SLIK4_HUMAN
ID SLIK4_HUMAN Reviewed; 837 AA.
AC Q8IW52; Q5JXG3; Q8TCM8; Q96DL3;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=SLIT and NTRK-like protein 4;
DE Flags: Precursor;
GN Name=SLITRK4;
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 {ECO:0000312|EMBL:AAH40986.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [2] {ECO:0000305}
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 [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain {ECO:0000312|EMBL:AAH40986.1};
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 149-837.
RC TISSUE=Brain;
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 [5] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 304-837.
RC TISSUE=Trachea {ECO:0000312|EMBL:BAB71535.1};
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 [6] {ECO:0000305}
RP IDENTIFICATION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain {ECO:0000269|PubMed:14557068}, and
RC Brain tumor {ECO:0000269|PubMed:14557068};
RX PubMed=14557068; DOI=10.1016/s0378-1119(03)00715-7;
RA Aruga J., Yokota N., Mikoshiba K.;
RT "Human SLITRK family genes: genomic organization and expression profiling
RT in normal brain and brain tumor tissue.";
RL Gene 315:87-94(2003).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, VARIANTS ILE-206 AND VAL-578, AND
RP CHARACTERIZATION OF VARIANTS ILE-206 AND VAL-578.
RX PubMed=27812321; DOI=10.3389/fnmol.2016.00104;
RA Kang H., Han K.A., Won S.Y., Kim H.M., Lee Y.H., Ko J., Um J.W.;
RT "Slitrk missense mutations associated with neuropsychiatric disorders
RT distinctively impair Slitrk trafficking and synapse formation.";
RL Front. Mol. Neurosci. 9:104-104(2016).
RN [8]
RP VARIANT [LARGE SCALE ANALYSIS] ILE-206.
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: It is involved in synaptogenesis and promotes synapse
CC differentiation (PubMed:27812321). Suppresses neurite outgrowth (By
CC similarity). {ECO:0000250|UniProtKB:Q810B8,
CC ECO:0000269|PubMed:27812321}.
CC -!- SUBUNIT: Interacts (via LRR 1 and 2 repeats) with PTPRD (via
CC extracellular domain). {ECO:0000250|UniProtKB:Q810B8}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Cell membrane
CC {ECO:0000269|PubMed:27812321}.
CC -!- TISSUE SPECIFICITY: Expressed in the cerebral cortex of the brain and
CC at higher levels in some astrocytic brain tumors such as astrocytomas,
CC glioblastomas and primitive neuroectodermal tumors.
CC {ECO:0000269|PubMed:14557068}.
CC -!- SIMILARITY: Belongs to the SLITRK family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB71535.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AL080239; CAI41650.1; -; Genomic_DNA.
DR EMBL; CH471170; EAW78020.1; -; Genomic_DNA.
DR EMBL; BC040986; AAH40986.1; -; mRNA.
DR EMBL; AL713693; CAD28493.1; -; mRNA.
DR EMBL; AK057619; BAB71535.1; ALT_INIT; mRNA.
DR CCDS; CCDS14679.1; -.
DR RefSeq; NP_001171678.1; NM_001184749.2.
DR RefSeq; NP_001171679.1; NM_001184750.2.
DR RefSeq; NP_775101.1; NM_173078.4.
DR RefSeq; XP_005262422.1; XM_005262365.4.
DR RefSeq; XP_011529567.1; XM_011531265.2.
DR AlphaFoldDB; Q8IW52; -.
DR SMR; Q8IW52; -.
DR BioGRID; 126540; 23.
DR IntAct; Q8IW52; 1.
DR STRING; 9606.ENSP00000469205; -.
DR GlyGen; Q8IW52; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q8IW52; -.
DR PhosphoSitePlus; Q8IW52; -.
DR BioMuta; SLITRK4; -.
DR DMDM; 46396931; -.
DR EPD; Q8IW52; -.
DR jPOST; Q8IW52; -.
DR MassIVE; Q8IW52; -.
DR MaxQB; Q8IW52; -.
DR PaxDb; Q8IW52; -.
DR PeptideAtlas; Q8IW52; -.
DR PRIDE; Q8IW52; -.
DR ProteomicsDB; 70818; -.
DR Antibodypedia; 438; 249 antibodies from 32 providers.
DR DNASU; 139065; -.
DR Ensembl; ENST00000338017.8; ENSP00000336627.4; ENSG00000179542.16.
DR Ensembl; ENST00000356928.2; ENSP00000349400.1; ENSG00000179542.16.
DR Ensembl; ENST00000596188.2; ENSP00000469205.1; ENSG00000179542.16.
DR GeneID; 139065; -.
DR KEGG; hsa:139065; -.
DR MANE-Select; ENST00000356928.2; ENSP00000349400.1; NM_001184749.3; NP_001171678.1.
DR UCSC; uc022cfm.2; human.
DR CTD; 139065; -.
DR DisGeNET; 139065; -.
DR GeneCards; SLITRK4; -.
DR HGNC; HGNC:23502; SLITRK4.
DR HPA; ENSG00000179542; Tissue enhanced (adrenal gland, brain, skeletal muscle).
DR MIM; 300562; gene.
DR neXtProt; NX_Q8IW52; -.
DR OpenTargets; ENSG00000179542; -.
DR PharmGKB; PA134926932; -.
DR VEuPathDB; HostDB:ENSG00000179542; -.
DR eggNOG; ENOG502QQXQ; Eukaryota.
DR GeneTree; ENSGT00940000160971; -.
DR HOGENOM; CLU_012706_1_0_1; -.
DR InParanoid; Q8IW52; -.
DR OMA; EPSMFIH; -.
DR OrthoDB; 217854at2759; -.
DR PhylomeDB; Q8IW52; -.
DR TreeFam; TF326378; -.
DR PathwayCommons; Q8IW52; -.
DR Reactome; R-HSA-388844; Receptor-type tyrosine-protein phosphatases.
DR SignaLink; Q8IW52; -.
DR BioGRID-ORCS; 139065; 7 hits in 679 CRISPR screens.
DR GenomeRNAi; 139065; -.
DR Pharos; Q8IW52; Tdark.
DR PRO; PR:Q8IW52; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q8IW52; protein.
DR Bgee; ENSG00000179542; Expressed in Brodmann (1909) area 23 and 145 other tissues.
DR Genevisible; Q8IW52; HS.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0007409; P:axonogenesis; IBA:GO_Central.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IBA:GO_Central.
DR GO; GO:1905606; P:regulation of presynapse assembly; IEA:InterPro.
DR GO; GO:0050807; P:regulation of synapse organization; IDA:SynGO.
DR Gene3D; 3.80.10.10; -; 2.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR043326; Slitrk.
DR PANTHER; PTHR45773; PTHR45773; 1.
DR Pfam; PF13855; LRR_8; 2.
DR SMART; SM00369; LRR_TYP; 9.
DR SMART; SM00082; LRRCT; 2.
DR PROSITE; PS51450; LRR; 13.
PE 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; Leucine-rich repeat; Membrane;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..837
FT /note="SLIT and NTRK-like protein 4"
FT /evidence="ECO:0000255"
FT /id="PRO_0000032679"
FT TOPO_DOM 19..618
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 619..639
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 640..837
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 60..81
FT /note="LRR 1"
FT REPEAT 84..105
FT /note="LRR 2"
FT REPEAT 108..129
FT /note="LRR 3"
FT REPEAT 132..153
FT /note="LRR 4"
FT REPEAT 156..177
FT /note="LRR 5"
FT REPEAT 179..200
FT /note="LRR 6"
FT DOMAIN 213..264
FT /note="LRRCT 1"
FT DOMAIN 333..375
FT /note="LRRNT"
FT REPEAT 378..399
FT /note="LRR 7"
FT REPEAT 402..423
FT /note="LRR 8"
FT REPEAT 426..447
FT /note="LRR 9"
FT REPEAT 450..471
FT /note="LRR 10"
FT REPEAT 474..495
FT /note="LRR 11"
FT REPEAT 497..518
FT /note="LRR 12"
FT DOMAIN 531..582
FT /note="LRRCT 2"
FT CARBOHYD 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 325
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 206
FT /note="V -> I (found in a patient with schizophrenia; found
FT as somatic mutation in a colorectal cancer sample; unknown
FT pathological significance; decreased localization to cell
FT membrane; decreased function in synaptogenesis;
FT dbSNP:rs143575705)"
FT /evidence="ECO:0000269|PubMed:16959974,
FT ECO:0000269|PubMed:27812321"
FT /id="VAR_036602"
FT VARIANT 578
FT /note="I -> V (found in a patient with schizophrenia;
FT unknown pathological significance; decreased localization
FT to cell membrane; decreased function in synaptogenesis;
FT dbSNP:rs781863874)"
FT /evidence="ECO:0000269|PubMed:27812321"
FT /id="VAR_077632"
SQ SEQUENCE 837 AA; 94331 MW; F25E3BBAF78F9299 CRC64;
MFLWLFLILS ALISSTNADS DISVEICNVC SCVSVENVLY VNCEKVSVYR PNQLKPPWSN
FYHLNFQNNF LNILYPNTFL NFSHAVSLHL GNNKLQNIEG GAFLGLSALK QLHLNNNELK
ILRADTFLGI ENLEYLQADY NLIKYIERGA FNKLHKLKVL ILNDNLISFL PDNIFRFASL
THLDIRGNRI QKLPYIGVLE HIGRVVELQL EDNPWNCSCD LLPLKAWLEN MPYNIYIGEA
ICETPSDLYG RLLKETNKQE LCPMGTGSDF DVRILPPSQL ENGYTTPNGH TTQTSLHRLV
TKPPKTTNPS KISGIVAGKA LSNRNLSQIV SYQTRVPPLT PCPAPCFCKT HPSDLGLSVN
CQEKNIQSMS ELIPKPLNAK KLHVNGNSIK DVDVSDFTDF EGLDLLHLGS NQITVIKGDV
FHNLTNLRRL YLNGNQIERL YPEIFSGLHN LQYLYLEYNL IKEISAGTFD SMPNLQLLYL
NNNLLKSLPV YIFSGAPLAR LNLRNNKFMY LPVSGVLDQL QSLTQIDLEG NPWDCTCDLV
ALKLWVEKLS DGIVVKELKC ETPVQFANIE LKSLKNEILC PKLLNKPSAP FTSPAPAITF
TTPLGPIRSP PGGPVPLSIL ILSILVVLIL TVFVAFCLLV FVLRRNKKPT VKHEGLGNPD
CGSMQLQLRK HDHKTNKKDG LSTEAFIPQT IEQMSKSHTC GLKESETGFM FSDPPGQKVV
MRNVADKEKD LLHVDTRKRL STIDELDELF PSRDSNVFIQ NFLESKKEYN SIGVSGFEIR
YPEKQPDKKS KKSLIGGNHS KIVVEQRKSE YFELKAKLQS SPDYLQVLEE QTALNKI
