Q9NQ75 (CASS4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cas scaffolding protein family member 4

Alternative name(s):
HEF-like protein
HEF1-EFS-p130Cas-like protein
Short name=HEPL

Gene names

Name:	CASS4
Synonyms:	C20orf32, HEFL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	786 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Docking protein that plays a role in tyrosine kinase-based signaling related to cell adhesion and cell spreading. Regulates PTK2/FAK1 activity, focal adhesion integrity, and cell spreading. Ref.7
Subunit structure	Interacts (via SH3 domain) with PTK2/FAK1 (via C-terminus). Ref.7
Subcellular location	Cytoplasm › cytoskeleton. Cell junction › focal adhesion Ref.7.
Tissue specificity	Expressed abundantly in lung and spleen. Also highly expressed in ovarian and leukemia cell lines. Ref.7
Post-translational modification	Phosphorylated on tyrosines by SRC. Ref.7
Sequence similarities	Belongs to the CAS family. Contains 1 SH3 domain.
Sequence caution	The sequence CAC00655.1 differs from that shown. Reason: Frameshift at positions 336 and 342.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell junction Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH3 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW phosphorelay signal transduction system Inferred from electronic annotation. Source: GOC signal transduction by phosphorylation Inferred from electronic annotation. Source: GOC
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell focal adhesion Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: InterPro
Molecular_function	phosphorelay sensor kinase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: Q9NQ75-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9NQ75-2)

The sequence of this isoform differs from the canonical sequence as follows:
     652-786: NPGPLIPQPS...HTRQFRGTLG → VSSEFQVIEKGASIVTWSSGY

Note: No experimental confirmation available.

Isoform 3 (identifier: Q9NQ75-3)

The sequence of this isoform differs from the canonical sequence as follows:
     215-651: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 786

786

Cas scaffolding protein family member 4

PRO_0000079425

Regions

Domain

11 – 73

63

SH3

Compositional bias

274 – 277

4

Poly-Ser

Compositional bias

373 – 429

57

Ser-rich

Amino acid modifications

Modified residue

200

1

Phosphoserine Ref.6

Modified residue

249

1

Phosphoserine Ref.6

Modified residue

305

1

Phosphoserine Ref.6

Natural variations

Alternative sequence

215 – 651

437

Missing in isoform 3.

VSP_003806

Alternative sequence

652 – 786

135

NPGPL…RGTLG → VSSEFQVIEKGASIVTWSSG Y in isoform 2.

VSP_003807

Natural variant

491

1

R → K.
Corresponds to variant rs16979936 [ dbSNP | Ensembl ].

VAR_054084

Natural variant

629

1

T → N.
Corresponds to variant rs6069755 [ dbSNP | Ensembl ].

VAR_054085

Natural variant

660

1

P → S. Ref.2
Corresponds to variant rs35031530 [ dbSNP | Ensembl ].

VAR_054086

Natural variant

780

1

Q → H.
Corresponds to variant rs7272702 [ dbSNP | Ensembl ].

VAR_054087

Experimental info

Sequence conflict

329

1

Y → N in CAC00655. Ref.1

Sequence conflict

350

1

Missing in CAC00655. Ref.1

Sequence conflict

488

1

E → A in CAC00655. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

786

Helix Strand Turn

Details...

Beta strand

14 – 20

7

Beta strand

25 – 29

5

Beta strand

38 – 43

6

Beta strand

51 – 58

8

Beta strand

61 – 64

4

Turn

65 – 67

3

Beta strand

68 – 70

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 10, 2002. Version 2. Checksum: 0E84CD7F60A361DB	FASTA	786	87,144
	10 20 30 40 50 60 MKGTGIMDCA PKALLARALY DNCPDCSDEL AFSRGDILTI LEQHVPESEG WWKCLLHGRQ 70 80 90 100 110 120 GLAPANRLQI LTEVAADRPC PPFLRGLEEA PASSEETYQV PTLPRPPTPG PVYEQMRSWA 130 140 150 160 170 180 EGPQPPTAQV YEFPDPPTSA RIICEKTLSF PKQAILTLPR PVRASLPTLP SQVYDVPTQH 190 200 210 220 230 240 RGPVVLKEPE KQQLYDIPAS PKKAGLHPPD SQASGQGVPL ISVTTLRRGG YSTLPNPQKS 250 260 270 280 290 300 EWIYDTPVSP GKASVRNTPL TSFAEESRPH ALPSSSSTFY NPPSGRSRSL TPQLNNNVPM 310 320 330 340 350 360 QKKLSLPEIP SYGFLVPRGT FPLDEDVSYK VPSSFLIPRV EQQNTKPNIY DIPKATSSVS 370 380 390 400 410 420 QAGKELEKAK EVSENSAGHN SSWFSRRTTS PSPEPDRLSG SSSDSRASIV SSCSTTSTDD 430 440 450 460 470 480 SSSSSSEESA KELSLDLDVA KETVMALQHK VVSSVAGLML FVSRKWRFRD YLEANIDAIH 490 500 510 520 530 540 RSTDHIEESV REFLDFARGV HGTACNLTDS NLQNRIRDQM QTISNSYRIL LETKESLDNR 550 560 570 580 590 600 NWPLEVLVTD SVQNSPDDLE RFVMVARMLP EDIKRFASIV IANGRLLFKR NCEKEETVQL 610 620 630 640 650 660 TPNAEFKCEK YIQPPQRETE SHQKSTPSTK QREDEHSSEL LKKNRANICG QNPGPLIPQP 670 680 690 700 710 720 SSQQTPERKP RLSEHCRLYF GALFKAISAF HGSLSSSQPA EIITQSKLVI MVGQKLVDTL 730 740 750 760 770 780 CMETQERDVR NEILRGSSHL CSLLKDVALA TKNAVLTYPS PAALGHLQAE AEKLEQHTRQ FRGTLG
	Isoform 2 [UniParc]. Checksum: 9100A597C52C415F	FASTA	672	74,587
	10 20 30 40 50 60 MKGTGIMDCA PKALLARALY DNCPDCSDEL AFSRGDILTI LEQHVPESEG WWKCLLHGRQ 70 80 90 100 110 120 GLAPANRLQI LTEVAADRPC PPFLRGLEEA PASSEETYQV PTLPRPPTPG PVYEQMRSWA 130 140 150 160 170 180 EGPQPPTAQV YEFPDPPTSA RIICEKTLSF PKQAILTLPR PVRASLPTLP SQVYDVPTQH 190 200 210 220 230 240 RGPVVLKEPE KQQLYDIPAS PKKAGLHPPD SQASGQGVPL ISVTTLRRGG YSTLPNPQKS 250 260 270 280 290 300 EWIYDTPVSP GKASVRNTPL TSFAEESRPH ALPSSSSTFY NPPSGRSRSL TPQLNNNVPM 310 320 330 340 350 360 QKKLSLPEIP SYGFLVPRGT FPLDEDVSYK VPSSFLIPRV EQQNTKPNIY DIPKATSSVS 370 380 390 400 410 420 QAGKELEKAK EVSENSAGHN SSWFSRRTTS PSPEPDRLSG SSSDSRASIV SSCSTTSTDD 430 440 450 460 470 480 SSSSSSEESA KELSLDLDVA KETVMALQHK VVSSVAGLML FVSRKWRFRD YLEANIDAIH 490 500 510 520 530 540 RSTDHIEESV REFLDFARGV HGTACNLTDS NLQNRIRDQM QTISNSYRIL LETKESLDNR 550 560 570 580 590 600 NWPLEVLVTD SVQNSPDDLE RFVMVARMLP EDIKRFASIV IANGRLLFKR NCEKEETVQL 610 620 630 640 650 660 TPNAEFKCEK YIQPPQRETE SHQKSTPSTK QREDEHSSEL LKKNRANICG QVSSEFQVIE 670 KGASIVTWSS GY
	Isoform 3 [UniParc]. Checksum: 0DC83EBD13CF6839	FASTA	349	38,346
	10 20 30 40 50 60 MKGTGIMDCA PKALLARALY DNCPDCSDEL AFSRGDILTI LEQHVPESEG WWKCLLHGRQ 70 80 90 100 110 120 GLAPANRLQI LTEVAADRPC PPFLRGLEEA PASSEETYQV PTLPRPPTPG PVYEQMRSWA 130 140 150 160 170 180 EGPQPPTAQV YEFPDPPTSA RIICEKTLSF PKQAILTLPR PVRASLPTLP SQVYDVPTQH 190 200 210 220 230 240 RGPVVLKEPE KQQLYDIPAS PKKAGLHPPD SQASNPGPLI PQPSSQQTPE RKPRLSEHCR 250 260 270 280 290 300 LYFGALFKAI SAFHGSLSSS QPAEIITQSK LVIMVGQKLV DTLCMETQER DVRNEILRGS 310 320 330 340 SHLCSLLKDV ALATKNAVLT YPSPAALGHL QAEAEKLEQH TRQFRGTLG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"HEF-like protein (HEFL) is involved in integrin signalling." Jahn T., Will T., Bresolin G., Coutinho S., Peschel C., Duyster J. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT SER-660. Tissue: Placenta.
[3]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[6]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-200; SER-249 AND SER-305, MASS SPECTROMETRY. Tissue: Platelet.
[7]	"A novel Cas family member, HEPL, regulates FAK and cell spreading." Singh M.K., Dadke D., Nicolas E., Serebriiskii I.G., Apostolou S., Canutescu A., Egleston B.L., Golemis E.A. Mol. Biol. Cell 19:1627-1636(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PTK2/FAK1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PHOSPHORYLATION BY SRC.
[8]	"Solution structure of RSGI RUH-036, an SH3 domain from human." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 14-71.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ276678 mRNA. Translation: CAC00655.1. Frameshift.
AK027760 mRNA. Translation: BAB55351.1.
AL121914 Genomic DNA. Translation: CAC12719.2.
AL121914 Genomic DNA. Translation: CAI19330.1.
CH471077 Genomic DNA. Translation: EAW75546.1.
CH471077 Genomic DNA. Translation: EAW75547.1.
BC027951 mRNA. Translation: AAH27951.1.

IPI

IPI00160340.
IPI00220358.
IPI00220359.

RefSeq

NP_001157586.1. NM_001164114.1.
NP_001157587.1. NM_001164115.1.
NP_001157588.1. NM_001164116.1.
NP_065089.2. NM_020356.3.

UniGene

Hs.473144.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CRE	NMR	-	A	14-71	[»]

ProteinModelPortal

Q9NQ75.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NQ75. 1 interaction.

STRING

9606.ENSP00000353462.

PTM databases

PhosphoSite

Q9NQ75.

Polymorphism databases

DMDM

23813906.

Proteomic databases

PaxDb

Q9NQ75.

PRIDE

Q9NQ75.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000360314; ENSP00000353462; ENSG00000087589.
ENST00000371336; ENSP00000360387; ENSG00000087589.
ENST00000434344; ENSP00000410027; ENSG00000087589.

GeneID

57091.

KEGG

hsa:57091.

UCSC

uc002xxp.2. human.
uc002xxq.4. human.
uc010gio.2. human.

Organism-specific databases

CTD

57091.

GeneCards

GC20P054987.

H-InvDB

HIX0015932.

HGNC

HGNC:15878. CASS4.

HPA

HPA012659.

neXtProt

NX_Q9NQ75.

PharmGKB

PA162381095.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG72030.

HOGENOM

HOG000111312.

HOVERGEN

HBG107575.

InParanoid

Q9NQ75.

OMA

IYDIPKA.

OrthoDB

EOG4K9BCF.

PhylomeDB

Q9NQ75.

Gene expression databases

Bgee

Q9NQ75.

CleanEx

HS_CASS4.

Genevestigator

Q9NQ75.

GermOnline

ENSG00000087589. Homo sapiens.

Family and domain databases

InterPro

IPR021901. CAS_DUF3513.
IPR014928. Serine_rich.
IPR001452. SH3_domain.
IPR003661. Sig_transdc_His_kin_sub1_dim/P.
[Graphical view]

Pfam

PF12026. DUF3513. 1 hit.
PF08824. Serine_rich. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

SMART

SM00388. HisKA. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF50044. SH3. 1 hit.

PROSITE

PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9NQ75.

GenomeRNAi

57091.

NextBio

62895.

Entry information

Entry name

CASS4_HUMAN

Accession

Primary (citable) accession number: Q9NQ75
Secondary accession number(s): E1P5Z8 , Q5QPD6, Q96K09, Q9BYL5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 10, 2002
Last sequence update:	October 10, 2002
Last modified:	May 1, 2013
This is version 114 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.