:UniProtKB.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; ISS:UniProtKB.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IMP:UniProtKB.
DR GO; GO:0043372; P:positive regulation of CD4-positive, alpha-beta T cell differentiation; ISS:UniProtKB.
DR GO; GO:0043378; P:positive regulation of CD8-positive, alpha-beta T cell differentiation; ISS:UniProtKB.
DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; ISS:UniProtKB.
DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0045588; P:positive regulation of gamma-delta T cell differentiation; ISS:UniProtKB.
DR GO; GO:0002687; P:positive regulation of leukocyte migration; IMP:UniProtKB.
DR GO; GO:0045621; P:positive regulation of lymphocyte differentiation; ISS:UniProtKB.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; ISS:UniProtKB.
DR GO; GO:1902624; P:positive regulation of neutrophil migration; IMP:UniProtKB.
DR GO; GO:0060100; P:positive regulation of phagocytosis, engulfment; ISS:UniProtKB.
DR GO; GO:0042327; P:positive regulation of phosphorylation; IMP:UniProtKB.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IMP:UniProtKB.
DR GO; GO:1904515; P:positive regulation of TORC2 signaling; IMP:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; ISS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:UniProtKB.
DR GO; GO:0043029; P:T cell homeostasis; ISS:UniProtKB.
DR InterPro; IPR019137; Nck-associated_protein-1.
DR PANTHER; PTHR12093; PTHR12093; 1.
DR Pfam; PF09735; Nckap1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm; Disease variant; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..1127
FT /note="Nck-associated protein 1-like"
FT /id="PRO_0000216175"
FT TRANSMEM 996..1016
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 638..670
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 650..670
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..50
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045191"
FT VARIANT 258
FT /note="R -> L (in IMD72; loss of function; decreased
FT protein levels in T-cells; T-cells display excessive
FT degranulation and granule release)"
FT /evidence="ECO:0000269|PubMed:32647003"
FT /id="VAR_084644"
FT VARIANT 359
FT /note="P -> L (in IMD72; loss of function; decreased
FT protein levels in T-cells; decreased interaction with WASF2
FT and poor formation of WAVE2 complex; T-cells display
FT excessive degranulation and granule release; cells exhibit
FT reduced cortical F-actin and aberrant membrane spikes and
FT WAS-mediated puncta, defective cell spreading and
FT lamellipodia and reduced migratory velocity, as well as
FT abnormal activation, blunted proliferation, decreased IL2
FT and TNF production and defective TCR-induced
FT phosphorylation of mTORC2 complex substrate AKT; homozygous
FT patient neutrophils migrating in chemokine gradients
FT exhibit reduced velocity and directional persistence,
FT unusual elongation and misdirected competing leading edges;
FT no effect on interaction with RICTOR; dbSNP:rs770633648)"
FT /evidence="ECO:0000269|PubMed:32647003"
FT /id="VAR_084645"
FT VARIANT 371
FT /note="M -> V (in IMD72; loss of function; T-cells display
FT excessive degranulation and granule release; no effect on
FT protein levels in T-cells, nor on interaction with WASF2;
FT when tested in a heterologous system, formed WAVE complexes
FT that poorly interact with ARF1 and could not promote F-
FT actin polymerization upon stimulation with an ARF1-RAC1
FT dimer; no effect on interaction with RICTOR;
FT dbSNP:rs750982844)"
FT /evidence="ECO:0000269|PubMed:32647003"
FT /id="VAR_084646"
FT VARIANT 391
FT /note="T -> A (in dbSNP:rs7311877)"
FT /id="VAR_059316"
FT VARIANT 402
FT /note="S -> L (in dbSNP:rs2270581)"
FT /id="VAR_049344"
FT VARIANT 519
FT /note="V -> L (in IMD72; loss of function; decreased
FT protein levels in T-cells; decreased interaction with WASF2
FT and poor formation of WAVE2 complex)"
FT /evidence="ECO:0000269|PubMed:32647003"
FT /id="VAR_084647"
FT CONFLICT 496
FT /note="T -> H (in Ref. 2; AAA35964)"
FT /evidence="ECO:0000305"
FT CONFLICT 768..769
FT /note="NA -> KP (in Ref. 2; AAA35964)"
FT /evidence="ECO:0000305"
FT CONFLICT 1060
FT /note="L -> V (in Ref. 2; AAA35964)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1127 AA; 128153 MW; 9389BAB163BAEA45 CRC64;
MSLTSAYQHK LAEKLTILND RGQGVLIRMY NIKKTCSDPK SKPPFLLEKS MEPSLKYINK
KFPNIDVRNS TQHLGPVHRE KAEIIRFLTN YYQSFVDVME FRDHVYELLN TIDACQCHFD
INLNFDFTRS YLDLIVTYTS VILLLSRIED RRILIGMYNC AHEMLHGHGD PSFARLGQMV
LEYDHPLKKL TEEFGPHTKA VSGALLSLHF LFVRRNQGAE QWRSAQLLSL ISNPPAMINP
ANSDTMACEY LSVEVMERWI IIGFLLCHGC LNSNSQCQKL WKLCLQGSLY ITLIREDVLQ
VHKVTEDLFS SLKGYGKRVA DIKESKEHVI ANSGQFHCQR RQFLRMAVKE LETVLADEPG
LLGPKALFAF MALSFIRDEV TWLVRHTENV TKTKTPEDYA DSSIAELLFL LEGIRSLVRR
HIKVIQQYHL QYLARFDALV LSDIIQNLSV CPEEESIIMS SFVSILSSLN LKQVDNGEKF
EFSGLRLDWF RLQAYTSVAK APLHLHENPD LAKVMNLIVF HSRMLDSVEK LLVETSDLST
FCFHLRIFEK MFAMTLEESA MLRYAIAFPL ICAHFVHCTH EMCPEEYPHL KNHGLHHCNS
FLEELAKQTS NCVLEICAEQ RNLSEQLLPK HCATTISKAK NKKTRKQRQT PRKGEPERDK
PGAESHRKNR SIVTNMDKLH LNLTELALTM NHVYSFSVFE HTIFPSEYLS SHLEARLNRA
IVWLAGYNAT TQEIVRPSEL LAGVKAYIGF IQSLAQFLGA DASRVIRNAL LQQTQPLDSC
GEQTITTLYT NWYLESLLRQ ASSGTIILSP AMQAFVSLPR EGEQNFSAEE FSDISEMRAL
AELLGPYGMK FLSENLMWHV TSQIVELKKL VVENMDILVQ IRSNFSKPDL MASLLPQLTG
AENVLKRMTI IGVILSFRAM AQEGLREVFS SHCPFLMGPI ECLKEFVTPD TDIKVTLSIF
ELASAAGVGC DIDPALVAAI ANLKADTSSP EEEYKVACLL LIFLAVSLPL LATDPSSFYS
IEKDGYNNNI HCLTKAIIQV SAALFTLYNK NIETHLKEFL VVASVSLLQL GQETDKLKTR
NRESISLLMR LVVEESSFLT LDMLESCFPY VLLRNAYREV SRAFHLN
