ID AINX_HUMAN Reviewed; 499 AA.
AC Q16352; B1AQK0; Q9BRC5;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2002, sequence version 2.
DT 27-MAR-2024, entry version 201.
DE RecName: Full=Alpha-internexin;
DE Short=Alpha-Inx;
DE AltName: Full=66 kDa neurofilament protein;
DE Short=NF-66;
DE Short=Neurofilament-66;
DE AltName: Full=Neurofilament 5;
GN Name=INA; Synonyms=NEF5;
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], AND VARIANT SER-92.
RC TISSUE=Fetal brain;
RX PubMed=7769995; DOI=10.1016/0169-328x(94)00268-j;
RA Chan S.-O., Chiu F.-C.;
RT "Cloning and developmental expression of human 66 kd neurofilament
RT protein.";
RL Brain Res. Mol. Brain Res. 29:177-184(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 PROTEIN SEQUENCE OF 46-83; 105-111; 121-130; 139-145; 216-228; 279-288;
RP 323-330; 339-367; 378-397 AND 407-430, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-496, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-290, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [8]
RP VARIANT [LARGE SCALE ANALYSIS] GLN-110.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Class-IV neuronal intermediate filament that is able to self-
CC assemble. It is involved in the morphogenesis of neurons. It may form
CC an independent structural network without the involvement of other
CC neurofilaments or it may cooperate with NEFL to form the filamentous
CC backbone to which NEFM and NEFH attach to form the cross-bridges. May
CC also cooperate with the neuronal intermediate filament protein PRPH to
CC form filamentous networks (By similarity).
CC {ECO:0000250|UniProtKB:P46660}.
CC -!- SUBUNIT: Forms homodimers (in vitro) (By similarity). Forms
CC heterodimers with NEFL, NEFM or NEFH (in vitro) (By similarity).
CC {ECO:0000250|UniProtKB:P23565}.
CC -!- INTERACTION:
CC Q16352; P05067: APP; NbExp=3; IntAct=EBI-366258, EBI-77613;
CC Q16352; P31947: SFN; NbExp=2; IntAct=EBI-366258, EBI-476295;
CC Q16352; P37840: SNCA; NbExp=3; IntAct=EBI-366258, EBI-985879;
CC Q16352; P62258: YWHAE; NbExp=2; IntAct=EBI-366258, EBI-356498;
CC -!- TISSUE SPECIFICITY: Found predominantly in adult CNS.
CC -!- DEVELOPMENTAL STAGE: Expressed in brain as early as the 16th week of
CC gestation, and increased rapidly and reached a steady state level by
CC the 18th week of gestation.
CC -!- PTM: O-glycosylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC {ECO:0000255|PROSITE-ProRule:PRU01188}.
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DR EMBL; S78296; AAB34482.1; -; mRNA.
DR EMBL; AL591408; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49653.1; -; Genomic_DNA.
DR EMBL; BC006359; AAH06359.1; -; mRNA.
DR CCDS; CCDS7545.1; -.
DR PIR; I52658; I52658.
DR RefSeq; NP_116116.1; NM_032727.3.
DR AlphaFoldDB; Q16352; -.
DR SMR; Q16352; -.
DR BioGRID; 114566; 128.
DR IntAct; Q16352; 69.
DR MINT; Q16352; -.
DR STRING; 9606.ENSP00000358865; -.
DR GlyCosmos; Q16352; 6 sites, 1 glycan.
DR GlyGen; Q16352; 6 sites, 1 O-linked glycan (6 sites).
DR iPTMnet; Q16352; -.
DR PhosphoSitePlus; Q16352; -.
DR SwissPalm; Q16352; -.
DR BioMuta; INA; -.
DR DMDM; 20141266; -.
DR EPD; Q16352; -.
DR jPOST; Q16352; -.
DR MassIVE; Q16352; -.
DR MaxQB; Q16352; -.
DR PaxDb; 9606-ENSP00000358865; -.
DR PeptideAtlas; Q16352; -.
DR ProteomicsDB; 60861; -.
DR Pumba; Q16352; -.
DR Antibodypedia; 1538; 561 antibodies from 41 providers.
DR DNASU; 9118; -.
DR Ensembl; ENST00000369849.9; ENSP00000358865.4; ENSG00000148798.11.
DR GeneID; 9118; -.
DR KEGG; hsa:9118; -.
DR MANE-Select; ENST00000369849.9; ENSP00000358865.4; NM_032727.4; NP_116116.1.
DR UCSC; uc001kws.3; human.
DR AGR; HGNC:6057; -.
DR CTD; 9118; -.
DR DisGeNET; 9118; -.
DR GeneCards; INA; -.
DR HGNC; HGNC:6057; INA.
DR HPA; ENSG00000148798; Group enriched (brain, pituitary gland, retina).
DR MIM; 605338; gene.
DR neXtProt; NX_Q16352; -.
DR OpenTargets; ENSG00000148798; -.
DR PharmGKB; PA29867; -.
DR VEuPathDB; HostDB:ENSG00000148798; -.
DR eggNOG; ENOG502RAU0; Eukaryota.
DR GeneTree; ENSGT00940000154418; -.
DR HOGENOM; CLU_012560_7_3_1; -.
DR InParanoid; Q16352; -.
DR OMA; EHYLCSA; -.
DR OrthoDB; 4640531at2759; -.
DR PhylomeDB; Q16352; -.
DR TreeFam; TF330122; -.
DR PathwayCommons; Q16352; -.
DR SignaLink; Q16352; -.
DR BioGRID-ORCS; 9118; 7 hits in 1143 CRISPR screens.
DR ChiTaRS; INA; human.
DR GenomeRNAi; 9118; -.
DR Pharos; Q16352; Tbio.
DR PRO; PR:Q16352; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q16352; Protein.
DR Bgee; ENSG00000148798; Expressed in cortical plate and 128 other cell types or tissues.
DR Genevisible; Q16352; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005882; C:intermediate filament; IBA:GO_Central.
DR GO; GO:0005883; C:neurofilament; TAS:ProtInc.
DR GO; GO:0099160; C:postsynaptic intermediate filament cytoskeleton; IBA:GO_Central.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0099184; F:structural constituent of postsynaptic intermediate filament cytoskeleton; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0045109; P:intermediate filament organization; IBA:GO_Central.
DR GO; GO:0060052; P:neurofilament cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0099170; P:postsynaptic modulation of chemical synaptic transmission; IEA:Ensembl.
DR GO; GO:0021762; P:substantia nigra development; HEP:UniProtKB.
DR Gene3D; 1.20.5.170; -; 1.
DR Gene3D; 1.20.5.500; Single helix bin; 1.
DR Gene3D; 1.20.5.1160; Vasodilator-stimulated phosphoprotein; 1.
DR InterPro; IPR018039; IF_conserved.
DR InterPro; IPR039008; IF_rod_dom.
DR InterPro; IPR006821; Intermed_filament_DNA-bd.
DR PANTHER; PTHR45652:SF18; ALPHA-INTERNEXIN; 1.
DR PANTHER; PTHR45652; GLIAL FIBRILLARY ACIDIC PROTEIN; 1.
DR Pfam; PF00038; Filament; 1.
DR Pfam; PF04732; Filament_head; 1.
DR SMART; SM01391; Filament; 1.
DR SUPFAM; SSF64593; Intermediate filament protein, coiled coil region; 2.
DR SUPFAM; SSF90257; Myosin rod fragments; 1.
DR PROSITE; PS00226; IF_ROD_1; 1.
DR PROSITE; PS51842; IF_ROD_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Coiled coil; Developmental protein; Differentiation;
KW Direct protein sequencing; Glycoprotein; Intermediate filament;
KW Neurogenesis; Phosphoprotein; Reference proteome.
FT CHAIN 1..499
FT /note="Alpha-internexin"
FT /id="PRO_0000063783"
FT DOMAIN 94..407
FT /note="IF rod"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188"
FT REGION 1..87
FT /note="Head"
FT REGION 88..129
FT /note="Coil 1A"
FT REGION 130..142
FT /note="Linker 1"
FT REGION 143..238
FT /note="Coil 1B"
FT REGION 239..262
FT /note="Linker 2"
FT REGION 263..408
FT /note="Coil 2"
FT REGION 409..499
FT /note="Tail"
FT REGION 441..466
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 444..459
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 72
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46660"
FT MOD_RES 219
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46660"
FT MOD_RES 290
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 335
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46660"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23565"
FT MOD_RES 496
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT VARIANT 92
FT /note="T -> S (in dbSNP:rs1063455)"
FT /evidence="ECO:0000269|PubMed:7769995"
FT /id="VAR_049808"
FT VARIANT 110
FT /note="E -> Q (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036369"
FT VARIANT 149
FT /note="D -> H (in dbSNP:rs1063456)"
FT /id="VAR_033497"
FT CONFLICT 37..41
FT /note="GFRSQ -> ASVE (in Ref. 1; AAB34482)"
FT /evidence="ECO:0000305"
FT CONFLICT 67
FT /note="R -> A (in Ref. 1; AAB34482)"
FT /evidence="ECO:0000305"
FT CONFLICT 128..132
FT /note="ALRQR -> RCDT (in Ref. 1; AAB34482)"
FT /evidence="ECO:0000305"
FT CONFLICT 141
FT /note="E -> Q (in Ref. 1; AAB34482)"
FT /evidence="ECO:0000305"
FT CONFLICT 147..152
FT /note="LRDLRA -> PRHLP (in Ref. 1; AAB34482)"
FT /evidence="ECO:0000305"
FT CONFLICT 191..198
FT /note="GAERALKA -> RRARLKR (in Ref. 1; AAB34482)"
FT /evidence="ECO:0000305"
FT CONFLICT 244
FT /note="A -> R (in Ref. 1; AAB34482)"
FT /evidence="ECO:0000305"
FT CONFLICT 263
FT /note="S -> A (in Ref. 1; AAB34482)"
FT /evidence="ECO:0000305"
FT CONFLICT 301
FT /note="S -> T (in Ref. 1; AAB34482)"
FT /evidence="ECO:0000305"
FT CONFLICT 310..311
FT /note="EE -> DQ (in Ref. 1; AAB34482)"
FT /evidence="ECO:0000305"
FT CONFLICT 318
FT /note="Missing (in Ref. 1; AAB34482)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 499 AA; 55391 MW; 4C972764E9E68D3E CRC64;
MSFGSEHYLC SSSSYRKVFG DGSRLSARLS GAGGAGGFRS QSLSRSNVAS SAACSSASSL
GLGLAYRRPP ASDGLDLSQA AARTNEYKII RTNEKEQLQG LNDRFAVFIE KVHQLETQNR
ALEAELAALR QRHAEPSRVG ELFQRELRDL RAQLEEASSA RSQALLERDG LAEEVQRLRA
RCEEESRGRE GAERALKAQQ RDVDGATLAR LDLEKKVESL LDELAFVRQV HDEEVAELLA
TLQASSQAAA EVDVTVAKPD LTSALREIRA QYESLAAKNL QSAEEWYKSK FANLNEQAAR
STEAIRASRE EIHEYRRQLQ ARTIEIEGLR GANESLERQI LELEERHSAE VAGYQDSIGQ
LENDLRNTKS EMARHLREYQ DLLNVKMALD IEIAAYRKLL EGEETRFSTS GLSISGLNPL
PNPSYLLPPR ILSATTSKVS STGLSLKKEE EEEEASKVAS KKTSQIGESF EEILEETVIS
TKKTEKSNIE ETTISSQKI
//
