LTBP4

Protein identityUniProt · HPA

UniProt accession

Q8N2S1

Gene

LTBP4

Ensembl

ENSG00000090006

Chromosome

19

Canonical length

1624 aa

Protein class

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

Secretome location

Secreted to extracellular matrix

OverviewNCBI Gene

The protein encoded by this gene binds transforming growth factor beta (TGFB) as it is secreted and targeted to the extracellular matrix. TGFB is biologically latent after secretion and insertion into the extracellular matrix, and sheds TGFB and other proteins upon activation. Defects in this gene may be a cause of cutis laxa and severe pulmonary, gastrointestinal, and urinary abnormalities. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

Canonical amino-acid sequenceUniProt

1624 residues, UniProt reviewed canonical sequence.

>Q8N2S1|LTBP4
     1  MPRPGTSGRR PLLLVLLLPL FAAATSAASP SPSPSQVVEV PGVPSRPASV AVCRCCPGQT
    61  SRRSRCIRAF CRVRSCQPKK CAGPQRCLNP VPAVPSPSPS VRKRQVSLNW QPLTLQEARA
   121  LLKRRRPRGP GGRGLLRRRP PQRAPAGKAP VLCPLICHNG GVCVKPDRCL CPPDFAGKFC
   181  QLHSSGARPP APAVPGLTRS VYTMPLANHR DDEHGVASMV SVHVEHPQEA SVVVHQVERV
   241  SGPWEEADAE AVARAEAAAR AEAAAPYTVL AQSAPREDGY SDASGFGYCF RELRGGECAS
   301  PLPGLRTQEV CCRGAGLAWG VHDCQLCSER LGNSERVSAP DGPCPTGFER VNGSCEDVDE
   361  CATGGRCQHG ECANTRGGYT CVCPDGFLLD SSRSSCISQH VISEAKGPCF RVLRDGGCSL
   421  PILRNITKQI CCCSRVGKAW GRGCQLCPPF GSEGFREICP AGPGYHYSAS DLRYNTRPLG
   481  QEPPRVSLSQ PRTLPATSRP SAGFLPTHRL EPRPEPRPDP RPGPELPLPS IPAWTGPEIP
   541  ESGPSSGMCQ RNPQVCGPGR CISRPSGYTC ACDSGFRLSP QGTRCIDVDE CRRVPPPCAP
   601  GRCENSPGSF RCVCGPGFRA GPRAAECLDV DECHRVPPPC DLGRCENTPG SFLCVCPAGY
   661  QAAPHGASCQ DVDECTQSPG LCGRGACKNL PGSFRCVCPA GFRGSACEED VDECAQEPPP
   721  CGPGRCDNTA GSFHCACPAG FRSRGPGAPC QDVDECARSP PPCTYGRCEN TEGSFQCVCP
   781  MGFQPNTAGS ECEDVDECEN HLACPGQECV NSPGSFQCRT CPSGHHLHRG RCTDVDECSS
   841  GAPPCGPHGH CTNTEGSFRC SCAPGYRAPS GRPGPCADVN ECLEGDFCFP HGECLNTDGS
   901  FACTCAPGYR PGPRGASCLD VDECSEEDLC QSGICTNTDG SFECICPPGH RAGPDLASCL
   961  DVDECRERGP ALCGSQRCEN SPGSYRCVRD CDPGYHAGPE GTCDDVDECQ EYGPEICGAQ
  1021  RCENTPGSYR CTPACDPGYQ PTPGGGCQDV DECRNRSFCG AHAVCQNLPG SFQCLCDQGY
  1081  EGARDGRHCV DVNECETLQG VCGAALCENV EGSFLCVCPN SPEEFDPMTG RCVPPRTSAG
  1141  TFPGSQPQAP ASPVLPARPP PPPLPRRPST PRQGPVGSGR RECYFDTAAP DACDNILARN
  1201  VTWQECCCTV GEGWGSGCRI QQCPGTETAE YQSLCPHGRG YLAPSGDLSL RRDVDECQLF
  1261  RDQVCKSGVC VNTAPGYSCY CSNGYYYHTQ RLECIDNDEC ADEEPACEGG RCVNTVGSYH
  1321  CTCEPPLVLD GSQRRCVSNE SQSLDDNLGV CWQEVGADLV CSHPRLDRQA TYTECCCLYG
  1381  EAWGMDCALC PAQDSDDFEA LCNVLRPPAY SPPRPGGFGL PYEYGPDLGP PYQGLPYGPE
  1441  LYPPPALPYD PYPPPPGPFA RREAPYGAPR FDMPDFEDDG GPYGESEAPA PPGPGTRWPY
  1501  RSRDTRRSFP EPEEPPEGGS YAGSLAEPYE ELEAEECGIL DGCTNGRCVR VPEGFTCRCF
  1561  DGYRLDMTRM ACVDINECDE AEAASPLCVN ARCLNTDGSF RCICRPGFAP THQPHHCAPA
  1621  RPRA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LTBP4 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

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.46

Highest tissue expression

549 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LTBP4.

Disease | AllUniProt

Conditions LTBP4 is implicated in, by any mechanism.

• Urban-Rifkin-Davis syndrome (URDS) MIM:613177
• Duchenne muscular dystrophy (DMD) MIM:310200

Disease | GeneticClinVar

72 pathogenic / likely-pathogenic of 1,373 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies
• LTBP4-related disorder
• Cutis laxa

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)

0.33

gnomAD pLI

0.5

gnomAD missense Z

2.35

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

• elastic fiber assembly
• hormone secretion
• protein folding
• regulation of cell growth
• regulation of transforming growth factor beta receptor signaling pathway
• transforming growth factor beta receptor signaling pathway

Molecular functions

• calcium ion binding
• glycosaminoglycan binding
• integrin binding
• transforming growth factor beta binding
• transforming growth factor beta receptor activity

Cellular components

• extracellular matrix
• extracellular region
• extracellular space
• microfibril

Protein domainsUniProt · Pfam · InterPro

• EGF-type aspartate/asparagine hydroxylation site
• EGF-like domain
• EGF-like calcium-binding domain
• Growth factor receptor cysteine-rich domain superfamily
• EGF-like, conserved site
• TB domain
• EGF-like calcium-binding, conserved site
• TGF-beta binding (TB) domain superfamily
• NOTCH1, EGF-like calcium-binding domain
• Extracellular matrix structural protein
• TB domain
• Calcium-binding EGF domain
• Human growth factor-like EGF

KeywordsUniProt

• Disulfide bond
• EGF-like domain
• Extracellular matrix
• Glycoprotein
• Growth factor binding
• Repeat
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of LTBP4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• EFEMP2
• LTBP1
• TGFB1
• ATXN7