SPTBN4

Protein identityUniProt · HPA

UniProt accession

Q9H254

Gene

SPTBN4

Ensembl

ENSG00000160460

Chromosome

19

Canonical length

2564 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Nucleoli

OverviewNCBI Gene

Spectrin is an actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton, and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. It is composed of two antiparallel dimers of alpha- and beta- subunits. This gene is one member of a family of beta-spectrin genes. The encoded protein localizes to the nuclear matrix, PML nuclear bodies, and cytoplasmic vesicles. A highly similar gene in the mouse is required for localization of specific membrane proteins in polarized regions of neurons. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

2564 residues, UniProt reviewed canonical sequence.

>Q9H254|SPTBN4
     1  MAQVPGEVDN MEGLPAPNNN PAARWESPDR GWEREQPAAS TAAASLFECS RIKALADERE
    61  AVQKKTFTKW VNSHLARVGC HIGDLYVDLR DGFVLTRLLE VLSGEQLPRP TRGRMRIHSL
   121  ENVDKALQFL KEQRVHLENV GSHDIVDGNH RLTLGLVWTI ILRFQIQVIK IETEDNRETR
   181  SAKDALLLWC QMKTAGYPEV NIQNFTTSWR DGLAFNALIH RHRPDLVDFS KLTKSNANYN
   241  LQRAFRTAEQ HLGLARLLDP EDVNMEAPDE KSIITYVVSF YHYFSKMKAL AVEGKRIGKV
   301  LDQVLEVGKI IERYEELAAE LLAWIHRTVG LISNQKFANS LSGVQQQLQA FTAYCTLEKP
   361  VKFQEKGNLE VLLFSIQSKL RACNRRLFVP REGCGIWDID KAWGELEKAE HEREAALRAE
   421  LIRQEKLELL AQRFDHKVAM RESWLNENQR LVSQDNFGYE LPAVEAAMKK HEAIEADIAA
   481  YEERVQGVAE LAQALAAEGY YDIRRVAAQR DSVLRQWALL TGLVGARRTR LEQNLALQKV
   541  FQEMVYMVDW MEEMQAQLLS RECGQHLVEA DDLLQKHGLL EGDIAAQSER VEALNAAALR
   601  FSQLQGYQPC DPQVICNRVN HVHGCLAELQ EQAARRRAEL EASRSLWALL QELEEAESWA
   661  RDKERLLEAA GGGGAAGAAG AAGTAGGAHD LSSTARLLAQ HKILQGELGG RRALLQQALR
   721  CGEELVAAGG AVGPGADTVH LVGLAERAAS ARRRWQRLEE AAARRERRLQ EARALHQFGA
   781  DLDGLLDWLR DAYRLAAAGD FGHDEASSRR LARQHRALTG EVEAHRGPVS GLRRQLATLG
   841  GASGAGPLVV ALQVRVVEAE QLFAEVTEVA ALRRQWLRDA LAVYRMFGEV HACELWIGEK
   901  EQWLLSMRVP DSLDDVEVVQ HRFESLDQEM NSLMGRVLDV NHTVQELVEG GHPSSDEVRS
   961  CQDHLNSRWN RIVELVEQRK EEMSAVLLVE NHVLEVAEVR AQVREKRRAV ESAPRAGGAL
  1021  QWRLSGLEAA LQALEPRQAA LLEEAALLAE RFPAQAARLH QGAEELGAEW GALASAAQAC
  1081  GEAVAAAGRL QRFLHDLDAF LDWLVRAQEA AGGSEGPLPN SLEEADALLA RHAALKEEVD
  1141  QREEDYARIV AASEALLAAD GAELGPGLAL DEWLPHLELG WHKLLGLWEA RREALVQAHI
  1201  YQLFLRDLRQ ALVVLRNQEM ALSGAELPGT VESVEEALKQ HRDFLTTMEL SQQKMQVAVQ
  1261  AAEGLLRQGN IYGEQAQEAV TRLLEKNQEN QLRAQQWMQK LHDQLELQHF LRDCHELDGW
  1321  IHEKMLMARD GTREDNHKLH KRWLRHQAFM AELAQNKEWL EKIEREGQQL MQEKPELAAS
  1381  VRKKLGEIRQ CWAELESTTQ AKARQLFEAS KADQLVQSFA ELDKKLLHME SQLQDVDPGG
  1441  DLATVNSQLK KLQSMESQVE EWYREVGELQ AQTAALPLEP ASKELVGERQ NAVGERLVRL
  1501  LEPLQERRRL LLASKELHQV AHDLDDELAW VQERLPLAMQ TERGNGLQAV QQHIKKNQGL
  1561  RREIQAHGPR LEEVLERAGA LASLRSPEAE AVRRGLEQLQ SAWAGLREAA ERRQQVLDAA
  1621  FQVEQYYFDV AEVEAWLGEQ ELLMMSEDKG KDEQSTLQLL KKHLQLEQGV ENYEESIAQL
  1681  SRQCRALLEM GHPDSEQISR RQSQVDRLYV ALKELGEERR VALEQQYWLY QLSRQVSELE
  1741  HWIAEKEVVA GSPELGQDFE HVSVLQEKFS EFASETGMAG RERLAAVNQM VDELIECGHT
  1801  AAATMAEWKD GLNEAWAELL ELMGTRAQLL AASRELHKFF SDARELQGQI EEKRRRLPRL
  1861  TTPPEPRPSA SSMQRTLRAF EHDLQLLVSQ VRQLQEGAAQ LRTVYAGEHA EAIASREQEV
  1921  LQGWKELLSA CEDARLHVSS TADALRFHSQ VRDLLSWMDG IASQIGAADK PRDVSSVEVL
  1981  MNYHQGLKTE LEARVPELTT CQELGRSLLL NKSAMADEIQ AQLDKLGTRK EEVSEKWDRH
  2041  WEWLQQMLEV HQFAQEAVVA DAWLTAQEPL LQSRELGSSV DEVEQLIRRH EAFRKAAAAW
  2101  EERFSSLRRL TTIEKIKAEQ SKQPPTPLLG RKFFGDPTEL AAKAAPLLRP GGYERGLEPL
  2161  ARRASDTLSA EVRTRVGYVR QELKPERLQP RIDRLPEIPG RVEPAALPAA PEDAAETPAT
  2221  PAAAEQVRPR PERQESADRA EELPRRRRPE RQESVDQSEE AARRRRPERQ ESAEHEAAHS
  2281  LTLGRYEQME RRRERRERRL ERQESSEQEM PIRGDLVKGK ATLADIVEQL QEKEAGPGLP
  2341  AGPSLPQPRE LPPGRLPNGL ELPERTPRPD RPRARDRPKP RRRPRPREGG EGGGSRRSRS
  2401  APAQGGSAPA PPPPPTHTVQ HEGFLLRKRE LDANRKSSNR SWVSLYCVLS KGELGFYKDS
  2461  KGPASGSTHG GEPLLSLHKA TSEVASDYKK KKHVFKLQTQ DGSEFLLQAK DEEEMNGWLE
  2521  AVASSVAEHA EIARWGQTLP TTSSTDEGNP KREGGDRRAS GRRK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SPTBN4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.38

Highest tissue expression

25 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SPTBN4.

Disease | AllUniProt

Conditions SPTBN4 is implicated in, by any mechanism.

• Neurodevelopmental disorder with hypotonia, neuropathy, and deafness (NEDHND) MIM:617519

Disease | GeneticClinVar

34 pathogenic / likely-pathogenic of 647 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurodevelopmental disorder with hypotonia, neuropathy, and deafness
• Inborn genetic diseases
• SPTBN4-related disorder

ReferencesPubMed · IEDB

Publications for SPTBN4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.19

gnomAD pLI

1

gnomAD missense Z

3.93

DepMap mean gene effect

-0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• actin cytoskeleton organization
• actin filament capping
• adult walking behavior
• axonogenesis
• cardiac conduction
• central nervous system projection neuron axonogenesis
• clustering of voltage-gated sodium channels
• fertilization
• negative regulation of heart rate
• neuromuscular junction development
• neuromuscular process
• positive regulation of multicellular organism growth
• protein localization to plasma membrane
• protein-containing complex assembly
• regulation of sodium ion transport
• sensory perception of sound
• transmission of nerve impulse
• vesicle-mediated transport

Molecular functions

• actin binding
• actin filament binding
• ankyrin binding
• cytoskeletal protein-membrane anchor activity
• phosphatase binding
• phospholipid binding
• spectrin binding
• structural constituent of cytoskeleton

Cellular components

• actin filament
• axon hillock
• axon initial segment
• cell body fiber
• cell junction
• cell projection
• cortical actin cytoskeleton
• cytoplasm
• cytosol
• extracellular exosome
• intercalated disc
• juxtaparanode region of axon
• membrane
• neuronal cell body
• node of Ranvier
• nuclear matrix
• paranode region of axon
• plasma membrane
• PML body
• spectrin

Protein domainsUniProt · Pfam · InterPro

• Actinin-type actin-binding domain, conserved site
• Pleckstrin homology domain, spectrin-type
• Calponin homology domain
• Pleckstrin homology domain
• Spectrin repeat
• PH-like domain superfamily
• Spectrin, beta subunit
• Spectrin/alpha-actinin
• CH domain superfamily
• Pleckstrin homology domain 9
• Calponin homology (CH) domain
• Spectrin repeat
• Pleckstrin homology domain

KeywordsUniProt

• Actin capping
• Actin-binding
• Cytoplasm
• Cytoskeleton
• Deafness
• Neuropathy
• Repeat

InteractionsUniProt · HPA

Protein binding partners of SPTBN4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• IQCJ-SCHIP1
• DISC1
• PTPRN